@article {pmid41666920, year = {2026}, author = {da Silva, AC and Lapkin, J and Yin, Q and Muller, E and Almeida, A}, title = {Meta-analysis of the uncultured gut microbiome across 11,115 global metagenomes reveals a candidate signature of health.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2026.01.013}, pmid = {41666920}, issn = {1934-6069}, abstract = {The human gut microbiome is important for host health, yet over 60% of gut species remain uncultured and inaccessible to experimental manipulation. Here, we analyze 11,115 human gut metagenomes from 39 countries, 13 noncommunicable diseases, and healthy individuals to understand the clinical relevance of the uncultured microbiome worldwide. We identify 317 species linked to distinct clinical states, noting an overrepresentation of uncultured bacteria in healthy subjects. The genus CAG-170 emerged as the strongest health-associated lineage across multiple diseases and geographies, standing as the most central taxon based on ecological networks of healthy populations. We find that CAG-170 is temporally stable, with its abundance and subspecies diversity negatively correlated with gut imbalance over time. Functional predictions show CAG-170 species have greater vitamin B12 biosynthesis capacity and cross-feeding potential, providing important biological insights into this elusive genus. Our findings shed light on the underexplored role of uncultured gut species in health and disease.}, } @article {pmid41666857, year = {2026}, author = {Kumar, A and Gantenbein, B}, title = {A Commentary on "The Gut-Disc Axis: Unraveling the Microbiome's Role in Lumbar Disc Herniation".}, journal = {Neurospine}, volume = {23}, number = {1}, pages = {29-30}, doi = {10.14245/ns.26520126.0063}, pmid = {41666857}, issn = {2586-6583}, support = {//iPSpine project/ ; //Marie Skłodowska Curie International Training Network/ ; //three Swiss National Science Foundation projects/ ; //Spark/ ; }, } @article {pmid41666856, year = {2026}, author = {Ambrosio, L and Schol, J and Sima, S and Ruiz-Fernandez, C and Chen, V and Russo, F and Han, IH and Sakai, D and Vadalà, G and Denaro, V and Diwan, AD and , }, title = {The Gut-Disc Axis: Unraveling the Microbiome's Role in Lumbar Disc Herniation.}, journal = {Neurospine}, volume = {23}, number = {1}, pages = {3-28}, doi = {10.14245/ns.2551584.792}, pmid = {41666856}, issn = {2586-6583}, support = {//AO Spine/ ; //AO Spine Knowledge Forum Degenerative/ ; }, abstract = {Lumbar disc herniation (LDH) is one of the most common causes of low back and leg pain. While mechanical and degenerative factors have long been considered the main contributors, persistent or recurrent symptoms in many patients suggest additional biological mechanisms. Recent research has highlighted the microbiome as a potential modulator of inflammation, immune response, and pain sensitization, introducing the "gut-spine axis" concept. This scoping review summarizes the current evidence on the role of both gut and local disc microbiota in LDH. A systematic search of PubMed/MEDLINE and Scopus was conducted up to June 2025, following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Twenty-six studies were included, encompassing preclinical and clinical investigations. Animal models showed that LDH may alter gut microbial composition and that microbiome-targeted interventions can reduce inflammation, neuroinflammatory signaling, and pain sensitivity. In human studies, low-virulence bacteria, particularly Cutibacterium acnes, were frequently detected in surgically excised intervertebral discs, although results were inconsistent due to methodological heterogeneity and potential contamination. Some studies reported associations between bacterial colonization and Modic changes, disc height loss, or chronic pain. Additionally, genetic and metabolomic data suggest that gut dysbiosis and related microbial metabolites may influence systemic immune and metabolic pathways implicated in disc degeneration and pain perception. Overall, the current evidence suggests the biological plausibility of microbiome involvement in LDH pathophysiology, acting through both systemic and local mechanisms. However, the available data remain preliminary, and no mechanistic study has confirmed the observed correlations to date. Further standardized, contamination-aware studies are required to clarify causality and explore microbiome-targeted therapeutic strategies.}, } @article {pmid41666847, year = {2026}, author = {Matijašević, D and Kljajević, N and Malešević, M and Gardijan, L and Stanovčić, S and Jovčić, B and Novović, K}, title = {Heating-season dynamics of the airborne microbiome, resistome and mobilome in Belgrade, Serbia.}, journal = {Environment international}, volume = {208}, number = {}, pages = {110114}, doi = {10.1016/j.envint.2026.110114}, pmid = {41666847}, issn = {1873-6750}, abstract = {Antimicrobial resistance (AMR) and air pollution are critical global health challenges, but their interplay remains poorly understood, particularly in Europe. Serbia, characterized by extensive antibiotic use, high prevalence of multidrug-resistant isolates and severe air pollution, provides a relevant model to study airborne AMR dissemination. During the heating season, air samples were collected at eight locations in Belgrade, representing industrial, traffic loaded and background environments. Shotgun metagenomics, co-occurrence networks and NMDS ordinations were applied to investigate the relationships between atmospheric pollutants, antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), metal resistance genes (MRGs) and mobile genetic elements (MGEs). Autumn microbiomes were dominated by Lactococcus spp., whereas winter lacked such dominance. ARGs associated with antibiotic inactivation accounted for > 50% in autumn and > 75% in winter, with β-lactam resistance (blaTEM) predominating in both seasons. Winter resistomes also showed more consistent patterns of BRGs and MRGs, with multibiocide/acid and multimetal resistance prevailing. Integron analysis revealed predominance of class 1 integrons (intI1) commonly associated with Escherichia coli. Plasmid-related contigs were most similar to sequences reported in Acinetobacter baumannii and E. coli, while plasmid signatures related to Lactococcus lactis were also detected in autumn. Crucially, the network analysis revealed a seasonal restructuring of the airborne resistome. Autumn networks displayed fragmented structure, showing antagonism between Lactococcus and Escherichia, whereas winter networks coalesced into a densely interconnected superhub that could facilitate horizontal gene transfer and co-selection of resistance determinants. These findings suggest that prolonged air pollution and seasonality jointly shape airborne resistomes, reinforcing the need for integrated environmental and AMR surveillance in highly polluted urban areas.}, } @article {pmid41666743, year = {2026}, author = {Tong, J and Zhang, W and Yu, F and Liu, R and Yan, Y and Li, Y}, title = {Flow regime specific regulation shapes microbial-mediated nitrogen cycling of plain tidal river network.}, journal = {Water research}, volume = {294}, number = {}, pages = {125510}, doi = {10.1016/j.watres.2026.125510}, pmid = {41666743}, issn = {1879-2448}, abstract = {Inter-basin water diversion projects are critical for mitigating regional water scarcity yet impose complex ecological pressures on recipient river networks. Understanding their microbial impacts is essential to optimize sluice operations and minimize ecosystem disruption. As pivotal regulators of biogeochemical cycles and ecological health, microbial communities in plain tidal networks remain poorly characterized under diversion-induced hydrodynamic shifts. This study integrated intensive field sampling across water and sediment sites in the lower tidal plain river network with a calibrated one-dimensional MIKE 11 hydrodynamic model, stratifying sampling points into low, medium, and high flow-velocity regimes. Results indicate a positive correlation between hydrological regime stability and microbial community stability. While community composition reorganizes along the flow gradient, microbial diversity and core taxa abundance remain resilient. Co-occurrence network analysis reveals that intermediate flow variability maximizes network connectivity and modular cohesion, whereas extreme hydrological conditions fragment network structures. Landscape modeling further identifies high-discharge variability zones as distinct "hotspots" for denitrification and organic matter processing, while hydrologically stable reaches act as "functional shadows" (coldspots). Structural equation modeling confirms that hydrological regulation operates not merely through direct physical forcing but via a "resource-diversity-function" cascade, indirectly driving biogeochemical cycles by modulating nutrient fluxes and reshaping microbial diversity. Consequently, this study recommends shifting management strategies toward maintaining intermediate flow variability to reinforce the robustness and self-purification capacity of riverine ecological networks.}, } @article {pmid41666736, year = {2026}, author = {Xu, A and Liu, Z and Gao, D and Gong, X and Wang, C and Huang, Z and Zhan, X and Liang, H}, title = {Core microbial community assembly driving greenhouse gas mitigation in tidal flow constructed wetlands treating polluted surface water.}, journal = {Journal of environmental management}, volume = {401}, number = {}, pages = {128864}, doi = {10.1016/j.jenvman.2026.128864}, pmid = {41666736}, issn = {1095-8630}, abstract = {The limited understanding of microbial assembly mechanisms in tidal flow constructed wetlands (TFCW) hinders the steering of microbiome for the pollutant removal and greenhouse gas (GHG) mitigation. In this study, TFCW with different flooding and draining (F/D) durations (TFCW1: 22 h/2 h; TFCW2: 21 h/3 h; TFCW3: 20 h/4 h; TFCW4: 19 h/5 h) were established to investigate nitrogen removal, GHG mitigation and microbial metabolic mechanisms for treating polluted surface water. A moderately shortened flooding period (20 h/4 h) reconfigured the core microbiome, resulting in an 90% total nitrogen removal and a 107 mg CO2-eq/m[2]/h global warming potential. This regime intensified habitat heterogeneity, fostering a complex and stable co-occurrence network. Structurally, this ecological restructuring enriched keystone taxa such as Nitrospira, Thauera, Candidatus Brocadia, facilitating nitrogen synergistic transformation. The structured microbial cooperation suppressed nitrous oxide production by promoting the complete reduction of nitrogen intermediates, while the draining period facilitated methane oxidation. Our findings elucidate a core ecological strategy whereby microbial communities adapt to hydraulic regime by restructuring interactions to maintain ecosystem functionality. Collectively, these findings offer guidance for the integrated optimization of GHG control in constructed wetlands.}, } @article {pmid41666555, year = {2026}, author = {Arisha, R and Sengupta, S and Dewangan, HK and Saeedan, AS and Ansari, MN and Rashid, S}, title = {The future of PCOS management: Disease modification through regenerative, metabolic, and digital therapeutics.}, journal = {Pathology, research and practice}, volume = {280}, number = {}, pages = {156397}, doi = {10.1016/j.prp.2026.156397}, pmid = {41666555}, issn = {1618-0631}, abstract = {Polycystic ovary syndrome (PCOS) represents the leading endocrine problem affecting women of reproductive age, leading to serious complications related to reproduction, metabolism, and psychosocial aspects. Nonetheless, due to the heterogeneous nature and complex pathophysiology associated with PCOS, this condition remains uncaptured or undertreated as it often gets diagnosed at an advanced age due to its prevalence. The pathophysiology associated with PCOS involves the combination of genetic factors, resistance, neuroendocrine imbalance, as well as environmental factors that contribute towards hyperandrogenism, ovulation defects, and metabolic disorders as well. Hence, a comprehensive literature survey was conducted using PubMed, Scopus, Web of Science, and Google Scholar, prioritizing international clinical guidelines, meta-analyses, randomized controlled trials, systematic reviews, and high-quality preclinical studies that covered publications from 2015 to 2025, with the search terms being keywords specific to the disease. At present, the treatments such as lifestyle correction, combined oral pills, and anti-insulin therapies along with anti-androgen drugs only have symptomatic roles with no impact on the underlying mechanism associated with PCOS. However, new therapeutic modalities have been proposed from the past few years that is addressed by this narrative review, including mesenchymal stem cell-based therapies, microbiome therapies, as well as second-generation pharmacotherapies such as GLP-1 agonists and SGLT2 inhibitors. This is being complemented by equal developments in artificial intelligence and the learning process. However, there is work that needs to be done in relation to harmonizing the criteria for diagnosis and the long-term safety and accessibility of effective treatments. Moving forward, the focus should be placed on phenotype-based, precision, and multidisciplinary treatments of PCOS, along with emphasizing the necessity of sturdy clinical validation before worldwide adoption.}, } @article {pmid41666549, year = {2026}, author = {Kang, X and Zhao, Z and Zhu, X and Ju, F}, title = {Uncovering plasticizer-degrading potential in landfill microbiomes with curated PzDE-HMM database and multi-scale validation from isolates to synthetic consortia.}, journal = {Journal of hazardous materials}, volume = {504}, number = {}, pages = {141398}, doi = {10.1016/j.jhazmat.2026.141398}, pmid = {41666549}, issn = {1873-3336}, abstract = {Plasticizers are widely used additives that leach from plastic products and accumulate in landfills, yet the microbial functions supporting their degradation remain poorly resolved. Here, we combined curated functional annotation, substrate-driven enrichment, and isolate-level validation to dissect plasticizer degradation in landfill microbiomes. A plasticizer-degrading enzyme (PzDE) hidden Markov model database (PzDE-HMM) was assembled from 49 experimentally validated enzyme families. It was applied to metagenomes from five landfill niches, identifying 2219 candidate plasticizer-degrading genes, which is 3.6- and 19-fold more than those identified by KofamScan- and BLASTp-based annotation methods, respectively. Enrichment with three legacy phthalates (DEHP, DIDP, DBP) and three non-phthalate plasticizers (DOTP, DOA, ATBC) drove pronounced shifts in landfill microbial communities and functional gene repertoires, revealing coexisting broad-spectrum and substrate-specific degraders. Culture-based isolation from enriched media yielded 51 strains, and three representative isolates showed concordance between PzDE-HMM-predicted gene repertoires, substrate breadth, and degradation ability. Synthetic consortia assembled from these strains exhibited complementary degradation capacities and achieved higher removal of several plasticizers than the best single strains, illustrating how complementary gene sets can be combined to enhance multi-substrate degradation. Together, PzDE-HMM annotation workflow and this multilevel prediction-enrichment-isolate-consortium framework uncover the plasticizer-degrading and bioremediation potential of landfill microbiomes and provide a reusable resource and workflow for future plasticizer-focused microbiome studies.}, } @article {pmid41666295, year = {2026}, author = {Werneburg, GT and Gross, MD and Hettel, DR and Lyon, M and Jeong, SH and McSweeney, S and Knorr, JM and Adler, A and Dang, T and Orji, P and Ramanujan, S and Goldman, HB and Vasavada, SP and Miller, AW}, title = {Urinary Microbiome and Metabolome Differentiate Overactive Bladder from the Physiological State, and Reflect Recent Antibiotic Use and Treatment Response.}, journal = {The Journal of urology}, volume = {}, number = {}, pages = {101097JU0000000000004990}, doi = {10.1097/JU.0000000000004990}, pmid = {41666295}, issn = {1527-3792}, abstract = {OBJECTIVE: To characterize and compare the bacterial urinary microbiome in individuals with and without overactive bladder (OAB), and secondarily compare its composition by phenotype, comorbidities, recent antibiotic exposure, and therapeutic response.

MATERIAL AND METHODS: We isolated DNA and metabolites from the urine of females without urologic diagnoses, and with OAB. Bacterial profiles were generated with 16S rRNA sequencing and metabolite profiles were generated with untargeted metabolomics. Alpha- and beta-diversity, relative abundance, and microbe-metabolite co-occurrence interaction networks were identified by OAB status and patient characteristics.

RESULTS: One hundred fifty-two participants were included, and bacteria were identified in all urine samples. Bacilliota was the most abundant phylum and Lactobacillus, Escherichia, and Prevotella the most abundant genera in individuals without urologic conditions. Megasphaera and Scardovia were the primary genera more abundant in individuals without OAB than those with OAB (each: log2-fold change [FC] -3.7 p<0.001). Escherichia (log2-FC 5.9), Enterococcus (log2-FC 3.5), and Proteus (log2-FC 3.1) were the primary genera significantly more abundant in the urine of individuals with OAB than those without (p<0.001). Beta diversity differed between individuals with and without OAB and by diabetes mellitus status (p<0.05). Relative abundance of bacterial genera differed by OAB phenotype, diabetes mellitus status, recent antibiotic exposure, and response to OAB treatment (p<0.05). Microbe-metabolite interaction networks demonstrated central microbes and metabolites in the healthy and OAB states.

CONCLUSIONS: The study provides new understanding regarding the physiological bacterial composition of urine, as well as that in the context of OAB. Further, microbiota differed by patient phenotype, comorbidities, recent antibiotic exposure, and therapeutic response. The results inform strategies of microbiological modulation to augment existing therapeutic strategies.}, } @article {pmid41666179, year = {2026}, author = {Gentilini, F and Ogundipe, TG and Turba, ME and Romagnoli, N and Lambertini, C and Pollera, C and Cremonesi, P and Stancampiano, L}, title = {Beyond the host: Unveiling the independent microbiome of equine gastrointestinal nematodes.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0339596}, pmid = {41666179}, issn = {1932-6203}, mesh = {Animals ; Horses/parasitology/microbiology ; *Nematoda/microbiology/genetics ; *Gastrointestinal Microbiome/genetics ; Female ; Male ; RNA, Ribosomal, 16S/genetics ; *Nematode Infections/veterinary/parasitology ; Feces/microbiology/parasitology ; *Horse Diseases/parasitology/microbiology ; Host-Parasite Interactions ; Bacteria/genetics/classification ; }, abstract = {Gastrointestinal nematode infections significantly impact equine health and welfare, with rising anthelmintic resistance demanding alternative control strategies. Emerging evidence suggests that parasitic nematodes harbour distinct microbiomes, potentially influencing host-parasite dynamics and parasite survival. This study aimed to characterize and compare the microbiomes of equine gastrointestinal nematodes and their hosts, focusing on differences in composition, diversity, and core microbiota structure across different intestinal sites, nematode subfamilies, and sexes. Faecal and nematode samples were collected from equids (Equus caballus and Equus asinus) at slaughterhouses. DNA was extracted, and the V3-V4 regions of the 16S rRNA gene were amplified and sequenced using the Illumina iSeq 100 platform. Bioinformatic analyses were performed with QIIME2 and MicrobiomeAnalyst, and statistical comparisons employed PERMANOVA, LEfSe, and alpha and beta diversity metrics. Nematodes exhibited a distinct microbiome dominated by Firmicutes, Proteobacteria, Bacteroidota, Verrucomicrobiota, and Actinobacteriota, differing significantly from the faecal microbiota. Alpha diversity analyses revealed lower richness in nematodes, while beta diversity indicated distinct community structures (p = 0.007). Microbial composition varied by gastrointestinal site, nematode subfamily, and sex. Proteobacteria were consistently enriched in nematodes, particularly in the caecum. Core microbiome analysis identified exclusive nematode-associated taxa such as Fusobacterium, Mesorhizobium, and Mycoplasma. Equine gastrointestinal nematodes harbour independent and structured microbiomes, distinct from those of their hosts. These findings underscore the ecological specialization of nematodes and highlight the potential of targeting parasite-associated microbiota for novel control strategies.}, } @article {pmid41666176, year = {2026}, author = {Ren, S and Wu, Q and Li, T and Jiang, L and Xiao, X}, title = {The predictive value of a multivariable model based on vaginal Lactobacillus relative abundance and microecological features at 24 weeks gestation and before delivery in spontaneous preterm birth: A Prospective cohort study.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0339775}, pmid = {41666176}, issn = {1932-6203}, mesh = {Female ; Humans ; *Premature Birth/microbiology/diagnosis ; Pregnancy ; *Vagina/microbiology ; Adult ; Prospective Studies ; *Lactobacillus/isolation & purification ; Risk Factors ; Gestational Age ; }, abstract = {BACKGROUND: Vaginal microecological imbalance, particularly reduced Lactobacillus dominance, is a significant risk factor for spontaneous preterm birth (sPTB).However, the predictive value of microbial composition, pathogen colonization, and vaginal inflammation biomarkers at different pregnancy stages remains unclear. This study aims to evaluate the predictive potential of vaginal microecology at 24 weeks of gestation and before delivery for spontaneous preterm birth.

METHODS: This was a prospective multicenter cohort study. Vaginal swabs were collected at 24 weeks of gestation and before delivery to assess Lactobacillus relative abundance(LRA), pathogen colonization, and biochemical markers (pH, hydrogen peroxide, leukocyte esterase, and sialidase). Multivariable logistic regression models, ROC curves, and Kaplan-Meier survival analysis were used to identify predictors of spontaneous preterm birth.

RESULTS: At 24 weeks of gestation, the preterm group showed significantly lower Lactobacillus relative abundance, higher AV and Nugent scores, and higher vaginal pH. Logistic regression revealed that an increase in Lactobacillus relative abundance(LRA) was negatively associated with sPTB (OR = 0.97, 95% CI = 0.96-0.98, P < 0.001), while higher parity (OR = 2.28, 95% CI = 1.56-3.32, P < 0.001) and a history of late miscarriage/preterm birth (OR = 6.96, 95% CI = 2.77-17.47, P < 0.001) increased the risk. Lactobacillus relative abundance(LRA) below 57.5% was linked to increased preterm birth risk in univariate analysis, but this was no longer significant after multivariable adjustment. Parity, late miscarriage/preterm birth history, vaginal pH > 4.5, and GBS positivity remained independent risk factors (AUC = 0.775). Kaplan-Meier survival analysis showed that women with LRA > 72.5% at 24 weeks and LRA > 57.5% before delivery had significantly higher term delivery probabilities (log-rank P < 0.001).

CONCLUSION: At 24 weeks, reduced vaginal LRA is an independent predictor of spontaneous preterm birth. Early vaginal microbiome assessment, combined with clinical features, can help identify high-risk pregnant women and improve outcomes.}, } @article {pmid41666032, year = {2026}, author = {Raghunath, R and Alvarez, MA and Bhattarai, S and Pujari, A and Solorzano Castillo, C and Arioglu-Tunçil, S and Wang, Y and Tunçil, YE and Lindemann, SR}, title = {Predicting Fiber Specificity on Gut Microbiome Modulation.}, journal = {Annual review of food science and technology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-food-053124-092050}, pmid = {41666032}, issn = {1941-1421}, abstract = {Dietary fibers are crucial in shaping gut microbial composition and functionality. Physical complexity and chemical interactions between fibers and the gut environment lead to diverse and specialized responses that involve entire food webs of gut bacteria; however, there is comparatively less emphasis on understanding ecological dynamics to predict these outcomes. These responses may potentially promote either a broader (less specific) or narrower (more specific) group of gut bacterial taxa, which may vary across individuals. This review examines fiber specificity at the organismal and community levels by exploring mechanistic interactions among dietary fibers and gut bacteria. We discuss the interplay of exogenous and endogenous factors and the structure-function relationships influencing fiber specificity. We establish a mathematical framework to describe specificity in fiber-microbiome interactions based on directionality, magnitude, and stochasticity of fiber-microbiome ecological responses. Finally, we identify research gaps to enhance fiber-microbiota predictions, with implications for strategies aimed at optimizing fiber design.}, } @article {pmid41665880, year = {2026}, author = {Bischoff, NS and Undas, AK and van Bemmel, G and Briedé, JJ and Van Breda, SG and Verhoeven, J and Verbuggen, S and Venema, K and Sijm, DTHM and de Kok, TM}, title = {Food Additive Titanium Dioxide (E171) Alters Gut Microbial Metabolic Activity and Butyrate Production in the TIM-2 In Vitro Colon Model.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxag042}, pmid = {41665880}, issn = {1365-2672}, abstract = {AIMS: ood-grade titanium dioxide (E171) is widely used as a food additive, yet concerns persist regarding potential gastrointestinal effects, possibly mediated by interactions with the gut microbiome. This study aimed to investigate the physicochemical behavior of E171 under different digestive contexts and to assess its effects on gut microbial composition and metabolic activity.

METHODS AND RESULTS: The dynamic in vitro colon model TIM-2 was used to expose human fecal microbiota to E171 under fasted (aqueous suspension; E171-aq) and fed (yogurt matrix; E171-yog) conditions. Particle size distribution, reactive oxygen species formation, microbiome composition (16S rRNA gene sequencing), and short-chain fatty acid production were analyzed. Larger aggregates were observed under fasted conditions (mean diameter ~210 nm), whereas digestion in yogurt produced smaller aggregates (mean diameter ~167 nm) and a higher nanoparticle fraction, reaching up to 20%. No ROS production was detected following fermentation. Both E171-aq and E171-yog significantly increased butyrate levels, indicating altered microbial metabolic activity. Microbiome profiling revealed compositional shifts, including a decreased relative abundance of Blautia and an increased relative abundance of Lachnospiraceae, taxa associated with inflammatory and metabolic responses.

CONCLUSIONS: E171 undergoes distinct physicochemical transformations depending on the digestive context, with enhanced nanoparticle formation under fed conditions. E171 exposure also modulates gut microbiome composition and function, notably by stimulating butyrate production.}, } @article {pmid41665694, year = {2026}, author = {Hill, CM and Malen, RC and Reedy, AM and Kahsai, O and Curtis, K and Ma, N and Randolph, TW and Ma, J and Thomas, CE and Ogino, S and Potter, JD and Buchanan, DD and Newcomb, PA and Hullar, MAJ and Phipps, AI}, title = {Associations of epidemiologic risk factors with Fusobacterium nucleatum and bacterial alpha diversity in the colorectal tumor-associated microbiota.}, journal = {Cancer causes & control : CCC}, volume = {37}, number = {3}, pages = {45}, pmid = {41665694}, issn = {1573-7225}, support = {T32CA094880/CA/NCI NIH HHS/United States ; R01CA076366/CA/NCI NIH HHS/United States ; R01CA217970/CA/NCI NIH HHS/United States ; C10674/A27140//Cancer Research UK Grand Challenge Award/ ; CRP-24-1185864-01-PROF//American Cancer Society/ ; U01CA167551/RC/CCR NIH HHS/United States ; }, mesh = {Humans ; Female ; *Fusobacterium nucleatum/isolation & purification/genetics ; Male ; *Colorectal Neoplasms/microbiology/epidemiology ; Risk Factors ; Middle Aged ; Aged ; *Fusobacterium Infections/epidemiology/microbiology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Adult ; Microbiota ; }, abstract = {BACKGROUND: Aspects of the gut microbiome, including presence of specific bacterial species and overall community structure, have been linked to the etiology and prognosis of colorectal cancer (CRC). Less is known about the epidemiologic risk factors that are associated with the composition of the microbiota in invasive colorectal tumors.

METHODS: Using tumor and paired normal colorectal tissue samples from a subset of participants in the population-based Seattle Colon Cancer Family Registry, we compared the presence of Fusobacterium nucleatum (F. nucleatum) (n = 898) measured via droplet digital PCR and alpha diversity (Shannon index) (n = 611) measured via 16S rRNA gene sequencing in colorectal tissue across demographics, health behaviors, and neighborhood socioeconomic status (nSES).

RESULTS: Normalized counts of F. nucleatum were consistently higher in tumor tissue than in patient-matched normal tissue across all risk factors, while alpha diversity was lower. Female sex was associated with high presence and enrichment of F. nucleatum in tumor tissue (odds ratio [OR] 1.61; 95% confidence interval [CI] 1.02, 2.54 and OR 1.58, 95% CI 1.10, 2.27, respectively). Relative to those aged 40-49 years, the youngest age group (< 40 years) had lower alpha diversity in tumor tissue (OR for highest vs. lowest tertile: 0.33; 95% 0.13, 0.83). Other factors, including diet, were not related to F. nucleatum presence or tumor tissue alpha diversity.

CONCLUSION: By uncovering epidemiologic risk factors for F. nucleatum presence and bacterial diversity in the intratumoral microbiota, this work informs our understanding of associations of the gut microbiota with CRC etiology and outcomes.}, } @article {pmid41665368, year = {2026}, author = {Flörl, L and Cabrera, PM and Moccia, MD and Plüss, S and Bokulich, NA}, title = {HighALPS: ultra-high-throughput marker-gene amplicon library preparation and sequencing on the Illumina NextSeq and NovaSeq Platforms.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0002326}, doi = {10.1128/msystems.00023-26}, pmid = {41665368}, issn = {2379-5077}, abstract = {Microbiome research using amplicon sequencing of microbial marker genes has surged over the past decade, propelled by protocols for highly multiplexed sequencing with barcoded primer constructs. Newer Illumina platforms like the NovaSeq and NextSeq series significantly outperform older sequencers in terms of reads, output, and runtime. However, these platforms are more prone to index-hopping, which limits the application of protocols designed for older platforms such as the Earth Microbiome Project protocols; hence, there is a need to adapt these established protocols. Here, we present an ultra-high-throughput amplicon library preparation and sequencing protocol (HighALPS) incorporating the capabilities of these newer sequencing platforms, designed for both 16S rRNA gene and fungal internal transcribed spacer domain sequencing. Our results demonstrate good run performance across different sequencing platforms and flow cells, with successful sequencing of mock communities, validating the protocol's effectiveness. The HighALPS library preparation method offers a robust, cost-effective, and ultra-high-throughput solution for microbiome research, compatible with the latest sequencing technologies. This protocol allows multiplexing thousands of samples in a single run at a read depth of tens of millions of sequences per sample.IMPORTANCEMarker gene amplicon sequencing on Illumina devices remains the most commonly used technology to profile microbial communities. Yet, most library preparation protocols are not adapted to harness the capabilities and deal with the caveats of the latest Illumina sequencing platforms, which highly outperform older platforms in terms of speed, quality, and output. Here, we present an ultra-high-throughput, cost-effective, and robust library preparation protocol (HighALPS) optimized to fully leverage the capabilities of the latest Illumina sequencing platforms. The combinatorial unique dual index strategy effectively combats miss-assignment of reads due to index-hopping, which is more prevalent in newer platforms. The HighALPS protocol incorporates technological (e.g., novel sequencing chemistry and lab automation platforms) as well as bioinformatics advances (e.g., denoising algorithms which make triplicate amplifications unnecessary) of the last few years to optimize and streamline library preparation for bacterial and fungal communities.}, } @article {pmid41665365, year = {2026}, author = {Anwyl, GA and Jimenez, NR and Hurwitz, B and Herbst-Kralovetz, MM}, title = {Draft genome sequence of endometrial Alloscardovia omnicolens strain Y28 identified in endometrial cancer.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0124425}, doi = {10.1128/mra.01244-25}, pmid = {41665365}, issn = {2576-098X}, abstract = {We report a 1.8 Mb draft genome of Alloscardovia omnicolens Y28 isolated from a patient with endometrial cancer.}, } @article {pmid41665359, year = {2026}, author = {Passarelli, GV and Whang, SN and Gilbert, NM and Hu, J}, title = {The vaginal microbiome, papillomavirus infection, and cervical cancer: established associations in search of model systems and mechanistic answers.}, journal = {mBio}, volume = {}, number = {}, pages = {e0267725}, doi = {10.1128/mbio.02677-25}, pmid = {41665359}, issn = {2150-7511}, abstract = {High-risk human papillomavirus (HPV) infection is the causative factor for approximately 5% of all human cancers and the leading cause of cervical cancer. High-risk HPV-associated cervical cancer still claims more than 340,000 women's lives globally each year despite the availability of prophylactic HPV vaccines. Currently, there is no medical treatment for HPV infections and associated lesions except invasive surgical procedures. For more than a decade, numerous studies have demonstrated a correlation between certain community state types (CSTs) of the vaginal microbiome and HPV-associated infection and cancer. This review aims to provide a general overview of the most recent studies on this topic, focusing primarily on clinical data linking a Lactobacillus-depleted vaginal microbiome (i.e., bacterial vaginosis and CST-IV) and HPV but also describing the limited mechanistic findings in the field. Finally, a novel mouse model addressing the causative effect of the vaginal microbiome on papillomavirus-associated disease progression and cancer development is proposed.}, } @article {pmid41665353, year = {2026}, author = {Talma, K and Sipe, J and Bossa, N and Stiffler, W and Hankinson, E and Gunsch, C and Wiesner, M}, title = {Material matters: a framework for integrating surface properties into built environment microbiome research.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0203625}, doi = {10.1128/aem.02036-25}, pmid = {41665353}, issn = {1098-5336}, abstract = {The built environment (BE), where we spend the majority of our time, contains a variety of surfaces with distinct properties. Our understanding of how these surfaces shape the microbiome of the BE (MoBE) is underdeveloped and limits the ability to develop a bioinformed microbial management framework. Lab-scale studies have shown the impact of surface properties (roughness, wettability, porosity) on microbial communities, but studies sampling the BE microbiome have often overlooked this metadata. A keyword search of the literature found that only 31% of studies that sampled the indoor microbiome reported material information, which did not include any material characterization data. We have used the kitchen as a case study to illustrate the complexity of the microbial community and material surfaces that are present in the BE. We also describe how the use of BE spaces, such as cleaning, can impact both the materials and microbial community. We propose an interdisciplinary approach to studying the MoBE, incorporating techniques from material characterization into environmental microbiological sampling to elucidate the role of materials and their surface properties on the MoBE. Utilizing this interdisciplinary approach, a bioinformed framework can be developed for managing healthy MoBEs-one that improves occupant health by incorporating material science into microbial risk assessment and design strategies.}, } @article {pmid41665079, year = {2026}, author = {Chen, C and Zhang, Y and Yin, G and Sun, D and Li, Y and Hou, L and Liu, M}, title = {Warming Modulates Microplastic Impacts on Coastal Nitrogen Cycling by Synergistically Amplifying Sediment Hypoxia and Restructuring the Denitrifying Microbiome.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c08930}, pmid = {41665079}, issn = {1520-5851}, abstract = {Global warming and microplastics (MPs) pollution are emerging stressors that threaten coastal ecosystems, yet their combined impacts on biogeochemical cycles remain poorly resolved. Here, we integrated a factorial microcosm experiment with stable isotope tracing and molecular techniques to disentangle how warming and MPs jointly regulate nitrogen (N) cycling in coastal sediments. We demonstrate that warming and MPs interacted nonadditively to reshape nitrification, denitrification, and associated nitrous oxide (N2O) production dynamics. Warming reversed the stimulatory effect of polyethylene (PE) on nitrification, turning it inhibitory, and amplified the suppressive impact of poly(butylene adipate-co-terephthalate) (PBAT), primarily through synergistic intensification of anoxic stress. In contrast, warming strengthened PE-driven stimulation of denitrification and mitigated PBAT-induced inhibition, likely due to the selective enrichment of nirS- and nosZ-harboring denitrifiers. Moreover, warming overturned the stimulatory effects of both PE and PBAT on N2O production, shifting toward inhibition through nitrifier denitrification, as substantiated by dual-isotope ([15]N-[18]O) tracing and genomic evidence. Collectively, these findings provide novel mechanistic insights into how warming interacts with MPs to reconfigure sedimentary N cycling, with broad implications for predicting the responses and evolution of coastal ecosystems under accelerating global change.}, } @article {pmid41665004, year = {2026}, author = {Wang, P and Wang, C and Wang, Y}, title = {Nucleotide salvage, genome instability, and potential therapeutic applications.}, journal = {Nucleic acids research}, volume = {54}, number = {4}, pages = {}, pmid = {41665004}, issn = {1362-4962}, support = {R35 ES031707/NH/NIH HHS/United States ; }, mesh = {*Genomic Instability ; Humans ; DNA Replication/genetics ; *Nucleotides/metabolism ; Animals ; Neoplasms/genetics/metabolism ; Mutagenesis ; Epigenesis, Genetic ; }, abstract = {Nucleotide salvage is crucial for maintaining DNA replication when de novo nucleotide synthesis is limited, but this metabolic flexibility poses potential threats to genome stability. Salvage kinases phosphorylate nucleosides broadly, allowing for oxidized and alkylated 2'-deoxynucleosides as well as posttranscriptionally modified ribonucleosides to enter the 2'-deoxynucleoside triphosphate (dNTP) pool. The ensuing contamination of the dNTP pool and the subsequent incorporation of modified nucleotides into genomic DNA promote mutagenesis, induce replication stress, elicit double-strand breaks, and disrupt epigenetic signaling. Although only a small subset of modified nucleosides have been assessed for salvage and genomic incorporation, the scope of salvageable substrates is probably much wider, with significant implications in mutational burden, chromatin instability, and epigenetic regulation. This overlooked aspect of genome instability is especially relevant in biological contexts of high salvage activity or elevated nucleoside damage, including chronic inflammation, cancer, aging, and dietary/microbiome exposures. Emerging evidence links salvage metabolism to tumor progression, where incorporation of salvage-derived nucleotides may contribute to unexplainable mutational signatures detected in cancers, such as gastrointestinal cancer. Recognizing salvage as a hidden source of mutagenesis reshapes our understanding of genome instability and provides potential opportunities for disease prevention, diagnosis, and therapeutic intervention.}, } @article {pmid41664846, year = {2026}, author = {Stolf, CS and Paz, HES and Paraluppi, MC and Miguel, MMV and Santamaria, MP and Monteiro, MF and Amgarten, DE and Franco, RRA and Branco-de-Almeida, LS and Shaddox, LM and Casarin, RCV}, title = {Molar-Incisor and Generalized Grade C Periodontitis: Distinct Microbiome-Immune Interactions Suggest Divergent Pathogenesis.}, journal = {Journal of periodontal research}, volume = {}, number = {}, pages = {}, doi = {10.1111/jre.70077}, pmid = {41664846}, issn = {1600-0765}, support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 2021/14430-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; R01DE019456/DE/NIDCR NIH HHS/United States ; }, abstract = {AIM: Molar-Incisor (PerioC-MIP) and Generalized (PerioC-G) Grade C Periodontitis could have distinctive etiopathogenesis behind their unique clinical patterns. Thus, this study aimed to distinguish these two phenotypes by analyzing the subgingival metagenomic profile and the inflammatory markers levels.

METHODS: In this cross-sectional comparative study, Gingival Crevicular Fluid (GCF) and Subgingival Biofilm (SB) were collected from 18 PerioC-MIP North Americans and 14 periodontally healthy controls (HC) from the same location (HC-MIP) and 20 PerioC-G Brazilians and 20 controls (HC-G). From GCF, immunoenzymatic analysis was performed. SB functional and taxonomic bacterial content was determined using shotgun metagenomics sequencing.

RESULTS: Taxonomic results showed significantly different alpha- and beta-diversity profiles between disease groups (p < 0.05). Aggregatibacter actinomycetemcomitans and Streptococcus sanguinis were associated with PerioC-MIP; levels of Tannerella forsythia, Filifactor alocis, Porphyromonas gingivalis, Fretibacterium fastidiosum, and Treponema denticola were significantly enriched at PerioC-G (p < 0.05). PerioC-G had the function for flagellar assembly enriched, while PerioC-MIP SB was associated with biofilm formation of Escherichia coli. Different GCF inflammatory marker levels for each pattern resulted in PerioC-G presenting higher levels of IL-1β, IL-6, and IL-10 than PerioC-MIP (p < 0.05).

CONCLUSION: PerioC-G and PerioC-MIP presented different taxonomical profiles and GCF cytokine levels, raising the hypothesis that they may represent two different stages/susceptibility patterns of Periodontitis Grade C.}, } @article {pmid41664751, year = {2026}, author = {Rams, TE and Gupta, CS}, title = {Povidone-Iodine Antimicrobial Activity In Vitro Against Periodontal Bacterial Pathogens.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e101128}, pmid = {41664751}, issn = {2168-8184}, abstract = {Background Povidone-iodine (PV-I) is known to be active in vitro against periodontal bacterial pathogens, but previous studies most often used ≥5-minute contact times for PV-I testing and/or evaluated laboratory reference strains of bacterial species. This study further examined the antimicrobial effects of PV-I by using a 60-second in vitro treatment time for 10% and 5% PV-I on freshly recovered clinical isolates of subgingival biofilm bacteria from severe human periodontitis lesions. Methods Subgingival biofilm samples from 22 adults with severe periodontitis were mixed in vitro with 10% PV-I, 5% PV-I, or no PV-I (n = 22 samples per group), with residual PV-I neutralized after 60 seconds with sodium thiosulfate. The samples were then inoculated onto enriched Brucella blood agar (EBBA), with samples not treated with PV-I additionally plated onto EBBA supplemented with breakpoint concentrations of either amoxicillin, clindamycin, doxycycline, or metronidazole to detect antibiotic-resistant test species. After 7 days of anaerobic incubation, total viable microbial counts and selected red/orange complex periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia/nigrescens, Parvimonas micra, Campylobacter rectus, Fusobacterium nucleatum, and Streptococcus constellatus) were phenotypically identified and quantitated on the EBBA plates, with additional cultivable isolates from PV-I-treated samples identified using matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry. Results Subgingival biofilm samples treated in vitro for 60 seconds with 10% or 5% PV-I yielded significantly lower mean total viable microbial counts (60-68% less) and significantly lower mean total cultivable proportions of red/orange complex periodontal pathogens (0.5%-0.7%) than samples not exposed to PV-I (14.8%) (P < 0.001), with no statistically significant differences between 10% and 5% PV-I in vitro treatments. All evaluated red/orange complex periodontal pathogens were culture-negative in 21 (95.5%) and 19 (86.4%) of the 22 subgingival biofilm samples after 10% and 5% PV-I in vitro treatment, respectively. Antibiotic-resistant and antibiotic-susceptible red/orange complex periodontal pathogens were similarly sensitive in vitro to 10% and 5% PV-I. Streptococcus species, particularly Streptococcus oralis, were the most prevalent cultivable isolates in subgingival samples treated in vitro with 10% or 5% PV-I for 60 seconds. Conclusions Both 10% and 5% PV-I significantly suppressed total viable microbial counts and red/orange complex periodontal pathogens, but not periodontal health-associated Streptococcus species, during 60 seconds of in vitro treatment on subgingival biofilm samples from patients with severe periodontitis, with no statistically significant differences in the antimicrobial activity of the two PV-I concentrations. These in vitro PV-I susceptibility findings with freshly isolated subgingival biofilm bacteria further support the clinical use of PV-I in periodontal therapy as an adjunct to mechanical root debridement in altering a pathogenic subgingival microbiome toward one compatible with periodontal health.}, } @article {pmid41664705, year = {2026}, author = {Ding, Z and Luo, Z and Zhang, L and Zhang, S and Zhang, R and Qiu, Z and Huang, C}, title = {State-of-the-Art Strategies for Circular RNA in Cancers: Opportunity and Challenge.}, journal = {MedComm}, volume = {7}, number = {2}, pages = {e70608}, pmid = {41664705}, issn = {2688-2663}, abstract = {Circular RNAs (circRNAs) are characterized by their covalently closed structure, remarkable stability, and precise spatiotemporal regulation, evolving from once-overlooked transcriptional byproducts to pivotal molecular regulators. In addition to their well-established function as microRNA sponges, circRNAs serve as protein scaffolds, transcriptional modulators, and even templates for functional peptide synthesis. This review synthesizes recent breakthroughs across the entire circRNA life cycle, encompassing biogenesis, degradation, nucleocytoplasmic transport, and extracellular vesicle-mediated secretion, while systematically analyzing their multifaceted involvement in tumorigenesis, immune evasion, metastatic dissemination, programmed cell death, and tumor-microbiome crosstalk. We highlight their exceptional potential as liquid biopsy biomarkers and critically assess translational applications in circRNA-based vaccines, targeted delivery platforms, and engineered cell therapies like CAR-T. Emerging artificial intelligence approaches that accelerate circRNA discovery, functional characterization, and therapeutic design are also discussed. Addressing current challenges in standardization and delivery methodologies, we propose future directions for incorporating circRNAs and their encoded proteins into precision oncology and next-generation immunotherapies. Together, these advances position circRNAs as a transformative paradigm with the potential to revolutionize cancer diagnostics, targeted therapeutics, and RNA vaccine development.}, } @article {pmid41664381, year = {2026}, author = {Li, C and Liu, J and Liu, J and Zhang, S and Zhang, J and Yang, B and Liu, Y and Du, S and Han, X and Zhang, L}, title = {Root exudate-microbe interactions mediated by Oceanobacillus picturae and stachyose promote cadmium tolerance in Perilla frutescens.}, journal = {Journal of integrative plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jipb.70183}, pmid = {41664381}, issn = {1744-7909}, abstract = {Cadmium (Cd) is a toxic heavy metal that poses serious risks to human health and the ecological environment. Perilla frutescens (L.) Britt. has important medicinal and culinary value, yet its seedlings are highly sensitive to cadmium exposure. Carbohydrates, which mediate key aspects of plant-microbe interactions, play an essential role in recruiting rhizosphere microbiota. In this study, we examined how inoculation with Oceanobacillus picturae alleviates cadmium toxicity by secreting carbohydrate metabolites that reshape the rhizosphere microbial community of perilla. Inoculation markedly reduced cadmium-induced root damage, increasing fresh and dry plant weights by 2.3-fold and 1.1-fold, and enhancing root length by 14% compared with the control. In addition, root exudate profiles showed clear changes following inoculation. Metabolomic analyses revealed that stachyose was a key exudate enriched under stress conditions and acted synergistically with Azospirillum brasilense and Acinetobacter pittii to enhance perilla growth and cadmium tolerance. These findings demonstrate that perilla recruits specific plant growth-promoting rhizobacteria through stachyose-mediated chemical signaling in response to cadmium stress. This work advances our understanding of plant-microbe interactions under heavy metal stress and provides a foundation for microbiome-based phytoremediation technologies. It also offers practical value for developing sustainable agricultural practices and supporting ecological conservation.}, } @article {pmid41664220, year = {2026}, author = {Wienholts, K and van Helsdingen, CPM and Wood, HM and Talboom, K and de Wilt, JHW and Bottomley, D and Young, C and Quirke, P and Derikx, JPM and Tanis, PJ and Hompes, R}, title = {The perioperative microbiome of patients undergoing rectal cancer surgery: A pilot study.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {28}, number = {2}, pages = {e70397}, pmid = {41664220}, issn = {1463-1318}, support = {12314//KWF Kankerbestrijding/ ; //B. Braun Surgical, S.A.U./ ; //Stryker European Operations B.V./ ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; NIHR203331//National Institute for Health and Care Research/ ; }, mesh = {Humans ; Pilot Projects ; *Rectal Neoplasms/surgery/microbiology ; *Gastrointestinal Microbiome/genetics/drug effects ; Male ; Middle Aged ; Female ; Aged ; Feces/microbiology ; Perioperative Period ; Anastomotic Leak/microbiology ; Proctectomy ; Ileostomy ; RNA, Ribosomal, 16S ; Enterococcus/isolation & purification ; Anti-Bacterial Agents/administration & dosage ; Streptococcus/isolation & purification ; }, abstract = {AIM: The gut microbiome plays a crucial role in health and disease, and its involvement in postoperative complications like anastomotic leakage (AL) is of growing interest. Despite substantial preclinical evidence linking microbiome alterations to surgical outcomes, human studies are scarce, particularly those exploring the perioperative dynamics of the gut microbiome beyond a single time point. This descriptive, hypothesis-generating pilot study aims to elucidate the perioperative changes in the faecal microbiome of patients undergoing rectal cancer surgery.

METHOD: Seventeen patients from Amsterdam University Medical Centers participated in the IMARI-study and the IntAct-trial between April 2020 and April 2022. All patients in these studies underwent rectal resection for malignancy with a primary anastomosis, with or without a diverting ileostomy. Samples collected included preoperative stool, intraoperative anastomotic colonic tissue and swab and postoperative stool. Bacterial DNA was extracted and analysed using 16S rRNA gene sequencing.

RESULTS: An increase in Enterococcus and Streptococcus was observed postoperatively compared to preoperative and intraoperative samples. Postoperative samples showed a significant decrease in alpha diversity compared to preoperative and intraoperative samples. Beta diversity analysis revealed distinct clustering of postoperative stool and ileostomy samples. Preoperative oral antibiotics significantly altered the intraoperative microbiome composition and reduced postoperative alpha diversity.

CONCLUSION: This pilot study reveals significant perioperative shifts in the gut microbiome of rectal cancer patients. These findings underscore the importance of considering microbiome dynamics perioperatively when designing and interpreting studies that correlate the microbiome with clinical outcomes. However, the conclusions should be viewed as preliminary and require confirmation in larger studies, including causal relation, to postoperative outcomes.}, } @article {pmid41664134, year = {2026}, author = {Huang, L and Yang, X and Pan, C and Zhang, W and Li, Y and Zhang, R and Li, H and Li, Y and Zhuo, Y and Jiang, X and Che, L and Lin, Y and Xu, S and Fang, Z and Feng, B and Wu, D and Hua, L}, title = {Effects of nicotinamide riboside supplementation during late gestation and lactation on sow performance, milk metabolome, and gut microbiome.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {26}, pmid = {41664134}, issn = {1674-9782}, support = {2023YFD1300804//Key Technologies Research and Development Program of China/ ; 32472948//National Natural Science Foundation of China/ ; CARS-35//Earmarked Fund for China Agriculture Research System/ ; }, abstract = {BACKGROUND: Nicotinamide riboside (NR) supplementation has been demonstrated efficacy in enhancing female reproductive outcomes, but its regulatory role in sow performance and gut microbiome remains undefined. This study systematically evaluated the impacts of dietary NR supplementation during late gestation and lactation on sow performance and gut microbiome remodeling. A total of 280 sows were randomized assigned to one of four groups: a control group fed basal diet or one of three groups receiving NR-supplemented diets (2, 4, or 8 g/d; n = 70/group). Sow reproductive performance, blood metabolic parameters, milk metabolome, and fecal 16S rRNA sequencing were measured.

RESULTS: Maternal NR supplementation linearly shortened farrowing duration (P < 0.01) and tended to decrease the incidence of intrauterine growth restriction and the number of late gestation mummies (P < 0.1), while concurrently increasing the within-litter uniformity (P = 0.1). Litter weaning weight and average daily gain increased quadratically with NR dosage (P < 0.05). NR supplementation orchestrated plasma metabolite regulation (triglycerides and total cholesterol; P < 0.05), enhanced antioxidant biomarkers (T-AOC, GSH-Px, T-SOD; P < 0.05), and reduced inflammatory cytokines (TNF-α; P < 0.05) across gestation and lactation. Milk yield, colostrum/milk dry matter, crude protein, and crude fat were increased (P < 0.05), together with higher levels of NAD[+] metabolites (NAD⁺, NR, nicotinamide) and beneficial bioactive factors (milk polar lipids, 3-aminosalicylic acid, fenugreekine; P < 0.05). Gut microbiota analyses at lactation day 14 revealed NR-enriched beneficial taxa (Bifidobacterium, Ruminococcus, Lachnospiraceae, Subdoligranulum, Clostridium butyricum, Succiniclasticum) across sow-offspring dyads, which was associated with the activation of microbial NAD⁺ enzymes (NadR/NAMPT; P < 0.05) and enhancement of systemic short-chain fatty acid flux, notably an increase in plasma butyrate acid (P < 0.05).

CONCLUSION: Maternal supplementation of NR during late gestation and lactation increases sow performance and promotes gut NAD[+] metabolic-associated microbiome remodeling. These findings propose maternal NR intervention as a novel strategy to enhance mammary lactogenesis and lactation metabolism in swine production, with potential applications for therapeutic strategies for lactation insufficiency.}, } @article {pmid41664082, year = {2026}, author = {Shi, K and Mou, D and Luo, X and Yang, Q}, title = {Bile acid profiles reflect metabolic adaptability to rapid weight loss in boxers.}, journal = {BMC sports science, medicine & rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13102-025-01462-2}, pmid = {41664082}, issn = {2052-1847}, support = {2025D01B143//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; KY2024095//Basic operating funds for public welfare research institutions in the Xinjiang Uyghur Autonomous Region/ ; }, abstract = {PURPOSE: This exploratory pilot study investigated serum bile acids (BAs) as metabolic regulators in boxers, focusing on their dynamic responses to rapid weight loss (RWL) and recovery across different training levels. A developmental control group of young athletes served as a physiological reference.

METHODS: Serum samples from 13 male boxers (5 elite, 8 national-level) and 10 young athletes were collected at baseline, post-RWL, and after 24 h recovery. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified 82 BA species. Multivariate (OPLS-DA), univariate, and KEGG pathway analyses assessed phase- and level-dependent differences.

RESULTS: Elite boxers showed higher baseline concentrations of conjugated and regulatory BAs (e.g., taurolithocholic acid [TLCA], glycohyocholic acid [GHCA]) and faster post-RWL restoration of BA balance. Non-elite athletes exhibited stronger shifts toward unconjugated secondary BAs (e.g., deoxycholic acid [DCA], lithocholic acid [LCA]) and incomplete recovery. Compared with young athletes, trained boxers displayed enhanced BA conjugation and FXR/TGR5-linked regulation. KEGG analysis indicated RWL-related disturbances in bile secretion and peroxisomal pathways, while elite profiles reflected greater hepatic-intestinal resilience.

CONCLUSION: BA composition may serve as a biochemical marker of metabolic adaptability in combat athletes. Elite boxers maintained tighter BA homeostasis through weight cycles, whereas non-elite athletes exhibited transient hepatic stress. Findings are preliminary and should be interpreted cautiously due to small subgroup sizes and unstandardized diet and microbiome control.}, } @article {pmid41663986, year = {2026}, author = {Petrosyan, K and Thijs, S and Krucon, T and Piwowarczyk, R and Wiśniewska, K and Kaca, W and Vangronsveld, J}, title = {Seed endophytic bacteria are involved in metal adaptation of Orobanche lutea: community dynamics and plant growth promotion traits.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08304-4}, pmid = {41663986}, issn = {1471-2229}, support = {BOF21BL12//Hasselt University grant BOF-BILA/ ; BOF24KV09//Special Research Fund (BOF - Incoming Mobility)/ ; SUPB.RN.25.231//Kochanowski University in Kielce grant/ ; RID/SP/0015/2024/01//Poland Minister of Science/ ; 08M03VGRJ//Hasselt University Methusalem project/ ; }, } @article {pmid41663943, year = {2026}, author = {Li, M and Yang, R and Bai, Q and Yang, Z and Huang, T and Qiao, Y and Yang, B and Chen, J and Lin, W}, title = {Manipulating root-associated microbiomes to boost drought resistance in dryland winter wheat with Streptomyces pactum Act12.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04812-3}, pmid = {41663943}, issn = {1471-2180}, support = {32401443//National Natural Science Foundation of China/ ; 2025CYJSTX02-16//the earmarked fund for Modern Agro-industry Technology Research System of Shanxi Province/ ; }, } @article {pmid41663939, year = {2026}, author = {Li, G and Liu, X and Han, M and Qin, X and Li, P}, title = {Rhizosphere bacterial characteristics reveal the invasive advantage of Sphagneticola trilobata compared to the greening grass Axonopus compressus.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04817-y}, pmid = {41663939}, issn = {1471-2180}, support = {ZDYF2025XDNY122//Key Research and Development Project of Hainan Province/ ; }, } @article {pmid41663924, year = {2026}, author = {Li, B and Shi, X and Yao, X and Yan, Y and Wu, K and Zhang, C and Ren, Y}, title = {Association of the residual feed intake (RFI) with the rumen microbiota composition and metabolism in Dorper-Hu crossbred lambs.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04788-0}, pmid = {41663924}, issn = {1471-2180}, support = {2020BQ53//The Science and Technology Innovation Program of Shanxi Agricultural University/ ; SXBYKY2021037//Shanxi Province Outstanding Doctor Award Fund/ ; J202011313//"1331 Project" Key Disciplines of Animal Sciences, Shanxi Province/ ; Modern Agro-industry Technology Research System in Shanxi Province//Modern Agro-industry Technology Research System in Shanxi Province/ ; }, } @article {pmid41663923, year = {2026}, author = {Tao, L and Zhao, T and Xu, Y and Chen, W and Zhu, X and Hao, Y and Zhu, L and Jiao, N and Cao, M and Pu, X and Zhu, R}, title = {Integrative multi-cohort analysis identifies urinary microbiota as non-invasive biomarkers of bladder cancer.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04829-8}, pmid = {41663923}, issn = {1471-2180}, support = {32470098//National Natural Science Foundation of China/ ; 92251307//National Natural Science Foundation of China/ ; BJJY2024098//Shanghai Oriental Talents Program/ ; }, } @article {pmid41663851, year = {2026}, author = {Guo, R and Li, Y and Tang, C and Zhao, Y and Wang, M and Qiao, G and Klosterman, SJ and Wang, Y}, title = {The bark latent fungus Botryosphaeria dothidea exacerbates branch dieback following the infection with Verticillium dahliae.}, journal = {Stress biology}, volume = {6}, number = {1}, pages = {13}, pmid = {41663851}, issn = {2731-0450}, support = {32130071//National Natural Science Foundation of China/ ; }, abstract = {Verticillium wilt, caused by the soilborne fungus Verticillium dahliae, has resulted in high mortality of Cotinus coggygria (smoke tree) in China. Symptoms of this disease are complex, many infected smoke trees exhibit wilting or dieback on some branches but no other branches. Whether other microbial taxa act synergistically to contribute to symptom development is unknown. Here, we investigated the microbial community assembly features associated with different branches of smoke trees with or without Verticillium wilt symptoms and established linkages between symptomatic branches and putative keystone taxa. Amplicon data analyses revealed that V. dahliae significantly affected the microbiota structure within tree branches. Microbial network connectivity indicated that Verticillium wilt destabilized the network, and fungal communities were more sensitive to Verticillium wilt than the bacterial communities. Based on taxonomic level information, the fungus Botryosphaeria dothidea was significantly enriched in diseased branches and positively correlated with the abundance of V. dahliae. Through microbial isolations, pathogen co-inoculations, histopathological assays, and RNA-seq analyses, the results indicated that plants infected with V. dahliae showed significantly increased susceptibility to B. dothidea and downregulated expression of defense-related genes. Overall, the results revealed that Verticillium wilt provokes changes in the structure of the smoke tree microbiome and that these changes likely influence symptom development in some but not all tree branches. The synergistic interplay between the commensal fungus B. dothidea and the soil-borne fungus V. dahliae promotes wilt progression in smoke trees, offering new insights into developing effective control strategies through fungicides plus enhancing host vigor.}, } @article {pmid41663651, year = {2026}, author = {Weng, Y and Han, Y and Wang, L and Zafar, MH and Wu, Q and Zhang, W and Wang, H}, title = {Cornus officinalis extract modulates rumen microbiome and growth of lambs fed a high-concentrate diet.}, journal = {AMB Express}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13568-026-02017-5}, pmid = {41663651}, issn = {2191-0855}, support = {NO. 31872988//National Natural Science Foundation of China/ ; 2024YFD300204//National Key Research and Development Program of China/ ; }, } @article {pmid41663543, year = {2026}, author = {}, title = {Culturing microbiome therapeutics with big data.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, pmid = {41663543}, issn = {1546-1696}, } @article {pmid41663351, year = {2026}, author = {Wang, Y and Tang, Y and Huang, Q and An, J and Zhou, Y and Yang, H and Song, F and Zhang, X and Huang, C}, title = {Engineered Lactobacillus reuteri for scavenging reactive oxygen species and modulating oral microflora in periodontitis therapy.}, journal = {International journal of oral science}, volume = {18}, number = {1}, pages = {16}, pmid = {41663351}, issn = {2049-3169}, support = {82471018//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82271010//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82301154//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Limosilactobacillus reuteri/genetics/metabolism ; *Periodontitis/microbiology/therapy ; *Reactive Oxygen Species/metabolism ; *Probiotics/therapeutic use ; Oxidative Stress ; Animals ; Humans ; Hyaluronic Acid/chemistry ; Bacterial Adhesion ; *Microbiota ; }, abstract = {The onset and progression of periodontitis are closely associated with subgingival dysbiosis and excessive localized oxidative stress. While some oral probiotics exhibit certain inhibitory effects on periodontitis-related pathogens, they often struggle to effectively colonize and antagonize these pathogens due to the complex oxidative stress at the site of periodontitis. In this study, we engineer Lactobacillus reuteri with a reactive oxygen species (ROS)-responsive adhesive polymer (phenylboric acid-dopamine-hyaluronic acid) (LR@PDH). In the periodontitis microenvironment, this polymer can consume ROS and then expose the phenolic hydroxyl group of dopamine, promoting the selective adhesion and colonization of Lactobacillus reuteri at the site of inflammation to antagonize pathogens. The results show that, compared to conventional probiotic therapy, inflammation-responsive adhesive Lactobacillus reuteri effectively alleviates local oxidative stress, reduces the abundance of pathogenic bacteria in the subgingival microbiome, and inhibits the progression of periodontitis. Additionally, its good biocompatibility and safety highlight its potential as a therapeutic approach for clinical treatment of periodontitis.}, } @article {pmid41663154, year = {2026}, author = {Yang, Y and Yang, R and Chen, Y and He, C and Zhang, Y and He, J and Zhang, J and Wang, H and Liang, J and Deng, Z and Teng, L}, title = {Acinetobacter baumannii promotes gastric cancer metastasis via NA-mediated NAD metabolism reprogramming and glycolytic activation.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336161}, pmid = {41663154}, issn = {1468-3288}, abstract = {BACKGROUND: Gastric cancer (GC) is one of the most common malignancies worldwide and it is the third leading cause of cancer-related death in China. While Helicobacter pylori is a known GC pathogen, its abundance declines in tumours and the role of other bacteria in GC metastasis remains unclear.

OBJECTIVE: We aim to investigate the mechanisms of other bacteria influencing GC progression and metastasis.

DESIGN: Integrated intratumoural microbiome-metabolome analysis identified GC-associated microbes and metabolites. We then demonstrated the pro-metastatic role of Acinetobacter baumannii (A. baumannii, Ab) and its metabolite nicotinic acid (NA) using genetic, molecular and in vivo approaches.

RESULTS: The abundance of A. baumannii was significantly increased in GC tissues, correlating with advanced tumour stage and intratumoural NA levels. Fluorescence in situ hybridisation confirmed its colonisation in GC tumours. In co-culture systems, A. baumannii increased NA levels, enhancing nicotinamide adenine dinucleotide (NAD) metabolism and increasing 1-Methylnicotinamide accumulation in tumour cells. Mutagenesis of the bacterial NA synthase gene pncA confirmed that A. baumannii excreted an NA-dependent pro-metastasis effect. Mechanically, A. baumannii promotes GC metastasis by reprogramming tumour cell glucose metabolism, reducing oxidative phosphorylation while enhancing glycolysis and activating the hypoxia-inducible factor-1 pathway in GC cells through metabolites both in vivo and in vitro.

CONCLUSIONS: This study elucidates the role of A. baumannii in enhancing NAD metabolism in GC cells through NA synthesis, consequently promoting GC metastasis. These findings establish a microbiota-metabolism axis as a mechanistic foundation for developing targeted therapeutic strategies against GC metastasis.}, } @article {pmid41662940, year = {2026}, author = {Wang, P and Li, M and Zhou, Y and Su, D and Zhao, C and Liu, W and Li, Z and Guo, S and Sun, M}, title = {Soil microbiome drives soil multifunctionality across slope positions in a mountain tea plantation ecosystem.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123994}, doi = {10.1016/j.envres.2026.123994}, pmid = {41662940}, issn = {1096-0953}, abstract = {Slope position, a key topographic factor, exerts a strong influence on terrestrial ecosystem multifunctionality. However, the contribution of soil microbiomes to driving soil multifunctionality (SMF) along slope positions remains poorly understood. Here, the changes in soil properties, microbial characteristics, and SMF induced by slope position, as well as the relationships between microbial indices and SMF were investigated. The results demonstrated that most soil parameters, such as soil organic carbon, microbial biomass carbon and β-1, 4-glucosidase enzyme activity, were the highest in the middle slope (MS), being 1.77 to 1.90 times that of the top slope (TS). SMF peaked at the MS (0.76), whereas the lowest value (-0.81) was recorded at the TS. Bacterial alpha diversity was greatest at the MS, while fungal diversity was highest at the foot of the slope (FS). Microbial community structure varied significantly among slope positions and showed strong correlations with SMF and multiple soil factors, such as pH and soil organic carbon. Co-occurrence network analysis indicated a decline in bacterial network complexity from 0.53 to 0.25, while fungal network complexity increased from 0.31 to 0.73 with the rising of slope position. Random forest analysis identified fungal and bacterial community compositions as the most important microbial predictors of SMF. Collectively, these findings reveal the slope-microbiome dynamics in sustaining SMF under topographic variation, highlighting microbe-based soil management for enhanced ecosystem functioning in mountainous landscapes.}, } @article {pmid41662935, year = {2026}, author = {Otaru, S and Carpenter, DO}, title = {Glyphosate Exposure and Metabolic Syndrome: A Scoping Review of Epidemiological and Mechanistic Evidence.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123992}, doi = {10.1016/j.envres.2026.123992}, pmid = {41662935}, issn = {1096-0953}, abstract = {BACKGROUND: Glyphosate, the active ingredient in many widely used herbicides, is a pervasive environmental contaminant due to extensive agricultural and residential use. Initially deemed safe, emerging evidence suggests chronic glyphosate exposure may impair metabolic health. This scoping review maps the evidence linking glyphosate exposure with metabolic syndrome (MetS), type 2 diabetes (T2DM), and related outcomes, integrating findings from human, animal, and cellular studies.

METHODS: We reviewed studies published from 2004 in PubMed and Google Scholar that examined glyphosate exposure in relation to metabolic outcomes. Thirteen epidemiological (cross-sectional and cohort) and 25 experimental (animal or in vitro) studies were included. Key data were extracted and synthesized narratively.

RESULTS: Most human studies, primarily cross-sectional analyses of U.S. NHANES data, reported positive associations between glyphosate biomarkers and metabolic risk factors. Higher exposure was consistently linked to elevated liver enzymes, insulin resistance, hyperglycemia, and increased odds of MetS. Two longitudinal studies supported these associations, while one occupational cohort found an inverse association with T2DM. Experimental models demonstrated that glyphosate induces hepatic steatosis, inflammation, oxidative stress, and mitochondrial dysfunction, disrupts glucose metabolism and insulin signaling, alters the gut microbiome, and modulates endocrine and epigenetic pathways, supporting its role as a metabolic disruptor.

CONCLUSION: While predominantly cross-sectional human data limit causal inference, the convergence of epidemiological associations and mechanistic findings indicate that glyphosate may be an environmental risk factor for metabolic syndrome and related conditions. Given its widespread use, even modest metabolic effects warrant further investigation through longitudinal studies with robust exposure assessment.}, } @article {pmid41662519, year = {2026}, author = {Shobu, K and Takai, M and Tanino, H and Fukuda, Y and Inoue, T}, title = {Structural and mechanistic diversity of glycogen phosphorylases from gut bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {7}, pages = {e2518513123}, doi = {10.1073/pnas.2518513123}, pmid = {41662519}, issn = {1091-6490}, support = {22K05442//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H02557//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP23ama121003 JP25ama121003 JP24ama121004//Japan Agency for Medical Research and Development (AMED)/ ; 25K08921//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 25K02216//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {*Gastrointestinal Microbiome ; Cryoelectron Microscopy ; Crystallography, X-Ray ; *Glycogen Phosphorylase/metabolism/chemistry/genetics ; Escherichia coli/enzymology ; Catalytic Domain ; Adenosine Monophosphate/metabolism ; Models, Molecular ; *Bacterial Proteins/metabolism/chemistry/genetics ; Protein Multimerization ; Protein Conformation ; }, abstract = {Glycogen phosphorylase (GP) plays a central role in glycogen metabolism. While the structure and regulation of mammalian GPs have been extensively studied, the corresponding mechanisms in gut bacterial GPs remain poorly understood. Here, we investigate GPs from Escherichia coli (EcGP), Segatella copri (ScGP), and Dorea longicatena (DlGP), which represent three phylogenetic clades of GPs, using enzymatic assays, cryo-electron microscopy (cryo-EM), and X-ray crystallography. We find that ScGP forms a unique pentamer that undergoes adenosine monophosphate (AMP)-dependent assembly into a dimer-of-pentamer, which inhibits activity by restricting substrate access to the catalytic site. EcGP exists in equilibrium among monomers, dimers, and tetramers, with AMP promoting tetramer dissociation and enhancing catalytic efficiency. In contrast, DlGP remains predominantly monomeric and is unresponsive to AMP. These findings uncover structural and regulatory diversity among gut bacterial GPs. Notably, the oligomeric states of GPs modulate substrate accessibility and enzyme activation, suggesting a distinct mode of allosteric regulation beyond the canonical T-to-R transition model. Because bacterial GPs contribute to the generation of glucose, their regulation may influence the composition of gut-derived metabolites that affect host glucose homeostasis and insulin sensitivity. Our study provides mechanistic insight into the structural and functional diversity of gut bacterial GPs and lays a foundation for future exploration of microbiome-mediated metabolic interactions.}, } @article {pmid41662488, year = {2026}, author = {Su, J and Zhang, S and Liang, L and Bai, H and Bai, M and He, H and Wang, Y and Liu, H and Liang, X and Sun, Y and Wu, H}, title = {Bacteria and Fungi Synergistically Reprogram Flavonoid Metabolites in the Pericarp of Citrus Reticulata 'Chachi' During Storage.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e00267}, doi = {10.1002/advs.202500267}, pmid = {41662488}, issn = {2198-3844}, support = {2022SDZG07//Open Competition Program of Ten Major Directions of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province/ ; 2020B020221001//Key Realm R&D Program of Guangdong Province/ ; 2060302//Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources/ ; }, abstract = {The mature pericarp of Citrus reticulata ' Chachi ' (PCRC) is a traditional Chinese medicine known for its enhanced efficacy through long-term storage and processing. However, the specific mechanisms underlying these enhancements remain unclear. This study employed widely targeted metabolomics, microbial amplicon sequencing, and fermentation assays to investigate the microbiome 's influence on PCRC 's flavonoid profile over 0-19 years of storage. Correlation analysis revealed that the accumulation of polymethoxyflavones (PMFs) was closely linked to specific bacterial and fungal communities. Solid-state fermentation showed that Bacillus subtilis N18-1 enhanced the content of certain PMFs, while Aspergillus tubingensis P21-1 reduced them. Liquid-state assays confirmed that A. tubingensis P21-1 converted nobiletin to 3 ' -demethylnobiletin, and B. subtilis N18-1 further converted this to tangeretin. Combined with genome sequencing and molecular docking, four candidate genes were identified. The catalytic activity verification assays demonstrated that At21-68 and At21-21 catalyze the conversion of nobiletin to 3 '-demethylnobiletin, while Bs18-51 and Bs18-84 catalyze the conversion of 3 ' -demethylnobiletin to tangeretin. These findings highlight the synergistic molecular mechanism by which microorganisms modulate PMFs during PCRC aging, providing insights for optimizing medicinal plant aging through microbial biotransformation.}, } @article {pmid41662332, year = {2026}, author = {Vettiatil, D and Soorajkumar, A and Dubin, RA and Pedrosa, EM and Schornagel, A and Lambert, JS and Costa, IP and McDonald, J and Swagemakers, SMA and van der Spek, PJ and Frankovich, J and Cunningham, JL and Lachman, HM}, title = {Ultrarare Variants in DNA Damage Repair and Mitochondrial Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome and Acute Behavioral Regression in Neurodevelopmental Disorders.}, journal = {Developmental neuroscience}, volume = {}, number = {}, pages = {1-28}, doi = {10.1159/000550301}, pmid = {41662332}, issn = {1421-9859}, abstract = {INTRODUCTION: We recently identified variants in 10 genes that are members of either the p53 pathway or Fanconi Anemia Complex (FAC), regulators of the DNA repair (DNA damage response; DDR) in 17 cases with Pediatric Acute-Onset Neuropsychiatry Syndrome (PANS) or regression in autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDD). We aimed to identify additional cases with genetic vulnerabilities in DDR and related pathways.

METHODS: Whole exome sequencing (WES) and whole genome sequencing (WGS) data from 32 individuals were filtered and analyzed to identify ultrarare pathogenic or likely pathogenic variants.

RESULTS: Variants affecting DDR were found in 14 cases diagnosed with PANS or regression (CUX1, USP45, PARP14, UVSSA, EP300, TREX1, SAMHD1, STK19, MYTl1, TEP1, PIDD1, ADNP, FANCD2, and RAD54L). The CUX1 variant is de novo, as are two cases who had mutations in genes that affect mitochondrial functions that are connected directly or indirectly to mitophagy (PRKN and POLG), which can trigger the same innate immune pathways when disrupted as abnormal DDR. We also found pathogenic or likely pathogenic secondary mutations in several genes that are primarily expressed in the gut that have been implicated in gut microbiome homeostasis (e.g., LGALS4, DUOX2, CCR9).

CONCLUSION: These findings align with previous genetic findings and strengthen the hypothesis that abnormal DDR and mitochondrial dysfunction underly pathogenic processes in neuropsychiatric decompensation. The potential involvement of genetic variants in gut microbiome homeostasis is a novel aspect of our study. Functional characterization of the downstream impact of DDR deficits may point to novel treatment strategies.}, } @article {pmid41661845, year = {2025}, author = {Arana Håkanson, C and Stiger, F and Brusselaers, N and Engstrand Lilja, H}, title = {Childhood appendectomy and subsequent psychiatric illness.}, journal = {PLOS mental health}, volume = {2}, number = {1}, pages = {e0000219}, pmid = {41661845}, issn = {2837-8156}, abstract = {AIM: The appendix is considered a reservoir for the gut microbiome to restore the gut microbiota after disruptions. Therefore, removal of the appendix because of appendicitis, might result in long-term disruption of the microbiome with related health consequences. The aims of the study were to explore if there is an association between childhood appendectomy, the risk of psychiatric illness and healthcare consumption later in life.

METHODS: Individuals (N = 752) who underwent childhood appendectomy in a tertiary paediatric surgical department in Sweden were included, individually-matched to 5 non-exposed individuals (N = 3760). Data on psychiatric diagnoses, healthcare visits, and use of psychiatric drugs were collected from population-based registers. Stratified Cox and Poisson regression analyses were used, adjusted for antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs.

RESULTS: Median age at appendectomy was 11 (2-16) years and median follow-up time 15.5 (6-21) years. The risk of psychiatric illness in general (HR 1.19; 95% CI 1.04-1.37; p-value 0.013) and affective disorders (HR 1.20, 95% CI 1.01-1.42; p-value 0.038) was higher among those with appendectomy. Out- (IRR 1.20; 95% CI 1.18-1.23; p-value <0.001) and in-patient visits (IRR 1.19, 95% CI 1.10-1.28; p-value <0.001) were more common among those with appendectomy.

CONCLUSION: Childhood appendectomy was associated with an increased risk of psychiatric illness and healthcare consumption.}, } @article {pmid41661350, year = {2026}, author = {Uğur Aydin, Z and Korucu, H and Bulak Yeliz, S and Demirkaya, K and Can Demirdöğen, B}, title = {A clinical next-generation sequencing study on the microbial profiles of asymptomatic apical periodontitis in type 2 diabetic and systemically healthy individuals following adjuvant antimicrobial photodynamic therapy.}, journal = {Clinical oral investigations}, volume = {30}, number = {2}, pages = {75}, pmid = {41661350}, issn = {1436-3771}, abstract = {OBJECTIVES: The aim was to evaluate the effect of type 2 diabetes mellitus on the root canal microbiota and its response to antimicrobial photodynamic therapy (aPDT) combined with chemomechanical preparation in asymptomatic apical periodontitis (AP), by next-generation sequencing.

MATERIALS AND METHODS: A total of 22 teeth with a single root and single canal, diagnosed with asymptomatic AP, were included in this study: 11 teeth from patients with T2D (T2D group) and 11 from systemically healthy individuals (Control group). Root canal samples were collected before root canal treatment and after aPDT combined with chemomechanical preparation. Following chemomechanical preparation, canals were incubated with methylene blue for 5 min and photoactivated with a 630 nm LED for 60 s. Root canal samples were collected at two time points—before treatment (Control.Pre, T2D.Pre) and after treatment (Control.aPDT, T2D.aPDT). Following propidium monoazide (PMA) treatment, genomic DNA was isolated using a silica column method and quantified fluorometrically. The V3–V4 regions of the 16S rRNA gene were amplified and sequenced using the Illumina MiSeq platform. Data were processed in QIIME2 with DADA2 for denoising and classified taxonomically using Human Oral Microbiome Database (HOMD). Diversity analyses and statistical evaluations (PERMANOVA and multivariable association analysis using MaAsLin3; FDR-corrected) were performed in R.

RESULTS: A total of 44 root canal samples (Control.Pre, Control.aPDT, T2D.Pre, T2D.aPDT; n = 11) were analyzed via 16S rRNA V3–V4 sequencing, yielding 4.6 million high-quality reads and 2,745 Amplicon Sequence Variants (ASVs). Alpha diversity did not differ between pre and post disinfection procedure samples in healthy individuals (p > 0.05), whereas a significant reduction in observed ASV richness was detected in the T2D group after the disinfection procedures (p < 0.05). The number of ASVs shared between pre and post disinfection procedure samples was lower in the T2D group than in controls. Beta diversity based on unweighted UniFrac distances showed significant shifts after the disinfection procedures in both groups (p < 0.05), while weighted UniFrac analyses showed no significant differences (p > 0.05). Taxonomic analysis revealed a post disinfection increase in oxygen tolerant taxa and a reduction in obligate anaerobes in both groups, with more pronounced changes in the T2D group.

CONCLUSIONS: Following chemomechanical preparation and aPDT, a pronounced restructuring of the root canal microbiota was observed in both healthy individuals and individuals with T2D. In individuals with T2D, the post-disinfection period was characterized by reduced alpha diversity and a lower number of shared ASVs, indicating more limited microbial continuity.

CLINICAL RELEVANCE: The reduced microbial stability observed in individuals with diabetes suggests that systemic metabolic status may affect microbial responses to chemomechanical disinfection combined with aPDT.}, } @article {pmid41661346, year = {2026}, author = {Kaja, E and Grupińska, J and Budzyń, M and Ciomborowska-Basheer, J and Szwed, A and Makałowska, I and Papadovasilakis, Z and Formanowicz, D}, title = {Disease- and chemotherapy-associated salivary microbiome changes in breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {216}, number = {1}, pages = {2}, pmid = {41661346}, issn = {1573-7217}, mesh = {Humans ; Female ; *Saliva/microbiology ; *Breast Neoplasms/drug therapy/microbiology/pathology ; *Microbiota/drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; *Dysbiosis/chemically induced/microbiology ; Adult ; Neoadjuvant Therapy/adverse effects ; Aged ; Bacteria/genetics/classification/isolation & purification ; Case-Control Studies ; }, abstract = {PURPOSE: The microbiome of the saliva can be influenced by various factors, including systemic diseases and chemotherapy. Oral dysbiosis manifests as altered bacterial composition and abundance, which often correlates with increased local and systemic inflammation. The aim of the study was to investigate the dysbiosis in the saliva of breast cancer (BC) patients before and during neoadjuvant chemotherapy (NAC).

METHODS: Saliva samples were collected from 50 breast cancer patients at three timepoints (before, during, and after NAC). Saliva from 10 healthy women was used as control samples. Full-length gene 16S rRNA sequencing and analysis were performed using the Microbiome Analyst platform, R and JADBIO AutomatedML platform to compare the abundances of bacterial taxa.

RESULTS: Alpha and beta diversity measures differed between breast cancer patients and healthy controls. In addition, eight bacterial genera differed significantly between breast cancer patients and controls, including Porphyromonas, Campylobacter, Oribacterium, Veillonella, and Alloprevotella. Longitudinal analysis revealed significant decrease of bacterial diversity in the course of neoadjuvant chemotherapy as well as significant change in the prevalence of a few low-abundant genera.

CONCLUSIONS: The obtained results confirm BC-related and NAC-related dysbiosis in saliva, which emphasizes the potential of saliva as a diagnostic and prognostic tool in patients with breast cancer.}, } @article {pmid41661278, year = {2026}, author = {Zhang, H and Zhai, C and Hu, H and Qian, G and Mao, M}, title = {A metagenomic study of the gut microbiome in patients with type 2 diabetes mellitus and myocardial infarction.}, journal = {Acta diabetologica}, volume = {}, number = {}, pages = {}, pmid = {41661278}, issn = {1432-5233}, support = {XFCX-DMYH//Jiaxing Institute of Arteriosclerotic Disease/ ; }, abstract = {OBJECTIVE: This study aimed to investigate gut microbiota composition and metabolic functions in patients with type 2 diabetes mellitus (DM) complicated by myocardial infarction (MI) and to explore potential mechanisms linking the gut microbiome to MI development.

METHODS: Sixty patients with DM complicated by MI and 52 patients with DM alone were initially recruited. After quality control, 29 DM + MI patients and 33 DM patients were included in the final analysis. Gut microbial profiles were characterized using shotgun metagenomic sequencing and bioinformatics analyses. Microbial diversity, composition, and gene functions were compared between groups based on KEGG, COG, and CAZy annotations.

RESULTS: Overall microbial diversity and metabolic profiles were comparable between the two groups; however, significant differences were observed in specific taxa and functional genes. Taxa enriched in the DM + MI group included Bacteroidales, Prevotellaceae, and Lachnospiraceae. In total, 510 KEGG orthology (KO) units and 21 pathways-including ABC transporters, quorum sensing, and general metabolic pathways-differed significantly between groups. Carbohydrate transport and metabolism, as well as glycoside hydrolase activity, represented the most enriched functional categories. Random forest models based on selected microbial species, KO units, and KEGG pathways achieved areas under the curve (AUCs) of 0.868, 0.885, and 0.820, respectively.

CONCLUSION: Patients with DM complicated by MI exhibit distinct gut microbial compositions and functional gene signatures compared with patients with DM alone. These microbiome-based markers may contribute to early risk stratification and provide potential targets for microbiota-focused interventions to mitigate MI risk in patients with diabetes.}, } @article {pmid41661275, year = {2026}, author = {Chakraborty, P and Basu, M and Mukhopadhyay, P and Chowdhury, R and Ghosh, S}, title = {Study of oral microbiome by next generation sequencing in T1DM adolescents with periodontal disease.}, journal = {Acta diabetologica}, volume = {}, number = {}, pages = {}, pmid = {41661275}, issn = {1432-5233}, support = {(Memo No: 94 (Sanc.) /ST/ P/S&T/9G-2/2016//Department of Science and Technology, Government of West Bengal/ ; WB-RSSDI/3/2016//RSSDl West Bengal/ ; }, abstract = {BACKGROUND: Periodontal disease (PD) is common in type 1 diabetes mellitus (T1DM); however, studies related to oral microbiome in PD in type 1 diabetes is limited.

METHODS: In this cross-sectional study,60 participants were enrolled in three groups. T1DM with PD (DMPD, n = 20), T1DM without periodontal disease (DM, n = 20)), and siblings without diabetes but with PD (PD, n = 20)). All the participants underwent comprehensive periodontal examination. Gingival plaque samples were collected for DNA isolation and next-generation sequencing to quantify microbiological abundance.

RESULTS: In total, 3294 operational taxonomic units were identified and analysed. Significant difference was observed across the groups, notably Prevotella, Megasphaera, Dialister, and Camphylobacter, Aggregatibacter, and Corynebacterium showed difference in abundance. Prevotella was found to have a very high and statistically significant abundance in DMPD. Prevotella, Veillonella, and Selenomonas were significantly higher in the poorly controlled glycemic group. Subjects with severe Gingival Index (GI) exhibit higher abundance of Capnocytophaga, Neisseria and Rothia compared to those with non-severe GI.

CONCLUSION: The Oral microbiome composition of individuals with T1DM varied significantly in the presence of periodontal disease. The oral microbiome also varies according to glycemic status of T1DM and severity of PD. The markedly increased abundance of certain phyla and genera in subjects with PD and diabetes suggests a role for the relevant microbiota in the development of periodontal infection in T1DM subjects.}, } @article {pmid41661179, year = {2026}, author = {Bhattacharjee, D and Millman, LC and Seesengood, ML and Martineau, LM and Seekatz, AM}, title = {Genomic insights into the functional and metabolic versatility of gut microbiome Anaerostipes species.}, journal = {Microbial genomics}, volume = {12}, number = {2}, pages = {}, pmid = {41661179}, issn = {2057-5858}, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; Feces/microbiology ; Genome, Bacterial ; Phylogeny ; Genomics ; *Eubacteriales/genetics/metabolism ; Butyrates/metabolism ; }, abstract = {Members of the class Clostridia, a polyphyletic group of pathogenic and beneficial Gram-positive, spore-forming anaerobes in the Bacillota (Firmicutes) phylum, are prevalent in the human gut. While this class includes select pathogens known to cause disease, many species are associated with beneficial functions, such as providing colonization resistance against pathogens. Despite a demonstrated value in maintaining Clostridial populations in the gut, functional strain diversity of most commensal Clostridial species remains understudied. Here, we isolated and characterized Clostridial isolates, focusing on the genomic diversity of Anaerostipes, a prevalent butyrate-producing genus within the gut microbiota. We conducted a genomic comparison across 21 Anaerostipes strains isolated from healthy human faecal samples (n=5) and publicly available genomes (n=105). Whole genome comparisons across the Anaerostipes genus demonstrated 12 species bins, clustering into three major functionally distinct clusters correlating with host origin. One cluster (representing mostly Anaerostipes caccae genomes) was distinguished by possessing a complete vitamin B12 biosynthesis pathway. Variability in genomic and phenotypic carbohydrate metabolism was demonstrated within dominant species of the human microbiota (Anaerostipes hadrus, A. caccae and Anaerostipes hominis). Collectively, these data indicate genomic metabolic variance across Anaerostipes species that may influence coexistence within the gut environment and variably influence health.}, } @article {pmid41661138, year = {2026}, author = {Bäcker, M and Doekes, HM and Garza, DR and Meijer, J and van Vliet, S and Allen, RJ and Hogeweg, P and Dutilh, BE and van Dijk, B}, title = {Spatial structure: Shaping the ecology and evolution of microbial communities.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuaf067}, pmid = {41661138}, issn = {1574-6976}, abstract = {Most microbes grow in spatially structured communities, and this profoundly shapes their ecology and evolution. At the microscale, short interaction ranges and steep nutrient gradients underlie cross-feeding, quorum sensing, and niche construction, generating spatial patterns that influence microbial behavior, community assembly, and stability. Here, we review theoretical and experimental evidence for how spatial organization drives eco-evolutionary processes, including founder effects during colonization, allele surfing during range expansion, emergent patterns that facilitate multilevel selection, and the exploration of rare epistatic genotypes. While the ecological and evolutionary consequences of spatial structure at the microscale are becoming clearer, linking these processes across scales to predict community- and ecosystem-level outcomes remains a major challenge. Addressing spatial interactions explicitly in microbiome research will be key. Recent advances in computational modeling, cultivation approaches, and omics now offer unprecedented opportunities to meet this challenge, providing fresh insights into how spatial structure governs the organization and dynamics of the microbial world across scales.}, } @article {pmid41661098, year = {2026}, author = {Michita, RT and Jimenez, N and Herbst-Kralovetz, MM and Mysorekar, IU}, title = {Underexplored maternal microbiomes: immune, metabolic, and microbial pathways shaping pregnancy outcomes.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0060825}, doi = {10.1128/iai.00608-25}, pmid = {41661098}, issn = {1098-5522}, abstract = {Maternal microbial ecosystems play critical roles in shaping reproductive physiology and pregnancy outcomes. During the pre-conception and prenatal periods, these communities modulate maternal physiology by regulating immune tolerance, nutrient metabolism, and susceptibility to pregnancy complications such as preterm birth, hypertensive disorders, and gestational diabetes. While the gut microbiota has been extensively studied, the roles of cervicovaginal, urinary, respiratory, oral, and upper reproductive tract microbiomes remain less clear. In this minireview, we synthesize current knowledge on these underexplored maternal microbiomes, with an emphasis on the cervicovaginal and urinary microbiota and their interactions with the placenta and fetus. We discuss cross-niche microbial signaling, the role of environmental and social determinants in shaping these ecosystems, and mechanisms by which microbes or their products influence host physiology without direct colonization. We also consider the translational potential of microbiota-based interventions to safely improve pregnancy outcomes. Finally, we identify major knowledge gaps and research priorities necessary to advance a more integrated understanding of maternal microbial influences on reproductive and neonatal health. Our synthesis reframes the maternal microbiome as a coordinated, multi-site network that modulates systemic immune and metabolic pathways critical for reproductive success. Understanding these connections will open new avenues for predicting, preventing, and treating pregnancy-related disorders through precision microbiome science.}, } @article {pmid41661001, year = {2026}, author = {Ou, T and Gao, H and Xiong, Y and Jiang, K and Qiu, C and Lin, K and Liu, X and Xie, J}, title = {Pseudomonas koreensis HLG18 improves mulberry waterlogging resilience in riparian zone by synergistically modulating endophytic microbiome and metabolic profiles.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0295925}, doi = {10.1128/spectrum.02959-25}, pmid = {41661001}, issn = {2165-0497}, abstract = {Endophytes play essential roles in protecting plants against abiotic stresses. However, whether and how they enhance waterlogging resilience in mulberry through changes in host-associated microbiota and metabolites remains unclear. Here, an endophytic bacterium strain HLG18, with plant growth promotion potential, was selected and identified as Pseudomonas koreensis HLG18. Genome analysis revealed that it possessed multiple genes involved in phytohormone biosynthesis, mineral dissolution, and stress adaptation. Greenhouse experiments consistently indicated that P. koreensis HLG18 significantly stimulated mulberry growth under waterlogging stress, accompanied by enhanced antioxidant enzyme activities and osmoprotectants. Amplicon sequencing revealed distinct endospheric microbiome profiles following HLG18 treatment, with notable changes in genera, such as Rhizorhapis, Bacillus, Caulobacter, and Rhodococcus. Meanwhile, soil potassium, phosphorus, and iron levels also differed. Correlation analyses indicated that the relative abundances of Rhizorhapis, Bacillus, Caulobacter, and Rhodococcus were significantly associated with soil properties and mulberry performance. Concurrently, metabolomic profiling revealed distinct metabolic signatures between treatments, including higher levels of stress-related metabolites (e.g., L-arginine, L-isoleucine) and differences in key metabolic pathways, such as tryptophan and purine metabolism. Overall, this study uncovers that P. koreensis HLG18 is linked to altered microenvironmental features and host metabolic patterns under waterlogging, providing new insights into endophyte-assisted plant stress adaptation.IMPORTANCEWaterlogging severely threatens the riparian zone of the Three Gorges Reservoir in China, causing extensive plant mortality and hindering restoration efforts. Mulberry is a promising candidate for ecological restoration, yet its growth is severely constrained under such conditions. Endophytes have emerged as key mediators of plant stress tolerance; however, their potential role in supporting mulberry adaptation to waterlogging in riparian zones remains largely unexplored. Our results show that the endophytic bacterium Pseudomonas koreensis HLG18 significantly promotes mulberry growth and enhances waterlogging tolerance. HLG18 inoculation is associated with distinct shifts in the host's endophytic microbiome, soil properties, and metabolite profiles, suggesting potential links to mulberry performance under waterlogging. Our findings highlight the potential of endophytes as bioinoculants to enhance mulberry waterlogging tolerance for ecological restoration in fragile riparian ecosystems and provide a valuable reference for harnessing beneficial microbial resources in sustainable agriculture under waterlogged conditions.}, } @article {pmid41660981, year = {2026}, author = {Li, M and Feng, Y and Cao, X and Li, N and Chen, X and Bai, Z and Fei, Z and Lu, Z and Zhang, H and Zhou, D}, title = {Comparable efficacy and mechanisms of sterile soil ingestion versus low hygiene exposure in DSS-induced colitis.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0241525}, doi = {10.1128/aem.02415-25}, pmid = {41660981}, issn = {1098-5336}, abstract = {Accumulating evidence suggests that exposure to low-hygiene environments (LHE) can alleviate chronic diseases by modulating the gut microbiota. Soil has been identified as a key factor in shaping microbial communities within the LHE. Furthermore, influenced by cultural customs and traditions, the practice of soil ingestion persists in many regions worldwide, serving both nutritional and medicinal purposes. However, whether soil confers efficacy comparable to that of LHE exposure or which intervention demonstrates better efficacy remains unexplored. This study compared the interventional effects and underlying mechanisms of sterile soil ingestion versus LHE exposure in dextran sulfate sodium (DSS)-induced chronic ulcerative colitis (UC) mice. Our results demonstrated that UC mice exhibited significant gut dysbiosis, characterized by reduced microbial diversity and disruption of microbial network structure. Both LHE exposure and soil ingestion markedly reshaped the gut microbial ecosystem, exhibiting highly similar regulatory patterns in microbial composition. LHE exposure increased fecal acetic acid concentrations, while soil ingestion elevated butyric acid levels. Moreover, both interventions effectively alleviated UC clinical symptoms, restored intestinal barrier integrity, and downregulated pro-inflammatory cytokine levels. In summary, sterile soil ingestion and LHE exposure exert comparable protective effects in UC mice. Given its operational simplicity and feasibility, sterile soil represents a promising translation and application. These findings support the potential of sterile soil as a practical therapeutic approach for alleviating UC-related gut ecological disruption in modern urban settings.IMPORTANCEUrbanization and excessive hygiene have reduced human exposure to soil and environmental microorganisms, contributing to the rising incidence of immune-related disorders such as inflammatory bowel disease. This study demonstrates that sterile soil ingestion and low-hygiene environment exposure comparably reshape the gut microbiota, enhance short-chain fatty acid production, and alleviate colitis in mice. These findings highlight sterile soil as a practical and controllable intervention to mimic the protective benefits observed in traditional, microbe-rich environments. Given the challenges of accessing low-hygiene settings in modern urban life, sterile soil represents a feasible therapeutic approach to alleviate gut dysbiosis and inflammation, with broad implications for microbiome-based therapeutics in industrialized societies.}, } @article {pmid41660969, year = {2026}, author = {Bautista, J and Bazantes-Rodríguez, E and Cedeño, H and Anrango-Flores, C and Carrera-Cruz, F and Cisneros-Nieto, Z and López-Cortés, A}, title = {Reprogramming human health through the microbiome and precision medicine.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/1040841X.2026.2629269}, pmid = {41660969}, issn = {1549-7828}, abstract = {The human microbiome, comprising trillions of microorganisms across multiple body sites, is increasingly recognized as a key contributor to host immunity, metabolism, and neurobiology, influencing development and disease susceptibility throughout life. Rather than acting in isolation, microbial communities operate within a complex host-environment system shaped by genetics, diet, lifestyle, and medical exposures. Conceptually, the microbiome can be understood as part of a host-microbe meta-organism and, from a translational perspective, as a dynamic and potentially modifiable organ system. While short-term perturbations such as antibiotics may transiently disrupt microbial ecosystems, persistent maladaptive configurations, commonly termed dysbiosis, are associated with metabolic disease, chronic inflammation, neurodevelopmental disorders, and cancer, although causality remains context dependent. This review synthesizes the functional roles of beneficial microbes and their metabolites, the mechanistic and clinical implications of dysbiosis, and immune pathways shaped by microbial signals. We further discuss emerging therapeutic strategies, including dietary modulation, probiotics, engineered microbial consortia, postbiotics, and fecal microbiota transplantation, enabled by multi-omics technologies, organoid models, and computational frameworks. Key challenges include defining context-specific microbial health, ensuring durable engraftment, and addressing regulatory and ethical considerations. Framing the microbiome as a dynamic component of host physiology provides a foundation for microbiome-guided precision and preventive medicine.}, } @article {pmid41660849, year = {2026}, author = {Zhang, Y and Wen, H and Tang, X and Yao, Y}, title = {Integrative analysis of immune and microbial subtypes predicts immunotherapy response in stomach adenocarcinoma.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0215125}, doi = {10.1128/spectrum.02151-25}, pmid = {41660849}, issn = {2165-0497}, abstract = {The tumor immune microenvironment and intratumoral microbiota play critical roles in cancer progression and immunotherapy response, yet their integrated functions in stomach adenocarcinoma (STAD) are not well understood. This study conducted a multi-omics analysis of transcriptomic and microbiome data from 348 patients with STAD. Using the ImmuCellAI algorithm, immune cell infiltration (ICI) was estimated, and non-negative matrix factorization classified samples into three immune subtypes (INC-1, INC-2, and INC-3). Differential expression analysis identified immune-related signature genes enriched in immune signaling pathways. Tumor mutational burden, microsatellite instability, immune checkpoint gene expression, and drug sensitivity were compared across subtypes. Microbiome clustering identified three subtypes (MC-1, MC-2, and MC-3), with associations to immune infiltration and microbial composition. The immune subtypes showed distinct patterns of ICI, clinical stage, and gene expression, with differentially expressed genes enriched in immune and tumor-related pathways. Microbiome subtypes exhibited unique diversity metrics and associations with the immune microenvironment. Integration of immune and microbial data improved immune checkpoint blockade (ICB) prediction, with genera like Staphylococcus and Ralstonia correlating with immune genes such as CD22, VIPR2, and FLT3. These findings provide insights into ICB response and support more precise immunotherapy strategies for STAD.IMPORTANCEDeciphering the interactions between the tumor immune microenvironment and the intratumoral microbiota is crucial for advancing precision immunotherapy in stomach adenocarcinoma (STAD). In this study, we present an integrative multi-omics framework that stratifies patients into distinct immune and microbial subtypes, uncovering their associations with immunogenomic profiles, immune cell infiltration patterns, and clinical features. Notably, we identify specific microbial genera correlated with immune-related gene expression and immune checkpoint blockade responsiveness. These findings provide novel insights into the immune-microbiome axis in STAD and underscore the potential of integrative multi-omics approaches to enhance patient stratification and guide more effective immunotherapeutic strategies.}, } @article {pmid41660769, year = {2026}, author = {Tahara, T and Shimogama, T and Shijimaya, T and Yamazaki, J and Nakamura, N and Takahashi, Y and Naganuma, M}, title = {Interaction of host genetic factor and gastric microbiome in DNA methylation induction.}, journal = {Epigenomics}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/17501911.2026.2627274}, pmid = {41660769}, issn = {1750-192X}, } @article {pmid41660430, year = {2026}, author = {Dong, X and Chen, X and Xu, Y and Zeng, D and Li, P}, title = {Gut microbiota composition and systemic immune-inflammatory marker correlations in infertile women with endometriosis: a pilot case-control study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1720894}, pmid = {41660430}, issn = {2235-2988}, mesh = {Humans ; Female ; *Endometriosis/microbiology/immunology/complications ; Case-Control Studies ; *Gastrointestinal Microbiome ; Pilot Projects ; Adult ; RNA, Ribosomal, 16S/genetics ; *Biomarkers/blood ; Feces/microbiology ; *Infertility, Female/microbiology/immunology ; *Bacteria/classification/genetics/isolation & purification ; Inflammation ; DNA, Bacterial/genetics/chemistry ; }, abstract = {BACKGROUND: The specific gut microbial signatures and their correlation with immune-inflammatory markers in infertile women with endometriosis remain underexplored.To investigate the differences in gut microbiota and their associations with biochemical immune markers in infertile women with endometriosis compared to controls.

METHODS: This case-control study enrolled 32 infertile women with endometriosis and 13 control women with male-factor infertility. Fecal samples were collected for 16S rRNA sequencing to profile the gut microbiota, and serum samples were obtained to measure inflammation-related biomarkers. Bioinformatics analyses were applied to compare gut microbial community structures and to examine correlations between differentially abundant bacteria and immune markers.

RESULTS: The endometriosis group exhibited significant enrichment of Lachnospira, Bacilli, Lactobacillales, Parasutterella, Enterococcus, and Veillonella. Comparative analysis revealed significantly altered abundances of multiple taxa, including Lachnospira, Parasutterella, Alistipes, Enterococcus, Veillonella, Streptococcus, Desulfovibrionaceae, Ruminococcaceae, Bilophila, and Peptoniphilus (all P < 0.05). Several inter-species correlations were identified among these bacteria. Importantly, specific microbiota were correlated with immune markers: Streptococcus and Veillonella were positively correlated with macrophage migration inhibitory factor (MIF); Bilophila and Enterococcus were positively correlated with TNF-α and IL-6; Veillonella was positively correlated with TNF-α; Desulfovibrionaceae was negatively correlated with TNF-α and IL-6; and Parasutterella was negatively correlated with CA125.

CONCLUSION: In this exploratory investigation, specific gut microbial signatures were observed in infertile patients with endometriosis, showing correlations with select systemic immune-inflammatory biomarkers. These initial observations point to a possible association between gut microbiota imbalance and the inflammatory aspects of endometriosis-associated infertility. Consequently, microbial modulation merits further investigation as a potential strategy to alleviate inflammation and potentially enhance reproductive outcomes.}, } @article {pmid41660426, year = {2026}, author = {Wang, S and Yang, Y and Lei, L and Wan, R and Su, Z and Liu, Y and Tang, H and Hu, G and Li, C and Li, C and Meng, J and Yang, K}, title = {SSTDhunter: a curated gene database for investigating androgen producing potential in microbiota species.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1754671}, pmid = {41660426}, issn = {2235-2988}, mesh = {*Androgens/biosynthesis/metabolism ; *Databases, Genetic ; Humans ; *Gastrointestinal Microbiome/genetics ; Male ; Transketolase/genetics/metabolism ; *Clostridium/genetics/enzymology/metabolism ; *Microbiota ; Prostatic Neoplasms ; }, abstract = {Androgens are critical for the growth of prostate cells, as well as prostate tumor cells. For prostate cancer patients under Androgen Deprivation Therapy (ADT) such as castration treatment, investigating the potential for androgen production by gut microbes is crucial. In microbe species, the side chain cleavage activity of steroid-17, 20-desmolase (SSTD) is responsible for 11-oxy-androgens production by biotransformation from cortisol, as well as from other endogenous steroids and pharmaceutical glucocorticoids. The side-chain cleavage product of prednisone could significantly promote the proliferation of prostate cancer cells. The SSTD is a complex formed by N-terminal and C-terminal transketolases encoded by desA and desB genes, whose activity has been well-characterized in Clostridium scindens ATCC 35704. While a void still existed in evaluating the androgen producing potential by gut microbiota owing to relatively low abundance of SSTD-carrying species and the lack of professional gene database. Meanwhile, mining SSTD encoding genes in explosion sequencing data has become computationally expensive and time-consuming using comprehensive database. Here, a professional database consisted of SSTD-coding genes, named SSTDhunter, was constructed using a large-scale genomic analysis along with homologous genes as background. These SSTD-coding genes were reconstruction through comprehensive characteristics consisted of operon structures, sequence identities, phylogenetic topologies and comparative analysis. To reduce false positives, protein sequences of homologous genes tktA, which encode component of sugar transketolase, were also included in SSTDhunter database as background noise. SSTDhunter is for rapid investigation of SSTD-coding genes in massive metagenomic data, which is freely available at http://www.orgene.net/SSTDhunter/.}, } @article {pmid41660425, year = {2026}, author = {Ni, H and Zhu, J and Chen, Y and Zheng, Y and Chen, B and Dong, C and Zhang, S and Xu, Y and Jiang, Y}, title = {Clinical characteristics and prognostic impact of streptococcal colonization in critically ill patients with severe pneumonia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {16}, number = {}, pages = {1647511}, pmid = {41660425}, issn = {2235-2988}, mesh = {Humans ; Male ; Female ; Critical Illness ; Retrospective Studies ; Prognosis ; Middle Aged ; Aged ; *Streptococcal Infections/microbiology/mortality ; Intensive Care Units ; *Streptococcus/genetics/isolation & purification ; Bronchoalveolar Lavage Fluid/microbiology ; *Pneumonia, Bacterial/microbiology/mortality ; }, abstract = {BACKGROUND: Streptococcus species are predominant commensal residents of the respiratory tract in healthy individuals and contribute to immune and metabolic regulation. However, the association between streptococcal colonization and clinical outcomes in patients with severe pneumonia remains undercharacterized. This study aimed to explore the clinical characteristics and the impact of streptococcal colonization on the prognosis of critically ill patients with pneumonia.

METHOD: We conducted a multicenter, retrospective, observational cohort study of critically ill pneumonia patients admitted to 12 intensive care units (ICUs) between January 2019 and December 2023 who underwent metagenomic next-generation sequencing (mNGS). Patients were stratified into Streptococcus-colonized and non-colonized groups based on bronchoalveolar lavage fluid (BALF) mNGS results, conventional microbiological testing (CMT), and clinical assessments. Propensity score matching (PSM) was utilized to minimize baseline confounding variables. Using nearest-neighbor matching at a 1:2 ratio, baseline characteristics were balanced between groups post-matching. The primary endpoint was 28-day all-cause mortality.

RESULTS: A total of 1,897 patients were enrolled in this study. Among them, 21 patients under 18 years of age, 139 patients lost to follow-up within 28 days, and 4 patients with confirmed streptococcal infection were excluded. Finally, 1,733 patients met the inclusion criteria. The cohort had a mean age of 65 years, with the majority being males (1,213/1,733, 70%). Among these, 148 (8.5%) were classified as Streptococcus-colonized, and 1,585 (91.5%) were Streptococcus-colonization-negative. No significant difference in 28-day all-cause mortality was observed between the colonized and non-colonized groups (35.81% vs. 38.51%, p=0.578). Patients with Streptococcus colonization had a significantly shorter median length of stay (LOS) (17 days, interquartile range [IQR] 11-30) than those without colonization (22 days, IQR 12-33; P = 0.044). Similarly, their median intensive care unit (ICU) LOS (11 days, IQR 7-16) was also significantly shorter than that of non-colonized patients (14 days, IQR 8-25; P = 0.003). Multivariable Cox regression analysis further demonstrated that Streptococcus colonization was not an independent risk factor for 28-day mortality (HR = 1.10, 95% CI: 0.79-1.51, p=0.579).

CONCLUSION: Our findings suggest a potential role for Streptococcus colonization in improving clinical outcomes in severe pneumonia. The presence or absence of Streptococcus colonization may influence short-term prognostic benefits in critically ill pneumonia patients. Further research is needed to clarify the clinical significance and potential mechanisms of Streptococcus colonization.}, } @article {pmid41660022, year = {2026}, author = {Shaji, A and Ramachandran, AK and Chandrasekaran, N and Savarimalai, KC and Adhira, R}, title = {A cross-sectional metagenomic analysis of the microbial ecology in symptomatic apical periodontitis - An in vivo study.}, journal = {Journal of conservative dentistry and endodontics}, volume = {29}, number = {1}, pages = {60-64}, pmid = {41660022}, issn = {2950-4708}, abstract = {BACKGROUND: Symptomatic apical periodontitis (SAP) is a painful inflammatory disease driven by root canal infection. A detailed understanding of its microbial ecology, compared to a noninfectious baseline, is needed.

AIMS: This study aimed to characterize the microbial ecology of SAP using 16S ribosomal (RNA) 16S rRNA metagenomic sequencing and compare it to control teeth undergoing root canal treatment after trauma.

MATERIALS AND METHODS: This cross-sectional study included 10 patients with SAP and 10 control patients. Pulpal samples were collected aseptically. Microbial DNA was extracted, and the full-length 16S rRNA gene was sequenced through Oxford Nanopore Technology. Analysis was performed using QIIME2.

STATISTICAL ANALYSIS USED: Microbial abundances and diversity indices were compared using an independent samples t-test or Mann-Whitney U-test (P < 0.05 significant).

RESULTS: The SAP microbiome was dysbiotic and enriched in anaerobes. Veillonella parvula was highly abundant in SAP (mean 13.1%) but absent in controls. Species like Dialister pneumosintes and Prevotella melaninogenica were found almost exclusively in SAP. Commensals including Faecalibacterium prausnitzii were significantly reduced.

CONCLUSION: SAP is associated with a distinct microbial signature defined by the enrichment of anaerobic pathobionts and a loss of commensals, revealing a polymicrobial, dysbiotic community.}, } @article {pmid41660005, year = {2026}, author = {Wicaksono, WA and Zukancic, E and Zlatnar, M and Suwanto, A and Berg, G}, title = {Traditional fermented foods of Indonesia harbour functionally redundant but phylogenetically diverse taxa.}, journal = {FEMS microbes}, volume = {7}, number = {}, pages = {xtag005}, pmid = {41660005}, issn = {2633-6685}, abstract = {Fermented foods represent complex microbial ecosystems that contribute to food quality, functionality, and potential health benefits, yet many traditional fermented foods remain poorly characterized. The aim of this study was to study microbial diversity, and functional potential of underexplored traditional Indonesian fermented food. The fermented products displayed substantial variation in bacterial richness, ranging from 65 to 614 bacterial amplicon sequence variants across samples. The microbial communities were dominated by bacterial taxa affiliated with the orders Bacillales and Lactobacillales, alongside fungal taxa from the order Mucorales. The plant-based products i.e. tape ketan and tape singkong had a higher bacterial abundance but lower diversity than animal-based terasi. We found significant correlations between bacterial and fungal communities dominated by positive cooccurrence patterns and highly complex networks especially in terasi. Each food product was characterized by a unique functional profile of genes linked to beneficial metabolic functions (biosynthesis of bacteriocins, short-chain fatty acids, and vitamins) but tape ketan samples demonstrated the highest diversity and abundance of them. Metagenome assembled genomes reflect a high diversity of health beneficial properties as well as substrate-specific degradation capabilities. Traditional Indonesian fermented foods harbour functionally redundant but phylogenetically diverse taxa offering a potential source for probiotic traits and functional food development.}, } @article {pmid41659981, year = {2025}, author = {Santangelo, A and Corsello, A and Villano, G and Diana, MC and Striano, P}, title = {Climate change, gut microbiome, and epilepsy-New paradigms beyond the gut-brain axis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1726561}, pmid = {41659981}, issn = {1664-2295}, } @article {pmid41659959, year = {2025}, author = {Abdelmegeid, M and Zeineldin, M and Seboussi, R and Mohamadin, M and Alharthi, AS and Mansour, N and Okasha, LA and Elolimy, AA and Saliu, EM}, title = {Metagenomic analysis of the camel rumen archaeome and its functional potential.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1738018}, pmid = {41659959}, issn = {2297-1769}, abstract = {The camel rumen harbors a unique and underexplored archaeal community that plays a critical role in methanogenesis and ruminal fermentation. This study aimed to characterize the taxonomic composition and functional potential of the camel rumen archaeome using whole-genome shotgun metagenomic sequencing. Across the seven healthy racing camel rumen samples, the archaeal community was dominated by Euryarchaeota (50.1 ± 0.02%) and the Methanomada group (49.7 ± 0.03%), with Methanobacteriaceae and Methanobrevibacter representing the predominant family and genus, respectively. Species-level analysis revealed Methanobrevibacter sp. YE315 and Methanobrevibacter millerae as the most abundant archaeal species across all samples. Alpha-diversity analyses indicated a diverse and evenly distributed archaeal population in the camel rumen. Beta-diversity based on Bray-Curtis and Jaccard dissimilarities demonstrated strong similarity among samples, highlighting a conserved archaeal community structure across individuals. Core microbiome assessment (≥ 80% occurrence) identified seven dominant Methanobrevibacter species as the stable core archaeome. Functional profiling revealed a consistent metabolic repertoire dominated by methanogenesis (PWY-5209), amino acid biosynthesis, and nucleotide metabolism pathways. Functional alpha-diversity metrics and beta-diversity clustering highlighted low inter-sample variability and a stable functional architecture. Overall, the camel rumen archaeome exhibited a stable and conserved community composition and functional architecture, underscoring its central role in hydrogen utilization and methane production within the rumen ecosystem. Although based on a small number of animals from a single location and therefore descriptive in nature, this study provides a comprehensive metagenomic overview of the taxonomic and functional profiles of the camel rumen archaeal community.}, } @article {pmid41659872, year = {2026}, author = {Zhou, W and Zhang, S and Wang, C}, title = {Gut microbial alterations associated with the exacerbation of experimental autoimmune uveitis in PGRN-deficient mice.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1641755}, pmid = {41659872}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Uveitis/immunology/microbiology/genetics ; *Progranulins/deficiency/genetics ; Mice ; *Autoimmune Diseases/immunology/microbiology/genetics ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Ribosomal, 16S/genetics ; }, abstract = {PURPOSE: Progranulin (PGRN) has been shown to play a protective role in the development of a variety of immune-mediated diseases, and the gut microbiome has been implicated in the pathogenesis of autoimmune diseases. In this study, we investigate the changes in the gut microbiota and their association with the severity of experimental autoimmune uveitis (EAU) in PGRN-deficient mice.

METHODS: WT and PGRN-deficient C57BL/6 mice were used to induce EAU using interphotoreceptor-binding protein peptide. Gastrointestinal (GI) contents collected from both groups of induced EAU were subjected to 16S rRNA gene sequencing analysis.

RESULTS: PGRN-deficient mice developed exacerbated EAU compared to wild-type (WT) mice. The microbial richness of the GI contents in PGRN-deficient EAU mice was significantly lower than in WT mice. The PGRN-deficient EAU mice showed a significantly reduced microbial abundance in five phyla, namely, Cyanobacteria, Epsilonbacteraeota, Firmicutes, Nitrospirae, and Patescibacteria, and a significantly increased abundance in the other four phyla, namely, Deferribacteres, Proteobacteria, Spirochaetes, and Tenericutes. More importantly, a newly emerged phylum named Chlamydiae was detected in the gut microbial community of PGRN-deficient EAU mice. The histopathological scores were significantly negatively correlated with gut microbial abundance and significantly positively correlated with chlamydial abundance.

CONCLUSION: Our results showed that PGRN plays a protective role in EAU, and the significant changes in the gut microbiome may be associated with the exacerbation of inflammation in the PGRN-deficient EAU mice.}, } @article {pmid41659810, year = {2025}, author = {Shi, L and Yu, Y and Ma, Z and Jiang, W}, title = {Gut microbiota, liver disease, and perioperative anesthesia: interactions, risks, and therapeutic opportunities.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1759076}, pmid = {41659810}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Liver Diseases/microbiology/therapy ; Dysbiosis ; *Anesthesia/adverse effects/methods ; Anesthetics/adverse effects ; Perioperative Care ; Animals ; }, abstract = {Liver disease is increasingly common worldwide and poses significant challenges during anesthesia and surgery. Growing evidence demonstrates that the gut microbiome plays an essential role in hepatic inflammation, metabolic imbalance, immune dysfunction, and the progression of conditions such as metabolic associated steatotic liver disease, alcohol related liver injury, and cirrhosis. This review summarizes the concept of the gut-liver-anesthesia axis, which describes how disturbances in the intestinal microbiome shape perioperative risk. Importantly, this framework conceptualizes the gut-liver-anesthesia axis as a unified perioperative risk model, integrating microbial dysbiosis, hepatic vulnerability, and anesthetic exposure into a single pathophysiological continuum. Patients with advanced liver disease frequently exhibit reduced microbial diversity, impaired intestinal barrier function, disordered bile acid signaling, and heightened systemic inflammation. These alterations increase susceptibility to infection, kidney injury, hemodynamic instability, and neurocognitive complications including hepatic encephalopathy and postoperative delirium. Anesthetic agents can further disrupt the gut ecosystem by weakening mucosal integrity and facilitating bacterial translocation, while the microbiome itself influences drug metabolism and clearance, leading to unpredictable anesthetic responses. Understanding this bidirectional interaction highlights opportunities for microbiome focused perioperative strategies. Approaches such as probiotic based preparation, opioid sparing anesthesia, regional techniques, early enteral feeding, and targeted microbial restoration may improve postoperative outcomes in patients with liver disease.}, } @article {pmid41659802, year = {2025}, author = {Zeng, D and Zhang, T and Zhu, Y and Feng, J and Ye, Z and Zhao, J and Huang, P and Zhang, L and Liu, T}, title = {Effects of modified fasting therapy on tongue coating and gut microbiome in overweight and obese adults: a controlled clinical trial.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1686416}, pmid = {41659802}, issn = {2296-861X}, abstract = {INTRODUCTION: Caloric restriction facilitates weight loss and metabolic improvement, in part by altering the gut microbiota. However, its influence via the tongue coating microbiota and gut microbiota remains largely unexplored.

METHODS: To address this gap, we conducted a single-center, prospective, controlled study from 23 April to 5 July 2021, enrolling 48 participants with a body mass index (BMI) ≥ 24 kg/m[2]. Participants were assigned to either a 7-day modified fasting group (550 kcal/day, n = 35) or a control group (n = 13) based on their personal preference.

RESULTS: In the fasting group, body weight decreased by 4.0 ± 1.6 kg (p < 0.01), BMI decreased by 1.51 ± 0.58 (p < 0.01), significantly, accompanied by marked improvements in blood glucose and lipid profiles (p < 0.05). 16S rRNA sequencing of tongue coating and fecal samples revealed distinct microbial alterations between groups. In the tongue microbiota, Haemophilus was reduced, while Prevotella and Actinomyces were enriched, along with suppression of nucleotide synthesis and glycolysis pathways. In the gut microbiota, Bacteroides decreased, and Clostridia increased, with significant upregulation of gluconeogenesis and branched-chain amino acid biosynthesis pathways (p < 0.05). Notably, specific taxa such as Haemophilus and Granulicatella were positively correlated with body weight and BMI (r > 0.4, p < 0.05).

DISCUSSION: These findings suggest that MFT improves metabolic outcomes by reshaping the taxonomic composition and possible functional capabilities of the tongue coating and gut microbiota in overweight and obese individuals. However, these findings should be interpreted in the context of the limitations of the study, including its non-randomized design and the preliminary nature of the gut microbiome analysis due to a small sample size.

CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/, identifier ChiCTR2100047532.}, } @article {pmid41659745, year = {2025}, author = {Xu, Q and Lv, T}, title = {New Highlights: The Microbiome of Bronchoalveolar Lavage Fluid Predicts the Prognosis of Lung Cancer.}, journal = {Phenomics (Cham, Switzerland)}, volume = {5}, number = {5}, pages = {630-632}, pmid = {41659745}, issn = {2730-5848}, } @article {pmid41659628, year = {2026}, author = {Della Libera, K and Adamowicz, EM and Muehlbauer, A and Priya, S and Alazizi, A and Luca, F and Blekhman, R}, title = {Metabolic modeling and functional genomics reveal taxa and host gene interactions in colorectal cancer.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.26.700635}, pmid = {41659628}, issn = {2692-8205}, abstract = {Colorectal cancer (CRC) is associated with changes in the microbial communities in the tumor microenvironment. Although metabolic reprogramming is an important feature of host cells in CRC, little is known about metabolic changes in the tumor-associated microbiota and how these microbial metabolic alterations can contribute to disease. Here, we investigated metabolic host-microbiome interactions in CRC using complementary computational and experimental approaches. Using patient-specific in silico metabolic models across three independent datasets, we discovered that Fusobacterium , a cancer-promoting taxon, consistently grows faster in tumor-associated versus normal tissue-associated microbiomes. This finding prompted us to investigate whether host metabolic changes drive these microbial growth advantages. By integrating our metabolic predictions with host transcriptomics data, we identified correlations between tumor gene expression and the growth of CRC-associated taxa (including Porphyromonadaceae , Blautia , and Streptococcus), as well as associations between host genes and microbial metabolism of dietary components (including choline, amino acids, and starch). To test whether these correlations reflect causal relationships, we simulated spent medium experiments in silico , demonstrating that Blautia preferentially grows on metabolites produced by tumor versus normal host cells. We further validated the direct impact of microbes on host metabolism using an in vitro system, where colon cancer cells exposed to human microbiomes showed gene expression changes in response to specific taxa including Bilophila , Anaerotruncus , and Escherichia . Together, these findings reveal a metabolic dialogue between host and microbiome in CRC, where tumor metabolic reprogramming creates a favorable environment for pathogenic microbes, which in turn may reinforce tumorigenic processes through metabolic crosstalk.}, } @article {pmid41659521, year = {2026}, author = {Zhou, Z and Nguyen, KL and Chen, S and Wang, Y and Li, M and Biachi, D and Ge, W and Kuo, S and Gharieb, S and Tung, E and Parmar, R and Ji, J and Khorana, R and Hetta, A and Cann, I and Mackie, R and Lau, G and Yang, J and Mei, W}, title = {Bacteroides intestinalis -Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.28.702158}, pmid = {41659521}, issn = {2692-8205}, abstract = {Insufficient dietary fiber intake is strongly associated with gut microbiome dysfunction and an increased risk of noncommunicable diseases. Synergistic synbiotics, which pair defined microbial strains with their preferred carbohydrate substrates, offer a promising strategy to restore these functions. However, the rational design of such interventions remains challenging by insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal Bacteroides intestinalis (B . intestinalis) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between B . intestinalis and its preferred substrate, insoluble wheat arabinoxylan abundant in dietary fiber, enhances the production of anti-diabetic and anti-steatotic bile acid species, hyocholic acid and hyodeoxycholic acid, anti-inflammatory, antioxidant phenolic compounds, and a spectrum of neuroactive compounds. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen implicating pathways governing circadian rhythm regulation, lipid metabolism, and immune defense. Importantly, these beneficial effects are preserved in conventionally raised mice with established high fat diet-induced obesity, where BI and inWAX improve glucose tolerance. Our findings uncover a mechanistic framework linking B . intestinalis -mediated fiber fermentation to gut-liver-brain crosstalk and establish a rational foundation for precision synbiotic design.}, } @article {pmid41659429, year = {2026}, author = {Vallecillo-Zuniga, ML and Akeefe, A and Brown, DG and Wahlig, TA and Marchetti, M and Heiner, T and Davis, KL and Nieznanski, C and Flynn, A and Leung, DT}, title = {Longitudinal Changes in Nasal and Oral Microbiome and Antimicrobial Resistance Gene Profiles in Response to Human Fecal Microbiota Transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.27.701854}, pmid = {41659429}, issn = {2692-8205}, abstract = {The gut-lung axis describes interactions between intestinal and respiratory mucosal systems through microbial, metabolic, and immune pathways, but the systemic impact of gut-targeted therapies on upper respiratory tract (URT) communities remains underexplored. We conducted a longitudinal study in adult patients undergoing fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) alongside healthy controls. Fecal, nasal, and oral samples were collected at baseline (Day 0) and on Days 14 and 56 following FMT. Shotgun metagenomic sequencing was performed to quantify microbial diversity, taxonomic composition, and the abundance of antimicrobial resistance genes (ARGs). FMT was associated with increased gut diversity and decreased levels of key intestinal taxa commonly considered pathobionts, including Klebsiella spp., Escherichia spp., Shigella spp., and Klebsiella pneumoniae . At the phylum level, fecal Bacteroidota increased, while Mucoromycota decreased following treatment. Post-FMT nasal microbiome changes included reduced richness and diversity, expansion of Moraxella , and decreases in taxa linked with respiratory colonization, including Staphylococcus aureus and Streptococcus pneumoniae . By Day 56, nasal communities partially recovered toward healthy profiles. Baseline nasal ARG abundance decreased following FMT, particularly among β-lactam, aminoglycoside, and fluoroquinolone resistance genes, and remained comparable to healthy controls by Day 56. In contrast, the oral microbiome and oral resistome remained largely stable, with only minor fluctuations, and no consistent increases in respiratory pathobiont-associated taxa. In summary, FMT was associated with broader effects beyond the gut, including changes in the URT microbial ecology and antimicrobial resistance profiles. Together, these findings are consistent evidence of gut-lung microbial interactions, linking intestinal dynamics with respiratory microbial composition and antimicrobial resistance patterns.}, } @article {pmid41659373, year = {2026}, author = {Farhan, M and Pan, J and Zhao, J and Yang, H and Zhang, S}, title = {Aphid adaptation to plant secondary metabolites: adaptive mechanism of resistance evolution and future prospects.}, journal = {Horticulture research}, volume = {13}, number = {1}, pages = {uhaf269}, pmid = {41659373}, issn = {2662-6810}, abstract = {Aphids are demonstrated to be voracious phloem feeders, among the most damaging insect pests, due to their capacity to decrease crop production and vector plant viruses. Plant secondary metabolites (PSMs) comprise an essential element of plant protection, which in most cases deters and affects aphid performance. Nonetheless, aphids have developed various resistance mechanisms to counteract these chemicals. This review provides an extensive overview of the biological and molecular adaptations that aphids employ to counteract PSMs, including enzymatic detoxification, antioxidant defense, sequestration, behavioral response shifts, suppression of plant defense mechanisms by symbionts, and manipulation of host signaling pathways by effector proteins. We also described the suppression of the defense pathways by aphid-associated viruses, which further complicates plant-aphid interactions. Although significant insights have been gained about each of the individual mechanisms, research gaps remain, particularly in the functional confirmation of detox genes, the communication interactions of the symbionts, and whether sequestration could play an ecological role across species. Intensive efforts involving molecular-based breeding of horticultural crops, as well as traditional breeding with wild relatives highly endowed with aphid-resistant PSM traits, should be employed in the future to provide sustainable crop protection. New technologies in crop genomics, the identification of effectors, and microbiome research promise the development of resistant cultivars that are not only resistant to aphids but also prevent the spread of disease by their vectors. Together, all this knowledge has the potential to produce high-yielding crops that are resistant to aphids and to implement sustainable farming practices.}, } @article {pmid41659330, year = {2025}, author = {Wu, H and Wei, G and Huang, S and Wan, L and Xu, Q and Huang, C}, title = {The gut-brain axis mediates precocious puberty induced by environmentally relevant low-dose endocrine-disrupting chemical mixtures.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1728811}, pmid = {41659330}, issn = {1664-2392}, mesh = {*Endocrine Disruptors/toxicity/adverse effects ; *Puberty, Precocious/chemically induced ; Humans ; Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; *Brain/drug effects ; Dysbiosis/chemically induced ; *Brain-Gut Axis/drug effects ; }, abstract = {BACKGROUND: The global rise in precocious puberty (PP) is increasingly linked to exposure to endocrine-disrupting chemicals (EDCs). However, the mechanisms by which environmentally relevant, low-dose mixtures of EDCs influence PP remain inadequately explained by direct endocrine disruption.

OBJECTIVE: This systematic review evaluates a novel hypothesis: that disruption of the gut-brain axis (GBA) serves as a pivotal mechanism in EDC mixture-induced PP.

METHODS: We synthesized evidence from 87 studies (45 human, 32 animal, 10 in vitro) following PRISMA 2020 guidelines. An exploratory Random Forest analysis was employed to identify key mediators and estimate the relative contribution of the GBA pathway.

RESULTS: Perinatal exposure to low-dose EDC mixtures consistently induced gut dysbiosis, characterized by reduced microbial diversity (Shannon Δ = -1.8), a 40% decrease in Lactobacillus, and a 1.5-fold increase in Bacteroides. This dysbiosis was linked to impaired production of butyrate (↓50%) and secondary bile acids, increased intestinal permeability (FITC-dextran ↑80%), and systemic inflammation (IL-6 ↑1.8-fold). Fecal microbiota transplantation from PP donors into germ-free mice recapitulated early pubertal onset, supporting a causal role for gut microbiota. Exploratory modeling suggested that mediators within the GBA pathway could be associated with a large share (approximately 68%) of the model-internal variance explanation for PP risk at low experimental doses (≤1 μg/kg/day), indicating its potential prominence over direct endocrine disruption in this analysis. Significant synergistic effects (Synergy Index > 2.3) were observed under mixture exposures.

CONCLUSION: This review identifies the GBA as a critical and previously underappreciated mechanism for low-dose EDC mixture-induced precocious puberty in a dose-dependent manner. Our findings underscore the need for regulatory paradigms and future research to integrate this pathway when assessing the risks of complex, real-world chemical mixtures.}, } @article {pmid41659075, year = {2026}, author = {Duggar, M and Sun, Y and Leardini, D and Jia, Q and Muratore, E and Dallas, RH and Ferrolino, J and Cherian, A and Cesaro, S and Faraci, M and Fraczkiewicz, J and Ussowicz, M and Englund, JA and Hakim, H and Hayden, RT and Klein, EJ and Wolf, J and Maron, G and Tang, L and Masetti, R and Margolis, EB}, title = {Pre-HCT Resistome Disruption Predicts ESBL Gene Expansion in Pediatric Transplant Recipients: A Prospective Multi-Center Study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.20.26344466}, pmid = {41659075}, abstract = {BACKGROUND: Infections are the leading cause of non-relapse mortality in pediatric hematopoietic cell transplant (HCT) recipients. Up to 90% of bacteremias in these patients originate from gut microbiome organisms. However, selection for resistance genes, such as Extended-spectrum β-lactamase (ESBL), in these patient's gut microbiomes remains poorly understood.

METHODS: Stools were prospectively collected from pediatric HCT recipients at multiple centers (n=133 patients, five centers) on the day of HCT, the day of neutrophil engraftment, and 30 days post-HCT. Bacterial DNA was isolated and sent for shotgun metagenomic sequencing. Antibiotic resistance genes were identified using the MEGARes database. Associations between ESBL gene abundance changes and antibiotic exposure were examined using univariate and Inverse Probability of Treatment Weighting linear regression models with covariate balancing propensity scores.

RESULTS: Pre-existing gut resistome disruption at the time of HCT showed a stronger correlation with ESBL gene expansion than post-transplant antibiotic exposure. Specifically, patients with greater baseline resistome distance from healthy children showed increased ESBL genes during the neutropenic period. Post-transplant β-lactam exposure (total or ESBL-cleavable) did not correlate with increases in ESBL genes in already-colonized patients. However, aminoglycosides and anaerobic active antibiotics were associated with acquisition of new ESBL organisms during the neutropenic period, while pre-existing microbiome disruption primarily drove selection of resistant bacteria already present.

CONCLUSIONS: These findings indicate that antibiotic stewardship before HCT, in addition to reducing the use of anaerobic active antibiotics during early transplant, may be necessary to prevent ESBL-related infections in pediatric transplant recipients.

LAY SUMMARY: Infections are the leading cause of death after HCT, and recently the role of the gut microbiome in harboring dangerous bacteria has been highlighted. This study aims to understand multidrug resistant bacteria changes in the gut microbiome early after HCT.}, } @article {pmid41658751, year = {2026}, author = {De, A and Sarveswari, KN and Tolat, S and Hameed, S and Bhat, S and Jain, S and Swami, OC}, title = {Oryza Ceramax in Dermatologic Care: A Multi-pathway Approach to Skin Hydration and Barrier Repair.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e100886}, pmid = {41658751}, issn = {2168-8184}, abstract = {Environmental stressors, including climate change, pollution, and lifestyle factors, can disrupt the skin barrier, leading to dryness and exacerbating conditions such as atopic dermatitis (AD), acne, and psoriasis. Effective barrier repair requires maintaining hydration and lipid balance, particularly the ceramide-cholesterol-fatty acid ratio of 3:1:1, which is recommended by dermatological societies for optimal skin restoration. Although traditional moisturizers provide hydration through occlusives, humectants, and emollients, they often do not achieve sustained barrier repair or adequate intracellular hydration. Next-generation moisturizers are designed with bioactive ingredients that aim to both hydrate and support barrier repair by reducing inflammation, modulating the microbiome, and promoting skin homeostasis. Oryza Ceramax (Alaina Healthcare; Alembic Pharmaceuticals Pvt. Ltd., Vadodara, India), a next-generation moisturizer incorporating a 3:1:1 ceramide-cholesterol-fatty acid ratio, includes aquaporin (AQP) boosters, naturally sourced betaine, saffron extract, hyaluronic acid, and other bioactive components that resemble the skin's natural lipid composition. Clinical evidence supports the efficacy of ceramide-dominant formulations in improving hydration and reducing transepidermal water loss (TEWL), with studies reporting TEWL reductions of approximately 10% and hydration improvement lasting up to 72 hours. Oryza Ceramax is formulated to align with dermatologic recommendations for use in dry or impaired skin and is free from parabens, alcohol, mineral oil, and soap (PAMS-free). Its formulation characteristics are consistent with evidence-based principles for skin barrier protection and hydration maintenance. This narrative review examines the science underlying multi-pathway approaches to skin barrier repair and hydration, using Oryza Ceramax as an example of a ceramide- and AQP-based formulation. The findings highlight emerging strategies in moisturizer design but also emphasize the need for independent, well-controlled clinical studies to validate these observations.}, } @article {pmid41658674, year = {2026}, author = {Ajmera, K and Patel, O and Shah, N}, title = {Artificial Intelligence in Gastroenterology: Beyond Diagnostics and Toward Lifestyle and Dietary Interventions For Gastrointestinal Disorders.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e100976}, pmid = {41658674}, issn = {2168-8184}, abstract = {Gastrointestinal (GI) diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, liver cirrhosis, and functional gastroesophageal reflux disorder (GERD) are often associated with a substantial increase in various symptoms, including pain, a reduced quality of life, and the need for medical attention. Dietary and lifestyle changes remain the backbone of treatment for many of these diseases, but they are not always implemented due to obstacles such as low adherence, a lack of customization, inadequate health insurance, and difficulty in accessing expert advice. Artificial intelligence (AI) has demonstrated significant potential in gastroenterology, particularly in diagnostics such as endoscopy and imaging. However, its therapeutic applications, especially in providing diet and lifestyle support, remain in early stages. To bridge this gap, this narrative review examines the potential of AI to deliver culturally responsive, scalable, and personalized dietary guidance to this patient population. The significance of this approach cannot be overstated, particularly for patients from diverse racial backgrounds and for those who lack access to medical treatment. AI offers a solution that utilizes natural language processing (NLP), predictive analytics, and real-time patient support, thereby helping to improve adherence, personalize advice, and extend treatment beyond the clinic. One option is to integrate digital medicines, microbiome data, wearables, and AI-driven systems to ensure proactive management of GI problems through continuous monitoring. When AI is developed in an ethical manner that protects data and emphasizes integrity, it can gradually transform the dietary management of GI disorders. AI could help improve GI health by encouraging a more proactive and personalized approach to treatment, increasing patient independence, and reducing unnecessary physician visits.}, } @article {pmid41658610, year = {2026}, author = {Bautista, J and Bedón-Galarza, R and Martínez-Hidalgo, F and Masache-Cruz, M and Benítez-Núñez, M and Valencia-Arroyo, C and López-Cortés, A}, title = {Decoding the microbial blueprint of pancreatic cancer.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1737582}, pmid = {41658610}, issn = {2296-858X}, abstract = {Pancreatic cancer (PC) represents one of the most formidable challenges in oncology, characterized by its asymptomatic onset, delayed clinical detection, and dismal prognosis. Among pancreatic neoplasms, pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of cases and remains the most aggressive form, driven by late diagnosis, intrinsic chemoresistance, and a profoundly immunosuppressive tumor microenvironment. Recent advances have reframed the human microbiome not as a passive bystander but as an active architect of pancreatic tumor biology. This review delineates the mechanistic axes through which microbial ecosystems orchestrate PDAC progression across four key anatomical niches-gastrointestinal, oral, urogenital, and intrapancreatic. We elucidate how microbial dysbiosis fosters oncogenesis through immune evasion, metabolic reprogramming, and chronic inflammation, implicating specific taxa such as Fusobacterium nucleatum, Malassezia spp., and Porphyromonas gingivalis in immune suppression and chemoresistance. Microbial enzymatic inactivation of gemcitabine and modulation of cytokine networks further underscore the microbiome's pivotal role in therapeutic failure. Conversely, commensal and probiotic species may potentiate immunosurveillance and enhance treatment efficacy. This review also explores microbiota-derived biomarkers for early detection and the translational promise of microbiome-targeted interventions, including fecal microbiota transplantation, probiotics, and selective antibiotics. By decoding the microbial blueprint of PC, we propose a paradigm in which the microbiome emerges as both a biomarker and a therapeutic axis, offering novel avenues for precision oncology. Furthermore, this integrative synthesis emphasizes the multi-omic, immunometabolic, and therapeutic dimensions of the pancreatic cancer-microbiome interface, where metagenomic, transcriptomic, metabolomic, and immunomic layers converge to shape tumor evolution and therapeutic response, advancing the vision of microbiome-informed precision oncology.}, } @article {pmid41658268, year = {2026}, author = {Tashkandy, NR}, title = {Alterations in gut microbial metabolic pathways following bariatric surgery assessed by 16S rRNA gene sequencing.}, journal = {Gut microbiome (Cambridge, England)}, volume = {7}, number = {}, pages = {e2}, pmid = {41658268}, issn = {2632-2897}, abstract = {Researchers have studied gut microbiota changes following bariatric surgery (BS), but not gut diversity and function in patients who fail to reduce weight. Stool samples were collected from three groups of women: 15 women who did not lose weight after BS ("Yes" group), 9 overweight women without surgery, and 8 slim women ("No" group). 16S ribosomal RNA gene sequencing and PICRUSt2 were used for the analysis. The surgery and control groups had equal alpha and beta diversity, perhaps due to the high proportion of overweight participants (n = 24). All groupings were dominated by Bacteroidota and Bacillota. Barnesiellaceae decreased with BS, although Streptococcaceae remained frequent in overweight people. The iron supplementation group had High abundance of Atopobiaceae and Prevotellaceae. Barnesiellaceae abundance was considerably lower in both surgical groups (with and without iron supplementation) than in the no-iron and no-surgery groups. The ornithine degradation and haem biosynthesis routes use different metabolites than the glycine super system. Finally, the "Yes" group significantly upregulated PWY0-1241, PWY-5177, and PWY-5855 signaling pathways. In conclusion, gut bacteria and metabolic functions may predict weight loss after surgery better than diversity markers. The requirement for orthogonal validation assays is suggested by pathway analysis outperforming diversity metrics.}, } @article {pmid41658015, year = {2026}, author = {Liao, S and Yang, H and Song, L and Shi, L and Lan, Z and Zhao, W and Bao, Z and Hu, Q and Tang, X and Zhuang, S and Wang, H and Zhong, S}, title = {Impact of obstructive sleep apnea on gut microbiome of patients with symptomatic intracranial atherosclerotic stenosis.}, journal = {Frontiers in aging neuroscience}, volume = {18}, number = {}, pages = {1713733}, pmid = {41658015}, issn = {1663-4365}, abstract = {INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is positively associated with increased risks of ischemic stroke. Patients with stroke exhibit remarkable gut microbiota dysbiosis. However, the impact of OSAS on gut microbiota of patients with symptomatic intracranial atherosclerotic stenosis (sICAS), one of the most common causes of stroke, remains unknown.

METHODS: This study included patients with sICAS, the severity of OSAS was defined by the apnea-hypopnea index (AHI). AHI < 5 was considered no sleep apnea, AHI 5-15 was defined as mild OSAS, AHI 15-30 as moderate OSAS, and AHI > 30 as severe OSAS. Fecal samples were collected and subjected to 16 s rRNA gene sequencing. PICRUSt2 was used to predict the functional properties of the bacterial communities.

RESULTS: In total, 99 sICAS patients were included, with No-OSAS (N = 22), Mild (N = 25), Moderate (N = 30), and Severe (N = 22). Patients with OSAS exhibited significantly altered gut microbiota composition compared to those without sleep apnea, characterized by increased abundances of pathogens such as Escherichia-Shigella and decreased abundances of beneficial microbes such as short-chain fatty acids-producing bacteria Blautia. Importantly, these microbes were significantly associated with AHI. Several microbial metabolic pathways such as Peptidoglycan biosynthesis, C5-branched dibasic acid metabolism, and Pantothenate and CoA biosynthesis were downregulated with OSAS.

CONCLUSION: OSAS is associated with gut dysbiosis and altered microbial metabolic functions in patients with sICAS.}, } @article {pmid41658004, year = {2025}, author = {Qiu, S and Zheng, B and Pan, J and Yu, S and Qian, J and Tung, TH and Shen, B}, title = {Difference analysis of intestinal microbiota in patients in the intensive care unit using different sampling methods: a systematic review and meta-analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1723862}, pmid = {41658004}, issn = {1664-302X}, abstract = {BACKGROUND: The normal intestinal microbiota undergoes rapid and notable changes in patients in the intensive care unit (ICU) because of factors such as host physiological stress, changes in gastrointestinal function, and antibiotic exposure. Different specimen types are used for intestinal microbial analysis because of sampling difficulties. Therefore, this study conducted a meta-analysis to investigate changes in the intestinal microbiota of patients admitted to the ICU and whether using different specimen types affects microbiota analysis.

METHODS: A systematic review was conducted encompassing studies published in electronic databases up to May 1, 2024. We included 11 studies that compared the abundance and diversity of the gut microbiota between ICU patients and healthy cohorts (HC). A standardized mean difference (SMD) meta-analysis using random effects models was performed to quantify microbial differences, including an assessment of various sampling methods.

RESULTS: After ICU admission, the intestinal microbiota of patients differed significantly from that of the normal population, showing lower diversity and richness. A significant difference in beta diversity was also observed. Specifically, the relative abundances of Proteobacteria and Fusobacteria were elevated in ICU patients, while Firmicutes abundance was diminished. Crucially, the comparison of stool versus rectal swab specimens demonstrated no significant difference in the measured alpha diversity of the gut microbiota.

CONCLUSION: The early intestinal microbiota of patients in the ICU differed from that of healthy individuals. A comprehensive understanding of the early changes in the intestinal microbiota of patients in the ICU can help formulate prevention and treatment strategies. Furthermore, using feces and swab samples for analysis did not significantly affect the diversity of the intestinal microecology. Therefore, rectal swabs may be an attractive method for sampling the gut microbiota and metabolome.

PROSPERO Registration number is CRD42022385146 (Available from: https://www.crd.york.ac.uk/PROSPERO/view/CRD42022385146).}, } @article {pmid41658001, year = {2025}, author = {Ruiz-Aymá, G and Romero-Arguelles, R and Rios-Del Toro, EE and Juarez-Gaspar, A and Olalla-Kerstupp, A and Loredo-Tovias, M and González-Rojas, JI and Villarreal-Treviño, L and Guzmán-Velasco, A and Gomez-Govea, MA}, title = {Postbiotic metabolites present in the supernatants of Lysinibacillus xylanilyticus and Bacillus cereus promote the germination and growth of Hibiscus sabdariffa and Prosopis juliflora.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1741549}, pmid = {41658001}, issn = {1664-302X}, abstract = {INTRODUCTION: The search for sustainable agricultural strategies has highlighted the importance of plant-microbe interactions within soil ecosystems. In particular, extracellular metabolites produced by soil bacteria represent a promising, yet underexplored, source of bioactive compounds capable of modulating plant germination and early development.

METHODS: This study evaluated the biostimulant potential of extracellular metabolites present in bacterial cell-free supernatants on the germination and early growth of Hibiscus sabdariffa and Prosopis juliflora under controlled laboratory conditions. Two native bacterial strains isolated from soils of Nuevo León, Mexico, were identified as Lysinibacillus xylanilyticus and Bacillus cereus using MALDI-TOF mass spectrometry. Supernatants obtained after cultivation in Luria-Bertani (LB) medium were applied directly to seeds, and germination and growth parameters were recorded. Phytochemical screening of the supernatants was also performed.

RESULTS: The L. xylanilyticus supernatant significantly enhanced seed germination (96.66 ± 5.77%; p < 0.0001) and promoted early growth in both plant species, increasing shoot length, leaf width, and fresh biomass. In contrast, the B. cereus supernatant inhibited H. sabdariffa germination (30 ± 10%; p = 0.0146) and showed limited effects on P. juliflora. Notably, a 50:50 mixture of both supernatants completely inhibited H. sabdariffa germination while significantly stimulating P. juliflora germination (90 ± 10%; p = 0.0130). Phytochemical analysis revealed low concentrations of carbohydrates and coumarins, suggesting that the observed effects were likely mediated by other, unidentified bioactive metabolites.

DISCUSSION: These findings demonstrate that extracellular metabolites produced by soil-derived bacteria exert species-specific and measurable biological effects on seed germination and early plant growth. The contrasting responses observed between plant species and supernatant combinations underscore the complexity of plant-microbe chemical interactions. Overall, this study highlights the potential of bacterial extracellular metabolites as microbiome-based tools for sustainable agriculture and ecological restoration.}, } @article {pmid41657993, year = {2025}, author = {Zhu, L and Zhang, H and Tang, M and Yang, X and Chen, Y}, title = {Parents-child multiple sites of microbial and metabolic signatures in autism spectrum disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1745874}, pmid = {41657993}, issn = {1664-302X}, abstract = {INTRODUCTION: To investigate the horizontal transmission of oral-gut microbiota in autism spectrum disorder (ASD) families and its potential implications for ASD pathogenesis.

METHODS: The research employed a paired cohort design using family cohorts (23 ASD children/17 parents vs. 18 Non-ASD children/16 parents), conducting integrated microbiome and metabolomic analyses of oral and fecal samples.

RESULTS: The findings revealed that ASD families exhibited significantly increased oral microbial species diversity alongside substantial alterations in gut microbiota composition, particularly demonstrating a lower Firmicutes/Bacteroidetes ratio (3.60/2.97) compared to Non-ASD families (5.59/5.35). Specific microbial changes included notable enrichment of Prevotella_9 in ASD gut microbiota. Metabolomic profiling identified significant disruptions in multiple metabolic pathways, including impaired L-rhamnose degradation and glutathione metabolism. The study observed coordinated oral-gut axis alterations through synchronized changes in Caulobacter and Serratia abundances, suggesting a distinct dysbiotic pattern along this microbial continuum. Additional metabolic findings demonstrated reduced levels of fecal glutamine and Ala-Gly in ASD children, with glycylproline exhibiting high predictive value for family typing (AUC = 0.91). Integrative analysis further revealed significant correlations between Holdemanella and various lipid metabolites.

DISCUSSION: It indicates that ASD families display characteristic oral-gut microbiota interactions accompanied by metabolic abnormalities, potentially reflecting familial microbial transmission patterns that may contribute to ASD pathophysiology.}, } @article {pmid41657979, year = {2025}, author = {Lin, S and Shi, E and Zhang, Y and Wang, X and Tian, Z and Han, J and Li, Q}, title = {Gut microbiota, circulating metabolites, and pancreatic cancer risk: a multi-method causal inference study with cross-population validation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1730313}, pmid = {41657979}, issn = {1664-302X}, abstract = {Pancreatic cancer (PC) is a lethal malignancy with limited early detection strategies and poor therapeutic response. Emerging evidence implicates the gut microbiota in carcinogenesis, yet whether microbial alterations are causal or secondary remains uncertain. In this study, we integrated cross-sectional 16S rDNA sequencing, two-sample Mendelian randomization (MR), and mediation analysis to investigate the causal role of gut microbiota in PC risk. We profiled fecal microbiota in a Beijing-based cohort of 26 newly diagnosed PC patients and 9 healthy controls, revealing significant dysbiosis characterized by reduced microbial diversity, depletion of butyrate-producing genera (e.g., Faecalibacterium), and enrichment of pro-inflammatory taxa such as Olsenella. Using European GWAS summary data, MR analysis identified 17 gut microbial taxa causally associated with PC risk, including Olsenella and Pauljensenia sp000411415. Notably, higher abundance of Pauljensenia sp000411415 was associated with increased PC risk, an effect partially mediated by reduced circulating levels of octanoylcarnitine (C8) and glutarylcarnitine (C5-DC)-metabolites independently linked to lower PC risk. Population-matched MR in East Asian cohorts validated several causal associations, enhancing ancestral relevance. Our findings support a causal role for specific gut microbes in pancreatic carcinogenesis and highlight a Pauljensenia-acylcarnitine axis whereby microbial suppression of protective metabolites may contribute to disease development. This integrative approach bridges microbial dysbiosis with functional mechanisms, offering novel insights for microbiome-informed strategies in PC prevention and early detection.}, } @article {pmid41657915, year = {2026}, author = {Till, JM and Brock, OD and Ahern, PP}, title = {Striking a balance: how the gut microbiome shapes the fate of intestinal CD4+ T cells.}, journal = {Discovery immunology}, volume = {5}, number = {1}, pages = {kyaf020}, pmid = {41657915}, issn = {2754-2483}, abstract = {The induction of immune tolerance, a state of immunologic hyporesponsiveness to an antigen, is essential to prevent the destructive potential of the immune system in response to harmless or beneficial agents. Early efforts to understand tolerance focused on model stimuli, self-antigens, transplanted organs, and the growing fetus. Through co-evolution, the microbiome and the host immune system have developed strategies that promote immunological tolerance to the microbiome. This dialogue ensures the maintenance of mutualistic interactions that provide a stable habitat for the microbiome which in turn confers numerous physiological benefits to the host. Despite the gut microbiome being a potent inducer of immune tolerance, the mechanisms through which specific members shaped immune function remained largely ignored for decades. The growing appreciation for the immunomodulatory capacity of the microbiome has led to a massive expansion of efforts to define how the balance between tolerance and inflammation is induced and maintained at mucosal sites like the intestine. While the ensuing research uncovered myriad fundamental insights into the concerted host and microbial functions promoting host-microbiome mutualism, inducing tolerance to clinically relevant antigens remains a major challenge in the development of tolerogenic therapies. Here, we trace the interaction between intestinal CD4+ T cells and the microbiome, from antigen uptake through to the development of a polarized collection of CD4+ T cells, whose functions are essential for immunological tolerance, and highlight the knowledge gaps that limit efforts to leverage these interactions for clinical benefit.}, } @article {pmid41657902, year = {2026}, author = {Wang, N and Fan, J and Geng, X and Zhang, S and Pan, Z and Jin, C and Chen, Y and Wu, N}, title = {Odoribacter splanchnicus inhibits toxin production in Clostridioides difficile: insights from clinical correlation and in vitro validation.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1741232}, pmid = {41657902}, issn = {1664-302X}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea. Although gut microbiota dysbiosis is central to CDI, the specific commensal species that confer protection are not well defined.

METHODS: We performed 16S rRNA sequencing on fecal samples from a clinical cohort of 30 CDI patients, 30 non-CDI diarrhea patients, 27 asymptomatic C. difficile carriers, and 30 healthy controls. To functionally validate the clinical finding, an in vitro anaerobic co-culture system was established between the Odoribacter splanchnicus type strain and C. difficile. Toxin protein levels in the supernatant were quantified by ELISA at multiple time points (24, 48, and 72 h). Sporulation was assessed via ethanol resistance assays, and the expression of toxin genes (tcdA/tcdB) was measured by quantitative PCR (qPCR).

RESULTS: Clinical analysis revealed a significant negative correlation between the abundance of Odoribacter splanchnicus and CDI severity. In vitro, a high initial ratio of O. splanchnicus significantly suppressed C. difficile toxin production during the stationary phase, without inhibiting bacterial growth. This reduction in vitro levels was accompanied by a concurrent increase in sporulation and was preceded by a downregulation of tcdB gene expression.

CONCLUSION: This work positions O. splanchnicus as a highly promising candidate for the development of next-generation, defined microbial therapeutics and provides a mechanistic foundation for future anti-virulence approaches to combat CDI.}, } @article {pmid41657896, year = {2026}, author = {Wicaksono, WA and Thorsen, J and Stokholm, J and Berg, G}, title = {Metagenomic analysis of the nasopharyngeal microbiomes and resistomes in asthma, COVID-19 infected, and healthy individuals.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1729707}, pmid = {41657896}, issn = {1664-302X}, abstract = {INTRODUCTION: The nasopharyngeal microbiome presents an important environmental human interface and a window in the fight against chronic diseases like asthma, respiratory infections, and antimicrobial resistance. To identify the microbial structure and function, we designed a pilot study with individuals with asthma, COVID-19 infection, and healthy controls.

METHODS: We compare the microbial and resistome profiles of healthy individuals, patients with asthma, and patients with PCR-confirmed COVID-19 using shotgun metagenome sequencing. Additionally, metagenome-assembled genomes were generated to assess the virulence potential of the bacteria identified in the nasopharynx.

RESULTS: We found different patterns in microbial diversity, richness, and structure between individuals with asthma and those who are healthy, but not for those with COVID-19. Our results revealed unexpected insights into the quite diverse nasopharynx resistome encompassing 23 distinct drug classes, mainly based on antibiotic efflux (63.9%) and antibiotic inactivation (24.6%), regardless of the disease state. The majority of the antimicrobial resistance genes (ARGs) confer resistance to multidrug (45%), followed by those genes that confer resistance to aminoglycosides, tetracyclines, polymyxin, beta-lactam, and macrolide-lincosamide-streptogramin. A high proportion of ARGs was associated with various Pseudomonas species, which was confirmed by analysing metagenome-assembled genomes. Pseudomonas brenneri exhibited the highest number of ARGs and virulence factors, indicating notable pathogenic potential.

CONCLUSION: The study reveals distinct bacterial community compositions in healthy individuals and individuals with asthma. Pseudomonadales, particularly Pseudomonas species, contribute to the nasopharyngeal resistome. No association was found between nasopharyngeal resistome profiles and asthma development. Future research may explore airway microbial functions' influence on asthma development.}, } @article {pmid41657853, year = {2026}, author = {Ayivi-Tosuh, SM and Dofuor, AK and Yamoah, JAA and Gayi, BK and Aiduenu, AF and Akomea, A and Anovunga, SA and Ekloh, W and Basing, LA}, title = {Gut-Microbiome Interactions: Characterization, Therapeutic Implications and Machine Learning.}, journal = {Sage open pathology}, volume = {19}, number = {}, pages = {30502098251415109}, pmid = {41657853}, issn = {3050-2098}, abstract = {The gut microbiome is vital in maintaining overall health, yet its complexity and dynamic interactions are still not fully understood. This diverse microbial community comprises bacteria, viruses, fungi, and archaea, contributing to metabolism, immune regulation, and disease susceptibility. However, imbalances in the gut microbiome (dysbiosis), have been linked to various diseases, underscoring the importance of understanding microbial interactions within the gut ecosystem. This review explores these interactions, focusing on biochemical and molecular mechanisms that shape microbial behavior and function. Additionally, it examines the therapeutic potential of the gut microbiome, particularly its involvement in disease progression, prevention, and treatment. The role of medicinal plants in influencing gut microbial composition is also discussed, given their potential to support microbiome health. Lastly, it highlights the integration of machine learning in microbiome research, offering new insights into microbial interactions, predictive disease modeling, and personalized medicine. By addressing these key areas, this review aims to deepen our understanding of gut-microbiome dynamics and their implications for human health and disease management.}, } @article {pmid41657562, year = {2025}, author = {Zhang, S and Song, X and Wen, Y and Wang, G}, title = {Chronic constipation and the brain-gut-microbiome axis: the role of 5-HT signaling and Traditional Chinese Medicine in pathophysiology and treatment.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1706411}, pmid = {41657562}, issn = {2296-858X}, abstract = {Chronic constipation (CC) is a prevalent functional gastrointestinal disorder involving complex interactions among the brain-gut-microbiome axis, with 5-hydroxytryptamine (5-HT) as a key signaling node. Aberrations in 5-HT synthesis, release, receptor expression, or reuptake disrupt gastrointestinal motility, contributing to CC pathogenesis. Traditional Chinese Medicine (TCM), including herbal compounds, monomers, acupuncture, and tuina, exerts therapeutic effects by modulating the 5-HT signaling pathway. Animal studies demonstrate that TCM interventions regulate gut microbiota, promote 5-HT production via metabolites like short-chain fatty acids (SCFAs) and bile acids, and target receptors (e.g., 5-HT3R, 5-HT4R) to enhance intestinal motility. Clinical trials validate TCM's efficacy in normalizing 5-HT levels and improving symptoms, with advantages in safety and holistic regulation. However, important gaps remain, including incomplete understanding of upstream and downstream 5-HT signaling mechanisms, paradoxical 5-HT expression, and limited investigation of comorbid emotional disorders. Future studies should explore how TCM interventions modulate the gut microbiota-5-HT axis and inflammation-related pathways to provide novel insights into CC management.}, } @article {pmid41657545, year = {2025}, author = {Jebril, N and Chabuk, S and Al-Sabary, A and Al-Mansouri, N and Al-Jobouri, W and Al-Saidi, S}, title = {Endospore-forming Bacillus subtilis isolated from third molar exudates and its association with cardiovascular disease: a retrospective cohort study.}, journal = {Frontiers in oral health}, volume = {6}, number = {}, pages = {1726295}, pmid = {41657545}, issn = {2673-4842}, abstract = {BACKGROUND: Various techniques have been previously modified to reduce early postoperative complications following third molar extraction. Given the influence of the oral microbiome, increasingly resistant bacteria have been linked to systemic diseases such as cardiovascular disease (CVD).

OBJECTIVE: In this study, we aimed to identify the spore-forming bacterium Bacillus subtilis isolated from third molar exudates and to investigate its potential association with CVD.

METHODS: In Iraq, dental hospitals don't keep thorough medical records for each patient. This lack of documentation makes it tough to carry out hospital-based research. Therefore, by collecting exudates from third molars, we conducted a retrospective cohort study of the population undergoing third molar exudate removal in a private dental clinic as an alternative setting to compare cardiovascular outcomes between individuals with cardiovascular disease and controls. Based on clinical assessments, body mass index, LDL cholesterol, C-reactive protein, systolic blood pressure, diastolic blood pressure, hypertension, and smoking status were measured. The study was conducted on 40 men, comprising 20 patients with diagnosed cardiovascular disease and 20 controls. Light and transmission electron microscopy were used to perform a phenotypic evaluation of the bacterial isolates (spore formation, biofilm production). Biofilm formation was assessed using Congo red agar, crystal violet staining, and scanning electron microscopy (SEM). In addition, systolic and diastolic blood pressure (SBP and DBP) values were obtained to further assess cardiovascular risk.

RESULTS: The number of B. subtilis isolates was higher in the CVD group than in the control group (non-CVD) and demonstrated significantly greater biofilm-forming ability (OD600 = 1.45 ± 0.22 vs 0.85 ± 0.19, p < 0.01). TEM confirmed dense endospore architecture from patients with CVD, while SEM revealed extensive extracellular matrix formation within CVD biofilms. Patients with oral colonization by B. subtilis showed a significantly higher prevalence of CVD (32.6%) compared to those without colonization (12.6%, p = 0.008). The presence of biofilm-positive B. subtilis strains was independently associated with CVD (OR 2.91; 95% CI, 1.23-6.83). Spore-forming B. subtilis isolates from third molars of patients with CVD demonstrated enhanced biofilm formation and sporulation phenotypes. A moderate positive correlation (r = 0.48) was also observed between B. subtilis presence and SBP and DBP. These findings suggest that these bacterial characteristics are potentially the cause of systemic inflammation and represent a potential microbial link to CVD.

CONCLUSION: In countries like Iraq, researchers run into real problems when they try to study links between oral health and other diseases. There's no NHS dental system, so they can't rely on existing records for data. Therefore, this study provides a protocol for conducting investigations related to oral health through collaboration with other institutions, such as universities. With respect to the main finding of this study, spore-forming B. subtilis isolated from third molar exudates demonstrated phenotypic characteristics that may contribute to persistent oral colonization and increase systemic inflammatory risk. The observed association with cardiovascular disease warrants further investigation into oral-systemic microbial pathways.}, } @article {pmid41657532, year = {2026}, author = {Ashaolu, TJ and Lee, CC and Tarhan, O and Rashidinejad, A and Jafari, SM}, title = {Nexus of Whey Proteins, Gut Dysbiosis, and Colonic Health.}, journal = {Food science & nutrition}, volume = {14}, number = {2}, pages = {e71487}, pmid = {41657532}, issn = {2048-7177}, abstract = {The gut microbiota is essential for colonic health, and its imbalance (dysbiosis) is linked to conditions like inflammatory bowel disease and metabolic disorders. Whey proteins (WPs), including β-lactoglobulin, α-lactalbumin, glycomacropeptide, and lactoferrin, possess antimicrobial, immunomodulatory, and prebiotic-like properties that may help restore microbial balance. Beyond modulating the microbiome, WPs play a significant role in reinforcing intestinal barrier integrity and regulating host metabolism. This review summarizes evidence from in vitro, in vivo, and clinical studies showing WPs can enhance beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) while suppressing harmful ones. Furthermore, WP supplementation has been shown to alleviate dysbiosis-related conditions such as colitis, obesity, and allergies by improving microbial diversity, enhancing short-chain fatty acid production, strengthening the mucosal barrier, and modulating immune responses. However, the effects vary depending on WP composition, processing, and individual microbiota. Despite encouraging results, knowledge gaps remain regarding optimal dosing and long-term impacts. Overall, WPs show promise as functional food components and potential therapeutic agents for promoting colonic health, metabolic homeostasis, and gut barrier function, but more research is needed to refine their clinical application.}, } @article {pmid41657529, year = {2026}, author = {Wang, H and Shi, Y and Wang, W and Li, X}, title = {Association of Anti-Inflammatory Dietary Adherence With Biomarkers and Gut Microbiota Related to Colorectal Cancer Risk: A Retrospective Study.}, journal = {Food science & nutrition}, volume = {14}, number = {2}, pages = {e71497}, pmid = {41657529}, issn = {2048-7177}, abstract = {Colorectal cancer is one of the most common cancers and a primary cause of death. The increased incidence in low- and middle-income nations highlights the need for better prevention. Chronic inflammation, obesity, and gut microbial dysbiosis are major risk factors for CRC, making nutritional interventions attractive. This study aims to examine the association between adherence to an anti-inflammatory diet and anthropometric, biochemical, inflammatory, molecular, and gut microbiota parameters related to colorectal cancer risk. In this retrospective analysis, anti-inflammatory diet adherents (n = 515) and non-adherents (n = 435) were compared. Hematological, hepatic, inflammatory, tumor, genetic/molecular, and gut microbiota tests were performed, and chi-square tests were used for categorical outcomes. Multiple regression was used to examine the association between adherence to an anti-inflammatory diet and the development of colorectal cancer. Multiple logistic regression analysis indicated that anti-inflammatory diets were associated with improved clinical, biochemical, and microbiome outcomes in patients with CRC. Diet adherence was associated with a lower risk of obesity, central obesity, dyslipidemia, anemia, and leukocytosis after adjusting for age, sex, BMI, smoking, and caloric intake (β = -1.90, SE = 0.26, OR = 0.15, 95% CI: 0.09-0.25). Several inflammatory markers, including CRP, IL-6, CEA, and MMP-9, decreased markedly (p < 0.001). Molecular alterations associated with CRC, including p53 mutation, Ki-67 overexpression, microsatellite instability, APC mutation, and β-catenin nuclear expression, were significantly decreased (p < 0.001). Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii, and Akkermansia muciniphila were increased, and pathogenic species decreased in the gut (ORs 2.10-2.30; Fusobacterium nucleatum, Clostridium difficile, pathogenic Escherichia coli; ORs 0.16-0.18). Anti-inflammatory diets significantly improve metabolic, inflammatory, tumor-related, and microbiome profiles in patients with CRC. Adherence to an anti-inflammatory dietary pattern is significantly associated with improved metabolic, inflammatory, molecular, and gut microbiota profiles, all of which are linked to colorectal cancer risk. These findings support anti-inflammatory dietary strategies as cost-effective and non-invasive approaches for colorectal cancer prevention and adjunctive management.}, } @article {pmid41657399, year = {2026}, author = {Abbondio, M and Tanca, A and Sau, R and Pira, G and Errigo, A and Manetti, R and Pes, GM and Bibbò, S and Dore, MP and Uzzau, S}, title = {A human fecal metaproteomic dataset from celiac disease patients on gluten-free diet with or without poly-autoimmunity.}, journal = {Data in brief}, volume = {65}, number = {}, pages = {112501}, pmid = {41657399}, issn = {2352-3409}, abstract = {This dataset provides the fecal metaproteome profiles of 28 celiac disease patients on a gluten-free diet, distinguished by the presence or absence of co-occurring autoimmune conditions. The resource includes raw liquid chromatography-tandem mass spectrometry (LC-MS/MS) files, database search results, protein/peptide identification outputs, and taxonomic/functional annotation outputs, along with comprehensive anthropometric, clinical, and dietary metadata for each patient. The identified proteins originate from microbial, human, and plant sources, consistent with the multi-database search strategy used. This collection is designed for reuse in meta-analyses and integrative studies exploring functional changes in the gut microbiome related to auto-immune status and dietary variables. The complete dataset is available via the ProteomeXchange Consortium with the identifier PXD069517.}, } @article {pmid41657369, year = {2026}, author = {Patil, LR and Shetty, VV and Patil, SG and Aithal, KR and Oli, AM and Kaulgud, R and Yenagi, VA and Dharne, M and Dastager, SG and Chandrasekran, AM and Prabhakaran, D}, title = {Influence of Yoga-based cardiac rehabilitation on gut-microbiome diversity and Gut-Heart-Brain axis (YoGH-Biome) in heart failure: a study protocol.}, journal = {BMJ open sport & exercise medicine}, volume = {12}, number = {1}, pages = {e003147}, pmid = {41657369}, issn = {2055-7647}, abstract = {Heart failure (HF) is a chronic and progressive cardiovascular condition associated with significant morbidity, mortality and healthcare burden. Increasing evidence points to a critical role of gut dysbiosis and the gut-heart-brain axis in HF pathophysiology. Altered gut microbiota may influence systemic inflammation, neurohormonal activity and cardiac function through gut-derived metabolites such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs). Yoga-based cardiac rehabilitation (Yoga-CaRe) is a cost-effective intervention that has been shown to improve quality of life, exercise capacity and cardiovascular outcomes in cardiac patients. However, the mechanism underlying its benefits remains unclear. Furthermore, its effect on gut microbiota diversity and the downstream impact on the gut-heart-brain axis in HF remains largely unexplored. This study outlines a prospective, randomised, open-label, blinded-endpoint trial investigating the effects of a 12-week Yoga-CaRe intervention versus enhanced standard care in 60 HF patients with reduced ejection fraction. Participants will be randomly assigned in a 1:1 ratio to either the Yoga-CaRe or the control group. The Yoga-CaRe group will participate in 20 supervised yoga sessions, complemented by guided daily home practice, while the control group will receive enhanced standard care. The trial will assess changes in gut microbiota composition, levels of gut-derived metabolites (TMAO and SCFAs), inflammatory biomarkers (TNF-α and high-sensitivity C reactive protein), heart rate variability, 6 min walk test (6MWT) and echocardiography. Biological samples and clinical data will be analysed using integrated bioinformatics and statistical approaches to evaluate intervention efficacy and identify potential mechanistic pathways. The YoGH-Biome study has received ethical clearance from the Institutional Ethics Committee of the SDM College of Medical Sciences and Hospital, India (SDMIEC/2025/1073). It is registered with the Clinical Trials Registry of India. Study results will be disseminated via scientific publications, conferences and stakeholder forums to inform integrative strategies for HF management. Trial registration number: CTRI/2023/12/060757.}, } @article {pmid41657363, year = {2026}, author = {Bujaldón, R and Montero, E and Chamorro, C and Marín, MJ and Iniesta, M and Sanz, M and Herrera, D}, title = {Subgingival microbiome and adjunctive use of probiotics in the treatment of periodontitis in patients with diabetes: a secondary analysis of a randomized clinical trial.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2624894}, pmid = {41657363}, issn = {2000-2297}, abstract = {BACKGROUND: Adjunctive therapies have been proposed to enhance periodontal outcomes by modulating the subgingival microbiome. However, the microbiological effects of probiotic supplementation in diabetic patients with periodontitis remain unclear, particularly when assessed using high-resolution sequencing methods.

AIM: To evaluate the effect of a Limosilactobacillus reuteri as an adjunct to subgingival instrumentation on the subgingival microbiome in the treatment of periodontitis in patients with diabetes.

METHODS: This was a secondary analysis of a randomized, triple-blind, placebo-controlled clinical trial. Forty patients with stage II-III periodontitis and diabetes received subgingival instrumentation and either L. reuteri lozenges (n = 19) or placebo (n = 21) for 3 months. Subgingival samples were collected at baseline, 3, and 6 months. The V3-V4 region of the 16S rRNA gene was sequenced and analyzed using QIIME2. Alpha diversity was analyzed with mixed-effects models, beta diversity with PERMANOVA, and differential abundance with linear models.

RESULTS: A total of 116 high-quality samples were included. Alpha and beta diversity metrics did not show significant differences between groups or across time points. L. reuteri was detected inconsistently in the subgingival microbiome, with low relative abundances and no sustained presence over time. No bacterial species exhibited significant changes in differential abundance between the probiotic and placebo groups over time.

CONCLUSIONS: Adjunctive L. reuteri supplementation did not significantly alter subgingival microbiome diversity or composition over 6 months.}, } @article {pmid41656827, year = {2026}, author = {Upadhyay, SK}, title = {Strigolactones Targeting Plant-Microbe Dialogues From Roots to Soil: Unlocking Pathways for Sustainable Agriculture.}, journal = {Physiologia plantarum}, volume = {178}, number = {1}, pages = {e70787}, doi = {10.1111/ppl.70787}, pmid = {41656827}, issn = {1399-3054}, mesh = {*Lactones/metabolism/pharmacology ; *Plant Roots/microbiology/metabolism ; *Plant Growth Regulators/metabolism ; *Agriculture/methods ; *Soil Microbiology ; Mycorrhizae/physiology ; Soil/chemistry ; Signal Transduction ; Plant Development ; }, abstract = {Strigolactones (SLs) are phytohormones derived from carotenoids that influence various aspects of plant growth, development, and the ability of plants to respond to environmental changes and microbial interactions. Initially categorized as shoot branching inhibitors, SLs are now recognized as crucial rhizospheric signaling molecules that govern nutrient availability, hormonal control, and microbial interactions. Despite significant progress in SL biology, a cohesive synthesis connecting SL molecular signaling, rhizosphere communication, and stress tolerance remains fragmented, hindering their practical use in sustainable agriculture. A more comprehensive understanding of their synthesis process (D27-CCD7/8-MAX1-CLA cascade), their perception (D14-MAX2-SMXL module), and the impact of SMXL7 on chromatin has revealed significant implications on physiology. To enhance plant development under stress conditions, SLs drive auxin transport, regulate ABA-dependent stress signaling, influence the antagonistic effects of cytokinins, and coordinate gibberellin activity with the circadian rhythm. SLs augment arbuscular mycorrhizal colonization, stimulate nodulation, and attract plant growth-promoting rhizobacteria through chemotactic and metabolic interactions. Using GR24 and SL-conjugated nanomaterials enhances plant resistance to drought, salt, and metal stress. Modifying SL-transporters with CRISPR improves SL signaling and fosters beneficial symbiotic associations. The study is crucial because it underscores the importance of SLs in recruiting beneficial microorganisms and facilitating microbial-hormonal interactions. This review proposes a cohesive conceptual framework that integrates receptor specificity, rhizospheric sensing, and microbial response, beyond mere descriptive synthesis. It sets distinct research targets, such as receptor-specific SL-analogues, in situ sensing techniques, and tailored SL-responsive microbial consortia, to make biostimulation more precise and assist crops in withstanding climatic stress more effectively.}, } @article {pmid41656717, year = {2026}, author = {Cho, G and Kim, DH and Kim, JS and Song, J and Kim, SJ}, title = {Bayesian Pairwise Compositional Lotka-Volterra Modeling Infers Potential Rhizosphere Microbial Suppressors of Ralstonia pseudosolanacearum.}, journal = {The plant pathology journal}, volume = {42}, number = {1}, pages = {50-60}, doi = {10.5423/PPJ.OA.10.2025.0143}, pmid = {41656717}, issn = {1598-2254}, support = {PJ01727501//Rural Development Administration/ ; }, abstract = {The Ralstonia solanacearum species complex (RSSC) is a major soil-borne pathogen of solanaceous crops. During a field experiment originally designed to monitor rhizosphere and episphere microbiomes in two pepper cultivars, a naturally emerging and asymptomatic Ralstonia dominance event was detected in the rhizosphere without visible wilt symptoms. This unexpected occurrence provided an opportunity to characterize asymptomatic RSSC dynamics and their microbial interactions under field conditions. Full-length 16S rRNA amplicon sequencing showed that one ASV (Sq_1) was nearly absent from the episphere but increased sharply in the rhizosphere from week 3 onward, dominating 20-80% of samples during weeks 7-10. Phylogenetic comparison with 93 historical Korean RSSC isolates placed Sq_1 within a 16S-defined lineage corresponding to pepper-associated R. pseudosolanacearum biovars 3 and 4. Sq_1 abundance accounted for a large portion of β-diversity turnover in the rhizosphere. After within-plot correlations were meta-analyzed, selected taxa were evaluated using a Bayesian pairwise compositional Lotka-Volterra (pcLV) model, which identified three taxa (Sq_272, TRA3-20; Sq_178, Bradyrhizobium; and Sq_124, Bryobacter) that consistently exerted inhibitory effects on Sq_1 per-interval growth. Supported by the longitudinal design and the high accuracy of PacBio full-length 16S sequencing, these findings highlight potential microbial suppressors of RSSC and demonstrate the utility of pcLV modeling for resolving directional interactions at the ASV level.}, } @article {pmid41656565, year = {2026}, author = {Akber, MA and Fang, X}, title = {Soil type and growth stage-dependent rhizosphere bacteriome of alfalfa under challenge by the fungal pathogen Rhizoctonia solani.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.70620}, pmid = {41656565}, issn = {1526-4998}, support = {32171678//National Natural Science Foundation of China/ ; 23ZDNA009//Gansu Provincial Science and Technology Major Projects/ ; }, abstract = {BACKGROUND: Alfalfa (Medicago sativa) is the most important forage legume crop in China, but its productivity is severely threatened by root rot caused by Rhizoctonia solani. The use of resistant varieties is regarded as the most effective and sustainable strategy for disease management. However, the interaction between the host genotypes of alfalfa and R. solani in shaping the rhizosphere microbiome, and the role of these microbial assemblages in host resistance, remains poorly understood. This study investigated the rhizosphere bacteriome of alfalfa varieties with contrasting resistance to R. solani across different soil types and growth stages. Disease severity, plant biomass, and antioxidant enzyme activities were also evaluated.

RESULTS: Significant changes were observed in the composition and diversity of the bacterial community under infection by R. solani. The resistant variety exhibited higher activities of superoxide dismutase, peroxidase, and catalase. Pathogen inoculation was associated with a more complex and positively interconnected microbial network, indicating shifts in potential microbial associations. Notable shifts in α-diversity, Bray-Curtis β-diversity, and growth-stage-specific bacterial genera were observed between 8 and 16 weeks. In contrast, differences between soil types were less pronounced, which shows that the growth stage strongly influenced rhizosphere bacteriome structure.

CONCLUSION: These findings advance understanding of host-microbiome-pathogen interactions and provide a basis for microbiome-assisted strategies in sustainable management of root rot in alfalfa cultivation. © 2026 Society of Chemical Industry.}, } @article {pmid41656437, year = {2026}, author = {Pan, L and Cai, B}, title = {The core microbiome of the AMF hyphosphere: mineralization mechanisms of key soil mineral elements.}, journal = {Mycorrhiza}, volume = {36}, number = {1}, pages = {6}, pmid = {41656437}, issn = {1432-1890}, support = {No. 31972502//National Natural Science Foundation of China/ ; }, mesh = {*Mycorrhizae/metabolism/physiology ; *Microbiota ; *Soil Microbiology ; *Soil/chemistry ; Phosphorus/metabolism ; Nitrogen/metabolism ; Sulfur/metabolism ; Carbon/metabolism ; *Minerals/metabolism ; }, abstract = {Arbuscular mycorrhizal fungi (AMF) lack the enzymatic capacity to directly mineralize many essential soil elements and therefore rely on their hyphosphere core microbiome, a microbial consortium increasingly recognized as the "second genome" of AMF. However, the definition, functional mechanisms, and ecological relevance of this core microbiome remain poorly resolved. This review addresses how hyphosphere core microorganisms regulate the mineralization of soil carbon, nitrogen, phosphorus, and sulfur. We first outline the conceptual development of the core microbiome and then, for the first time, propose a five-dimensional screening framework integrating abundance stability and universality, functional stability, dynamic responsiveness, ecological niche specificity, and community supportiveness to identify authentic core members. Using this framework, we synthesize evidence on the mechanisms by which the hyphosphere core microbiome mediates biomineralization, highlighting its role in converting organically bound nutrients into plant-available forms. By integrating the functions of hyphosphere core microorganisms across carbon, nitrogen, phosphorus, and sulfur cycles, this review provides a unified ecological perspective on how the AMF hyphosphere core microbiome drives soil nutrient turnover (Fig. 1). Overall, this framework advances understanding of hyphosphere ecology and offers practical implications for soil ecosystem restoration and sustainable agricultural management.}, } @article {pmid41656241, year = {2026}, author = {Liu, X and Qiao, Y and He, W and Chen, X and Zhou, Q and Xu, Y and Yang, Y and Li, C and Yu, J and Luo, P}, title = {Integrated multi-omics profiling reveals effects of exogenous plant growth regulators on tobacco rhizosphere under Vulpia myuros rotation.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08312-4}, pmid = {41656241}, issn = {1471-2229}, support = {110202101009 (XJ-01)//Key Science and Technology Project of China National Tobacco Corporation/ ; 110202201040 (XJ-11)//Key Science and Technology Project of China National Tobacco Corporation/ ; }, } @article {pmid41655925, year = {2026}, author = {Ren, J and Zhang, B and Luo, K and Zhao, Y}, title = {Exploring the role of type 3 resistant starch crystalline polymorphs in modulating gut health and alleviating inflammation in colitis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {150805}, doi = {10.1016/j.ijbiomac.2026.150805}, pmid = {41655925}, issn = {1879-0003}, abstract = {Type 3 Resistant starch (RS3) has garnered increasing attention for its potential therapeutic effects in inflammatory bowel diseases (IBD), such as colitis. However, the impact of different crystalline forms of RS3 on the alleviation of colitis remains unclear. This study examined A-type and B-type crystalline RS3 microparticles (ARS and BRS) derived from debranched waxy maize starch. BRS exhibited higher crystallinity and RS content than ARS by around 8% and 11%, respectively. Treatment with ARS and BRS led to a 12.5-31.1% reduction in cytokine levels (TNF-α, IL-1β, IL-6) compared to NS, while improving colon morphology. Notably, BRS more effectively promoted Lactobacillus growth, suppressed harmful Patescibacteria, and increased SCFA levels (by 5.1 μmol/g) compared to ARS. The findings underscore the significance of RS3's crystalline structure in its anti-inflammatory potential, suggesting it as a promising strategy for colitis management and offering insights into RS's benefits for gut health.}, } @article {pmid41655800, year = {2026}, author = {Zhu, J and Yang, L and Fang, Z and Chen, J and Fu, R and Liu, S and Chen, M}, title = {Xin-Jia-Tong-Xie-Yao-Fang restores the intestinal barrier to alleviate irritable bowel syndrome via microbial butyrate mediated PI3K/Akt pathway suppression.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108344}, doi = {10.1016/j.micpath.2026.108344}, pmid = {41655800}, issn = {1096-1208}, abstract = {BACKGROUND: Xin-Jia-Tong-Xie-Yao-Fang (XJTXYF) is a proven prescription for managing diarrhea-predominant irritable bowel syndrome (IBS-D), which is a prevalent functional gastrointestinal disorder. However, the underlying mechanism of XJTXYF remains unclear. This study aims to explore the material basis and potential mechanisms of XJTXYF against IBS-D.

METHODS: The constituents of XJTXYF were identified by UPLC-Q-TOF-MS/MS, and potential targets and pathways were screened by network pharmacology. Changes in the intestinal microbiome and fecal butyric acid levels after XJTXYF administration were analyzed through 16S rRNA sequencing and HPLC respectively. The abdominal withdrawal reflex score, serum levels of FITC-D and the expression of intestinal epithelial tight junction proteins, as well as the activity of the PI3K/Akt pathway were assessed. In-vitro experiments involved silencing GPR109A using small interfering RNA and inducing barrier damage with LPS pre-treatment in the Caco-2 cell line. Barrier function was evaluated by FITC-D permeability and tight junction protein expressions. The activity of the PI3K/Akt pathway was determined through Western blotting analysis.

RESULTS: The major active compounds of XJTXYF identified by UPLC-Q-TOF-MS/MS include Saikosaponin C, Hesperetin, Neohesperidin, Albiflorin, Quercetin and so on. The PI3K/Akt signaling pathway was predicted by network pharmacology as a potential target of XJTXYF in treating IBS-D. Animal experiments demonstrated that XJTXYF could increase body weight, improve visceral hypersensitivity, rebalance gut flora dysbiosis and upregulate fecal butyric acid content in IBS mice. The XJTXYF also showed the abilities of intestinal barrier repairment and PI3K/Akt pathway suppression. Fecal microbiota transplantation and the positive controls (NaB and Clostridium Butyricum) verified that a causal relationship existed between gut microbiome changes and IBS-D improvement after XJTXYF treatment. In-vitro experiments revealed the role of butyrate in barrier protection via PI3K/Akt inhibition.

CONCLUSION: Overall, in this study, we revealed that XJTXYF could restore intestinal barrier function through microbial butyrate mediated PI3K/Akt inhibition and improve IBS-D symptoms.}, } @article {pmid41655731, year = {2026}, author = {Teng, J and Li, W and Wei, Y and Wang, C and Yun, X and Lu, Y and Chen, J and Ma, X and Zhao, Y}, title = {Gut microbiome diversity and functional profiles of Culicoides across Sanya, Ruili, and Linyi, China.}, journal = {Acta tropica}, volume = {}, number = {}, pages = {108013}, doi = {10.1016/j.actatropica.2026.108013}, pmid = {41655731}, issn = {1873-6254}, abstract = {BACKGROUND: Biting midges (Culicoides spp.) are vectors of diverse microbes such as viruses, bacteria, protozoa, and nematodes that cause diseases in both wild and domestic animals. Despite their ecological significance and role in disease transmission, the composition and underlying mechanisms shaping the gut microbiota of Culicoides remain poorly characterized.

OBJECTIVES: This study aimed to investigate the composition and functional profiles of the gut microbiota of adult Culicoides collected from three representative cities spanning tropical, subtropical, and temperate climate zones in China.

METHODS: 16S high-throughput sequencing was used to study the microbial composition and function of Culicoides in the three regions. This study further incorporated six environmental factors and seven genetic diversity indices to explore their relationships with the microbial community.

RESULTS: The findings revealed significant variations in the gut microbial composition, dominant species, and diversity of Culicoides across different climate zones. NoTable differences were observed in microbial functions related to insect growth, development, and oxidative stress, with Culicoides from the Sanya zone exhibiting a greater abundance of functions and participating in more signaling processes. Environmental factors and host genetic diversity across different habitats collectively shape the composition of the gut microbiota of Culicoides. Structural equation modeling (SEM) revealed that environmental factors exert predominantly direct selective effects on microbial community assembly, whereas host genetic diversity plays a critical indirect regulatory role. These environment-host-microbiota interactions exhibit significant spatial heterogeneity. In low-latitude regions (Sanya), environmental factors mainly manifest direct filtering effects, whereas in ecotone areas (Ruili), environmental pressures indirectly modulate microbial composition by altering host genetic adaptation.

CONCLUSIONS: Our findings revealed that Culicoides gut microbiomes exhibit distinct biogeographical divergence, characterized by environment-driven variations in microbial community structure and functional potential. Host genetic adaptation serves as a key mediator and synergistic modulator of these patterns. This tripartite environment-host-microbiome interaction demonstrates clear dependence on geographic gradient.}, } @article {pmid41655688, year = {2026}, author = {Jin, M and Xu, F and Liu, Y and Jiang, Z}, title = {Limosilactobacillus fermentum LF61: A Multidimensional Study on Safety and Functionality from Genomics to Clinical Application.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {116002}, doi = {10.1016/j.fct.2026.116002}, pmid = {41655688}, issn = {1873-6351}, abstract = {This study presents a comprehensive multidimensional assessment of the safety and functional efficacy of Limosilactobacillus fermentum LF61, a strain isolated from human milk. Genomic analysis revealed no virulence factors (VFDB), drug resistance genes (CARD), or toxin synthesis gene cluster (antiSMASH) within its chromosome (2.04 Mb) and plasmid (15.5 kb), meeting EFSA's QPS safety criteria. In vitro studies demonstrated that LF61 exhibited a 2-hour survival rate of > 98% in gastric acid (pH 2.0) and a survival rate of 99.66% in intestinal fluid (pH 8.0). LF61 was also nontoxic to Caco-2 cells (metabolic activity at 20% concentration: 100.3 ± 2.1%). An acute oral toxicity test (in ICR mice) demonstrated an LD50 >2 × 10[10] CFU/kg. In a randomized, double-blind clinical trial (n = 49), daily intake of 3×10[10] CFU of LF61 for 8 weeks increased serum levels of the antimicrobial peptide LL-37 by 12.3% (p < 0.05), and IgA, IgG, and IgM by 18.7%, 15.2%, and 9.8%, respectively (p < 0.05). Metagenomic analysis revealed that LF61 promoted colonization by short-chain fatty acid-producing bacteria, such as Mitsuokella and Turicibacter (LDA > 3), activated the carbohydrate metabolism pathway (p = 0.002), and maintained stable α-diversity in the microbiome (Shannon index p > 0.05).Collectively, our findings indicate that LF61 exerts beneficial effects via a gut-immune axis bidirectional regulatory mechanism, offering a theoretical basis and clinical evidence for the development of novel immunomodulatory probiotics targeting the gut-immune axis.}, } @article {pmid41655417, year = {2026}, author = {Chen, Z and Tang, X and Su, Y and Liu, T and Klümper, U and Ju, F and Liu, M and Han, P}, title = {Impact of human activities on groundwater biogeochemical cycles and microbial communities: Insights from metagenomic analysis.}, journal = {Water research}, volume = {294}, number = {}, pages = {125493}, doi = {10.1016/j.watres.2026.125493}, pmid = {41655417}, issn = {1879-2448}, abstract = {Anthropogenic nitrogen pollution poses a systemic threat to microbial interaction networks and biogeochemical cycling in groundwater ecosystems, yet the underlying mechanisms remain poorly understood. Employing an endpoint gradient comparison, we conducted metagenomic analyses of urban groundwater under severe nitrogen stress (Shanghai, China; with NH4[+] and NO3[-] concentrations ∼28× and ∼10× background levels, respectively) versus a near-pristine mountain aquifer (Calistoga, USA). This revealed a multi-level collapse and adaptive restructuring of microbial communities under nitrogen stress. Pollution triggered a fundamental restructuring of bacterial communities, with system type (urban vs. mountain) explaining 74 % of the compositional variation, accompanied by a significant reduction in bacterial alpha-diversity (Shannon index decreased by 34 %) and a taxonomic shift from Actinomycetota-dominated mutualistic networks in the mountain system to Pseudomonadota-dominated communities (> 0.86 relative abundance) in urban groundwater. Functionally, urban systems exhibited multi-pathway suppression of energy-intensive processes, including nitrification (e.g., hao, nxrB genes), methanogenesis, and inorganic sulfur oxidation, aligning with the theory of "pollution-induced metabolic decoupling." To survive, the microbial community pivoted to low-energy strategies, significantly enriching genes for organic sulfur metabolism (e.g., dddT, tsdB), which may exacerbate nitrogen retention by inhibiting denitrifiers via metabolites like H2S. Co-occurrence network topology analysis indicated a catastrophic loss of complexity in urban groundwater, with a ∼90 % reduction in connectivity and a collapse in modularity (from 19.94 to 3.33), alongside an abnormally high proportion of positive correlations (94.4 %), signaling a major loss of ecosystem stability and functional redundancy. Random Forest and redundancy analyses jointly identified ammonium (NH4[+]) as the core environmental driver of this cascading failure, explaining 86 % of the variance in functional gene profiles and likely disrupting the nitrification pathway through specific suppression of the rate-limiting hao gene (which explained 76 % of the variance in nitrification rates). Based on these insights, we propose a dual-track restoration framework that couples external NH4[+] source control with internal microbial network rewiring (e.g., restoring keystone taxa, regulating sulfur feedback loops) to break the nitrogen-sulfur inhibition cycle and restore ecological function. Our findings underscore the critical importance of integrating microbial network resilience into strategies for managing and rehabilitating contaminated groundwater ecosystems.}, } @article {pmid41655382, year = {2026}, author = {Gupta, N and Biswas, R and Koley, A and Mukherjee, R and Das, N and Balachandran, S and Hoque, RR}, title = {Degradation of chrysene by Rhodococcus pyridinivorans C7 isolated from earthworm gut - Deciphering microbial community dynamics of the earthworm gut.}, journal = {Journal of hazardous materials}, volume = {504}, number = {}, pages = {141328}, doi = {10.1016/j.jhazmat.2026.141328}, pmid = {41655382}, issn = {1873-3336}, abstract = {This study investigates the degradation of chrysene (a priority polycyclic aromatic hydrocarbon) by Rhodococcus pyridinivorans C7, isolated from the gut of Perionyx excavatus after 60 days acclimatization in petroleum-contaminated soil. After six days of incubation, strain C7 exhibited notable enzymatic activities, with catechol 1,2-dioxygenase (1.72 ± 0.14 U/mL) and catechol 2,3-dioxygenase (2.26 ± 0.19 U/mL). The strain achieved up to 75 % degradation of chrysene (40 mg/L) within this period. Gas chromatography-mass spectrometry analysis identified dibutyl phthalate as an intermediate product on day 2 and phenol 2,6-di-tert-butyl on days 4 and 6. Cytotoxicity assays revealed that the initial byproduct was highly toxic (IC50 = 0.19 µg/mL), whereas the final metabolite exhibited markedly reduced toxicity (IC50 = 19 µg/mL), indicating detoxification. Comparative genomics using Mauve software revealed strong genomic synteny between strain C7 and other PAH-degrading Rhodococcus species. Metagenomic analysis of earthworm gut microbiomes under different treatment - control (EG-C), petroleum contaminated (EG-P) and fly ash (EG-F) identified Proteobacteria as the predominant phylum with relative abundance of 21.17 %, 33.3 %, and 34.53 % respectively. Notably, the Rhodococcus genus exhibited a 1.46-fold and 1.42-fold increase in EG-P and EG-F, respectively compared to EG-C. R. pyridinivorans was detected in both EG-P and EG-F gut samples confirming its isolation through the earthworm gut. These results demonstrate that environmental perturbations can drive distinct shifts in gut microbial composition, enriching for hydrocarbon-degrading taxa. Understanding such adaptive microbial communities provides valuable insights for developing sustainable bioremediation strategies and identifying novel microbes for environmental cleanup.}, } @article {pmid41655373, year = {2026}, author = {Sharma, S and Hassan, H and Abdelaziz, K}, title = {Comparative efficacy of oral and cloacal administration of Lactobacillus probiotics and postbiotics against Campylobacter jejuni colonization in broiler chickens.}, journal = {Poultry science}, volume = {105}, number = {4}, pages = {106576}, doi = {10.1016/j.psj.2026.106576}, pmid = {41655373}, issn = {1525-3171}, abstract = {Campylobacter jejuni remains a major cause of foodborne illness worldwide, with poultry serving as the primary reservoir. In the absence of commercial vaccines or effective feed additives, probiotics and their byproducts (postbiotics) represent a promising and sustainable approach to reducing Campylobacter colonization in poultry. This study compared the efficacy of oral and cloacal administration of probiotic lactobacilli and their postbiotics in reducing Campylobacter colonization and modulating the cecal microbiome in broiler chickens. Day-old chicks were assigned to seven treatment groups that received either probiotics (live cells of four poultry-derived Lactobacillus strains: L. reuteri P43, L. acidophilus P42, L. animalis P38, and L. crispatus C25) or postbiotics (Lactobacillus supernatants) or their combination (whole cultures) orally or intracloacally, with a non-treated group serving as a control. Chickens were challenged with C. jejuni strain 81-176 at the second week of age, and cecal contents were collected at the fifth week for Campylobacter enumeration and microbiome profiling. The results revealed that both oral and cloacal administration of Lactobacillus cells significantly reduced Campylobacter cecal loads by 0.34 and 0.78 log10, respectively, compared to the control. Significant differences in microbial richness and evenness were observed among treatment groups, with groups administered orally with probiotics, postbiotics, or their combination consistently showing higher alpha diversity indices than controls. NMDS ordination confirmed distinct community clustering among the treatment groups. Differential abundance analysis (MaAsLin2) further revealed that Ruminococcus was significantly enriched in the group receiving intracloacal postbiotic treatment, whereas the genus unclassified Firmicutes was more abundant in the group that received the combined probiotic-postbiotic treatment orally. Opportunistic genera, such as Escherichia-Shigella and Faecalicoccus, were significantly higher in the control group compared to all treated groups. Overall, while probiotics and postbiotics, whether given alone or together, modulated the gut microbial composition in Campylobacter-infected broilers, the administration of probiotic cells offered additional benefits by reducing Campylobacter colonization.}, } @article {pmid41655211, year = {2026}, author = {Su, XJ and Ma, L and Xiong, X and Meng, JH and Wu, Q and Zhang, Y and Dong, SG and Wang, YF and Wu, JH and Zeng, QY and Zhang, HF and Li, LL and Meng, L and Peng, M and Huang, XD and Wu, LQ and Wang, X}, title = {DRD2 Deficiency Underlies Pituitary Adenoma Dependent on Escherichia coli Translocation from the Gut.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e04247}, doi = {10.1002/advs.202504247}, pmid = {41655211}, issn = {2198-3844}, support = {2020]74//Hubei Provincial Engineering Research Center for Inflammation Repair/ ; 2020ZYYD026//Special Funds for Local Science and Technology Development guided by the Central Government/ ; 2023AFA079//Hubei Science Foundation for Distinguished Young Scholars/ ; WX23Z27//Scientific Research Project Funds for Wuhan Health and Family Planning Commission/ ; WZ22A01//Scientific Research Project Funds for Wuhan Health and Family Planning Commission/ ; WZ24B86//Scientific Research Project Funds for Wuhan Health and Family Planning Commission/ ; }, abstract = {Pituitary adenoma (PA) are common intracranial tumor types that have harmful effects on human health. However, the pathogenesis of PA remains unclear yet. The intratumoral microbiome has been reported playing an important impact on the occurrence, metastasis, immune monitoring, and drug resistance of various tumors. While normal dopamine receptor D2 (DRD2) expression is enriched in the apical junction of pituitary epithelium and colonic enterocytes, various factors-induced drd2 loss dampened its expression at both sites. DRD2 deficiencies are characterized by chronic hyperprolactinemia, pituitary lactotroph hyperplasia, and prolactinomas in mice, but the role of intratumoral microbiome in prolactinomas is not known. We employed specific pathogen-free (SPF) and germ-free (GF) mice models and patient samples of pituitary adenoma. In the mice pituitary tumor model, we used mice that developed prolactinomas following estradiol treatment or DRD2 deficiencies. Pituitary tumor samples from patients with nonfunctional pituitary adenoma or prolactinomas were obtained after surgical excision. Various molecular, cellular, and sequencing techniques were used to determine the role of intratumoral microbiome in pituitary adenoma. We demonstrate that human patients or murine bearing estradiol-induction or DRD2 loss are all characterized by the presence of live intratumor bacteria in the pituitary adenoma. Using metagenomic next-generation sequencing and mass spectrometry techniques, we confirm that the bacterial species of pituitary tumor tissues is Escherichia coli. In vitro tracing and immunofluorescence assay results showed that the pathobiont Escherichia coli translocates from the gut into the pituitary gland along with DRD2 loss while the blood pituitary barrier were both destroyed in mice. The Escherichia coli are phagocytosed by the microglial cells in the pituitary gland, then activate GSDMD protein releasing HMGB1, and promote the tumorigenesis of pituitary adenoma by activating the MAPK pathway. The depletion of bacteria systemically, microglial depletion or HMGB1 inhibitor ethyl pyruvate rescued prolactinomas. Our findings suggest that DRD2 deficiency underlies pituitary adenoma dependent on Escherichia coli translocation from the gut and activating microglia GSDMD/ HMGB1/MAPK pathway, and provide a novel preclinical rationale for antimicrobial agents, microglial depletion, or HMGB1 inhibitor ethyl pyruvate for the treatment of pituitary adenoma.}, } @article {pmid41655160, year = {2026}, author = {Rathod, H and Jain, P and Dharme, KK and Ajazuddin, }, title = {cGAS-STING Pathway in Gastrointestinal Malignancies: Mechanistic Insights and Translational Therapeutic Opportunities.}, journal = {Journal of gastrointestinal cancer}, volume = {57}, number = {1}, pages = {38}, pmid = {41655160}, issn = {1941-6636}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism/agonists ; *Gastrointestinal Neoplasms/immunology/therapy/drug therapy/metabolism/pathology ; Signal Transduction/drug effects ; Tumor Microenvironment/immunology/drug effects ; Animals ; STING Protein ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; }, abstract = {BACKGROUND: An important regulator of tumor immunosurveillance and innate immune activation in gastrointestinal (GI) malignancies is the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. The release of type I interferons, dendritic cell (DC) maturation, and cytotoxic T lymphocyte recruitment are the final steps of a pathway that is typically set in motion by aberrant DNA damage, microbiome-derived DNA, or mitochondrial stress.

METHODS: Tumour has it that immunologically "cold" gastrointestinalcancers can be made more sensitive to immune-checkpoint blockade (ICB), radiation, and chemotherapy by therapeutically activating the cGAS-STING pathway, which turns them into inflamed, T-cell-permissive niches.

RESULTS: Progress in nanomedicine, small-molecule STING agonists, and tumour-microenvironment-responsive drug delivery systems has broadened the translational scope of this pathway across colorectal, gastric, and pancreatic malignancies. However, tumour-intrinsic heterogeneity, the dual immunostimulatory and immunosuppressive functions of chronic STING signalling, and delivery-related toxicities continue to pose substantial challenges.

CONCLUSION: This review consolidates current mechanistic insights, preclinical evidence, and emergent clinical data regarding the cGAS-STING pathway in gastrointestinal cancers, while emphasising biomarker-guided patient stratification and AI-powered predictive tools that could facilitate the precise application of STING-targeted therapies.}, } @article {pmid41654986, year = {2026}, author = {Finck, J and Chowdhury, S and Griffiths, RI and Malik, AA and Eisenhauer, N and Lange, M and Mendes, LW and Gleixner, G}, title = {Plant diversity induces shifts from microbial generalists to specialist by enhancing niche differentiation, microbiome connectivity, and network stability in a temperate grassland.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00857-z}, pmid = {41654986}, issn = {2524-6372}, abstract = {BACKGROUND: Soil microbiota are key players of terrestrial ecosystem functioning, including decomposition, soil organic matter formation, and nutrient cycling, and interact strongly with plants in the rhizosphere. Several studies have demonstrated the potential of plants to alter soil microbiome assembly and functioning (i.e., through manipulation of soil organic matter pools via root exudation), which can be critical for sustaining soil ecosystem functioning. Using soil from a long-term biodiversity experiment in Germany, we investigated how soil microbial communities responded to variations in plant species richness (1-16 species), functional group richness (1-4 groups), and plant identity (grasses, legumes, small herbs, and tall herbs) using 16S rRNA gene and ITS amplicon sequencing. We examined bacterial and fungal community structure, metabolic potential, and microbial network architecture to better understand the role of the soil microbiome and its net positive relationship between biodiversity and ecosystem functioning.

RESULTS: Plant diversity induced gradual shifts in microbial community composition, while increasing soil organic carbon and nitrogen stocks. Microbial networks exhibited increased connectivity, particularly between bacteria and fungi. Meanwhile, mutualistic and antagonistic functional guild representation increased, that is the sum total of plant-beneficial (i.e., endophytes) and plant- or fungi-detrimental (i.e., pathogens and parasites) fungal guilds, respectively. Key nodes shifted from generalist taxa at low plant diversity to more specialized communities at high plant diversity. Notably, fungi responded more strongly than bacteria, and their functional potential was driven by plant functional identity rather than species richness.

CONCLUSION: At low plant diversity, generalist taxa likely exploit less complex and diverse organic carbon inputs, allowing them to dominate available niches. In contrast, higher plant diversity promotes a broader array of specialist taxa that likely benefit from the greater diversity of organic carbon compounds, and thus greater niche availability. As network complexity grows, ecosystem functions are being distributed across more taxa, leading to greater microbiome stability, and ultimately more efficient soil carbon and nutrient cycling. Our findings suggest that higher plant diversity strengthens microbial functioning and enhances microbiome resilience, that is the capacity of the microbial community to maintain soil functioning despite environmental disturbances.}, } @article {pmid41654956, year = {2026}, author = {Renchinsengee, N and Batsaikhan, S and Khangai, A and Boldbaatar, G and Luvsandagva, B and Lazatkhan, A and Duger, D and Khasag, O and Matsumoto, T and Yamaoka, Y}, title = {Species-level dynamics of gastric microbiome after Helicobacter pylori eradication in high-risk Mongolian population.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-026-00805-9}, pmid = {41654956}, issn = {1757-4749}, support = {2021B13; K.O//Research Center for Global and Local Infectious Diseases, Oita University/ ; 23836904//Japan Agency for Medical Research and Development (AMED) [Adopting Sustainable Partnerships for Innovative Research Ecosystem (ASPIRE),/ ; 21357105//Science and Technology Research Partnership for Sustainable Development (SATREPS)/ ; }, abstract = {BACKGROUND: Species-level resolution is essential to understand gastric microbiome recovery after Helicobacter pylori eradication, yet short-read 16 S rRNA approaches often obscure clinically relevant changes.

METHODS: Gastric biopsies from 121 adults in Bayan-Ölgii, Mongolia (71 H. pylori-positive, 50 H. pylori-negative) were analyzed, including nine paired pre- and post-eradication gastric biopsy samples collected six months apart, enabling exploratory longitudinal analysis. Full-length 16 S rRNA (V1-V9) sequencing was performed using the Oxford Nanopore platform with EMU taxonomic assignment (SILVA v138.1/NCBI RefSeq). Ecological changes were evaluated using diversity indices, principal coordinates analysis (PCoA) with PERMANOVA, and differential abundance testing (DESeq2, FDR < 0.05). Eradication therapy (esomeprazole-bismuth-doxycycline-levofloxacin) achieved success in 54 of 57 H. pylori-positive patients (94.7%).

RESULTS: H. pylori-positive microbiomes were dominated by H. pylori (91.8% ± 3.9%) and exhibited markedly reduced diversity (Shannon = 0.44 ± 0.11) compared with H. pylori-negative samples (2.08 ± 0.25; p < 0.001). Six months after eradication, diversity increased significantly (2.17 ± 0.20; p = 0.0001), with enrichment of oral commensals including Streptococcus mitis (↑ 11.9×), Neisseria elongata (↑ 13.7×), and Prevotella melaninogenica (↑ 13.0×). However, post-eradication profiles at six months remained distinct from H. pylori-negative communities (PERMANOVA R² = 0.12; p = 0.02). In total, 174 amplicon sequence variants changed significantly, including persistence of Fusobacterium nucleatum.

CONCLUSIONS: Nanopore full-length 16 S sequencing reveals fine-scale, clinically relevant shifts that are masked by partial-gene assays. Eradication rapidly restores microbial diversity, but at six months, is associated with a novel ecological equilibrium rather than complete normalization. This species-resolved approach offers a practical framework for post-eradication microbiome monitoring and may inform strategies to reduce residual gastric cancer risk in high-burden populations.}, } @article {pmid41654735, year = {2026}, author = {Ma, Y and Jia, T and Zhu, W and Fan, L}, title = {Characteristics comparative of gut microbiota in four small mammal species co-occurring in the Hengduan Mountains: differences in environmental adaptation strategies between alien and endemic species.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04820-3}, pmid = {41654735}, issn = {1471-2180}, support = {32560262//National Natural Scientific Foundation of China/ ; 202401AS070039//Yunnan Fundamental Research Projects/ ; }, abstract = {The composition of gut microbiota is jointly determined by the host's food habit, ecological niche, and genetic background, serving as a direct reflection of the host's adaptation to its environment and evolutionary pressures. To investigate the distinct adaptation mechanisms of four sympatric small mammal species in the Hengduan Mountains region, this study compared the environmental adaptation strategies of endemic and alien species. This study collected ten wild specimens each of the Eothenomys miletus, Eothenomys oliter, Tupaia belangeri, and Apodemus chevrieri from Yunlong County, Yunnan Province. Using 16SrRNA gene sequencing technology, we analyzed the gut microbial composition, abundance, and community structure across species, investigating the distinct gut microbial community characteristics between the endemic species (E. miletus and E. oliter) and the alien species (T. belangeri and A. chevrieri.). Results indicate: E. miletus and E. oliter possess complex and diverse gut microbial communities with plant-degrading functions. These communities with sparse interactions are capable of utilizing multiple plant sources for nutrition and exhibit strong resilience against environmental disturbances. In contrast, T. belangeri and A.chevrieri exhibit simple, specialized, yet tightly cooperative omnivorous gut microbial communities. While capable of utilizing diverse food resources within specific adaptive environments, they demonstrate extreme specificity in adaptation to particular habitats or survival strategies and are relatively sensitive to external disturbances. Furthermore, the E. miletus, widely distributed across the Hengduan Mountains, its gut bacterial community is dominated by stochastic processes. In contrast, the T. belangeri shows a positive correlation with various gut bacteria associated with omnivorous characteristics. The distinction between these two distinct environmental adaptation strategies is particularly pronounced. In summary, Among these four sympatric small mammal species in the Hengduan Mountains, the gut microbiota of endemic and alien species showed high similarity respectively and exhibited convergence.}, } @article {pmid41654729, year = {2026}, author = {Wang, P and Yao, Y and Yan, K and Wang, S and Wang, M and Liu, X and Hu, C and Dong, Y and Li, J}, title = {A validation for sex differences in gut microbiome of essential hypertension based on cohort analysis.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04500-8}, pmid = {41654729}, issn = {1471-2180}, abstract = {BACKGROUND: Prior research has demonstrated sex-specific differences in hypertension (HTN). The gut microbiota (GM) and its metabolic functions have emerged as key players in the development of HTN. To explore potential sex-based heterogeneity in gut bacteria among hypertensive patients, we conducted this study with the aim of validating sex differences in the gut flora associated with HTN.

METHODS: Here, we leveraged a metagenomic dataset comprising 106 fecal samples from a Chinese cohort of individuals with essential HTN to systematically analyze and compare alterations in the gut microbiome between male and female patients, as well as relative to a healthy control group.

RESULTS: Our study confirmed a statistically significant difference in the β-diversity of GM between hypertensive patients and healthy controls. When the subjects were further stratified by sex, significant differences in the distribution of gut flora were observed exclusively in females, whereas none was noted between groups in males. It was observed that certain genera of GM exhibit negative correlations with blood pressure. Notably, the relative abundance of these bacterial genera, including Lachnospira, Faecalibacterium, and Roseburia, was significantly diminished in female hypertensive patients. These organisms are primarily involved in the biosynthesis of short-chain fatty acids (SCFAs), with a notable emphasis on butyrate production. Ruminococcus gnavus was specifically enriched in hypertensive males, whereas certain bacteria, such as Lactobacillus, were notably depleted. The abnormality of the SCFAs-producing flora in female hypertensive patients may be related to that women are more likely to develop hypertensive organ damage.

CONCLUSIONS: The findings of our study indicate that GM dysbiosis is more significantly associated with HTN in females. Consequently, sex constitutes a critical factor in evaluating the role of intestinal flora in the pathogenesis of HTN.}, } @article {pmid41654532, year = {2026}, author = {Mohidin, AF and Ng, TCA and Santillan, E and Yang, L and Cokro, A and Wuertz, S}, title = {Enhanced resistance and resilience of anaerobic digestion microbiome after single and dual short-term disturbances.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {5391}, pmid = {41654532}, issn = {2045-2322}, } @article {pmid41654531, year = {2026}, author = {Fernandes, AC and Reverter, A and Conteville, LC and Afonso, J and Cardoso, TF and Palhares, JCP and Mourão, GB and Regitano, LCA and Coutinho, LL}, title = {Microbiome by transcriptome interactions triggered by a switch to an alternative diet in Nellore cattle.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {5371}, pmid = {41654531}, issn = {2045-2322}, support = {88887.620015/2021-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 2021/14321-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2018/11953-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2019/04089-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, } @article {pmid41654247, year = {2026}, author = {van Vugt, WLJ and Boogaard, EVD and Tuuk, KV and Spinnewijn, L and Kreukels, BPC and Both, S and Huirne, JAF and van Mello, NM}, title = {Gynecologic function and dysfunction in transmasculine and gender diverse individuals using testosterone therapy: a systematic review.}, journal = {American journal of obstetrics and gynecology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajog.2026.01.036}, pmid = {41654247}, issn = {1097-6868}, abstract = {OBJECTIVE: To systematically review the current literature on gynecologic function and dysfunction in transmasculine and gender diverse individuals in the context of testosterone therapy, with a focus on menstrual suppression, contraceptive needs, pelvic pain, vulvovaginal changes, and sexual health.

DATA SOURCES: PubMed, Embase and Web of Science databases were searched through September 2025 using search terms related to transmasculine individuals, assigned female at birth, reproductive organs, and testosterone and gender-affirming hormone therapy. No restrictions on publication year were applied.

STUDY ELIGIBILITY CRITERIA: Studies were included if they reported on the impact of exogenous testosterone on gynecologic or sexual (dys)function, as well as contraceptive use and choices, in transmasculine and gender diverse individuals. Only original human research studies were eligible. Studies focusing on fertility, reproductive outcomes, malignancy, histology, animal models, or individuals with differences of sex development were excluded.

All included studies were critically appraised using Joanna Briggs Institute (JBI) quality assessment tools, and findings were synthesized narratively.

RESULTS: Fifty-seven studies were included. Testosterone was generally effective in achieving menstrual suppression, though breakthrough bleeding and ovulatory activity occurred in a substantial proportion of individuals. Contraceptive needs were frequently unmet, partly due to misinformation and provider-related barriers. Pelvic pain was commonly reported, with varied etiologies. While testosterone often increased sexual desire, dyspareunia and genital discomfort were frequently described. Vaginal microbiome alterations and epithelial changes were observed, though their clinical implications remain unclear.

CONCLUSION: Testosterone-based gender-affirming hormone therapy has diverse effects on gynecologic function in transmasculine and gender diverse individuals, including both physiologically expected as well as underexplored effects. Clinicians should adopt an individualized and affirming approach to care, while further research is needed to understand long-term outcomes, improve assessment tools, and close gaps in inclusive gynecologic healthcare.}, } @article {pmid41654223, year = {2026}, author = {Fondevila, MF and Kreimeyer, H and Hsu, CL and Tamargo-Azpilicueta, J and Day, LZ and Gritsenko, M and Attah, K and Cabré, N and Harberts, A and Tonetti, FR and Yang, Y and Yamazaki, T and Schöler, D and Eguileor, A and Blasio, C and Meijnikman, AS and Zhang, X and Garcia-Carbonell, R and Hook, V and Zhou, E and Sun, Z and Jacobs, JM and Turner, JR and Llorente, C and , and Glass, CK and Stärkel, P and Reinheckel, T and Diaz-Moreno, I and Gonzalez, DJ and Schnabl, B}, title = {Macrophage-derived cathepsin B disrupts intestinal tight junctions through occludin degradation and promotes alcohol-associated liver disease.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2026.01.013}, pmid = {41654223}, issn = {1600-0641}, abstract = {BACKGROUND & AIMS: Disruption of the intestinal barrier facilitates microbial translocation to the liver and contributes to chronic liver disease. We aimed to study the role of the fecal proteome for disease progression in patients with alcohol-associated hepatitis.

METHODS: We used fecal proteomics data from a multicenter cohort of patients with alcohol-associated hepatitis (n=80), alcohol use disorder (n=20), and controls (n=19) (InTeam), and a cathepsin B activity assay in an independent multicenter cohort of patients with alcohol-associated hepatitis (n=80), alcohol use disorder (n=20), and controls (n=18) (AlcHepNet). Mice lacking cathepsin B in myeloid cells and transgenic mice overexpressing occludin in intestinal epithelial cells, were subjected to the chronic-plus-binge ethanol feeding model (NIAAA).

RESULTS: Fecal proteomics and activity analysis revealed that the protease cathepsin B progressively increased with alcohol use disorder and alcohol-associated hepatitis compared to controls, and is associated with higher short-term mortality in patients with alcohol-associated hepatitis. Cathepsin B is predominantly expressed in intestinal macrophages and is upregulated by ethanol. Cathepsin B deficiency in myeloid cells or oral treatment with the gut-restricted cathepsin B inhibitor CA074 stabilized gut barrier by preserving the tight junction protein occludin, lowered serum LPS levels, and attenuated ethanol-induced steatohepatitis. Transgenic overexpression of occludin in intestinal epithelial cells sufficed to reduce steatohepatitis and blunted the effects of CA074 in ethanol-fed mice. Cathepsin B proteolytically cleaves occludin in enzymatic assays, and its inhibition prevented occludin degradation and barrier disruption in intestinal organoids and epithelial monolayers. Molecular modeling and peptide profiling reveal specific cathepsin B-induced cleavage sites in the extracellular region of occludin.

CONCLUSIONS: Intestinal cathepsin B is an essential mediator of gut barrier dysfunction and therapeutic target in alcohol-associated liver disease.

IMPACT AND IMPLICATIONS: Intestinal barrier disruption facilitates the microbial translocation to the liver, contributing to the progression of alcohol-associated hepatitis, however the molecular mechanisms driving barrier dysfunction remain incompletely understood. Our study identified the protease cathepsin B as a key contributor to the progression of alcohol-associated liver disease by degrading the extracellular region of tight junction protein occludin in the intestine, which in turn leads to barrier disruption. This work advances the field by addressing causality, uncovering the molecular target, and proposing cathepsin B as a promising therapeutic target in alcohol-associated hepatitis, a condition for which liver transplantation remains the only effective treatment in a limited subset of patients.}, } @article {pmid41653958, year = {2026}, author = {Gamez, I and Fouladi, F and Gonzalez, A and Ward, J and Wang, Z and Beane Freeman, LE and Motsinger-Reif, A and Peddada, SD and Knight, R and Lee, M and London, SJ}, title = {Household Environmental Characteristics Influence House Dust Metagenome.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123889}, doi = {10.1016/j.envres.2026.123889}, pmid = {41653958}, issn = {1096-0953}, abstract = {Environmental exposures can shape microbial community compositions inside homes. Metagenomic sequencing methods can further elucidate the role of household exposures like indoor moisture and the surrounding landscape. To identify household environmental exposures associated with the house dust metagenome. Microbial communities in vacuumed dust from 771 homes in the Agricultural Lung Health Study were characterized using whole metagenome shotgun sequencing (5,821 taxa across 45 phyla). Household characteristics (i.e. presence of leaks, de-humidifier, humidifier use) were assessed by questionnaires or field technicians. We evaluated associations between exposures and both overall microbial diversity and differentially abundant taxa (ANCOM-BC2). Additionally, we explored microbial networks based on Spearman correlations (SECOM). Microbial diversity was higher in homes with mold/mildew (p-value<0.05), leaks, humidifier use, or occupants removing shoes before entering (p-value<0.1). Examining individual species, <10 taxa were significantly differentially abundant (p-value<0.05 after Holm-Bonferroni correction) in relation to both mold/mildew and leaks. Greater than 10 species were significantly differentially abundant in relation to removing shoes and humidifier use. Additionally, the genera Clostridium, Prevotella, and Cryptobacteroides were positively associated with removing shoes. In this farming population, the house dust microbiome differed by moisture-related exposures, and removing shoes before entering the home. Many novel associations were identified between individual taxa and these exposures. Our findings further knowledge of the impact of environmental conditions inside the home on the indoor microbiome.}, } @article {pmid41653954, year = {2026}, author = {Egea, LG and Jiménez-Ramos, R and Rodríguez-Arias, L and Infantes, E}, title = {Microplastics reduce eelgrass tolerance to heat stress with implications for restoration and blue carbon.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123980}, doi = {10.1016/j.envres.2026.123980}, pmid = {41653954}, issn = {1096-0953}, abstract = {Seagrass beds are key blue-carbon ecosystems, yet their resilience is increasingly challenged by microplastic (MP) pollution and marine heatwaves (MHWs). We experimentally tested how these stressors, alone and combined, affect the seagrass Zostera marina (eelgrass) using a controlled mesocosm experiment grounded in multiple-stressor and trait-based ecological theory. Plants were grown for 43 days in sediments with or without polyethylene/polypropylene MPs and a simulated MHW, (+5°C for 15 days) was imposed in the final phase. MP exposure significantly reduced rhizome elongation (-35%), total root length (-65%), and below-ground biomass, and depleted non-structural carbohydrates (NSC) in leaves and rhizomes (-35% to -40%). Warming alone stimulated leaf growth but further reduced NSC, while the MP × MHW interaction produced the lowest below-ground growth and carbohydrate reserves, consistent with synergistic stress predicted by multiple-stressor theory. MP exposure also reshaped the microbiome enriching putative sulfur-cycling taxa in the rhizosphere and indicating more reducing sediment conditions. With a carbon-balance and holobiont framework, MPs appear to constrain resource supply (oxygen and nutrients) and increase maintenance costs, whereas warming amplifies metabolic demand. The resulting carbon deficit limits below-ground growth, traits that underpin restoration success and blue-carbon function. These findings show the importance of incorporating microplastic monitoring into seagrass management to anticipate cumulative stress under a warming ocean.}, } @article {pmid41653836, year = {2026}, author = {Zhu, Y and Liu, SL and Lu, X and Luo, G and Xiao, ZH and Wang, YK and Zhou, J and Qiao, SC}, title = {Clinical, Immunological and Microbiological Improvements With Zinc-Coated Healing Abutments During the Healing Phase.}, journal = {International dental journal}, volume = {76}, number = {2}, pages = {109338}, doi = {10.1016/j.identj.2025.109338}, pmid = {41653836}, issn = {1875-595X}, abstract = {PURPOSE: The aim of this study was to evaluate the clinical, immunological, and microbiological effects of zinc-coated healing abutments (Zn-TiO2 abutments) on peri-implant soft tissue as compared with the commercially used ones (Ti abutments).

METHODS: The study was a prospective, non-randomised, single-centre, open-label, proof-of-concept clinical trial. The Ti and Zn-TiO2 abutments were non-randomly connected to 2 neighbouring implants in the posterior region in each eligible patient. The bleeding-on-probing proportion (BOP%), probing pocket depth (PPD), the concentration of the pro-inflammatory cytokine (TNF-α, IL-6) in the peri-implant crevicular fluid (PICF), and the early microbial communities assessed by 16S rRNA sequencing were recorded.

RESULTS: Eleven patients with 22 implants attended the 8-week examination. The BOP% was significantly lower in the Zn-TiO2 abutments than that in the Ti abutments (24.23% ± 13.67% versus 42.42% ± 29.22%, P = .019). The concentration of TNF-α in PICF was significantly lower in the Zn-TiO2 abutments than that in the Ti abutments (22.86 ± 11.21 versus 32.05 ± 16.28, P = .022). No significant differences in PPD and IL-6 were found between the two groups. Based on the microbiome assessments, higher microbial richness and lower presence of Lancefieldella were also observed in the Zn-TiO2 abutments as compared with the Ti abutments.

CONCLUSION: Within the limitations of the study, the zinc-coated healing abutments improved early peri-implant soft tissue health clinically and immunologically. However, further studies are still needed to exclude the interference of soft tissue phenotype and confirm the relationship between microbial and clinical findings.}, } @article {pmid41653708, year = {2026}, author = {Pearson, M and Engen, PA and Green, SJ and Emerson, J and Naqib, A and Gattuso, P and Keshavarzian, A and Coogan, C}, title = {Microbial profiling of urothelial carcinoma and benign bladder tissue from formalin-fixed specimens.}, journal = {Urologic oncology}, volume = {44}, number = {4}, pages = {110997}, doi = {10.1016/j.urolonc.2026.110997}, pmid = {41653708}, issn = {1873-2496}, abstract = {PURPOSE: Host-associated microbiota can influence host immunity and tumor responses. Emerging evidence suggests the bladder microbiome contributes to urothelial cell carcinoma (UCC), though most data come from urine samples. Urinary microbiomes are different in UCC compared to inflamed bladder, though their impact on host immune responses is understudied. Similarly, the effect of Bacillus Calmette-Guérin (BCG) treatment on bladder microbiome remains unexplored.

MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) transurethral resection of bladder tumor (TURBT) specimens from UCC tumor stages (T1 = 42), (T2 = 5), and 16 benign pathologies were examined. Six patients who underwent BCG vaccine with post-treatment TURBT specimens were examined. Microbial communities were characterized using RNA extraction, reverse transcription, and 16S rRNA amplicon sequencing.

RESULTS: UCC patients exhibited greater microbial diversity and distinct bladder microbiome compositions compared to those with benign pathology. Several genera in the bladder including Streptococcus, Staphylococcus, Actinomyces, and Cutibacterium were more abundant in the benign group. Conversely, T1-UCC patients showed higher relative abundances of putative proinflammatory genera including Escherichia-Shigella and unclassified Yersiniaceae, plus commonly reported skin-associated dysbiotic genera Enhydrobacter and Micrococcus. Five of 6 BCG-treated patients showed marked reduction in microbial diversity along with significant alteration in their microbiome composition, including decreased relative abundance of bacteria from genera Streptococcus and Rothia.

CONCLUSIONS: This proof-of-concept study suggests that: (1) microbiome sequencing from FFPE TURBT specimens can be used for microbiota assessment and can effectively distinguish UCC from benign pathology. (2) bladder microbiomes are heavily depleted following BCG treatment, indicating therapy-induced microbiome alterations.}, } @article {pmid41653553, year = {2026}, author = {Ghosh, A and Bhakta, S and Kapse, N and Dhakephalkar, PK and Patra, C and Gorain, B}, title = {Micro/nanoplastic-mediated gut dysbiosis and its impact on cardiac and neuroimmune function in zebrafish model: A multi-omics approach.}, journal = {The Science of the total environment}, volume = {1017}, number = {}, pages = {181443}, doi = {10.1016/j.scitotenv.2026.181443}, pmid = {41653553}, issn = {1879-1026}, abstract = {The pervasive distribution of micro- and nanoplastics (M/NPs) across ecosystems necessitates a mechanistic investigation into their toxicological consequences. Chronic exposure to M/NPs through combined intestinal uptake and branchial contact in aquatic animals disrupts epithelial barrier integrity, alters gastric secretions and luminal pH, and induces microbial dysbiosis, evidenced by the depletion of commensal taxa and expansion of pathogenic strains. These local perturbations trigger systemic sequelae, including neurotoxicity and cardiotoxicity. Consequences on cross-species analyses demonstrate translational concordance, as human studies similarly link M/NP bioaccumulation with inflammatory bowel disease, cognitive decline, and cardiovascular dysfunction. Integrative multi-omics approaches, encompassing transcriptomic, metabolomic, and microbiome analyses, have begun to elucidate the molecular cascades underpinning M/NP toxicity, providing high-resolution insights into host-microbe-environment interactions. Notwithstanding these advances, critical gaps remain in chronic exposure modelling, capturing particle heterogeneity, and ensuring ecological realism. In this context, zebrafish (Danio rerio) provide a uniquely tractable system for gnotobiotic rearing, microbial transplantation, and live imaging, thereby enabling causal inference and functional validation in real-time. Collectively, this review establishes zebrafish as a pivotal model for elucidating M/NP-induced gut dysbiosis, neurotoxicity, and cardiotoxicity. Multi-omics analyses and translational evidence reveal systemic inflammation, immune-metabolic disruptions, and mechanistic links to human health, providing a foundation for targeted research, regulatory frameworks, and interventions to mitigate environmental M/NP exposure.}, } @article {pmid41653320, year = {2026}, author = {Kashyap, S and Bhattacharyya, PN and Agarwala, N}, title = {Developing Effective Bioinoculant and Engineering Plant Microbiome for Climate Resilient Agriculture: Lessons Learned and Future Roadmap.}, journal = {Current microbiology}, volume = {83}, number = {3}, pages = {161}, pmid = {41653320}, issn = {1432-0991}, support = {CRG/2023/002423//Anusandhan National Research Foundation,India/ ; }, mesh = {*Microbiota ; *Agriculture/methods ; Climate Change ; *Plants/microbiology ; *Crops, Agricultural/microbiology ; }, abstract = {Ensuring plant resilience is crucial for maintaining global food security amidst a changing climate. Leveraging the multitude of microorganisms in different environmental conditions appears to be a promising and sustainable approach to boosting agricultural productivity. However, understanding the legacy of microbial bioinoculants in agroecosystems remains a challenging issue, thereby hampering their widespread applicability and acceptance. This review offers an in-depth insight into the intricacies of designing effective bioinoculants, orchestrated by an understanding of the ecological contexts that drive their success. Furthermore, this article emphasizes the importance of adopting a holistic approach to designing effective bioinoculants, thereby enhancing their application in agriculture.}, } @article {pmid41652998, year = {2026}, author = {Desorcy-Scherer, K and McNamara, K and Luellwitz, R and Stanton, E and Zuniga-Chaves, I}, title = {Early Insights Into Maternal Antidepressant Use and the Human Infant Gut Microbiome.}, journal = {Biological research for nursing}, volume = {}, number = {}, pages = {10998004261423546}, doi = {10.1177/10998004261423546}, pmid = {41652998}, issn = {1552-4175}, abstract = {Maternal selective serotonin reuptake inhibitor (SSRI) use is common during pregnancy and lactation. Changes in serotonin signaling may affect diversity and composition of microbes in the gut. Although research suggests SSRI drives microbial change, the extent to which the infant gut microbiome is affected is unknown. The infant gut microbiome is critical in early life for support of developmental health including early training of the immune system and metabolic programming. A total of N = 20 (10 SSRI, 10 control) maternal/infant dyads were enrolled in a pilot study. Thirty-six infant stool samples were collected at 1-2 and 4-6 weeks of life and sequenced using 16S rRNA sequencing. Investigative models included SSRI exposure as the primary variable of interest with infant feeding pattern and mode of delivery included as covariates. Maternal antidepressant use was not associated with infant alpha (within-sample) diversity. The SSRI use may shape beta (between-sample) diversity, particularly at weeks 4-6 of life (p = .072). Increases in the genera Gemella, Staphylococcus and Corynebacterium were observed with SSRI exposure. Additionally, results reveal a SSRI-associated decrease in Lactobacillus. While this pilot study is not intended to provide conclusive evidence, it is an important step in informing future research directions. Results suggest a modest influence of maternal SSRI exposure on the infant gut microbiome. Future studies should seek to use techniques like metagenomics, providing functional information to assess for local or systemic health impact and ultimately, clinical relevance.}, } @article {pmid41652967, year = {2026}, author = {Rose, AM and O'Brien, AM}, title = {Observing weak adaptation of duckweeds to their local microbiome depends on local pondwater.}, journal = {American journal of botany}, volume = {}, number = {}, pages = {e70165}, doi = {10.1002/ajb2.70165}, pmid = {41652967}, issn = {1537-2197}, support = {2300059//Division of Molecular and Cellular Biosciences/ ; Hatch NH00724//National Institute of Food and Agriculture/ ; }, abstract = {PREMISE: Populations can locally adapt to the biotic and abiotic factors of environments. However, detecting adaptation to biotic factors can depend on the abiotic conditions in which the adaptation is tested, and vice versa. The microbiome is one important aspect of the biotic environment: Interactions between microbiomes and their hosts are critical for host fitness and trait expression. If hosts adapt to local microbiomes, they may therefore depend on interactions with local microbes to express trait values adapted to the local abiotic environment.

METHODS: Using Lemna minor (duckweed) as a model host, we examined differences in host fitness when grown in local and nonlocal microbiomes and in local and nonlocal water. We experimentally recombined duckweeds, microbes, and water from four ponds around Durham, New Hampshire (United States) in well-plate microcosms in a growth chamber.

RESULTS: The source of duckweeds, microbes, and water all affected microbial growth, duckweed growth, and duckweed traits. However, weak, marginally significant local adaptation resulted in higher frond area only when duckweeds were paired with their local water and local microbes. Microbial growth was also marginally reduced when duckweeds were paired with microbes and water from their local site.

CONCLUSIONS: While microbiome impacts on duckweed growth and traits varied across abiotic contexts, local microbiomes provided only limited growth benefits. Harnessing the effects of plant microbiomes is an exciting area of applied research. Despite our findings, bioprospecting in local microbiomes could still be fruitful: It may be ecologically safer, and other plants may locally adapt to microbiomes.}, } @article {pmid41652869, year = {2026}, author = {Neil, RC and Barton, JA and Heyward, A and Francis, DS and Nankervis, L and Mock, TS and Humphrey, C and Bourne, DG}, title = {Nutritional and Microbial Responses of Pocillopora verrucosa to Co-Culture With Chromis viridis Damselfish.}, journal = {Environmental microbiology reports}, volume = {18}, number = {1}, pages = {e70291}, pmid = {41652869}, issn = {1758-2229}, support = {//Great Barrier Reef Foundation/ ; }, mesh = {Animals ; *Anthozoa/microbiology/growth & development/physiology/chemistry ; Bacteria/classification/genetics/isolation & purification ; Coculture Techniques ; Symbiosis ; Aquaculture ; Animal Feed/analysis ; Fatty Acids/analysis ; *Perciformes ; Microbiota ; }, abstract = {Associations with fish can benefit corals by increasing growth and stress tolerance. To investigate microbial and nutritional responses of corals to fish associations in the context of enhancing coral aquaculture outcomes, Pocillopora verrucosa were cultured for 3 months with different combinations of live feeds and schools of juvenile Chromis viridis damselfish. The combined live feeds and fish treatment resulted in a bacterial community most similar to wild P. verrucosa, dominated by Endozoicomonas-affiliated taxa. Protein content was enhanced in corals with access to live feeds and/or dissolved fish wastes compared to unfed controls. Total lipid concentrations were elevated in captive corals with access to dissolved fish wastes and at moderate levels in those supplied live feeds, likely due to the activity of corals' symbionts and deposition of derived lipids from live feeds, respectively. However, all captive corals demonstrated a significant reduction in storage lipid concentration compared to samples from the wild. Fatty acid analysis indicated these shifts were likely the result of higher light levels in the field supporting Symbiodiniaceae photosynthesis and potentially feeding on wild zooplankton. Co-culturing captive corals with fish and providing appropriate live feeds may therefore offer an effective approach to improve coral nutrition, health and microbiome stability.}, } @article {pmid41652766, year = {2026}, author = {Ovai, B and Onuh, J and Aryee, ANA}, title = {The role of plant-food derived bioactives in modulating the gut microbiome, inflammation and metabolic syndrome: Regulatory and market dynamics.}, journal = {Food research international (Ottawa, Ont.)}, volume = {227}, number = {}, pages = {118243}, doi = {10.1016/j.foodres.2025.118243}, pmid = {41652766}, issn = {1873-7145}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Metabolic Syndrome/prevention & control/microbiology ; *Inflammation/prevention & control ; *Phytochemicals/pharmacology ; Anti-Inflammatory Agents ; Antioxidants ; }, abstract = {The global increase in metabolic disorders including obesity, type 2 diabetes (T2DM), and cardiovascular disease (CVD) highlights the need for adjunctive strategies beyond conventional pharmacotherapy. Bioactive compounds (BACs) derived from plant-based foods, such as carotenoids, glucosinolates (GSLs), and bioactive peptides (BAPs), have garnered considerable interest for their capacity to modulate the gut microbiome, attenuate systemic inflammation, and mitigate key features of metabolic syndrome (MetS). Carotenoids have been associated with antioxidant and anti-inflammatory activities including inhibition of lipid peroxidation; GSLs contribute to phase II detoxification and glycemic control; while BAPs demonstrate antihypertensive activity and support probiotic growth. Despite promising mechanistic data, clinical translation remains limited. Human trials are few, generally short in duration, and often rely on surrogate biomarkers such as heme oxygenase-1, superoxide dismutase 1, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Effective dosing varies by compound and formulation, with lipid and inflammatory outcomes typically assessed over 8-12 weeks, and hepatic or structural endpoints requiring ≥24 weeks. Efficacy is further influenced by interindividual variability in gut microbiota composition, dietary matrix, food processing methods, and BAC bioavailability. To advance clinical relevance, long-term, adequately powered trials in diverse populations are essential. Furthermore, regulatory challenges, commercialization constraints, and the need for standardized formulations must be addressed to expand the development of functional foods and nutraceuticals, particularly given their favorable safety profiles and potential for preventive health applications.}, } @article {pmid41652742, year = {2026}, author = {Van Meulebroek, L and Ghyselinck, J and Van Elst, D and Duysburgh, C and Gessner, A and Thas, O and Marzorati, M}, title = {The impact of Symprove™ multi-strain probiotic on enterotoxigenic Escherichia coli- or antibiotic-induced gut microbiome dysbiosis using high-throughput in vitro screening.}, journal = {Food research international (Ottawa, Ont.)}, volume = {227}, number = {}, pages = {118172}, doi = {10.1016/j.foodres.2025.118172}, pmid = {41652742}, issn = {1873-7145}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Probiotics/pharmacology ; *Dysbiosis/microbiology/chemically induced ; *Anti-Bacterial Agents/adverse effects ; Feces/microbiology ; *Enterotoxigenic Escherichia coli/drug effects ; Fatty Acids, Volatile/metabolism ; Adult ; Male ; High-Throughput Screening Assays ; Female ; Escherichia coli Infections/microbiology ; Fermentation ; Young Adult ; }, abstract = {The gut microbiome plays a significant role in host physiology, both in health and disease. Assessment of changes in microbial metabolites beyond short-chain fatty acids (SCFAs) following probiotic supplementation may identify additional metabolic pathways that are activated or suppressed in response to probiotics. This study assessed changes in microbial metabolites in healthy and dysbiosed microbiomes following supplementation with Symprove™, a multistrain probiotic, using the Colon-on-a-plate® miniaturized short-term batch fermentation system with a fractional factorial design. The fecal microbiome from 10 healthy human donors was evaluated under healthy and dysbiosed (enterotoxigenic Escherichia coli infection and/or low-, medium-, or high-dose antibiotics) conditions. Samples were supplemented with Symprove™ or water (control) and evaluated for microbial metabolites at 24 h and 48 h using untargeted metabolic fingerprinting, capillary gas chromatography, and targeted metabolic profiling. Favorable impacts were observed with Symprove™ supplementation across the different antibiotic doses. SCFA levels (acetate, propionate, butyrate) were significantly increased and levels of branched SCFAs were significantly decreased with Symprove™ supplementation versus control in both the healthy and dysbiosed populations. Significant increases and decreases in several other microbial metabolites were also observed with Symprove™, many of which could be considered to have beneficial effects on intestinal inflammation, intestinal barrier health, and the gut-brain axis. Symprove™ supplementation significantly affected microbial metabolism, with many of the observed changes being considered positive for human health. Importantly, these benefits were shown not only in healthy fecal microbiomes, but also in fecal microbiomes with in vitro antibiotic-induced dysbiosis, showing therapeutic potential.}, } @article {pmid41652641, year = {2026}, author = {Lu, J and Satten, GA and Meyer, KA and Launer, LJ and Ling, W and Zhao, N}, title = {Identifying unmeasured heterogeneity in microbiome data via quantile thresholding (QuanT).}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02282-9}, pmid = {41652641}, issn = {2049-2618}, support = {R01GM147162/NH/NIH HHS/United States ; 75N92023D00002/NH/NIH HHS/United States ; R01HL155417/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Microbiome data, like other high-throughput data, suffer from technical heterogeneity stemming from differential experimental designs and processing. In addition to measured artifacts such as batch effects, there is heterogeneity due to unknown or unmeasured factors, which lead to spurious conclusions if unaccounted for. With the advent of large-scale multi-center microbiome studies and the increasing availability of public datasets, this issue becomes more pronounced. Current approaches for addressing unmeasured heterogeneity in high-throughput data were developed for microarray and/or RNA sequencing data. They cannot accommodate the unique characteristics of microbiome data such as sparsity and over-dispersion.

RESULTS: Here, we introduce quantile thresholding (QuanT), a novel non-parametric approach for identifying unmeasured heterogeneity tailored to microbiome data. QuanT applies quantile regression across multiple quantile levels to threshold the microbiome abundance data and uncovers latent heterogeneity using thresholded binary residual matrices. We validated QuanT using both synthetic and real microbiome datasets, demonstrating its superiority in capturing and mitigating heterogeneity and improving the accuracy of downstream analyses, such as prediction analysis, differential abundance tests, and community-level diversity evaluations.

CONCLUSIONS: We present QuanT, a novel tool for comprehensive identification of unmeasured heterogeneity in microbiome data. QuanT's distinct non-parametric method markedly enhances downstream analyses, serving as a valuable tool for data integration and comprehensive analysis in microbiome research. Video Abstract.}, } @article {pmid41652512, year = {2026}, author = {Limijadi, EKS and Nishani, F and Daliu, P and Qorri, E and Hadinata, E and Santini, A and Nurkolis, F}, title = {Marine nutraceuticals and their role in modulating diabetes-induced carcinogenesis.}, journal = {Diabetology & metabolic syndrome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13098-026-02113-3}, pmid = {41652512}, issn = {1758-5996}, } @article {pmid41652405, year = {2026}, author = {Chen, KL and Liao, IC and Chen, CA and Kuo, CY and Jiang, YY and Lin, YC and Yuan, K and Lung, J}, title = {Distinct bacteria profiles in primary and secondary/persistent endodontic infections: a 16S rRNA gene sequencing study.}, journal = {BMC oral health}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12903-026-07821-w}, pmid = {41652405}, issn = {1472-6831}, support = {CMFHR10889//Chi Mei Medical Center/ ; CORPG6N0311//Chiayi Chang Gung Memorial Hospital/ ; 109-2314-B-182A-146-MY2//Ministry of Science and Technology, Taiwan/ ; 113-2314-B-182A-057//National Science and Technology Council/ ; }, } @article {pmid41652394, year = {2026}, author = {Xiao, Z and Shi, Y and Zhao, D and Wang, Y and Gu, Y}, title = {Triggering mechanisms of acute thunderstorm asthma: epithelial barrier disruption and immune dysregulation.}, journal = {Respiratory research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12931-026-03532-6}, pmid = {41652394}, issn = {1465-993X}, support = {No. 2023NYFYPY005//the National Natural Cultivation Project of China/ ; No. YSXH2024KYF028//the Clinical Medical Research and Clinical New Technology Promotion Project of the Inner Mongolia Physicians Association/ ; No. 2024GLLH0314//the Public Hospital Research Joint Fund Project of the Inner Mongolia Academy of Medical Sciences/ ; }, abstract = {Thunderstorm asthma (TA) refers to a phenomenon characterized by sudden onset, large-scale outbreaks, and potentially fatal acute exacerbations of asthma. Despite accumulating epidemiological evidence, its cellular and molecular mechanisms remain unclear. Recent studies have proposed a core framework involving "environmental triggers-epithelial barrier damage-immune dysregulation." During thunderstorms, high humidity and strong convection can cause pollen to hydrate and rupture into sub-pollen particles (SPPs) smaller than 2.5 μm, which may further combine with other pollutants such as particulate matter ≤ 2.5 μm(PM2.5) and ozone (O3) to form bioaerosols capable of penetrating small airways. These factors can lead to damage of the airway epithelial barrier, with sequential cellular and molecular pathophysiological changes including downregulation of various tight junction proteins in the epithelial barrier, imbalance of mucociliary clearance function, and upregulated secretion of epithelial alarmins such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). This results in increased disease severity through activation of innate and adaptive immunity (e.g., type 2 innate lymphoid cells (ILC2)/T helper 2(Th2) axis activation leading to immunoglobulin E(IgE) upregulation, eosinophil activation, and mast cell degranulation; Th17-mediated neutrophilic inflammation; and toll-like receptor(TLR)-mediated innate immune processes and mucosal inflammation) and enhancement of intrinsic susceptibility factors (e.g., TLR gene polymorphisms and abnormal expression, DNA methylation and histone modifications, as well as microbiome-host interactions). According to research in meteorology, exposomics, and molecular immunology, we believe that airway epithelial barrier dysfunction and immune dysregulation play significant roles in TA. Future translational directions primarily involve establishing a population stratification and early warning system through combinations of meteorological factors with allergens/pollutants, thereby enhancing public protection and health management efforts to improve the early warning, prevention, and clinical management of TA.}, } @article {pmid41652368, year = {2026}, author = {Wang, L and Fang, X and Shi, L and Wang, P and Chen, W and Yang, J and Ding, Y and Cao, Z and Xie, D and Meng, K}, title = {Identification and optimized detection of two type 2 diabetes-associated enteric pathogens: Klebsiella and EPEC.}, journal = {BMC infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12879-026-12786-w}, pmid = {41652368}, issn = {1471-2334}, } @article {pmid41652328, year = {2026}, author = {Patin, C and Monot, C and Marchand-Martin, L and Ancel, PY and Butel, MJ and Rozé, JC and Lepage, P}, title = {Intestinal microbiome in very-preterm infants at one month of age and association with neurodevelopmental outcome.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04789-z}, pmid = {41652328}, issn = {1471-2180}, abstract = {BACKGROUND: Preterm birth is the leading cause of death in children under five years of age worldwide. The association between preterm birth and long-term outcomes is vaguely known. In very preterm infants, the gut microbiome is highly variable and impacted by the neonatal intensive care unit environment. Our objective was to better understand the crosstalk between the gut microbiome and the host at one month of age in very preterm infants and its impact on neurological outcomes at two years of age. We performed a multi-omics analysis of fecal samples collected in 2011 from 73 very preterm French infants at one month of age, grouped according to their neurodevelopment assessed at two years of age using the Ages & Stages questionnaire. Multi-omics profiling and integrative analyses were performed between 2022 and 2023, including fecal microbiome, metabolome, and host transcriptome characterization using 16 S rRNA gene sequencing, LC-MS, and mRNA sequencing, respectively.

RESULTS: The gut microbiome of very preterm infants at one month is mostly driven by either Escherichia or Staphylococcus, which are differentially associated with host immune markers (CAMP), metabolomic pathways, notably the energy pathway due to the presence of various nicotinamide adenine dinucleotides (NAD+) and two-year neurodevelopmental outcomes.

CONCLUSION: The gut microbiome at one month of age could be a noninvasive biomarker of gut immaturity and metabolic defects. Escherichia and Staphylococcus proportions were found to be the best indicators of physiological maturity and immaturity, respectively. Escherichia may help the process of intestinal maturation in preterm infants through specific metabolites production and is associated with a better neurodevelopment.}, } @article {pmid41652299, year = {2026}, author = {He, J and Chen, J and Liao, Y and Zhang, K and Yang, C and Huang, H and Dou, X}, title = {Facial Skin Mycobiome in Atopic Dermatitis With and Without Facial Involvement and Healthy Controls: A Case-Control Study.}, journal = {Experimental dermatology}, volume = {35}, number = {2}, pages = {e70221}, doi = {10.1111/exd.70221}, pmid = {41652299}, issn = {1600-0625}, support = {81972930//National Natural Science Foundation of China/ ; JCYJ20210324105411030//Natural Science Foundation of Shenzhen Municipality/ ; KYQD2024401//Scientific Research Foundation of Peking University Shenzhen Hospital/ ; }, mesh = {Humans ; *Dermatitis, Atopic/microbiology ; *Mycobiome ; Case-Control Studies ; Adult ; Female ; Male ; *Skin/microbiology ; Malassezia/isolation & purification ; Middle Aged ; Young Adult ; Face/microbiology ; Adolescent ; }, abstract = {With the growing interest in the skin microbiome in atopic dermatitis (AD), alterations in cutaneous fungal communities have garnered increasing attention. However, their role in AD pathogenesis and their association with clinical parameters remain unclear. This study characterised the facial skin mycobiome in AD patients with and without facial involvement, compared to healthy controls. Fungal composition was analysed across multiple taxonomic levels, along with assessments of alpha and beta diversity and predicted functional pathways. Basidiomycota and Ascomycota were the predominant phyla across all groups, with Malassezia as the dominant genus. At the species level, Malassezia_globosa and Malassezia_japonica were enriched in AD patients with facial involvement, whereas Malassezia_restricta was reduced compared with the other groups. In the full cohort, no significant differences in overall fungal diversity were observed; however, richness-based alpha diversity indices differed between facial AD and healthy controls in an adult-only sensitivity analysis, while Shannon and Simpson indices remained comparable. Notably, distinct differences in predicted metabolic pathways were identified among groups. Correlation analyses showed that Malassezia_restricta abundance was positively associated with body mass index (BMI), whereas Malassezia_globosa was negatively associated with disease severity. Collectively, these findings indicate that facial AD is associated with distinct mycobiome alterations, with potential age-related effects on specific taxa and diversity metrics. Further longitudinal and mechanistic studies are warranted to elucidate causal relationships and explore therapeutic implications.}, } @article {pmid41651994, year = {2026}, author = {Huang, S and Yu, S and Zhang, W and Qi, D and Pei, X and Lu, D and Ba, M and Xuan, S and Huang, D and Yang, J and Li, Z}, title = {Sleep deprivation disrupts lacrimal gland homeostasis via hypothalamic-pituitary-adrenal axis and gut dysbiosis in mice.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-026-09657-0}, pmid = {41651994}, issn = {2399-3642}, support = {82101089//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Sleep deprivation (SD) disrupts systemic homeostasis, but how it drives ocular surface disease remains unclear. Using a male mouse SD model, we show that chronic SD activates the hypothalamic-pituitary-adrenal (HPA) axis, elevates corticosterone, alters gut microbiota, and depletes short-chain fatty acids (SCFAs). These alterations coincide with lacrimal gland atrophy, reduced tear secretion, and increased CD4[+]/CD8[+] T cell infiltration, accompanied by activation of IL-17-associated inflammatory pathways. Pharmacological inhibition of glucocorticoid synthesis with metyrapone preserves lacrimal gland structure and function while attenuating immune activation. Microbiome-directed interventions, including SCFA supplementation and fecal microbiota transplantation, rebalance gut communities, suppress pro-inflammatory T cell responses, and maintain lacrimal gland homeostasis. Transcriptomic and immunohistochemical analyses further reveal that all three interventions converge on the downregulation of IL-17 signaling. Collectively, these findings establish an HPA-gut microbiome-lacrimal gland axis that links neuroendocrine stress to microbial dysbiosis and ocular inflammation, and they suggest therapeutic strategies for SD-associated lacrimal gland dysfunction.}, } @article {pmid41651947, year = {2026}, author = {Sadeghi, S and Faramarzi, MA and Siroosi, M}, title = {Enhanced meropenem activity by a microbiome derived peptide targeting oxacillinase 48 carbapenemase in carbapenem resistant Klebsiella pneumoniae isolates.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-37644-2}, pmid = {41651947}, issn = {2045-2322}, support = {1402-3-101-68180//Tehran University of Medical Sciences and Health Services/ ; }, } @article {pmid41651883, year = {2026}, author = {Pantiukh, K and Org, E}, title = {Human gut archaea collection from Estonian population.}, journal = {Scientific data}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41597-026-06742-1}, pmid = {41651883}, issn = {2052-4463}, support = {PRG1414//Eesti Teadusagentuur (Estonian Research Council)/ ; 3573//European Molecular Biology Organization (EMBO)/ ; }, abstract = {While microbiota plays a crucial role in maintaining overall health, archaea, a component of microbiota, remain relatively unexplored. Here, we present a newly assembled set of archaeal metagenome-assembled genomes (MAGs) from 1,878 fecal microbiome samples. These MAGs were reconstructed from metagenomic reads of the Estonian Microbiome Deep (EstMB-deep) cohort, which were reused here specifically for archaeal MAG reconstruction. We identified 273 archaeal MAGs, representing 21 species and 144 strains which we curated into the "EstMB MAGdb Archaea-273" MAGs collection.}, } @article {pmid41651877, year = {2026}, author = {Zhang, E and Claesson, MJ and Cotter, PD}, title = {Adopting omics-based approaches to facilitate the establishment of microbial consortia to generate reproducible fermented foods with desirable properties.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00740-8}, pmid = {41651877}, issn = {2396-8370}, support = {23/FFP-A/11857//Research Ireland/ ; 23/FFP-A/11857//Research Ireland/ ; 101060218//European Commission/ ; }, abstract = {The quality of fermented foods is governed by the composition, function, and interactions of their microbial communities. However, fermentations carried out using traditional approaches are often variable with respect to their composition and are difficult to control, thereby limiting industrial reproducibility. Recent advances in omics technologies-including metagenomics, metatranscriptomics, metaproteomics, metabolomics, and culturomics-have greatly enhanced our ability to analyze and reconstruct the microbial ecosystems in fermented foods. This review first highlights the importance of omics analyses for characterizing microbial composition, metabolic potential, and functional interactions. It then discusses the bipartite structure of defined microbial consortia (DMCs), distinguishing between the core microbiome, comprising taxa consistently associated with fermentation performance, and the supplementary microbiome, consisting of variable species that influence flavor diversity and system stability. Finally, we describe a multi-omics-guided strategy for the design and refinement of DMCs, framed within the Assembly-Assessment-Redesign (A-A-R) workflow, which enables iterative optimization of microbial consortia for reproducible and desirable fermentation outcomes. Integrating omics insights with DMC engineering provides a systematic approach for precision fermentation, paving the way for next-generation fermented food production.}, } @article {pmid41651593, year = {2026}, author = {Adame, MD and Stringer, KA and Dickson, RP}, title = {The Gut Microbiome and Short-Chain Fatty Acid Metabolites in Sepsis.}, journal = {Clinics in chest medicine}, volume = {47}, number = {1}, pages = {119-128}, doi = {10.1016/j.ccm.2025.11.006}, pmid = {41651593}, issn = {1557-8216}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sepsis/metabolism/microbiology/physiopathology ; *Fatty Acids, Volatile/metabolism ; }, abstract = {Sepsis profoundly perturbs the intestinal microbiome and its metabolite output, yet the mechanisms by which these changes influence organ injury remain incompletely defined. In this review, we focus on short-chain fatty acids (SCFAs) as key mediators linking gut microbes to sepsis pathophysiology. We first summarize how sepsis and its treatments reshape gut communities, depleting SCFA-producing anaerobes and altering the gut metabolome. We then examine determinants of SCFA concentrations in the intestinal lumen and describe how gut-blood trafficking of these charged metabolites depends on epithelial transporters and tight-junction-regulated paracellular pathways. We highlight emerging data on how leak and pore pathways, including claudin-2-dependent pores, are upregulated in sepsis and may misdirect microbial products into the portal and systemic circulation. Finally, we synthesize experimental and human evidence for organ-specific effects of individual SCFAs: butyrate as a colonocyte fuel and barrier stabilizer, propionate as a modulator of lung immune tone, and acetate as a systemic immunometabolite that shapes inflammatory responses and sepsis outcomes. Across these sections, we outline therapeutic strategies that aim to preserve or restore SCFA-producing microbes, modify diet, target transport and permeability pathways, or deliver microbial metabolites directly. Together, these data position SCFAs and their trafficking as central to the gut-sepsis axis and as promising targets for future precision therapies.}, } @article {pmid41651581, year = {2026}, author = {Mondal, R and Yano, Y}, title = {Reply to: "Considerations on statistical analysis of NHANES data in oral microbiome diversity and mortality study".}, journal = {Atherosclerosis}, volume = {413}, number = {}, pages = {120630}, doi = {10.1016/j.atherosclerosis.2025.120630}, pmid = {41651581}, issn = {1879-1484}, } @article {pmid41651580, year = {2026}, author = {Shen, Y and Hu, W}, title = {Considerations on statistical analysis of NHANES data in oral microbiome diversity and mortality study.}, journal = {Atherosclerosis}, volume = {413}, number = {}, pages = {120629}, doi = {10.1016/j.atherosclerosis.2025.120629}, pmid = {41651580}, issn = {1879-1484}, } @article {pmid41651403, year = {2026}, author = {Suss, NR and Barat, B and Ravari, MR and Shogan, BD}, title = {The impact of the microbiome on colorectal cancer recurrence.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {102360}, doi = {10.1016/j.gassur.2026.102360}, pmid = {41651403}, issn = {1873-4626}, abstract = {Surgical resection of a colorectal adenocarcinoma remains a cornerstone in its treatment. Yet, despite proper patient selection and neoadjuvant and/or adjuvant chemotherapy/radiation, up to 30% of patients thought to be cured will develop a postoperative recurrence. Unfortunately, the outcomes in patients who develop a postoperative recurrence are poor and are associated with high morbidity and mortality. The gut microbiome has emerged to play a role in virtually all aspects of human health. In this manuscript, we critically examine the current literature implicating the gut microbiome's role in the pathogenesis of postoperative recurrence following attempted curative resection. We discuss how microbes can drive a more advanced stage and explore how surgery itself can precipitate a gut microenvironment with tumorigenic bacteria and bacterial derived metabolites that can drive postoperative tumor formation. Finally, we review evidence as to how the gut microbiome can be manipulated to improve oncological outcomes.}, } @article {pmid41651389, year = {2026}, author = {Shi, B and Zhang, L and Jia, X and Tao, Y and Wang, M}, title = {Profiles of gut microbiome in Litopenaeus vannamei artificially infected with Vibrio parahaemolyticus causing translucent post-larva disease.}, journal = {Developmental and comparative immunology}, volume = {176}, number = {}, pages = {105565}, doi = {10.1016/j.dci.2026.105565}, pmid = {41651389}, issn = {1879-0089}, abstract = {As the primary defense against pathogen invasion, the dynamic equilibrium of the shrimp gut microbiome is recognized as a critical factor influencing pathogen colonization. In recent years, translucent post-larva disease (TPD) outbreaks during the early stages of shrimp farming have become a serious threat to the sustainable development of the shrimp industry. Compared with other vibriosis, TPD caused by certain Vibrio strains possessing drug resistance and high-virulence genes exhibits greater virulence in shrimp tissues, with mortality rates reaching up to 90%. However, no studies have yet explored the association between this pathogen and the gut microbiome. This study employed metagenomic sequencing technology to analyze differences in the axial distribution of the gut microbiome in shrimp at varying degrees of TPD infection. Histopathological sections revealed that multiple tissue lesions induced by TPD infection in shrimp were primarily concentrated in the midgut. Alpha diversity analysis indicated that the alpha diversity index of the shrimp gut microbiome showed an upward trend as pathogen load increased. Beta diversity analysis revealed the intestinal segment with the most significant microbial community changes during pathogen colonization. Within this region, the abundance of probiotics decreased, while that of pathogenic bacteria increased. Functional prediction results indicate that under TPD stress, the gut microbiome activates a multi-layered, synergistic defense adaptation program through nutritional metabolism shifts, biofilm reinforcement, and toxin efflux. This study elucidates the pathogenic mechanism of TPD from the perspective of pathogen-gut microbiome interactions, suggesting that controlling pathogen load and restoring targeted probiotics may serve as effective strategies for preventing and controlling TPD.}, } @article {pmid41651372, year = {2026}, author = {Muhffel, MM and Aly, SS and Lucey, PM and Lean, IJ and Rossow, HA}, title = {Feeding preweaning Holstein calves a synbiotic supplement increases their energy-corrected milk yield as lactating cows.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-27567}, pmid = {41651372}, issn = {1525-3198}, abstract = {Prebiotics and probiotics are feed additives that can benefit the host by modulating the gut microbiome, which is crucial in digestion, immunity, and overall animal health. This study aims to evaluate the effects of supplementing prebiotics, probiotics, or synbiotics to preweaning Holstein calves on their future milk yield. This study is a retrospective analysis of milk yield records from dairy cows that were randomized at birth to 1 of 4 twice-daily treatments administered during the preweaning period: (1) control, no additive (CON), (2) prebiotic (PRE; 7 mL of Saccharomyces cerevisiae yeast culture), (3) probiotic (PRO; Bacillus subtilis and Lactobacillus plantarum, delivering ∼1 billion and 250 million cfu per head per day, respectively), or (4) synbiotic (SYN; combination of both PRE and PRO at the same dosages as the PRE and PRO treatments). The study was conducted on a dairy farm in Fresno County, California, between 2019 and 2023, involving 1,296 Holstein cows over their first 3 lactations for a total of 2,735 lactations. Monthly test day records for milk yield, fat, and protein were used to calculate ECM, standardized to 4% fat and 3.3% protein, totaling 26,464 monthly test day milk records. A 2-piece splines mixed-effect regression model evaluated the effect of treatments on ECM yield. For the first lactation, ECM yield was estimated at 28.66 kg on the first DIM, peaked at 42.1 kg, and declined to 21.34 kg by 305 DIM. For parity ≥2, ECM yield was 41.06 kg at 1 DIM, peaked at 54.2 kg, and 33.74 kg at 305 DIM. The SYN treatment increased ECM yield by 1.00 kg/d compared with CON. This increase was primarily due to an increase in milk fat yield, with 0.048 kg/d more fat produced compared with the control group. No differences in ECM yield between PRE, PRO, or CON were observed. These findings suggest that supplementing SYN during the preweaning period increased milk, milk fat, and ECM yield across lactations 1, 2, and 3.}, } @article {pmid41651364, year = {2026}, author = {Hu, G and Gao, J and Padmakumar, V and Joshi, N and Zhu, W and Cheng, Y}, title = {The impact of methane inhibitors on ruminants: A systematic review and meta-analysis.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-27479}, pmid = {41651364}, issn = {1525-3198}, abstract = {The impact of methane inhibitors on ruminant performance and rumen microbial community composition is unclear. The aim of this study was to summarize the effects of methane inhibitors on the performance of ruminants and the structure of rumen microbial communities. A total of 13,043 studies were retrieved from the Web of Science database. Ultimately, 256 studies containing the variables we needed were included. The data were further extracted and processed. The study revealed the negative effects of methane inhibitors on ruminants, which were reflected in the reduction of feed intake and digestibility in ruminants. Adding methane inhibitors reduced the acetate concentration in the rumen and increased the propionate content in the rumen. There was no significant change in the α-diversity of the rumen microbiome, whereas the β-diversity of rumen microbes was enhanced. The effects of methane inhibitor supplementation showed dose-dependent significant differences, particularly in modulating rumen fermentation parameters and the structure of the microbial community. Furthermore, when the total VFA in the rumen were below 96.98 mmol/L, or the acetate concentration was below 61.26 mmol/L, or the acetate-to-propionate ratio was below 3.86, the suppression of methane production was most effective. The addition of methane inhibitors has a positive effect on the performance of ruminants, particularly by improving the structure of the rumen microbiota. Additionally, VFA have a certain threshold effect on methane production. This provides a reference for the application and selection of methane inhibitors.}, } @article {pmid41651362, year = {2026}, author = {Cahyo, HN and Niu, P and Pope, PB and Gimsa, U and Kuhla, B and Schwarm, A}, title = {Methane category, immune response, feed efficiency, and rumen microbial community in lactating dairy cows.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-26925}, pmid = {41651362}, issn = {1525-3198}, abstract = {This study aimed to assess relationships of enteric methane (CH4) yield (g/kg of DMI) with immune response, feed efficiency (ECM/DMI), and rumen microbiome in dairy cows, both in early and in late lactation. The DMI, BW, ECM yield, and CH4 emission were measured in respiration chambers in early (n = 20, 32 ± 7 DIM) and nonpregnant late lactating (n = 14, 359 ± 90 DIM) multiparous Holstein cows. The in vitro immune response was studied in response to (1) LPS using whole blood, and (2) phytohemagglutinin and concanavalin A using peripheral blood mononuclear cells. The DNA was extracted from rumen content samples (esophageal tubing) for 16S rRNA microbial analysis. Cows were divided retrospectively into an equal number of cows with low (LMY) and high (HMY) CH4 yield within each lactation group. In early lactation, CH4 yields in LMY (n = 10) and HMY cows (n = 10) were on average (±SD) 18.8 ± 1.4 and 23.5 ± 2.8 g/kg of DMI, respectively. In late lactation, CH4 yields in LMY (n = 7) and HMY cows (n = 7) were 20.8 ± 2.0 and 23.6 ± 1.7 g/kg of DMI, respectively. Statistical analysis was performed separately for each lactation group. In early lactation, we found that whole blood and isolated peripheral blood mononuclear cells from LMY compared with HMY animals were less responsive to stimulants in vitro. In addition, feed conversion efficiency was lower in LMY than HMY cows, and the relative abundance of the archaeal genus Methanospaera and the bacterial genus Marvinbryantia were higher. In late lactation, we observed no differences in immune response and feed conversion efficiency between LMY and HMY cows. Still, in LMY cows several bacterial genera including Prevotella 7, Ruminococcus gauvreauii group, and Shuttleworthia were enriched, whereas in HMY cows Methanobrevibacter, Veillonellaceae UCG-001, Succinivibrionaceae UCG-002, Rikenellaceae RC9, and CAG-352 were enriched. The results indicate that in early lactation the animals with low CH4 yield reach energy balance faster, at the expense of an inadequate immune response. Meanwhile, increased CH4 yield in early lactation may reflect higher rumen fermentation activity, fostering feed efficiency and energy availability for supporting immune function.}, } @article {pmid41651359, year = {2026}, author = {Xie, L and Rashid, MH and Dong, Q and Ricci, A and Opsomer, G and Pascottini, OB}, title = {Transcriptomic landscapes of the endometrium of dairy cows with clinical or subclinical endometritis.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-27374}, pmid = {41651359}, issn = {1525-3198}, abstract = {Subclinical (SCE) and clinical endometritis (CE) are distinct manifestations of reproductive tract inflammatory disease in dairy cows. The development of both conditions stems from postpartum dysregulation of the inflammatory response or a shift in the composition of the uterine microbiome. To gain further insight into the host responses associated with these distinct conditions, we aimed to identify changes in the endometrial transcriptomic landscape in healthy postpartum dairy cows compared with those diagnosed with SCE or CE. Twenty-four multiparous Holstein cows were evaluated for uterine health status at 35 or 36 d postpartum using vaginal discharge scoring (Metricheck) and endometrial cytology (cytobrush). Based on these evaluations, cows were classified into 3 groups: healthy (n = 12; clear or no vaginal discharge and ≤5% endometrial PMN), SCE (n = 6; clear or no vaginal discharge and >5% PMN), and CE (n = 6; mucopurulent or worse discharge and >5% PMN). Endometrial samples collected via cytobrush were stored at -80°C and total RNA was isolated; RNA sequencing was performed using an Illumina NextSeq 500 platform, generating 75 bp single-end reads. Differentially expressed genes (DEG) were identified using DESeq2 with a significance threshold of P < 0.05 and |fold change| > 2. Pathway enrichment analyses were performed using the OmicShare platform to identify enriched biological pathways among the DEG. A total of 250 DEG were identified between healthy and SCE cows, 1,291 between healthy and CE cows, and 829 between SCE and CE cows. In SCE (as compared with healthy) cows, TNF, IL-17, NOD-like receptor signaling, and cytokine-cytokine receptor interaction pathways were upregulated, whereas the FoxO signaling pathway was downregulated. In CE compared with healthy cows, upregulated DEG were enriched in IL-17, TNF, chemokine, NOD-like receptor, NF-kappa B, and toll-like receptor signaling pathways, whereas downregulated DEG were enriched in PI3K-AKT, MAPK, AMPK, Wnt, PPAR, and metabolic pathways. In CE compared with SCE, upregulated DEG were enriched in NOD-like receptor, IL-17, chemokine, B cell receptor, and cytokine-cytokine receptor interaction pathways, and downregulated DEG were enriched in the metabolic pathways, fatty acid metabolism, insulin signaling pathway, and adipocytokine signaling pathway. These findings underscore that CE and SCE conditions involve an inflammatory event but likely arise from different mechanisms. The enrichment of immune signaling pathways in CE reflects a classic infectious response, whereas the metabolic and regulatory pathway alterations in SCE suggest a dysregulated inflammatory state linked to impaired resolution mechanisms. These results highlight the need for tailored prevention and treatment strategies, such as modulating immune regulation in SCE and targeting bacterial dysbiosis and tissue damage in CE cases.}, } @article {pmid41651219, year = {2026}, author = {Remmani, NB and Harous, ZS and Alzaidy, RQ and Ahmednour, SA and Egusa, H and Soliman, SSM}, title = {The role of Fusobacterium nucleatum in the pathogenesis of endometriosis: A microbial and microenvironmental perspective.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {103030}, doi = {10.1016/j.anaerobe.2026.103030}, pmid = {41651219}, issn = {1095-8274}, abstract = {Endometriosis is a chronic, inflammatory gynecological condition characterized by the ectopic growth of endometrial-like tissue, with an unclear etiology and limited treatment efficacy. Recent studies implicate the oral and gut commensal bacterium Fusobacterium nucleatum in the pathogenesis of endometriosis, with uterine colonization reported in up to 64% of affected women. This review highlights the potential role of F. nucleatum in disease progression, particularly through its metabolic activation within the endometrial microenvironment. We explore the contribution of key bacterial metabolites (formate, lactate, and hydrogen sulfide), proteins (FadA and Fap2), and lipids (oxidized LDL, lysophosphatidylcholines, and saturated fatty acids) to inflammation, immune evasion, and epithelial-mesenchymal transition (EMT), features that overlap with tumor biology. The review also investigates the preferential triggers of F. nucleatum translocation into the endometrium. Host factors such as hypoxia, estrogen dominance, and retrograde menstruation appear to create a permissive microenvironment that potentially facilitates F. nucleatum colonization and virulence. While current therapeutic strategies largely neglect microbial involvement, emerging approaches including targeted antimicrobials, probiotics, immunomodulators, and microenvironmental modulation offer promising avenues for microbiome-informed endometriosis management. This narrative review also underscores the urgent need for longitudinal, in vivo studies to characterize the relationship between the oral, gut, and endometrial microbiomes and their impact on disease onset and progression.}, } @article {pmid41651145, year = {2026}, author = {Wang, Y and Sun, T and Li, L and Wang, M and Hu, B and Chen, Z and Hu, S}, title = {Synergistic effects of carbon dots and arbuscular mycorrhizal fungi on mitigating PFAS stress and reinforcing the purification performance of constructed wetlands.}, journal = {Environmental research}, volume = {295}, number = {}, pages = {123952}, doi = {10.1016/j.envres.2026.123952}, pmid = {41651145}, issn = {1096-0953}, abstract = {Per- and polyfluoroalkyl substances (PFASs) are highly persistent pollutants that disrupt plant-microbe interactions and compromise the performance of constructed wetlands (CWs). Here, we demonstrate a synergistic strategy combining carbon dots (CDs) and arbuscular mycorrhizal fungi (AMF) to alleviate PFAS-induced stress and enhance CW remediation efficiency. CD amendment markedly improved plant physiological performance under PFAS exposure, increasing photosynthetic efficiency and antioxidant enzyme activities, while simultaneously facilitating AMF colonization. Under high PFAS concentrations, the AMF-CDs treatment increased AMF colonization density by 33.3-100% relative to AMF alone, indicating substantial protection of symbiotic functionality. Metagenomic and community analyses revealed that the AMF- CDs combination reshaped the rhizosphere microbiome, enriching taxa such as Chloroflexi, Planctomycetes, and Campylobacterota that are functionally linked to nitrogen cycling, PFAS transformation, and metabolic resilience. These microbial shifts enhanced nutrient turnover and strengthened redox coupling processes critical for pollutant degradation. Consequently, the AMF-CDs system achieved pronounced improvements in water quality, with total phosphorus (TP), chemical oxygen demand (COD), total nitrogen (TN), and NH4[+]-N removal efficiencies elevated by 34.3-158.3% compared with untreated controls. This study provides the first evidence that CDs function as nano-bridging agents that stabilize the root-microbe interface, reinforce AMF-plant symbiosis, and drive microbial community specialization toward pollutant degradation. The AMF-CDs synergistic mechanism offers a sustainable and scalable nano-bio strategy for restoring PFAS-contaminated ecosystems and advancing next generation constructed wetland technologies.}, } @article {pmid41651131, year = {2026}, author = {Hantsoo, L and Ford, E and Friedman, ES and Hao, F and Patterson, AD and Bittinger, K and Wu, GD and Zemel, BS and Tanes, C}, title = {The impact of adverse childhood experiences on gut microbiota and markers of inflammation is mediated by obesity and depression.}, journal = {Brain, behavior, and immunity}, volume = {134}, number = {}, pages = {106479}, doi = {10.1016/j.bbi.2026.106479}, pmid = {41651131}, issn = {1090-2139}, abstract = {BACKGROUND: Adverse childhood experiences (ACEs) are associated with poor health outcomes in adulthood including obesity, psychiatric symptoms, and elevated levels of inflammatory markers. Our previous work found ACEs are associated with altered gut microbiota composition. In the present work, we examined ACE associations with gut microbiota and peripheral measures of inflammation in pregnant women with or without obesity, and explored potential modifying factors including diet and depressive symptoms.

METHODS: Female participants were recruited in the third trimester of pregnancy as part of a larger growth study of African-American infants. Participants were categorized as healthy weight (BMI < 25) or obese (BMI ≥ 30) based on their early pregnancy BMI. They completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and Center for Epidemiologic Studies Depression Scale (CES-D). Stool samples, blood, and dietary data were collected in the third trimester. Shotgun metagenomic sequencing was performed on DNA isolated from stool. Statistical models assessed relationships between gut microbiota and ACE. A false discovery rate (fdr) adjusted p-value q < 0.1 was considered statistically significant.

RESULTS: 107 women completed questionnaires and provided stool in the third trimester. ACEs were positively associated with BMI and depressive symptom severity but not with gut microbiota composition. Depressive symptoms were significantly negatively associated with abundance of gut Bifidobacterium longum (q = 0.02) and positively associated with Bacteroides thetaiotaomicron (q = 0.02). Path analysis revealed that ACEs predicted pre-pregnancy BMI which predicted elevated inflammatory markers. ACEs also predicted more severe depressive symptoms in pregnancy, which was associated with gut microbiome composition. Finally, ACEs interacted with dietary intake of sugar and whole grains to impact markers of inflammation, the gut microbiome, and enzymes produced by gut microbiota.

DISCUSSION: ACEs led to two risk pathways in pregnancy: one in which high pre-pregnancy BMI was linked with high levels of serum inflammatory markers during pregnancy, and the other in which greater depressive symptom severity was associated with alterations to the gut microbiome. Further, data suggested ACEs may influence the metabolic potential of the gut microbiome.}, } @article {pmid41651126, year = {2026}, author = {Tandon, D and Batgire, JS and Bharmal, Z and Karandikar, K and Patil, AD and Munne, K and Aranha, C and Bhor, VM}, title = {Mapping Cervical Microbiome Diversity and Inflammatory Milieu and Its Perturbation in Asymptomatic Bacterial Vaginosis and Candida Infections: Insights from a Community Clinic in Mumbai.}, journal = {Indian journal of medical microbiology}, volume = {}, number = {}, pages = {101067}, doi = {10.1016/j.ijmmb.2026.101067}, pmid = {41651126}, issn = {1998-3646}, abstract = {PURPOSE: The interplay between the local microbiome and inflammatory environment is crucial in modulating the immune response. This research addresses the paucity of studies in the Indian context by mapping the cervical microbiome and associated inflammatory milieu in 43 apparently healthy women and evaluating its perturbations with various asymptomatic vaginal infections.

METHODS: Cervical microbiome was mapped for forty three participants, aged 18-45, who were enrolled from a community clinic as a part of longitudinal contraceptive study from October 2021 to September 2023. Sociodemographic data, clinical history, and cervical and cervicovaginal lavage specimens were collected. Microbiome analysis involved nanopore sequencing of the entire 16S rRNA region amplicon, while cytokine assessment in cervicovaginal lavage specimens utilized multiplex immunoassays.

RESULTS: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Fusobacteria appeared as dominant phyla with 32.55% having asymptomatic bacterial vaginosis (BV),16.27% asymptomatic Candida, and 13.95% coinfections. The cervical microbiome was dominated by Lactobacillus iners (45.69%), followed by Lactobacillus helveticus (6.53%) and Lactobacillus reuteri (5.86%). Women with BV exhibited an increased abundance of Prevotella and Streptococcus, while Candida infections were associated with elevated Atopobium and Collinsella species. Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8) showed variable levels, with Lactobacillus positively correlating with the regulatory cytokine TNF-α in in Candida infections. In BV Lactobacillus species such as L. agilus, L.iners and L. salivarius showed positive correlation with TNF-α. Additionally, Lactobacillus manihotivoranswas negatively associated with IL-1β, while Lactobacillus brevis and Lactobacilluszeae showed negative correlations with IL-8 .

CONCLUSION: This study maps the cervical microbiome and cytokine profile of healthy Indian women and demonstrates that asymptomatic bacterial vaginosis and Candida infections induces variations, highlighting the complex host-microbe interactions that govern vaginal health.}, } @article {pmid41651116, year = {2026}, author = {Graber, LC and Moreau, CS}, title = {Insect-microbiome interactions in a changing world.}, journal = {Current opinion in insect science}, volume = {}, number = {}, pages = {101495}, doi = {10.1016/j.cois.2026.101495}, pmid = {41651116}, issn = {2214-5753}, abstract = {Humans have greatly altered the Earth and its environments through activities such as agriculture, industry, and urbanization. In recent years, the impact of anthropogenic global change on insect populations has become a topic of increased interest, with much written for both scientists and the public on how insect populations are in decline due to climate change, land use change, and exposure to chemical pollution. Additionally, many insects host microbial symbionts, which some insect species rely on for a wide range of physiological needs such as nutrient acquisition, detoxifying diet substrate, or reproduction. This review summarizes recent experimental and observational studies on the effects of anthropogenic global change on insect microbial symbioses from multiple ecosystems and continents, with a focus on the impacts of climate change and habitat loss and degradation. Each of these modes of change has been demonstrated to affect the composition of insect microbial communities, with reduction of species diversity within microbial communities (alpha diversity) as the most common result. Results of experimental study on heat stress response in bacterial symbionts suggest that warming temperatures often associated with climate change may have direct impacts on symbiont mortality, as symbionts tend to be more sensitive to thermal stress than free-living bacteria. Habitat loss and degradation impact insect microbial symbionts via the changed microbiomes of host food and environmental substrate. Chemical pollution associated with habitat degradation has altered the microbiomes of insects, though some insects may be able to detoxify chemical pollutants with symbiotic microbial taxa. While early research has shown that human-induced climate change can have negative impacts on insect symbionts, there is still much to learn about how the changing world will impact insect microbiomes and how this in turn will impact entire ecosystems at a global scale.}, } @article {pmid41615476, year = {2026}, author = {Long, J and Liao, X and Han, K and Chen, J and Tang, Z and Wang, W and Wang, X and Chi, Q and Zhang, X and Zhang, H}, title = {Microbiota-gut-brain axis and neuroendocrine pathways underlie divergent mechanisms of intermittent and continuous theta-burst stimulation in autism spectrum disorder.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {83}, number = {1}, pages = {98}, pmid = {41615476}, issn = {1420-9071}, support = {CDPF2023KF00001//China Disabled Persons' Federation/ ; }, abstract = {OBJECTIVE: Theta-burst stimulation, including intermittent (iTBS) and continuous (cTBS) protocols, is a promising neuromodulatory intervention for autism spectrum disorder (ASD). This study aims to elucidate the therapeutic mechanisms of iTBS and cTBS for ASD.

METHODS: Prenatal valproic acid-induced ASD rats were established and were randomized into VPA, VPA + iTBS, and VPA + cTBS groups, with a saline group as control. Core and comorbid ASD behaviors in rats were assessed. Multi-omics analyses included 16 S rRNA sequencing of cecal contents, non-targeted fecal metabolomics, and prefrontal cortex transcriptomics. Key pathways were validated via Western blot, ELISA, and immunofluorescence. Integrative analyses correlated multi-omics data with neuroendocrine findings.

RESULTS: Behavioral assessments demonstrated that both iTBS and cTBS significantly ameliorated social deficits and repetitive behaviors in VPA-exposed rats. However, protocol-specific effects on comorbidities were observed: cTBS, but not iTBS, effectively alleviated anxiety-like behaviors, whereas iTBS, but not cTBS, significantly improved learning and memory. The multi-omics approach demonstrated that iTBS primarily modulated inflammatory immune responses and energy metabolism, while cTBS predominantly regulated oxidative stress, lipid metabolism, and nucleotide metabolism. Both interventions suppressed the hyperactivated PI3K/AKT/mTOR signaling pathway, an effect potentially linked to the normalization of hypothalamic-pituitary axis function. Furthermore, we identified a potential interplay between the GH/IGF-1 axis and the gut microbiome in ASD, which was differentially modulated by iTBS and cTBS.

CONCLUSION: iTBS modulated inflammatory-immune responses and energy metabolism, while cTBS regulated oxidative stress, lipid metabolism, and nucleotide metabolism. The inhibition of the central GH/PI3K/AKT/mTOR pathway by both protocols may involve their specific regulation of distinct gut microbiota communities.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-026-06096-2.}, } @article {pmid41652781, year = {2023}, author = {Wang, L and Fang, H and Xue, Z and De, J and Guo, X}, title = {Agrochemical exposure-induced seed microbiome response in barley.}, journal = {Crop health}, volume = {1}, number = {1}, pages = {16}, pmid = {41652781}, issn = {2948-1945}, support = {2021YFE0113700//Key Technologies Research and Development Program/ ; }, abstract = {The seed microbiota has great potential for enhancing agricultural practices and promoting sustainable plant growth. However, excessive and improper application of agrochemicals may have unforeseen effects on the seed microbiota, posing potential risks to crop health and even ecological integrity. Despite this, the impact of agrochemicals on seed microbiota in domesticated crops remains largely unexplored. Here, we aimed to analyze the effects of four common agrochemicals on the seed microbiome of highland barley in Tibet using high-throughput sequencing. Community diversity analysis suggests that the differences in seed microbial groups under different agrochemical treatments are not significant. Interestingly, we found that the key microbial taxa in barley seeds responded distinctly to specific agrochemicals. Lactobacillus spp. were identified as positive biomarkers in response to tebuconazole and lambda-cyhalothrin due to an increase in relative abundance as a probiotic. Conversely, Leuconostoc and Helicobacter were recognized as positive biomarkers upon exposure to pydiflumetofen, attributed to a notable reduction in the abundance of pathogens. Collectively, our findings have revealed the unique responsiveness of seed microbial taxa to agrochemical exposure. Further mechanistic insights into the responsiveness of these microbial biomarkers to agrochemicals may establish a foundational framework for microbiome-targeted verification of agrochemical application, ensuring food safety throughout the cultivation of Tibetan barley.}, } @article {pmid41651111, year = {2026}, author = {Fujii, T and Harada, N and Katami, H and Tanaka, A and Shimono, R}, title = {Oral Antibiotic Exposure and the Risk of Overweight and Obesity in Children with Vesicoureteral Reflux.}, journal = {Journal of pediatric surgery}, volume = {}, number = {}, pages = {163003}, doi = {10.1016/j.jpedsurg.2026.163003}, pmid = {41651111}, issn = {1531-5037}, abstract = {BACKGROUND: Continuous antibiotic prophylaxis (CAP) is widely used in children with vesicoureteral reflux (VUR) to prevent recurrent urinary tract infections, but its long-term metabolic effects are uncertain. We evaluated whether oral antibiotic exposure is associated with overweight and obesity in young children with VUR.

METHODS: Using the TriNetX Research Network, we conducted a retrospective cohort study of children aged <5 years diagnosed with VUR between 2005 and 2025. Patients were classified as antibiotic-exposed or unexposed based on prescription patterns, and propensity score matching balanced baseline covariates. Overweight and obesity were defined using body mass index (BMI) percentiles and diagnosis codes. We performed U.S.-only sensitivity and age-stratified analyses (<1 year; 1-4 years) and calculated the number needed to harm (NNH).

RESULTS: After matching, 2,665 patients were included per group. In the primary cohort aged <5 years, BMI percentile-defined overweight and obesity occurred in 60 (2.3%) of antibiotic-exposed patients and 21 (0.8%) of unexposed patients (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.97-5.34; log-rank p < 0.001). Results were similar using diagnosis code-based definitions (1.3% vs. 0.6%; HR, 2.30; 95% CI, 1.27-4.17; log-rank p = 0.005). Associations persisted in U.S.-only analyses and were stronger in children aged <1 year. The NNH for BMI-defined overweight/obesity was 69.

CONCLUSIONS: Early oral antibiotic exposure in children with VUR was significantly associated with increased risk of overweight and obesity. However, given the low absolute number of events, these findings should be interpreted cautiously and weighed against the potential benefits of CAP.}, } @article {pmid41651105, year = {2026}, author = {Muro, BBD and Carnevale, RF and Monteiro, MS and Leal, DF and Poor, AP and Pereira, FA and de Azevedo Ruiz, VL and Garbossa, CAP}, title = {Soluble and insoluble fiber blend improves farrowing performance and colostral immunoglobulin concentration in sows without altering fecal microbiota.}, journal = {Veterinary journal (London, England : 1997)}, volume = {316}, number = {}, pages = {106574}, doi = {10.1016/j.tvjl.2026.106574}, pmid = {41651105}, issn = {1532-2971}, abstract = {The aim of this trial was to provide a fibrous supplement in the transition diet of sows to decrease sows' constipation, improve farrowing kinetics, increase colostrum antibodies, and modulate sows' and piglets' microbiota. At day 90 of pregnancy sows were fed a standard gestation diet until farrowing (CON, n = 101) or a standard gestation diet added of 400 g of a fibrous supplement (40 % wheat bran, 25 % lignocellulose, 25 % citrus pulp, and 10 % guar gum) (FIB, n = 101). After farrowing, sows were fed a standard lactation diet, and FIB sows were fed 400 g of the fibrous supplement on top of the feed for five days. Sows from FIB had a lower (p < 0.01) incidence of constipation pre-farrowing and on the day of farrowing. Sows from FIB had a 23 min shorter (p = 0.01) farrowing duration compared to CON-sows. Sows from CON had a higher (p < 0.01) feed intake on days two and three post-farrowing. Both IgG and IgA concentrations were higher in the FIB-supplemented sows (p = 0.01). The fecal microbiome of sows and piglets was similar (p > 0.43) between groups. During the first week of life, piglets born from FIB-sows had decreased (p = 0.04) diarrhea incidence. In conclusion, the benefits of the fibrous supplement were evident in peripartal sows by decreasing farrowing duration and constipation and by increasing the concentration of immunoglobulins in the colostrum. For newborn piglets, the fibrous supplement fed to the sows did not significantly alter the fecal microbiome of sows and their litters. Nevertheless, benefits were observed in their resistance to neonatal diarrhea. Thus, using a fiber supplement in transition diets in farms may ease the management in the farrowing room and improve early-life robustness in piglets, which may decrease medication demands during the first week, contributing to more efficient neonatal care and better overall litter performance.}, } @article {pmid41650974, year = {2026}, author = {Ghaddar, B and Blaser, MJ and De, S}, title = {Reliable detection of Host-Microbe Signatures in cancer using PRISM.}, journal = {Cancer cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ccell.2026.01.007}, pmid = {41650974}, issn = {1878-3686}, abstract = {Recent controversy in the cancer microbiome field highlights the need for more reliable microbial detection from human genomic data. Here, we develop PRISM, an efficient computational framework for precise microorganism identification and decontamination from low-biomass sequencing data. PRISM achieves robust performance when benchmarked on 230 independent datasets with known true-positive and contaminant taxa. We then use PRISM to profile 25 cancer types from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium. We identify consistent microbial signatures in gastrointestinal tract, head-and-neck, and urogenital tract tumors, and sparse signal elsewhere. In pancreatic cancer, we associate microbial detection with altered host protein glycosylation pathways and greater smoking exposure. Lastly, we consider the impact of sequencing approaches on positive and negative data interpretation. Overall, PRISM improves the reliability of microbial profiling and allows leveraging of existing human genomic data for the concurrent detection of host-microbial signatures with potential molecular and clinical significance.}, } @article {pmid41650849, year = {2026}, author = {Seto-Tetsuo, F and Katase, N and Sasaki, Y and Yukitake, H and Naito, M}, title = {Supernatants from DNase-deficient Prevotella intermedia strains enhance oral squamous cell carcinoma cell migration and invasion by activating inflammatory and epithelial-mesenchymal transition pathways.}, journal = {Biochemical and biophysical research communications}, volume = {805}, number = {}, pages = {153304}, doi = {10.1016/j.bbrc.2026.153304}, pmid = {41650849}, issn = {1090-2104}, abstract = {INTRODUCTIONS: Oral squamous cell carcinoma (OSCC) has been increasingly associated with dysbiosis of the oral microbiome. Among oral pathogens, Prevotella intermedia (P. intermedia) is frequently enriched in patients with OSCC; however, the role of its virulence factors-particularly its deoxyribonuclease (DNase) activity-remains poorly understood.

METHODS: We compared the effects of culture supernatants from wild-type P. intermedia OMA14 and DNase-deficient mutant strains (nucA, nucD and nucA nucD) on the migration and invasion of the OSCC cell line SAS, using wound healing and Matrigel invasion assays. Transcriptomic profiling of SAS cells exposed to bacterial supernatants was performed using RNA sequencing (RNA-seq), followed by differential gene expression and pathway enrichment analyses.

RESULTS: Supernatants from the nucA nucD mutant strain significantly enhanced SAS cells migration and invasion compared with those from the OMA14 strain. RNA-seq revealed marked transcriptomic reprogramming, including upregulation of genes related to extracellular matrix degradation, epithelial-mesenchymal transition (EMT), and inflammatory signaling. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses confirmed the enrichment of EMT, cytokine signaling, and tumor-promoting pathways.

CONCLUSIONS: Our findings demonstrate a dual role of bacterial DNase activity in SAS cell. Although DNases contribute to immune evasion via neutrophil extracellular trap degradation, their absence enhances tumor invasion by promoting proinflammatory and EMT-related transcriptional programs. These results highlight the complex interplay between microbial nucleases, extracellular DNA, and host signaling, providing novel insights into the contribution of the oral microbiome to OSCC pathogenesis.}, } @article {pmid41650638, year = {2026}, author = {Caputi, V}, title = {Functional role of the enteric nervous system in poultry intestinal health and production.}, journal = {Poultry science}, volume = {105}, number = {4}, pages = {106563}, doi = {10.1016/j.psj.2026.106563}, pmid = {41650638}, issn = {1525-3171}, abstract = {Like mammals, the avian intestinal epithelium is innervated by three neuronal pathways: vagal and sympathetic terminals, which originate from ganglia outside the gut wall and send information to the brain to modulate visceral sensitivity, appetite, and gut homeostasis; and the enteric nervous system (ENS), a complex network embedded within the gut wall that functions independently from the brain. The ENS coordinates essential GI physiological functions, such as intestinal motility, peristalsis, digestion, and absorption of nutrients and water. Recent studies conducted in mammals have shown that enteric neurons can orchestrate the intestinal immune response and reduce Salmonella colonization in the GI tract. However, such neuronal-mediates defense mechanisms have not yet been explored in the poultry gut. This review will provide a comprehensive overview of the avian ENS, highlighting similarities and differences with the well-known mammalian ENS. Additionally, particular focus will be given on ENS-dependent neuroimmune interactions that could reveal novel biomolecular mechanisms to mediate health, disease susceptibility, behavior, and other aspects as affected by the chicken GI tract.}, } @article {pmid41650276, year = {2026}, author = {Chen, L and Camargo, AP and Qin, Y and Koonin, EV and Wang, H and Zou, Y and Duan, Y and Li, H}, title = {Animal-associated jumbo phages as widespread and active modulators of gut microbiome ecology and metabolism.}, journal = {Science advances}, volume = {12}, number = {6}, pages = {eaeb6265}, pmid = {41650276}, issn = {2375-2548}, mesh = {*Gastrointestinal Microbiome ; *Bacteriophages/genetics/physiology ; Animals ; Humans ; Metagenome ; Phylogeny ; Genome, Viral ; Bacteroides/virology ; }, abstract = {Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (jumbo gut) phages with genomes of 360 to 402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola. Although three of the four major groups of Jug phages shared >90% genome-wide sequence identity, their large terminase subunits exhibited only 38 to 57% identity, suggesting horizontal acquisition from other phages. Over 1500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology.}, } @article {pmid41650184, year = {2026}, author = {Hamidabad, NM and Manzato, M and Toya, T and Lerman, LO and Lerman, A}, title = {Gut microbiome compositional clusters in association with cardiovascular risk: An observational cohort study.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0341111}, pmid = {41650184}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; Middle Aged ; *Gastrointestinal Microbiome/genetics ; Aged ; Prospective Studies ; *Cardiovascular Diseases/microbiology/epidemiology ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Cluster Analysis ; }, abstract = {AIMS: The gut microbiome (GM) is increasingly recognized for its role in atherosclerosis development. However, its potential as a biomarker for risk-stratification in patients with atherosclerotic cardiovascular (CV) comorbidities remains under-explored. This study aimed to identify distinct GM clusters associated with elevated CV risk.

METHODS: In this prospective observational cohort, patients with coronary artery disease, hypertension, hyperlipidemia, or diabetes mellitus referring to Mayo Clinic from 2013 to 2018 were enrolled. Bacterial DNA was analyzed in the V3-V5 region of 16S rDNA. Beta-diversity was plotted using Principal Coordinates Analysis. Unsupervised hierarchical clustering of the GM classified participants into two clusters. Cox regression evaluated the association between clusters and Major Adverse Cardiac Events (MACE), defined as a composite of cardiac events, heart failure, and all-cause mortality. Permutational Multivariate Analysis of Variance identified clinical factors contributing to cluster assignment. Linear Discriminant analysis identified GM taxa with differential abundance among clusters and their effect sizes.

RESULTS: Among 211 participants (median age 60 [IQR: 50-70] years; 57.3% male), two distinct GM profiles emerged (Cluster H: N = 104; Cluster L: N = 107, P < 0.001). Cluster L participants were younger (P < 0.001), more likely female (P = 0.009), and had healthier CV profiles, including lower BMI (P = 0.007), hypertension (P = 0.010), hyperlipidemia (P = 0.005), and lower coronary artery disease prevalence (P = 0.003). Over a median follow-up of 7.4 years, Cluster L had a significantly lower incidence of MACE compared to Cluster H (HR = 0.48, 95% CI: 0.26-0.91, P = 0.024). Cluster L had higher operational taxonomic units (P < 0.001) and lower Bacillota-to-Bacteroidetes ratio (P < 0.001) compared to Cluster H. The predominant taxa in Cluster L included Bacteroides, Alistipes, and Parabacteroides, whereas Blautia, Agathobacter, and Clostridium sensu stricto-1 were more abundant in Cluster H.

CONCLUSION: Distinct GM profiles are associated with varying CV risk, highlighting the potential of unsupervised GM profiling as a novel tool for risk stratification and individualized therapy.}, } @article {pmid41649942, year = {2026}, author = {Haines, RR and Basuki, A and Tenaglia, VP and Zar, HJ and Nicol, MP and Kar Bahal, R}, title = {Corynebacterium drakensteinense sp. nov., isolated from the nasopharynx of a healthy South African infant.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {76}, number = {2}, pages = {}, pmid = {41649942}, issn = {1466-5034}, mesh = {*Corynebacterium/classification/isolation & purification/genetics ; *Nasopharynx/microbiology ; Humans ; *Phylogeny ; South Africa ; RNA, Ribosomal, 16S/genetics ; Infant ; DNA, Bacterial/genetics ; Bacterial Typing Techniques ; Genome, Bacterial ; Whole Genome Sequencing ; Sequence Analysis, DNA ; Base Composition ; Nucleic Acid Hybridization ; }, abstract = {Emerging evidence supports the role of the nasopharyngeal microbiome in respiratory health, including association with conditions such as asthma and respiratory tract infections. One dominant commensal genus is Corynebacterium, members of which are commonly present in the nasopharynx of infants. These commensal Corynebacterium spp. have been reported to correlate with respiratory health. In this paper, we present isolate MNWGS58[T] isolated from the nasopharynx of a South African infant. Genomic analysis of the whole-genome sequence of MNWGS58[T] revealed that it is phylogenetically closely related to other Corynebacterium spp. found in the nasopharynx, Corynebacterium propinquum [85% average nucleotide identity (ANI)] and Corynebacterium pseudodiphtheriticum (84% ANI). Bacterial identification using matrix-assisted laser desorption/ionization time-of-flight MS identified MNWGS58[T] as C. pseudodiphtheriticum. The API Coryne assay identified the novel isolate as C. propinquum, and the VITEK 2 ANC assay identified the novel isolate as Corynebacterium otitidis. Both genomic analyses and phenotypic analyses show striking similarities to C. propinquum and C. pseudodiphtheriticum. The cell wall is consistent with closely related Corynebacterium spp., albeit with a higher C17:0 content. The genome is 2.48Mbp with a G+C content of 56.9 mol%. Digital DNA-DNA hybridization values for MNWGS58[T] were low when compared to C. pseudodiphtheriticum MNWGS56 and C. propinquum MNWGS51 (27.4 and 28.4%, respectively). Although there are phenotypic similarities, 85% ANI with the closest Corynebacterium spp. strongly supports the classification of a novel species of Corynebacterium, for which we propose the name Corynebacterium drakensteinense sp. nov., with the type strain MNWGS58[T] (=TSD-445[T]=NCTC 15058[T]). It will be important to elucidate the role of this novel species of Corynebacterium in the human nasopharynx and identify additional niches for this species in future studies.}, } @article {pmid41649710, year = {2025}, author = {Cheng, R and Ke, T and Gui, F and Li, J and Zhang, X and Vílchez, JI and Matsumoto, H}, title = {drSMALL: Database for disease resistance-shaping small molecules derived from the plant microbiome.}, journal = {Crop health}, volume = {3}, number = {1}, pages = {2}, pmid = {41649710}, issn = {2948-1945}, support = {32122074//National Natural Science Foundation of China/ ; 32302291//National Natural Science Foundation of China/ ; U21A20219//National Natural Science Foundation of China/ ; 2024SZRZDC130001//Natural Science Foundation of Hangzhou/ ; 2023YFD1400901//National Key R&D Program of China/ ; 226-2024-00070//the Fundamental Research Funds for the Central Universities/ ; 2020ZL008//Strategic Research on 'Plant Microbiome and Agroecosystem Health'(Cao Guangbiao High Science and Technology Foundation)/ ; }, abstract = {Recent evidence highlights the potential of the plant microbiota to increase host plant disease resistance through the production of bioactive small molecules. However, the absence of comprehensive platforms for rapid access to this information hampers progress in the field. To address this gap, we developed the Disease Resistance-Shaping Small Molecules Database (drSMALL), a freely accessible and continuously updated resource that compiles profiles of microbial small molecules, which were experimentally evidenced to be associated with host disease resistance. drSMALL interlinks detailed information on microbial species, the small molecules they produce, host plants, and targeted pathogens, facilitating streamlined access to essential data. This initiative aims to advance the understanding of small molecules in disease resistance, filling a critical gap in data accessibility while fostering deeper exploration of sustainable agricultural practices. By leveraging the natural capabilities of plant microbiomes, drSMALL seeks to support innovative strategies for enhancing crop health and resilience against diseases.}, } @article {pmid41649672, year = {2025}, author = {Wang, Z and Yin, J and Tsuda, K}, title = {Harnessing Aspergillus and host M genes for sustainable phyllosphere microbiome engineering.}, journal = {Crop health}, volume = {3}, number = {1}, pages = {6}, pmid = {41649672}, issn = {2948-1945}, support = {2022YFA1304400//National Key R&D Program of China/ ; 32250710139//National Natural Science Foundation of China/ ; 32170298//National Natural Science Foundation of China/ ; GZC20230915//Postdoctoral Fellowship Program of CPSF/ ; 590323043//Hubei postdoctoral fund project/ ; }, } @article {pmid41649661, year = {2025}, author = {Romão, IR and do Carmo Gomes, J and Silva, D and Vilchez, JI}, title = {The seed microbiota from an application perspective: an underexplored frontier in plant-microbe interactions.}, journal = {Crop health}, volume = {3}, number = {1}, pages = {12}, pmid = {41649661}, issn = {2948-1945}, support = {UIDB/04551/2020//Fundação para a Ciência e a Tecnologia/ ; UIDP/04551/2020//Fundação para a Ciência e a Tecnologia/ ; LA/P/0087/2020//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {Seed-associated microbiota represent a critical yet underexplored frontier in plant-microbe interactions, offering unique insights into plant health, resilience, and development. Unlike the soil or rhizosphere microbiome, the seed microbiota is closely tied to plant reproduction, facilitating both vertical and horizontal transmission of microbes. These microbial communities influence key plant processes, including germination, stress tolerance, nutrient acquisition, and pathogen resistance, providing plants with a pre-assembled microbial consortium tailored to their needs. Despite recent advances, significant gaps remain in understanding how seed-associated microbes are acquired, their ecological dynamics, and their functional roles. High-throughput sequencing, metagenomics, and spatial imaging techniques have revealed the diversity and complexity of the seed microbiota, emphasizing their potential for agricultural innovation. This research highlights the importance of these communities in shaping plant resilience and productivity, yet questions about their ecological and evolutionary significance persist. The present review synthesizes current knowledge on the composition, inheritance mechanisms, and functional roles of the seed microbiota. It also explores strategies to harness these microbes for sustainable agriculture, including microbiome engineering and breeding for microbial compatibility. By addressing these gaps, seed microbiota research could revolutionize sustainable agriculture, enhancing crop resilience and reducing reliance on chemical inputs.}, } @article {pmid41519703, year = {2026}, author = {Lin, J and Ling, Z and Fan, W and Cai, Q and Yang, J and Tao, M and Guo, H and Wang, Y and Yan, X and Yang, C}, title = {Establishment of a microbial abundance prognostic model for colorectal cancer.}, journal = {BMC cancer}, volume = {26}, number = {1}, pages = {197}, pmid = {41519703}, issn = {1471-2407}, support = {(No. 2024M762749)//China Postdoctoral Science Foundation/ ; (No. SBK2023022610)//Natural Science Foundation of Jiangsu Province/ ; (No. MS2024140)//program of Jiangsu Traditional Chinese Medicine Science and Technology Development/ ; (No. 2023-2-01, 2024-2-08 and 2025-2-08)//Yangzhou City Basic Research Program (Joint Special Project) - Health and Wellness Category/ ; (No.81902422 82303937)//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Previous studies have demonstrated a close association between gut microbiota and the onset and progression of colorectal cancer (CRC). However, the prognostic and therapeutic value of microbiota in CRC remains controversial. This study integrates multiomics approaches to investigate the prognostic and therapeutic implications of microbiota in CRC.

METHODS: A CRC microbial abundance prognostic model (MAPM) was constructed utilizing bioinformatics approaches to evaluate its prognostic value. The relationship between MAPM and the clinical characteristics of CRC, as well as the immune microenvironment, was analyzed. Furthermore, key prognostic genes associated with the MAPM were identified and validated in vitro and in vivo assays.

RESULTS: The MAPM comprised 12 microbes and effectively stratified the prognosis of CRC patients. The risk score of this model exhibits a close association with the immune infiltration of CRC. Remarkably, HSF4, identified as a key gene from the MAPM, is found to be overexpressed in the tumor tissues, and its high expression independently predicts poor prognosis in CRC patients. Knockdown of HSF4 significantly inhibits the proliferation, colony formation, migration, and invasion of CRC cells in vitro, as well as the growth of xenografts in nude mice.

CONCLUSION: A MAPM is established to predict the prognosis of CRC patients, further highlighting the potential of detecting the microbiome in clinical practice. Moreover, HSF4, as a prognostic gene from the MAPM, is a promising drug target for CRC treatment.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-025-15524-8.}, } @article {pmid41501621, year = {2026}, author = {Ferriol-González, C and Hernanz-Grimalt, A and Valdivia, C and García-Cobos, S and Heredia, A and García-Hernández, J and Andrés, A and Domingo-Calap, P}, title = {Effects of phage-based treatments against an OXA-48-producing Klebsiella pneumoniae isolate in simulated human gut microbiomes.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {102}, pmid = {41501621}, issn = {1471-2180}, support = {UV-INV_PREDOC-1913324//Universitat de València/ ; PREP2023-001677//Ministerio de Ciencia, Innovación y Universidades/ ; PID2023-150309OB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; CIACIF/2023/126//Generalitat Valenciana/ ; }, abstract = {BACKGROUND: Carbapenem-resistant K. pneumoniae (CRKP) is one of the most prevalent antimicrobial-resistant pathogens, primarily causing nosocomial infections. These bacteria often colonize the gut microbiota, and their carriage is an important risk factor for later infection. Phages are an emerging alternative against antimicrobial-resistant bacteria causing infections, but their effect on the microbiota is still poorly understood.

RESULTS: Here, we simulated the colonization of the gut microbiota of three healthy adults by an OXA-48-producing CRKP isolate in a dynamic in vitro colonic simulator (SHIME®) and evaluated the effect of phage treatments in reducing CRKP load. Phage growth dynamics in the system seemed to be dependent on phage host range, rather than the donor’s microbiota composition. Additionally, phage treatment significantly reduced K. pneumoniae load and blaOXA-48 copy number, highlighting its potential for controlling the CRKP population. Importantly, phage treatment did not affect the microbiota diversity of any of the three donors, suggesting it has a minimal impact on the microbiome.

CONCLUSIONS: Our results support the potential of phage-based strategies for the biocontrol of CRKP in the gut microbiota, reducing the abundance of this pathogen in its main reservoirs and preventing nosocomial CRKP infections.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04653-6.}, } @article {pmid41649413, year = {2026}, author = {Jo, S and Lee, HG and Nam, DH and Park, C}, title = {Use of metabarcoding detects the rapid onset of cultivation bias in the culture-based profiling of marine sediment bacterial communities.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovag020}, pmid = {41649413}, issn = {1472-765X}, abstract = {When cultivation-based microbiology is used to isolate strains from environmental samples, the cultured populations may not represent ecologically relevant taxa in the source community. To address this, we employed pre-cultivation metabarcoding to establish a baseline community profile and detect cultivation bias. Using time-resolved cultivation of marine sediment bacteria, we demonstrated the need for initial community characterization. Sediment-derived microbiomes were cultured in Marine Broth 2216 and analyzed using 16S rRNA gene metabarcoding at 0, 6, 12, 18, and 24 h. A rapid 10-fold reduction in alpha diversity was observed within the 6 h (from 1029 amplicon sequence variants to 34-106), with the genus Vibrio reaching near-complete dominance (>95%) from 18 to 24 h, while environmentally dominant taxa such as Acinetobacter were quickly excluded. This dramatic shift illustrates that, without baseline characterization, cultivation-induced artifacts cannot be clearly distinguished from ecologically meaningful patterns. Fast-growing generalists can quickly outcompete ecologically significant taxa, distorting isolation outcomes and hindering the recovery of functionally important microorganisms. We show that metabarcoding at 0 h can identify cultivation biases, help interpret isolation results, and suggest targeted strategies for recovering ecologically relevant taxa. This integrated approach facilitates more accurate recovery and analysis of functionally significant microbial diversity.}, } @article {pmid41649278, year = {2026}, author = {Selleri, E and Tarracchini, C and Petraro, S and Mancabelli, L and Milani, C and Turroni, F and Shao, Y and Browne, HP and Lawley, TD and van Sinderen, D and Ventura, M and Lugli, GA}, title = {Assessment of genome evolution in Bifidobacterium adolescentis indicates genetic adaptation to the human gut.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0117325}, doi = {10.1128/msystems.01173-25}, pmid = {41649278}, issn = {2379-5077}, abstract = {UNLABELLED: Bifidobacterium adolescentis is one of the most frequently encountered bifidobacterial species present in the adult human gut microbiota, with a prevalence of approximately 60%. Despite its high prevalence, B. adolescentis has not been extensively studied and characterized, and our understanding of its physiological traits, genetic diversity, and potential interactions with other members of the human gut microbiota or with its host is therefore fragmentary. In the current study, a data set comprising 1,682 B. adolescentis genomes was compiled by combining publicly available data and metagenome assemblies from 131 projects to uncover the unique genetic characteristics of this species. A pangenome analysis of B. adolescentis identified 203 clusters of orthologous genes absent from the other five human-associated Bifidobacterium species, six of which were in silico predicted to encode functions unique to this taxon. Furthermore, 2,597 genes were predicted to have been acquired by horizontal gene transfer, including genes encoding extracellular structures involved in interaction with the host and other microorganisms, and phage defense mechanisms against bacteriophages. Detailed phylogenetic analysis revealed seven clusters within the B. adolescentis species, each partially associated with the origin of strain isolation, suggesting phylogenetic differentiation shaped by geographical strain origin. Moreover, a large-scale metagenomic analysis of over 10,000 human gut metagenomes from healthy adults revealed that B. adolescentis co-occurs with 36 putative beneficial commensals and butyrate-producing taxa, highlighting its role as a key bifidobacterial species involved in microbial networking within the adult human gut microbiota.

IMPORTANCE: To comprehensively explore the biodiversity within a microbial species, the reconstruction of a substantial number of genomes is essential. In this study, we successfully uncovered the genetic diversity of Bifidobacterium adolescentis by retrieving a large number of genomes from human gut metagenomic samples. The complete overview of the B. adolescentis pangenome enabled us to investigate the genetic features that distinguish this gut commensal from other bifidobacterial species residing in the human intestinal microbiota.}, } @article {pmid41649265, year = {2026}, author = {Gu, C and Han, M and Chen, X and Liu, Y and Jian, G and Qin, Q and Yin, H and Zhou, L and Cai, D and Zhang, L and Wang, D and Li, P}, title = {Gut microbiota and metabolomic changes across preterm stages: potential associations with bronchopulmonary dysplasia.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0274025}, doi = {10.1128/spectrum.02740-25}, pmid = {41649265}, issn = {2165-0497}, abstract = {UNLABELLED: The coordinated post-natal development of the gut microbiome and metabolome is essential for preterm infant health, yet its disruption is increasingly linked to adverse outcomes such as bronchopulmonary dysplasia (BPD). In this study, we performed an integrated multiomics analysis of fecal samples collected from preterm infants to characterize temporal changes in gut microbial and metabolic profiles and explore their potential associations with BPD development. This study observed a distinct trajectory of the phylum Bacteroidota as a hallmark of normal gut maturation, with its abundance progressively declining across non-BPD infants. In contrast, infants who later developed BPD exhibited early depletion followed by irregular enrichment of Bacteroidota. Correlation analysis revealed that Streptococcus abundance was positively associated with elevated cysteic acid, a metabolite linked to oxidative stress. Together, these findings suggest that altered Bacteroidota succession and Streptococcus-associated oxidative imbalance may reflect early microbial-metabolic perturbations in infants at risk of BPD. This work provides preliminary, hypothesis-generating insights into gut-associated signatures potentially relevant to BPD pathogenesis.

IMPORTANCE: Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity in preterm infants, yet early biomarkers and targeted preventive strategies are limited. By integrating microbiome and metabolome data from a pilot cohort, this study identified patterns of disrupted Bacteroidota succession and Streptococcus-associated oxidative stress that are associated with BPD risk. These findings highlight the gut as a potential extrapulmonary contributor to disease susceptibility and support early risk assessment and guide future microbiome-targeted interventions in preterm infants.}, } @article {pmid41648806, year = {2026}, author = {Lebeuf-Taylor, E and Cottenie, K}, title = {Marginal link between sociality and gut microbiome in disparate mammalian hosts.}, journal = {FEMS microbes}, volume = {7}, number = {}, pages = {xtag004}, pmid = {41648806}, issn = {2633-6685}, abstract = {Studies in model organisms and wild populations have uncovered manifold links between the gut microbiome and sociality, which, considering the adaptiveness of social behaviour, suggest a potentially generalized coevolution between microbiomes and social behaviour. Here, we leverage phylogenetically and ecologically diverse data from the Earth Microbiome Project to test the generality of the links between sociality and the gut microbiome in wild animals. We find evidence of a small but significant link between sociality and microbiome beta diversity, but not alpha diversity, in mammalian taxa, potentially due to socially mediated microbial transmission. Our work highlights the value of leveraging large-scale multi-study datasets to test fundamental questions about the role of sociality in host-microbiome coevolution.}, } @article {pmid41648774, year = {2025}, author = {Freidl, J and Huber, D and Bischof, M and Zechner, R and Pichler, C and Fickel, L and Fischer, V and Weingartner, H and Hausmann, B and Pjevac, P and Kiefel, M and Prinz, T and Gruber, G and Hartl, A}, title = {From urban to alpine: environmental microbial transfer in urban adults - the ALM Study.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1747693}, pmid = {41648774}, issn = {2296-2565}, mesh = {Humans ; Adult ; Male ; Female ; Prospective Studies ; *Microbiota ; Austria ; Feasibility Studies ; *Urban Population/statistics & numerical data ; *Agriculture ; }, abstract = {BACKGROUND: Urbanization is linked to reduced microbial exposure, increased prevalence of lifestyle-related diseases, and diminished psychological resilience. In contrast, traditional alpine farming environments offer high biodiversity and low pollution, potentially promoting restorative health effects. The ALM Study (ALpine Farming and Human Nasal Microbiome Diversity) explored the feasibility and physiological impact of a 7-day immersion in such an environment among previously unexposed ("Alm-naive") individuals.

METHODS: This prospective, single-arm feasibility study was conducted in the Riedingtal Valley, Austria. Twenty-two healthy adults (median age: 30.5 years), with no prior agricultural exposure, participated in a 7-day immersive intervention involving daily alpine farming activities. Biological (nasal swabs, venous blood), physiological (VO₂max), and psychological (WHO-5 psychological wellbeing index, EQ-5D VAS, NR-6) data were collected immediately before and after the intervention. The primary outcome was the change in nasal microbiome diversity (16S rRNA gene amplicon sequencing); secondary outcomes included hematological markers, lipid metabolism, inflammatory parameters, and wellbeing scores. Pre-post changes were analyzed using Wilcoxon signed-rank tests.

RESULTS: Nasal microbiome analysis revealed significant increases in species richness and evenness (p < 0.001). In addition, descriptive analyses indicated changes in relative phylum-level composition, with reduced Proteobacteria dominance and variable increases in Firmicutes and Actinobacteriota. Hematocrit (+3.1%, p = 0.01), reticulocyte count (+0.39%, p < 0.001), and platelet count (+27 G/L, p = 0.02) increased significantly, suggesting erythropoietic and immunological activation. Additionally, activation of the immune system became evident, as reflected by a slight but significant rise in CRP (+0.04 mg/dL, p = 0.01), in the absence of concurrent changes in IL-6 or leukocyte counts. Total cholesterol (-8.08 mg/dL, p = 0.02) and non-HDL cholesterol (-2.00 mg/dL, p = 0.01) decreased, VO₂max showed a positive trend (+3.43 mL· kg[-1]·min[-1], p = 0.07). WHO-5 psychological wellbeing scores improved markedly (+12%, p < 0.001), while other psychometric scales remained unchanged.

CONCLUSION: A 1-week immersion in a biodiverse alpine environment was associated with measurable changes in the nasal microbiome, hematological and metabolic profiles, and psychological wellbeing. These findings support both the feasibility and the potential health relevance of short-term, nature-based interventions for urban populations.}, } @article {pmid41648756, year = {2025}, author = {Grønbæk, IMB and Halkjær, SI and Hansen, EH and Mollerup, S and Paulsen, SJ and Konrad, CV and Engel, S and Bulinska-Balas, M and Wellejus, A and Haaber, AB and Christensen, AH and Engsbro, AL and Petersen, AM}, title = {Eight weeks of treatment with probiotic Bifidobacterium breve, Bif195 lowers fatigue scores in patients with diarrhoea-predominant irritable bowel syndrome: results from a randomised, clinical trial.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1701341}, pmid = {41648756}, issn = {2296-861X}, abstract = {UNLABELLED: Patients with irritable bowel syndrome experience abdominal pain and stool habit disturbances, and often also extraintestinal symptoms, such as fatigue. The disorder is linked to gut dysbiosis, and manipulation of the microbiota is considered a possible treatment strategy. This randomised, double-blinded, placebo-controlled study aimed to investigate the effects of the probiotic strain Bifidobacterium breve, Bif195™ (DSM 33360) (Bif195), on symptoms and gut microbiome composition in patients with diarrhoea-predominant irritable bowel syndrome. Sixty-one patients with moderate-severe disease activity were allocated to 8 weeks of treatment with either Bif195 or placebo (1:1), followed by 8 weeks of follow-up. The primary outcome was a change in symptom scores measured by the validated questionnaire, IBS-symptom severity scale. Secondary and explorative outcomes were the effects of Bif195 on intestinal symptoms, quality of life, fatigue, and the gut microbiota. Modulation of the transepithelial electrical resistance (TEER) of Caco-2 cells by Bif195 was investigated in vitro as a model of barrier integrity. The results showed no effect of Bif195 on primary or secondary outcomes; however, Bif195 lowered fatigue scores compared to placebo. Significantly increased TEER readings in vitro indicated enhanced barrier integrity, suggesting GI permeability as a mechanism for further clinical exploration.

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT04808271.}, } @article {pmid41648417, year = {2026}, author = {Arasti, S and Şapcı, AOB and Rachtman, E and El-Kebir, M and Mirarab, S}, title = {Deconvolving Phylogenetic Distance Mixtures.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.18.700179}, pmid = {41648417}, issn = {2692-8205}, abstract = {Mixtures of multiple constituent organisms are sequenced in several widely used applications, including metagenomics and metabarcoding. Characterizing the elements of the sequence mixture and their abundance with respect to a reference set of known organisms has been the subject of intense research across several domains, including microbiome analyses, and methods must overcome two key challenges. First, the mixture constituents are related to each other through an evolutionary history, and hence, should not be considered independent entities. Second, sequence data is noisy, with each short read providing a limited signal. While existing approaches attempt to address these challenges, addressing both challenges simultaneously has proved challenging. For evolutionary dependencies, methods either define hierarchical clusters (e.g., taxonomies or operational taxonomic/genomic units) or use phylogenetic trees. For the second challenge, they either assemble reads into contigs, use statistical priors to summarize read placements, or attempt to analyze all reads jointly using k-mers. Despite this rich literature, a natural approach to simultaneously address both challenges has been underexplored: compute a distance from the mixture to all references, deconvolve those distances, and place the sample on multiple branches of a reference phylogeny with associated abundances. This multi-placement approach is a natural extension of the single-read phylogenetic placement used in practice. We argue that by placing the entire sample on multiple branches instead of placing reads individually, we can obtain a less noisy profile of the mixture. We formalize this approach as the phylogenetic distance deconvolution (PDD) problem, show some limits on the identifiability of PDDs, propose a slow exact algorithm, and an efficient heuristic greedy algorithm with local refinements. Benchmarking shows that these heuristics are effective and that our implementation of the PDD approach (called DecoDiPhy) can accurately deconvolve phylogenetic mixture distances while scaling quadratically. Applied to metagenomics, DecoDiPhy consolidates reads mapped to a large number of branches on a reference tree to a much smaller number of placements. The consolidated placements improve the accuracy of downstream tasks, such as sample differentiation and detection of differentially abundant taxa.}, } @article {pmid41648390, year = {2026}, author = {Riedmuller, KC and Dyer, JE and Ottesen, EA}, title = {Large temperature excursions have modest impacts on community composition in the high diversity gut microbiome of omnivorous American cockroaches (Periplaneta americana).}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.21.700893}, pmid = {41648390}, issn = {2692-8205}, abstract = {UNLABELLED: Microbial residents of ectothermic hosts are exposed to variations in temperature that have the potential to impact their physiology and the host-microbe symbiotic relationship. In this experimental warming study, laboratory populations of American cockroaches (Periplaneta americana) were kept at a baseline low room temperature of 20-22°C or a high temperature of 30°C for two weeks. We quantified bacterial load and performed high-throughput 16S rRNA gene sequencing to assess the hindgut microbiome's response to a near 10°C shift in environmental temperature. We report modest impacts of temperature on cockroach gut microbiome composition. The high temperature treatment induced increases in the relative abundance of Proteobacteria and Euryarchaeota phyla as well as the Lactobacillaceae and Enterococcaceae families. We also observed increased interindividual variability. There were no significant differences in the dominant Bacteroidota or Firmicutes phyla and no significant losses or reductions in taxa or bacterial load, respectively. This suggests that the gut community of American cockroaches is largely resilient to prolonged increases in temperature and has implications for the cockroach to withstand the impacts of climate change.

IMPORTANCE: Insects, as with most animals, often harbor microbial symbionts that play an essential role in host health and nutrition. As insects are ectotherms, these microbial symbionts are subject to the same temperature fluctuations as their hosts, potentially impacting host temperature responses. Here, we demonstrate that the American cockroach (Periplaneta americana) gut microbiome exhibits only modest changes following an ∼10°C increase in environmental temperature. This contrasts with studies in other insects, whose microbiota were highly responsive to temperature variation. This work illustrates that the microbiota of insects may vary in their sensitivity to long-term temperature shifts, providing a more comprehensive understanding of potential variability in insect responses to climate change.}, } @article {pmid41648363, year = {2026}, author = {Da Silva, AC and Flantzer, L and Weinberg, J and Kyu, S and Daley-Bauer, L and Santana, AC and Talla, A and Rittgers, AL and Welbourn, S and Gordon, DE and Tomalka, JA and Marconi, VC and Jones, DP and Younes, SA}, title = {Microbiome-Derived Metabolites Shape CD4[+] T-Cell Differentiation and Immune Aging in Chronic HIV-1 Infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.13.699280}, pmid = {41648363}, issn = {2692-8205}, abstract = {The role of aromatic gut-derived bacterial metabolites (GDBMs) in shaping immune cell metabolism and function remains poorly explored. Using ex vivo metabolomic profiling of paired plasma and CD4[+] T-cells from people living with HIV-1 (PLWH), we identified a network of aromatic GDBMs whose cell-associated abundance, rather than systemic levels, was linked to broad alterations in CD4[+] T-cell metabolic and functional states. Among these metabolites, p-cresol sulfate (PCS) emerged as a mechanistic prototype investigated in depth. Ex vivo flow cytometry and single-cell RNA sequencing of CD4[+] T-cells stratified by cell-associated PCS levels revealed dose-dependent enrichment of transcriptional programs associated with impaired differentiation capacity, regulatory-like identity, and cellular senescence. Consistently, in vitro transcriptomic and proteomic analyses of PCS-exposed CD4[+] T cells demonstrated induction of cell-cycle arrest, mitochondrial dysfunction, and senescence-associated programs, including upregulation of p16 and p21. Integration of these immunometabolic features with measurements of HIV-1 reservoir size in PLWH revealed that CD4[+] T-cell states defined by cell-associated GDBMs track with intact proviral DNA levels in vivo. Together, these findings define a microbiome-derived axis that reshapes CD4[+] T-cell metabolism and fate and promotes immune aging-associated states in PLWH. Our data suggest that cell-associated GDBMs may foster immunometabolic CD4[+] T-cell states previously linked to long-term HIV-1 reservoir persistence in vivo.}, } @article {pmid41648328, year = {2026}, author = {Baker, JL and Tang, J and Guo, M and Farias-da-Silva, FF and Barbisan, M and Burnside, M and Crofton, K and Williams, S and Rao, S and Lee, M and Drucker, SG and Higashi, D and Merritt, J and Hirose, Y and Veening, JW and Nizet, V}, title = {Monounsaturated fatty acid biosynthesis is critical for streptococcal envelope homeostasis and stress tolerance.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.14.699484}, pmid = {41648328}, issn = {2692-8205}, abstract = {The genus Streptococcus contains some of the most important commensals and pathogens of the human microbiome. To obtain the fatty acids required for cell membranes, Streptococcus either produce fatty acids de novo through the fatty acid biosynthesis (fab) pathway or uptake host fatty acids through the fatty acid kinase (fak) pathway. Although both the fab and fak pathways represent potential therapeutic targets to prevent or treat infection, progress is limited because of an incomplete understanding of taxon-to-taxon variability in streptococcal lipid metabolism. Here, we examined the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. In all three species, deletion of fabM abolished MUFA production and caused severe growth defects, decreased stress tolerance, increased antibiotic susceptibility, and defects in cell viability, morphology, and division. In S. mutans, loss of fabM also markedly reduced competence signaling and production of the mutacin IV bacteriocin. Deletion of fabM increased susceptibility to killing by human neutrophils in S. mutans and S. pneumoniae, but not S. pyogenes . Together, these findings illustrate that MUFA synthesis is broadly important for streptococcal physiology and cell membrane homeostasis, while its contribution to pathogenesis is strongly species- and context-dependent, providing leads to guide development of novel therapeutic and/or preventative strategies.}, } @article {pmid41648281, year = {2026}, author = {Ramachandran, SL and Pasupuleti, N and Abdill, RJ and Adikari, G and Ahlawat, B and Blekhman, R and Burgo, V and Davenport, ER and Dwivedi, A and Gupta, S and Ijinu, TP and Jamir, T and Karu, R and Kaushik, A and Komarabathini, JM and Laithangpuii, and Lalzarliana, J and Norbu, T and Pautu, T and Pawar, K and Raman, AS and Ramaswamy, R and Ranasinghe, R and Rashmi, and Sasidharan, SP and Satheesh, T and Shaji, S and Shapiro, JW and Singh, E and Singson, V and Sundararajan, A and Tennekoon, KH and Tetso, D and Urban Aragon, JA and Welikala, AHJ and Yhome, RR and Rai, N and Raghavan, M}, title = {Distinct trajectories of urbanization shape the human gut microbiome across South Asia.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.22.701183}, pmid = {41648281}, issn = {2692-8205}, abstract = {Human gut microbiomes respond to lifestyle transitions, yet the extent to which these responses are conserved across spatio-cultural contexts remains undercharacterized. We present the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Although urbanization is consistently associated with increased abundance of disease-linked taxa, microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase non-persistence. Microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography and underscoring the need for community-specific investigations of health impacts.}, } @article {pmid41648232, year = {2026}, author = {Palayyan, SR and Siddiqui, AH and Sukumaran, SK}, title = {Expression of Calca gene-derived peptides in the murine taste system.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.16.700005}, pmid = {41648232}, issn = {2692-8205}, abstract = {The Calcitonin Related Polypeptide Alpha (Calca) gene is a source of four biologically active peptides with varied physiological roles. Alternative splicing of the Calca messenger RNA generates either prepro calcitonin gene related peptide (CGRP) or preprocalcitonin encoding transcripts. Proteolytic processing of preprocalcitonin generates procalcitonin, calcitonin and katacalcin. Calcitonin is a ligand for the G-protein coupled receptor calcitonin receptor (CALCR) while CGRP is a ligand for the CGRP receptor (CGRP1R) formed by the calcitonin receptor like receptor (CALCRL)receptor activity modifying protein 1 (RAMP1) complex. Interestingly, procalcitonin too, is a ligand for the CGRP1R where it can antagonize CGRP. CGRP expression in taste neurons has been documented and is posited to regulate taste signaling. Single cell and bulk RNASeq of taste papillae revealed that the preprocalcitonin but not the CGRP transcript is expressed in Tas1r3 - expressing type II taste cells, while Calcrl (but not Calcr) and Ramp1 are expressed in stem/progenitor and type I cells in the circumvallate papillae. The CGRP1R is also expressed by fibroblasts in the lingual mesenchyme. We confirmed this expression pattern using quantitative polymerase chain reaction (qPCR), RNAScope and immunohistochemistry. qPCR of geniculate and nodose-petrosal ganglia revealed that both express Cgrp and CGRP1R subunit mRNAs, but not procalcitonin and Calcr . This interesting expression patterns suggests that procalcitonin and CGRP might reciprocally regulate the CGRP1R in taste cells and lingual fibroblasts and thereby influence taste signaling, taste cell regeneration and the taste microbiome.}, } @article {pmid41648228, year = {2026}, author = {Dockman, RL and Ottesen, EA}, title = {Niche specialization and cross-feeding interactions shaping gut microbial fiber degradation in a model omnivore.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.22.701066}, pmid = {41648228}, issn = {2692-8205}, abstract = {The gut microbiome plays an active role in host health, producing gut metabolites that influence host digestive and immune function while also mediating microbial crosstalk. Dietary fiber is a major source of important fermentation byproducts that are generally implicated in gut community stability and host wellbeing, but dissecting microbe-specific contributions to polysaccharide metabolism in the context of a complex gut community is challenging with conventional model organisms. Using the American cockroach (Periplaneta americana) as a model omnivore, we use chemically-defined synthetic diets to identify how complex gut microbial communities respond to two of the most abundant plant polysaccharides, xylan and cellulose. To do so, we fed cockroaches synthetic diets containing one of these fibers or a mix of both in differing ratios. Through both 16S rRNA gene profiling and RNA-seq, we show that mixed fibers enrich for organisms characteristic of the source fibers as well as additional organisms only enriched in mixed-fiber diets. Through an organism-centric pangenome approach, we identify the impact of these fibers on gut microbiome activity. We found that gut communities responded strongly to xylan, with Bacteroidota belonging to Bacteroides, Dysgonomonas, and Parabacteroides producing xylan-active CAZymes at high levels. Multiple groups of Bacillota also responded strongly to a xylan diet, but appeared to act as cross-feeding secondary degraders, producing primarily xylosidases and transcripts associated with xylose utilization. In contrast, cellulose diets were associated with higher transcriptional activity among Fibrobacterota, which are typically a minor component of the cockroach gut microbiome but were the primary producers of CAZymes associated with cellulose and cellobiose degradation. These experiments provide new insight into gut microbial metabolism of these complex plant polysaccharides. Further, they highlight the utility of the cockroach model and synthetic diets to answer fundamental questions about gut microbial responses to different polysaccharides alone and in combination.}, } @article {pmid41648142, year = {2026}, author = {Mastrorilli, E and Herd, P and Rey, FE and Goodman, AL and Zimmermann, M}, title = {Linking interpersonal differences in gut microbiota composition and drug biotransformation activity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.21.700809}, pmid = {41648142}, issn = {2692-8205}, abstract = {Individuals vary widely in their responses to drugs, and growing evidence implicates the gut microbiome as a contributor to this variability. While prior studies show that gut bacteria can metabolize drugs, how differences in microbial community composition influence drug metabolism remains poorly understood. Here, we characterize the biotransformation of 271 drugs by 89 gut microbial communities derived from human donors and preclinical animal models. Over 90% of tested drugs were metabolized by at least one microbiome. We identified 66 drugs exhibiting highly variable metabolism across human-derived microbiomes and several drugs whose biotransformation differed markedly between human and animal microbiomes. To enable prediction of microbiota-mediated drug metabolism, we developed and compared multiple modeling approaches based on metagenomic data. These results, together with the provided data and analytical resources contribute to a better understanding of microbiome-drug interactions and support their future integration into drug discovery, personalized prescription, and therapeutic drug monitoring.}, } @article {pmid41648012, year = {2025}, author = {Cortez, F and Nanetti, E and Chaves, G and Pereira, AC and Mendes, MC and Oliveira, I and Leuzzi, D and Abreu, H and Martins, M and Leite, RB and Keller-Costa, T and Costa, R}, title = {Prokaryotic community structure and auxin biosynthesis in early developmental stages of farmed Atlantic Nori (Porphyra spp.).}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1750184}, pmid = {41648012}, issn = {1664-302X}, abstract = {INTRODUCTION: Algal-microbiome interactions are considered pivotal for host health and development. Current understanding of the diversity and function of algal-associated microorganisms in aquaculture settings remains limited, preventing the development of microbiome-based solutions for sustainable algal growth.

METHODS: We employed cultivation-dependent and -independent approaches to determine the structure of bacterial communities associated with farmed Atlantic Nori (Porphyra dioica and Porphyra umbilicalis) at early developmental stages. 16S rRNA gene amplicon sequencing and cultivation of bacterial symbionts were performed for algal and culturing water samples harvested from indoor photobioreactors at stages S1 (conchocelis cultures growing vegetatively), S2 (conchosporangia), and S3 (young blades).

RESULTS: The phyla Pseudomonadota (Alpha- and Gammaproteobacteria classes) and Bacteroidota were dominant in algal samples, followed by Planctomycetota, Actinobacteriota, and Verrucomicrobiota. At the phylotype level, these communities were highly structured throughout the host's life cycle. Uncultivated lineages Sva0996 (Actinomycetota), OM190 (Planctomycetota), Pir4 (Planctomycetota), and the genera Blastopirellula, Algoriphagus, Hyphomonas, and Marinobacter, among others, were enriched in algal samples and presented significantly different abundances across developmental stages. In some cases (e.g., genera Aquimarina, Sulfitobacter, Maribacter, and Nonlabens), those changes were also observed in culturing water. Moreover, the genera Ensifer (Rhizobiaceae), Paraglaciecola (Alteromonadaceae), and the uncultivated lineages DEV007 (Verrucomicrobiota) and Pir4 (Planctomycetota) were consistently present in P. dioica and P. umbilicalis samples at multiple developmental stages. Several Porphyra-associated bacterial genera and putative novel species, mostly belonging to the families Roseobacteraceae, Flavobacteriaceae, and Alteromonadaceae were identified via cultivation. Many cultured members of the Porphyra microbiome produced the growth-promoting hormone auxin, particularly those belonging to the genera Alteromonas, Marinobacter, Sulfitobacter, Leucothrix, and Roseovarius.

DISCUSSION: This study unveils complex, phylogenetically distinct, and temporally structured bacterial communities possessing algal morphogenesis-inducing capacities during early developmental stages of Porphyra spp., highlighting the potential of microbiome-based interventions for sustainable growth of marine algae in aquaculture.}, } @article {pmid41648004, year = {2025}, author = {Goncalves, AR and Ranganathan, H and Valdes, C and Zhu, H and Zhang, B and Kok, CR and Martí, JM and Mulakken, NJ and Thissen, JB and Jaing, C and Be, NA}, title = {Beyond microbial abundance: metadata integration enhances disease prediction in human microbiome studies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1695501}, pmid = {41648004}, issn = {1664-302X}, abstract = {Multiple studies have highlighted the interaction of the human microbiome with physiological systems such as the gut, immune, liver, and skin, via key axes. Advances in sequencing technologies and high-performance computing have enabled the analysis of large-scale metagenomic data, facilitating the use of machine learning to predict disease likelihood from microbiome profiles. However, challenges such as compositionality, high dimensionality, sparsity, and limited sample sizes have hindered the development of actionable models. One strategy to improve these models is by incorporating key metadata from both the human host and sample collection/processing protocols. This remains challenging due to sparsity and inconsistency in metadata annotation and availability. In this paper, we introduce a machine learning-based pipeline for predicting human disease states by integrating host and protocol metadata with microbiome abundance profiles from 68 different studies, processed through a consistent pipeline. Our findings indicate that metadata can enhance machine learning predictions, particularly at higher taxonomic ranks like Kingdom and Phylum, though this effect diminishes at lower ranks. Our study leverages a large collection of microbiome datasets comprising 11,208 samples, therefore enhancing the robustness and statistical confidence of our findings. This work is a critical step toward utilizing microbiome and metadata for predicting diseases such as gastrointestinal infections, diabetes, cancer, and neurological disorders.}, } @article {pmid41648003, year = {2025}, author = {Wei, X and Wang, L and Zhang, H and Tan, L and Yang, S and Li, J and Liu, Z and Zhong, Q and Sun, X}, title = {Cold-resistant lactic acid bacteria in Jerusalem artichoke silage: quality, microbiome and metabolome dynamics during aerobic exposure on the Qinghai-Tibet Plateau.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1699658}, pmid = {41648003}, issn = {1664-302X}, abstract = {Forage scarcity during the cold season poses a major challenge to livestock farming on the Qinghai-Tibet Plateau. Jerusalem artichoke (Helianthus tuberosus) offers a promising alternative, but aerobic exposure of its silage leads to nutrient loss and microbial spoilage under low temperatures. This study aimed to evaluate the effects of inoculating cold-resistant lactic acid bacteria (LAB)-Lactiplantibacillus plantarum GN02 (homofermentative) and Levilactobacillus brevis XN25 (heterofermentative)-on silage quality, microbiome, and metabolome dynamics during aerobic exposure. Silage was prepared from Jerusalem artichoke stems and leaves, treated with sterile water (CK), Lpl. plantarum (YZ), Lv. brevis (YD), or their mixture (YZD), and ensiled for 60 days at -5 to 8 °C. Samples were analyzed at 0, 7, and 14 days of aerobic exposure (-10 to 5 °C) for fermentation parameters (pH, organic acids, dry matter, water-soluble carbohydrates, crude protein, fibers), microbial communities via 16S rRNA and ITS sequencing, and metabolites using LC-MS-based untargeted metabolomics. Inoculation with Lpl. plantarum maintained lower pH (<5), higher lactic acid, dry matter, and water-soluble carbohydrates, while suppressing spoilage bacteria (e.g., Carnobacterium, Citrobacter) and enriching Lactobacillus. Metabolomics revealed upregulated flavonoids and octadecanoids, enhancing antioxidant defenses and downregulating carbohydrate degradation pathways. Lv. brevis accelerated spoilage with elevated pH and nutrient loss, whereas the mixture showed intermediate effects. These findings demonstrate Lpl. plantarum's efficacy in mitigating aerobic deterioration, providing a theoretical basis for optimizing silage preservation and supporting sustainable livestock production in high-altitude regions.}, } @article {pmid41648002, year = {2025}, author = {Zhang, H and Chen, K and Chen, R and Jia, E}, title = {Feeding patterns reprogram a gut microbial virulence-iron-quorum sensing functional axis linked to atherosclerotic risk.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1751844}, pmid = {41648002}, issn = {1664-302X}, abstract = {The feeding rhythm is a major temporal regulator of metabolic physiology, yet its impact on microbiome-derived functional traits relevant to cardiometabolic disease remains insufficiently understood. Our previous work demonstrated that ad libitum, daytime-restricted, and nighttime-restricted feeding produce markedly different atherosclerotic outcomes in Apoe[-]/[-] mice, indicating that the feeding rhythm acts as a modifiable determinant of atherogenic susceptibility. Here, we used shotgun metagenomics to profile risk-associated microbial functional modules-including Type III and Type VI secretion systems (T3SS/T6SS), siderophore-based iron acquisition pathways, quorum-sensing (QS) regulators, and antimicrobial resistance determinants-across feeding regimens. The feeding rhythm induced pronounced functional segregation independent of α-diversity, which was consistent with selective functional reprogramming rather than taxonomic restructuring. Daytime feeding, which is misaligned with the murine active phase, is associated with coordinated enrichment of the T3SS/T6SS, iron uptake, and QS pathways, forming a tightly interconnected "virulence-iron-QS-ARG" functional consortium. In contrast, circadian-aligned nighttime feeding resulted in attenuated virulence orientation and enhanced metabolic-cooperative signatures. Network inference further revealed strong coactivation of virulence secretion, iron mobilization, and QS modules under circadian misalignment. These findings show that the feeding rhythm modulates atherogenic susceptibility not only through host metabolism but also by remodeling gut microbial functional capacities, highlighting microbial functional ecology as an integral component of diet-host interactions.}, } @article {pmid41647997, year = {2025}, author = {Lee, IT and Dohlman, A and Gao, T and Zhang, Z and Kasai, Y and Kim, GE and Thirlwell, C and Nakakura, E and Meyerson, M and Mäkinen, N}, title = {Characterization of tumor-associated microbiome in multifocal small intestinal neuroendocrine tumors (SI-NETs).}, journal = {ESMO gastrointestinal oncology}, volume = {9}, number = {}, pages = {100229}, pmid = {41647997}, issn = {2949-8198}, abstract = {BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are among the most common neoplasms of the small bowel; however, the molecular mechanisms underlying their pathogenesis are largely unknown. The multifocal nature of SI-NETs, their putative distinct genomic origins, and their enrichment in the distal ileum led us to hypothesize that environmental factors, such as pathogenic organisms, might play a role in the development of these lesions.

MATERIALS AND METHODS: To study the tumor-associated microbiome of multifocal SI-NETs and its potential role in pathogenesis, we used matched whole genome and transcriptome sequencing data from a cohort of 10 multifocal SI-NET patients, including 70 primary ileal NETs and their matched normal ileal mucosa and/or whole blood specimens.

RESULTS: Microbial communities in the ileal tissue samples were primarily composed of bacteria. The most abundant genera included well-known gastrointestinal, oral, and mucosal bacteria. Ileal tissue samples from individual patients contained distinct patient-specific microbial communities. Although the microbiota composition did not show significant differences between ileal NET and normal ileal tissues, genus Propionibacterium was found to be enriched in the normal tissue specimens.

CONCLUSIONS: This study comprehensively characterizes the tissue-resident ileal microbiome of multifocal SI-NET patients. We provide clear evidence that the microbial communities in the ileum are largely patient specific, whereas our genus-level analyses suggest that SI-NET pathogenesis is unlikely driven by individual microorganisms present in the tumors at the time of surgical resection.}, } @article {pmid41647993, year = {2025}, author = {Jayakrishnan, T and Sangwan, N and Nair, KG and Kamath, SD and Patel, MH and Joyce, D and Walsh, M and Simon, R and Vadehra, D and Iyer, RV and Fountzilas, C and Khorana, AA}, title = {Tumor microbiome differences in early-onset versus average-onset pancreatic adenocarcinoma.}, journal = {ESMO gastrointestinal oncology}, volume = {9}, number = {}, pages = {100194}, pmid = {41647993}, issn = {2949-8198}, abstract = {BACKGROUND: Compelling evidence supports the biomarker potential of microbiome in pancreatic adenocarcinoma. Given the knowledge gap on the characteristics and significance of microbiome in early-onset pancreatic ductal adenocarcinoma (eoPDAC, age <50 years), we aimed to evaluate microbiome profiles in resected specimens from individuals with eoPDAC and average-onset PDAC (aoPDAC, age >50 years).

MATERIALS AND METHODS: We carried out shotgun metagenomic sequencing in resected specimens from individuals with eoPDAC (n = 24) and aoPDAC (n = 20). Statistical tests included Wilcoxon test, permutational analysis of variance, multiomic classifier modeling, differential abundance analysis, and linear regression. All P values were adjusted for multiple testing and P < 0.05 was considered statistically significant.

RESULTS: We successfully sequenced several bacteria and fungi in the tumor specimens from 44 individuals with resected PDAC (24 eoPDAC and 20 aoPDAC). The alpha diversity of the bacterial microbiome was higher in eoPDAC tumor tissue compared with aoPDAC (P = 0.04). In contrast, the fungal mycobiome's alpha diversity was higher for aoPDAC tumor tissue (P = 0.02). Key organisms with differential abundance between tumor tissue from individuals with eoPDAC and aoPDAC included Bacillus, Candida, Collimonas, Cupriavidus, Enterobacter, Escherichia, Klebsiella, Malasseiza, Mucilaginibacter, Neisseria, and Sphingomonas. Higher bacterial diversity in tumor tissue was associated with better overall survival for individuals with eoPDAC (R = 0.26, P = 0.02).

CONCLUSIONS: Shotgun metagenomic sequencing identified bacterial microbiome and fungal mycobiome in tumors from individuals with eoPDAC and aoPDAC. We observed significant differences in alpha and beta diversity and relative abundances of organisms suggesting distinct microbiome signatures. Microbiome associations with survival were observed in eoPDAC indicating unique potential as prognostic biomarker.}, } @article {pmid41647970, year = {2025}, author = {Boilève, A and Brugel, M and Rémond, M and Valéry, M and Ducreux, M and Turpin, A and Smolenschi, C}, title = {The increasing burden of early-onset pancreatic and biliary tract cancers: a review of risk factors.}, journal = {ESMO gastrointestinal oncology}, volume = {9}, number = {}, pages = {100204}, pmid = {41647970}, issn = {2949-8198}, abstract = {The rising incidence of early-onset pancreatic and biliary tract cancers (PBTCs) challenges conventional assumptions that these malignancies primarily affect older populations. Although early-onset PBTCs have a similarly poor prognosis to later-onset cases, emerging evidence suggests that unique or mixed genetic, environmental, and lifestyle factors contribute to their distinct etiologies. This review synthesizes current data on the epidemiology, risk factors, and molecular features of early-onset (in individuals <50 years of age) pancreatic ductal adenocarcinoma and biliary tract cancers. Recent studies indicate a significant increase in early-onset PBTC incidence, with variations by sex, geographic region, and genetic predisposition. Hereditary factors, including BRCA1/2, CDKN2A, and mismatch repair gene mutations, contribute to familial clustering, while other nonhereditary risk factors such as obesity, smoking, pancreatitis, and diabetes seem to disproportionately impact younger patients. Additionally, environmental exposures, including air pollution, pesticides, and endocrine-disrupting chemicals, are suggested to contribute to carcinogenesis, while changes in microbiota may cause inflammation, immune modulation, and treatment resistance. As the burden of early-onset PBTCs grows, refining screening strategies and integrating microbiome-based risk assessment into biobanking strategies will be critical. Future research should focus on age-stratified genetic risk profiling, microbiota-driven interventions, and personalized therapeutic approaches to improve early detection and patient outcomes.}, } @article {pmid41648027, year = {2024}, author = {Cella, CA and Ciardiello, D and Gervaso, L and van Laarhoven, H and Nezi, L and Catozzi, C and Lordick, F and Smyth, E and de Pascale, S and Benini, L and Valenza, C and Guidi, L and Fumagalli Romario, U and Fazio, N}, title = {Role of the microbiome in the development and treatment of gastric cancer: an overview of the biological and clinical landscape.}, journal = {ESMO gastrointestinal oncology}, volume = {4}, number = {}, pages = {100048}, pmid = {41648027}, issn = {2949-8198}, abstract = {For decades, the stomach was considered a sterile organ, due to the acid environment. However, starting from the discovery of Helicobacter pylori, this concept has progressively refined. By damaging the hydrochloric acid-secreting glands, H. pylori infection primes the progression from acute to chronic inflammation in gastric mucosa resulting in atrophic gastritis, intestinal metaplasia, dysplasia and ultimately gastric cancer (GC). Due to the challenging identification of culturing bacteria, the carcinogenic role of gastric microbial community, other than H. pylori, remains underestimated. More recently, a growing body of evidence has pointed out the dynamism of gastric microbiota as a crucial step for GC development, besides elucidating some additional activity in modulating the efficacy of cancer treatments. In turn, anticancer therapies can shape gastric microbiota with consequent dysbiosis and a potential correlation with drug-related toxicity. In conclusion, the current review aims to deepen the role of gut microbiota as a key factor in gastric disease at multiple levels, from carcinogenesis to the metastatic phase. It also provides novel insights on gastric microbiota as potential target for tailoring multimodal strategies, either surgical or oncological, to finally provide our patients with more individualized treatment options.}, } @article {pmid41647966, year = {2025}, author = {Twhigg, L and Ng, HM and Glyn, T and Wall, C and Purcell, R}, title = {Fibre, microbes and radiotherapy: unravelling the gut's impact on radiotherapy in cancer.}, journal = {ESMO gastrointestinal oncology}, volume = {9}, number = {}, pages = {100174}, pmid = {41647966}, issn = {2949-8198}, abstract = {The gut microbiome plays an integral role in many physiological functions, including immunity, metabolism, maintenance of membrane integrity and protection against pathogenic bacteria. Conversely, adverse changes in the gut microbiome-termed dysbiosis-have been linked to many diseases, including cancer. Dysbiosis can result from a range of endogenous and exogenous factors. Diet is one of the most important modulators of the gut microbiome; the indirect benefits of modulating the microbiome through diet interventions are beginning to be used in many disease settings. Beneficial microbes (commensals) can modulate the local and systemic immune environment through the production of metabolites, such as short-chain fatty acids (SCFAs). Commensal bacteria ferment dietary fibre to produce SCFAs, and increasing dietary fibre intake has been shown to both increase SCFA production in the colon and affect immune responses. Recent studies have shown that dietary fibre can increase tumour responses to immunotherapy and chemotherapy, but data on the effect of increased fibre and changes in the microbiome on radiotherapy are limited. In this article, we review the current evidence regarding dietary fibre interventions and modulation of the gut microbiome in improving outcomes in patients receiving pelvic radiotherapy.}, } @article {pmid41647440, year = {2026}, author = {Xu, H and Yu, J and Xia, L and Lei, X and Zhou, L and Lin, P and Su, S and Li, Y and Chen, C}, title = {Antibiotic exposure impairs the efficacy of first-line chemoimmunotherapy in non-small cell lung cancer through the regulation of gut microbiome and bile acid metabolism.}, journal = {Precision clinical medicine}, volume = {9}, number = {1}, pages = {pbag001}, pmid = {41647440}, issn = {2516-1571}, abstract = {OBJECTIVE: Previous antibiotic therapy is acknowledged to potentially reduce the efficacy of single-agent immune checkpoint inhibitors. Nevertheless, the impact of antibiotics on the results for patients undergoing chemoimmunotherapy remains unclear. This research investigated the influence of antibiotic treatment on the effectiveness of chemoimmunotherapy in advanced non-small cell lung cancer (NSCLC).

METHODS: We recorded the characteristics of patients with advanced NSCLC and assessed potential associations between the use of antibiotics and the efficacy of chemoimmunotherapy. A mouse model using Lewis lung carcinoma (LLC) cell lines was developed to assess the effects of antibiotics on the gut microbiome and metabolites. Fecal samples were analyzed using 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) methods. Mouse fecal and serum samples and 16 human stool samples were used to validate the identified differentially metabolites. Deoxycholic acid (DCA) was further applied to a LLC mouse model.

RESULTS: This study included 387 NSCLC patients, among whom 86 patients had used antibiotics within the 30 days before the first cycle of chemoimmunotherapy (ATB group), and 301 patients had not used antibiotics (non-ATB group). Notable discrepancies were observed in overall survival and progression-free survival between the two groups, with overall survival recorded at 18.4 months versus 32.0 months, and progression-free survival at 7.6 months versus 13.0 months, in the ATB and non-ATB groups respectively. At the phylum level, the relative abundances of Proteobacteria, Cyanobacteria, and Deinococcus were increased in the ATB mice, while Firmicutes, Bacteroidetes, and Verrucomicrobia were decreased. We detected significant differences in DCA levels in the fecal and serum samples from mice as well as in the fecal sample from humans between the ATB and non-ATB groups. The respective proportions of CD4+ and CD8+ cells were greater in the non-ATB group than in the ATB group, whereas the proportion of Ki67-positive cells was greater in the ATB group. DCA was applied to LLC mice, and DCA along with chemoimmunotherapy effectively inhibited tumor growth in a LLC mouse model. The expression of programmed cell death ligand 1 increased in the DCA group.

CONCLUSIONS: Antibiotic exposure is associated with decreased efficacy of chemoimmunotherapy in patients with NSCLC via dysregulation of the gut microbiome and DCA metabolism.}, } @article {pmid41647262, year = {2025}, author = {Wang, Y and Chen, H and Chen, Y and Lu, Y and Wei, B and Wu, Z and Gao, H and Feng, L and Xie, F and Li, Q and Lin, W and Sun, X and Lin, H and Dong, B and Sun, P}, title = {Age-specific vaginal microecological dysbiosis associated with HPV infection: a large-scale cross-sectional study with targeted functional sequencing validation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1722367}, pmid = {41647262}, issn = {2235-2988}, mesh = {Female ; Humans ; Middle Aged ; *Papillomavirus Infections/microbiology/complications/virology ; Adult ; Cross-Sectional Studies ; *Vagina/microbiology/virology ; *Dysbiosis/microbiology ; Young Adult ; Adolescent ; Age Factors ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Papillomaviridae/genetics/classification ; Aged ; Bacteria/classification/genetics/isolation & purification ; Risk Factors ; Genotype ; }, abstract = {PURPOSE: The vaginal microecological parameters as a critical immune barrier, yet their age-dependent interaction with Human papillomavirus (HPV) infection remains poorly understood. To characterize age-dependent vaginal microbiota composition and function across the female lifespan, and to evaluate the selective impact of HPV infection on microecological stability and infectious risk.

METHODS: A total of 23,672 women were stratified into four age groups (18-34, 35-44, 45-55, and >55 years). Vaginal microecology was evaluated using Gram-staining, pH, hydrogen peroxide (H2O2), leukocyte esterase, and sialidase assays. HPV genotyping was performed in 2,116 women. Statistical analysis employed univariate screening, LASSO regression for variable selection, and multivariate logistic regression to identify independent microecological risk factors, with Benjamini-Hochberg false discovery rate (FDR) correction applied across all tests. A targeted subset (n = 88) underwent 16S rRNA sequencing with differential taxa analysis using LEfSe and Random Forest, as well as BugBase phenotype prediction and COG/KEGG pathway analysis, to validate age-specific HPV-microbiome interactions.

RESULTS: Normal flora prevalence declined linearly with age (78.7% vs. 48.8% postmenopause, q<0.001), while microbial diversity peaked during perimenopause. HPV infection was selectively associated with increased bacterial vaginosis (BV) (41.58% vs. 36.46%, q=0.032) and sialidase activity (28.14% vs. 21.69%, q=0.002), but decreased vulvovaginal candidiasis (VVC, 10.57% vs. 15.66%, q=0.003). Functional analyses revealed HPV-driven anaerobic enrichment (Gardnerella, Atopobium) and profound metabolic reprogramming specifically in women aged 35-44 years, marked by upregulation of lipopolysaccharide biosynthesis (fold change [FC] = 37.3, q = 0.028), arachidonic acid metabolism (FC = 33.3, q = 0.038), and NOD-like receptor signaling (FC = 62.1, q < 0.001), with concurrent apoptosis suppression (FC = 0.35, q = 0.046). Age-stratified risk modeling identified loss of H2O2-producing Lactobacilli as the strongest HPV risk factor in younger women (18-34 years, adjusted odds ratio [aOR] = 0.59), whereas BV and sialidase dominated in midlife (35-44 years, aOR = 1.64); no significant risk factors emerged postmenopause.

CONCLUSION: HPV infection selectively remodels vaginal microbiota composition and metabolic function in an age-dependent manner, with midlife women (35-44 years) representing a critical window for microbiota-based HPV prevention strategies.}, } @article {pmid41647191, year = {2025}, author = {Yamasaki, A and Tomita, K}, title = {Editorial: Exploring the interconnection: obesity's role in asthma development and management.}, journal = {Frontiers in allergy}, volume = {6}, number = {}, pages = {1759789}, doi = {10.3389/falgy.2025.1759789}, pmid = {41647191}, issn = {2673-6101}, } @article {pmid41647190, year = {2025}, author = {Rank, MA and Barroso, DL and Conn, KA and Pecak, M and Scandura, M and Hirsch, AH and Gu, H and Whisner, CM and Shearer, H and Johnson, D and Argel, N and Bauer, CS and Williams, SN and Wright, BL and Woodward, J and Cope, EK}, title = {A randomized, double-blind, placebo-controlled trial of soluble corn fiber supplementation for children with asthma.}, journal = {Frontiers in allergy}, volume = {6}, number = {}, pages = {1707834}, pmid = {41647190}, issn = {2673-6101}, abstract = {INTRODUCTION: Asthma is a multifactorial disease influenced by genetic and environmental factors, including diet. The gut microbiome contributes to airway inflammation via the gut-lung axis, partly through production of short chain fatty acids (SCFAs) from bacterial fermentation of dietary fiber. We hypothesized that dietary fiber supplementation could modulate the gut microbiome and increase SCFAs in children with asthma.

METHODS: This is a double-blind, placebo-controlled trial of children who were randomized to consume 12 g of soluble corn fiber (SCF) as a supplement to their usual daily diet (50% the recommended daily fiber intake) or placebo for 4-6 weeks (clinicaltrials.gov NCT03673618). Dietary surveys, asthma symptom questionnaires, fecal, blood and nasal samples were collected before and after the intervention period to quantify fiber intake, asthma control, nasal and gut microbiome, and serum short chain fatty acids (SCFAs).

RESULTS: Of the 20 children enrolled, 15 completed the intervention with an average adherence rate of 83%. SCFA concentrations and gut microbiome changes varied by individual and treatment group. No significant differences in gut or nasal alpha or beta diversity were observed between groups post-intervention. However, differential abundance analysis showed a trend toward increased Bifidobacterium in the SCF group compared to placebo (ANCOM-BC p = 0.0004, FDR q = 0.073).

DISCUSSION: Supplementation of 50% of recommended daily fiber intake had minimal impact on asthma symptoms, the microbiome, or SCFA levels. Future studies should consider higher fiber doses, different fiber types, or targeting individuals with low baseline fiber intake to account for observed variability in microbiome and SCFA responses.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT03673618, identifier NCT03673618.}, } @article {pmid41646975, year = {2025}, author = {Wang, H and Zhou, C}, title = {Advances in the pathogenesis of rosacea.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1705588}, pmid = {41646975}, issn = {1664-3224}, mesh = {Humans ; *Rosacea/etiology/metabolism/immunology/pathology/genetics ; Animals ; *Skin/immunology/metabolism/pathology/microbiology ; Signal Transduction ; Immunity, Innate ; Dysbiosis ; Gastrointestinal Microbiome/immunology ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Toll-Like Receptor 2/metabolism ; Cathelicidins/metabolism ; }, abstract = {Rosacea is a chronic inflammatory cutaneous disorder predominantly affecting the centrofacial region, whose pathogenesis is complex and not yet fully understood. In this review we summarized the latest significant advances in the pathogenesis of rosacea in recent years. In genomic studies, the application of bioinformatics techniques such as whole-genome sequencing has identified novel susceptibility genes and linked multiple pathogenic mechanisms. Neurovascular dysfunction resulting from abnormal neuropeptides expression and dysregulated amino acid metabolism constitutes an important pathogenic factor in rosacea. The TLR2/LL-37/mTORC1 signaling axis, as a core regulatory pathway in innate immunity has been elucidated in detail. In addition, the dysbiosis of skin and gut microbiota, together with the impairment of skin barrier function, is also closely associated with the onset and progression of this disease. The deeper understanding of the pathogenesis of rosacea will benefit the development of new drugs and promote individualized diagnosis and treatment.}, } @article {pmid41646872, year = {2026}, author = {Song, X and Zhai, Y and Zhang, M and Guo, J and Guo, B and Zhang, C and Jin, J and Wang, W and Xu, Y and Zhu, B and Li, X}, title = {Stochasticity Prevails but Differs: Tissue-Specific Assembly of Gut Microbiomes Across Seasons in an Amphibian Model.}, journal = {Ecology and evolution}, volume = {16}, number = {2}, pages = {e73041}, pmid = {41646872}, issn = {2045-7758}, abstract = {Gut microbiota generally undergoes dynamic remodeling in concert with multifaceted self-regulation of amphibian hosts during key life stages, such as metamorphosis and hibernation. However, the spatiotemporal dynamics of amphibian gut microbiomes across the lifecycle remain poorly understood. In this study, we applied 16S rRNA gene amplicon sequencing to characterize the gut microbiomes of cultivated Black-spotted frog (Pelophylax nigromaculatus) across seasons. The gut microbiomes exhibited tissue-specific succession, and structural discrepancies between gut regions fluctuated temporally. Both small- and large-intestine microbiomes showed temporal decay patterns in abundance-unweighted intercommunity indices, but not in abundance-weighted indices. Compared with large-intestine microbiomes, small-intestine microbiomes were more randomized yet more centralized in terms of amplicon sequence variants, particularly within Proteobacteria (especially Pseudomonas). The alpha diversity of small-intestine microbiomes was comparatively lower, and their taxonomic composition was more stable over time. We further elucidated the assembly mechanisms of gut microbiomes by systematically analyzing dominant driving factors, ecological processes, phylogenetic traits, source-sink relationships, and co-occurrence networks. Stochastic processes played a dominant role in gut microbiome assembly, while deterministic processes (e.g., habitat filtering and microbial interaction) contributed more strongly to large gut microbiomes than to small gut microbiomes. Overall, this study provides insights into the ecological dynamics and assembly mechanisms of amphibian gut microbiomes across the lifecycle and may inform targeted microbiome modification for amphibian breeding and conservation.}, } @article {pmid41646795, year = {2026}, author = {Bivens, E and Atiq, O and Evans, T and Bimali, M and Brown, G and Crane, J and Darwish, N and Faulkner, JL and Govindarajan, R and Johnson, A and Kurilung, A and Lazarenko, O and Lu, YC and Marsh, K and Moreno, M and Nookaew, I and Robeson, M and Sunde, J and Ussery, D and Vural, E and Wilman, M and Nakagawa, M}, title = {A Randomized Double-Blind Placebo-Controlled Phase I/II Clinical Trial of a Human Papillomavirus Therapeutic Vaccine, PepCan, for Reducing Head and Neck Cancer Recurrence.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.09.26343801}, pmid = {41646795}, abstract = {OBJECTIVES: Head and neck cancer (HNC) has a high recurrence rate. Safety and effectiveness of PepCan in reducing recurrence for HNC patients were assessed.

METHODS AND ANALYSIS: PepCan consists of four human papillomavirus 16 (HPV 16) E6 peptides and a Candida skin testing reagent (Candin®, Nielsen Biosciences) as a vaccine adjuvant. Since Candida was known to have a general immune stimulating effects, patients were recruited regardless of their HPV status. Men and women with HNC who had no evidence of disease after standard surgery, chemotherapy, and/or radiation treatments were enrolled. They were randomized at 3:1 to PepCan versus placebo. Seven intradermal injections of PepCan or placebo (saline) were given every 3 weeks (first 4 injections) or 3 months (last 3 injections). They were followed with two visits 6 months apart. Safety was assessed using Common Terminology Criteria for Adverse Events version 5, and efficacy was assessed based on not having recurrence within 2 years. In addition, immune responses were examined using enzyme-linked immunospot assay for HPV 16 E6 response, fluorescent-activated cell sorter analysis for peripheral immune cells, and T cell repertoire analysis. Peripheral cytokines and gut and oral microbiome were also analyzed.

RESULTS: Seventeen patients were enrolled. The most common adverse events were grades 1 and 2 injection site reactions, and they occurred more frequently in the PepCan group (p <0.0001). Two patients had allergic reactions (grade 2 and grade 3), at the 6th vaccination, which were considered to be a dose-limiting toxicity (DLT). No serious adverse events were reported. In the intention-to-treat analysis (ITT), 45% (5/11) had non-recurrence in the PepCan group while 80% (4/5) had non-recurrence in the placebo group. For the per-protocol (PP) analysis, non-recurrence was 56% (5/9) for PepCan and 80% (4/5) for placebo. These differences were not statistically significant. Those who received PepCan and experienced non-recurrence had higher new T cell immune responses to HPV 16 E6 (p =0.05 for ITT and p =0.02 for PP). Pre-vaccination T helper type 1 cells were higher in the PepCan non-recurrence group compared to the PepCan recurrence group (p =0.01 for ITT and PP).

CONCLUSIONS: PepCan is safe although DLT can occur after multiple injections of PepCan. PepCan does not seem to be effective in reducing recurrence; however, the results are inconclusive given the small patient numbers. What is already known on this topic Head and neck cancer (HNC) has a high recurrence rate after reaching no evidence of disease status after standard therapies including chemotherapy, radiation, immunotherapy and survey. However, no intervention is available to reduce recurrence. What this study adds A therapeutic human papillomavirus vaccine called PepCan was tested in a clinical trial and has been shown to be safe. How this study might affect research, practice or policy If a sufficiently powered study demonstrates efficacy in reducing recurrence rate, then how HNC patients are treated after achieving the no evidence of disease status will change.}, } @article {pmid41646784, year = {2026}, author = {Ng, J and Trannguyen, J and Wilkinson, R and Conrad, F and Fehrenbach, S and Ebersole, B and Ghosh, D and Apewokin, S}, title = {Conditioning chemotherapy exposure is associated with epigenetic modifications in Clostridioides difficile isolates from stem cell transplant recipients.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.12.25342741}, pmid = {41646784}, abstract = {Clostridioides difficile is a highly methylated organism within the gut microbiome that is responsible for Clostridioides difficile infection (CDI), a common disease that is mediated by toxins production from the bacterium. C. difficile infection is ten times more common in chemotherapy patients than the average patient, but the reasons for this disparity are unclear. Conditioning chemotherapy (CC), an integral part of cancer treatments, has the ability to induce methylation changes in many cell types. We posit that CC induces methylation changes within C. difficile that may promote toxin production and consequently CDI. To test our hypothesis, we sought to identify the epigenetic changes, particularly methylation changes, within C. difficile isolates before and after chemotherapy and within isolates that express toxin and isolates that do not. After stool sampling, we isolated C. difficile by culture then sequenced and created a hybrid assembly of each isolate using nanopore long read sequencing and Illumina short read sequencing. Bioinformatics tools such as Dorado and Samtools were used to basecall and determine methylation states, while Unicycler was used for genome assembly. Methylartist was then used for data visualization. Genome-wide methylation profiling revealed distinct epigenetic signatures in Clostridioides difficile associated with toxin expression and chemotherapy exposure. Whole-genome 6mA analysis demonstrated significant differences between toxin-positive and toxin-negative isolates, with prominent methylation changes in tcdA and tcdE , while selected sporulation genes were unmethylated in toxin-negative strains. Chemotherapy was associated with a significant shift in global 6mA methylation patterns. Targeted 5mC analysis of the pathogenicity locus revealed reduced methylation around tcdB and across multiple toxin genes following chemotherapy, whereas sporulation genes remained unaffected. These findings indicate chemotherapy-associated epigenetic remodeling of toxin-associated loci in C. difficile .}, } @article {pmid41646535, year = {2026}, author = {Okeah, IR and Afzal, UM and Ali, FR}, title = {Impact of environmental pollution on acne: a systematic review.}, journal = {Skin health and disease}, volume = {6}, number = {1}, pages = {12-19}, pmid = {41646535}, issn = {2690-442X}, abstract = {In an increasingly urbanized world, environmental pollution is recognized for its adverse effects on both systemic and skin health. While its role in conditions such as atopic dermatitis and psoriasis is well documented, its impact on acne vulgaris remains less clear. This review aims to evaluate existing literature examining the association between environmental pollutants - such as particulate matter (PM2.5, PM10), nitrogen oxides (NO2, NOx) and traffic-related emissions - and the development, severity or exacerbation of acne. A systematic search of peer-reviewed English-language studies published between 2010 and 2025 was conducted using PubMed. Search terms included 'air pollution', 'particulate matter', 'PM2.5', 'PM10', 'NO2', 'NOx', 'environmental pollution', 'traffic pollution', 'acne' and 'acne vulgaris'. Studies were included if they investigated the relationship between environmental pollutants and acne in human populations. Of the 27 studies identified, 17 met inclusion criteria. Systematic reviews were also incorporated to provide broader context. Several studies demonstrated significant associations between pollutant exposure and acne exacerbation. A time-series study in China involving 71 625 outpatient visits found that each 10 μg m[-3] increase in SO2 and NO2 correlated with 1.02% and 2.13% increases in acne-related visits, respectively. Other studies appear to show pollutants being associated with increased sebum production and reduction of antioxidants. Proposed mechanisms include oxidative stress, microbiome disruption and follicular hyperkeratinization. However, study heterogeneity, lack of diversity and limited control for confounders limit generalizability. Longitudinal research is needed to clarify pollution's role in acne and inform targeted prevention strategies.}, } @article {pmid41646429, year = {2026}, author = {Doren, VV and Smith, S and Grimsley-Ackerley, C and Keith, J and Arthur, R and Claussen, H and Murray, P and Tangpricha, V and Hu, Y and Su, C and He, M and Kelley, C}, title = {The Biosocial Microbiome: Gender Identity, Geography, and Mucosal Microbial Phenotypes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-8368158/v1}, pmid = {41646429}, issn = {2693-5015}, abstract = {Background Transgender women (TGW) experience unique hormonal contexts and high HIV incidence, yet the mucosal microbiome among TGW remains understudied. Sex hormones and geography may shape microbial composition, but the relative contributions of gender identity, feminizing hormone therapy (FHT), and location to mucosal microbial phenotypes among key populations such as TGW are unknown. Methods We conducted a multi-site study of cisgender men who have sex with men (MSM) and TGW using FHT, both without HIV, in Atlanta, Georgia, USA (n = 58; 25 TGW, 33 MSM) and Bangkok, Thailand (n = 147; 97 TGW, 50 MSM), using cross-sectional sampling (n = 205). We also conducted longitudinal sampling in TGW (n = 21) pre/post FHT initiation. Rectal mucosal swabs were collected from all participants with optional neovaginal sampling in TGW. Microbiota composition was analyzed using 16S rRNA sequencing, and associations with gender identity, geography, and serum estradiol and testosterone concentrations were assessed using linear decomposition modeling (LDM)(1) and BOUTH analysis(2). Results Rectal microbiota differed significantly by both gender identity and geography via LDM and BOUTH analyses. TGW exhibited enrichment of estrogen-metabolizing taxa across sites, while MSM showed Prevotellaceae enrichment in Atlanta but not Bangkok. Alpha diversity varied by location but not gender identity. Neovaginal microbiota differed markedly from rectal composition, showing enrichment of skin- and gut-associated taxa (e.g., Prevotella, Peptostreptococcus, Porphyromonas) and anaerobic taxa associated with HIV seroconversion. Longitudinal analysis revealed no significant rectal microbiota shifts after short-term FHT initiation, possibly reflecting subtherapeutic hormone exposure. Conclusions These findings underscore the need to consider gender identity as a complex biosocial phenotype in HIV prevention and highlight the potential role of mucosal microbiota in shaping HIV vulnerability in TGW.}, } @article {pmid41646428, year = {2026}, author = {Lima, RD and Bauer, OR and Pauer, H and Hajiarbabi, K and Moreira, DA and Parente, TE and Ferreira, RBR}, title = {Cutibacterium acnes inhibits Staphylococcus lugdunensis biofilm formation through inhibition of autolysis and purine biosynthesis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-8408722/v1}, pmid = {41646428}, issn = {2693-5015}, abstract = {Cutibacterium acnes is a predominant member of the human skin microbiome that plays a pivotal role in maintaining homeostasis and protecting the host against pathogen colonization. Staphylococcus lugdunensis , while also a resident of the skin microbiota, is an opportunistic pathogen capable of causing severe infections, associated with its ability to form biofilms. Building on our previous observation that C. acnes secretes molecules capable of inhibiting S. lugdunensis biofilm formation without inhibiting planktonic growth, we investigated the underlying molecular mechanisms of this phenomenon and its impact on pathogenicity. Here, we demonstrate that cell-free supernatants from various C. acnes strains exhibit dose-dependent antibiofilm activity targeting the initial stages of S. lugdunensis biofilm development. Additionally, extracellular molecules from C. acnes cultures significantly reduced the ability of S. lugdunensis to adhere to and invade human epithelial cells (A549) and to adhere to keratinocytes (HaCaT). Transcriptomic analysis revealed that C. acnes -derived molecules significantly repressed the expression of genes involved in purine biosynthesis in S. lugdunensis , while inducing the expression of the negative regulators of autolysis, lrgA and lrgB . Functional assays confirmed that C. acnes -derived molecules inhibit autolysis and extracellular DNA (eDNA) release by S. lugdunensis . Crucially, the addition of exogenous guanine suppressed the effect of C. acnes molecules on both biofilm formation and lrgA gene expression. Collectively, our data indicate that C. acnes molecules inhibit S. lugdunensis biofilm formation by depleting the intracellular guanine pool, which leads to repression of autolysis, thereby reducing the release of eDNA essential for biofilm structural integrity. These findings underscore the potential of exploiting interspecies microbiome interactions to better understand their role in pathogen exclusion.}, } @article {pmid41646408, year = {2026}, author = {Bosquet, JG and Osazuwa-Peters, O and Wagner, VM and Polio, A and Hoyd, R and Tarhini, AA and Cosgrove, CM and Huang, MS and Corr, BR and Leiser, AL and Salhia, B and Darcy, K and Dood, RL and Dockery, LE and Cavnar, MJ and Landrum, L and Chambers, L and Tan, AC and Jin, N and Rounbehler, RJ and Churchman, ML and Spakowicz, D}, title = {Intrinsic tumor factors and extrinsic environmental and social exposures contribute to endometrial cancer recurrence patterns.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-8682460/v1}, pmid = {41646408}, issn = {2693-5015}, abstract = {Purpose In a previous study, we trained, validated and tested models of endometrial cancer (EC) recurrence integrating clinical, genomic and pathological data from the Oncology Research Information Exchange Network (ORIEN). Preliminary studies also have demonstrated that bacterial communities may influence the risk of EC recurrence by altering the local environment within the upper female genital tract. The objective of this study was to evaluate whether extrinsic and environmental factors, including tumor-associated bacterial communities, tumor immune contexture and air pollution alongside clinical, pathologic and genomic features are associated with EC recurrence across clinically relevant risk groups. Patients and Methods: We performed a retrospective, multi-institution, case-control study with data from the ORIEN network EC dataset. Data was stratified into low-risk, FIGO grade 1 and 2, stage I (N = 329), high-risk, or FIGO grade 3 or stages II-IV (N = 324), and non-endometrioid histology (N = 239) groups. RNA and DNA were extracted from tumor specimens and processed to obtain the necessary genomic/metagenomic data. Genus level microbiome data were extracted and curated) from RNA sequencing using Kraken2 , Bracken and exotic software packages. Risk of EC recurrence was evaluated by integrating microbiome and environmental data alongside existing clinical, pathological and genomic data using topic modelling with latent dirichlet allocation (LDA). Prediction models of EC recurrence were created using machine and deep learning analytics (ML and DL) with MATLAB apps and TensorFlow . Finally, performance of both topic and prediction models were externally validated in an independent EC dataset from TCGA. Results The resulting models, analyzed with topic modelling, demonstrated the complexity of factors involved in recurrence of disease for EC. The components of the resulting topic models, and specifically the microbiome, changed when environmental factors, like air pollutants, were introduced in the model. In the low-risk EC group, microbes that were quite abundant in models before introducing environmental factors, were scarcely seen afterwards, like genera Thermothielavioides , Theileria , Rhizoctonia . Bacillus was the genus with higher per-topic probability within all risk groups, especially for low-risk EC (28%). Ozone (O 3) was a resulting component of all risk groups' models. BMI was the sole informative clinical variable after data integration, and only present in the low-risk group. Resulting models from the high-risk and non-endometrioid groups included differential gene expressions: MMP13, S100A7, SMOC1, ACACA and ADD2, DLX5, SLCO2B1, NWD1 respectively. CNVs also were present in both low-risk and non-endometrioid groups, but their per-topic probabilities were low. The same was true for the immune contexture data. The components of the resulting topic models were used to train, validate and test prediction models of EC recurrence by risk groups. Performances of these models were excellent (@ 0.9). Despite some missing microbiome data in TCGA from resulting topic models, prediction models trained in the ORIEN set, had similar performances in TCGA testing set, with overlapping AUC 95% CIs. Conclusion Both extrinsic factors (tumor-associated bacterial communities, tumor immune contexture and air pollution) and intrinsic factors predict EC recurrence. The complexity of tumor and host factors influencing cancer relapses underscore the need for more individualized prediction models of disease outcomes.}, } @article {pmid41646275, year = {2025}, author = {Naddaf, R and Shmilovich, H and Carasso, S and Keshet-David, R and Herren, R and Gefen, T and Goshen-Lago, T and Zwang, Y and Livyatan, I and Shental, N and Haberfeld, O and Straussman, R and Markar, SR and Nilsson, M and Kashtan, H and Ben-Aharon, I and Geva-Zatorsky, N}, title = {Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients.}, journal = {ESMO gastrointestinal oncology}, volume = {8}, number = {}, pages = {100172}, pmid = {41646275}, issn = {2949-8198}, abstract = {BACKGROUND: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients.

MATERIALS AND METHODS: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs.

RESULTS: Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication.

CONCLUSIONS: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.}, } @article {pmid41646110, year = {2024}, author = {Kennedy, J and Iyer, K and Grinspan, A and Lai, J}, title = {Safe and successful fecal microbiota transplantation for recurrent Clostridioides difficile infection in a child with an intestinal transplant.}, journal = {Intestinal Failure (New York, N.Y.)}, volume = {4}, number = {}, pages = {100046}, pmid = {41646110}, issn = {2950-4562}, abstract = {Fecal microbiota transplantation (FMT) treats patients with recurrent Clostridioides difficile infections (CDI) by restoring the colonic flora with a balanced microbiome. There are currently no reports of safe and successful FMT in pediatric patients with history of intestinal transplant on immunosuppression. Our case report describes a 6-year-old boy with a multi-visceral transplant (including: stomach, small bowel, colon, liver, pancreas, and en-bloc bilateral kidneys) who had recurrent CDI episodes treated with antibiotics (including prolonged tapers). After multiple recurrences, he had a FMT via colonoscopy. The fecal preparation was inserted in the transplanted cecum without complication. The patient did well without any adverse events or need for hospitalization and the FMT was a success, as he had no recurrent symptoms in the 3 months following FMT.}, } @article {pmid41645949, year = {2025}, author = {Narang, H and Ahuja, V}, title = {'Mining' the Gut: The Microbiome 'Lassonde curve'.}, journal = {The National medical journal of India}, volume = {38}, number = {5}, pages = {257-263}, doi = {10.25259/NMJI_1737_2025}, pmid = {41645949}, issn = {2583-150X}, } @article {pmid41645895, year = {2026}, author = {Krishna, M and Boyer, JL}, title = {Ileal Bile Acid Transporter Inhibitors in Cholestasis: Potential for More Than Just Paediatrics?.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {46}, number = {3}, pages = {e70524}, doi = {10.1111/liv.70524}, pmid = {41645895}, issn = {1478-3231}, mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Cholestasis/drug therapy ; *Ileum/metabolism/drug effects ; Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors ; Pruritus/drug therapy/etiology ; Enterohepatic Circulation/drug effects ; Carrier Proteins ; Membrane Glycoproteins ; Methylamines ; Thiazepines ; }, abstract = {Ileal bile acid transporter inhibitors (IBATi) are a new, attractive therapeutic mechanism to alter the enterohepatic circulation through depletion of the bile acid pool by blocking bile acid reuptake in the ileum leading to improvements in pruritus and liver function in cholestatic liver diseases. These drugs may also have an impact on immunity, the gut microbiome, and motility. IBATi are approved in Japan for the treatment of idiopathic chronic constipation. There are two IBATi, maralixibat and odevixibat, that have been extensively investigated in clinical trials and are FDA approved for cholestatic pruritus in progressive familial intrahepatic cholestasis and Alagille syndrome. Clinical trials exploring IBATi in other cholestatic conditions, such as biliary atresia, primary biliary cholangitis, and primary sclerosing cholangitis, are currently ongoing. In this review, we will outline the emerging data regarding the physiology and mechanism of action for the IBATi class, an overview of clinical trials that led to the approval of maralixibat and odevixibat, ongoing clinical trials in adult cholestatic liver diseases, and the future of this drug class in systemic apical sodium bile acid transporter inhibitors.}, } @article {pmid41645696, year = {2026}, author = {Peng, J and Yan, Q and Hassan, MU and Imran, M and Haider, FU and Liang, J and Wang, X and Ali, S}, title = {Metarhizium anisopliaeMitigates the Phytotoxicity of Lead and Nanoplastics on Rice by Modifying Physiological, Transcriptomic, Metabolomic Activities, and Soil Microbiome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e21570}, doi = {10.1002/advs.202521570}, pmid = {41645696}, issn = {2198-3844}, support = {YNDG202402YY02//Yunnan Daguan Laboratory/ ; 2023530000241004//Key Science and Technology Projects of YNTC/ ; 2024CXTD11//Modern Agricultural Technology Industry System of Shandong province/ ; }, abstract = {Polyethylene nanoplastics (NP) and lead (Pb) increasingly co-occur in agriculture, where their effects exacerbate phytotoxic impacts. We tested whether the endophytic entomopathogenic fungus, Metarhizium anisopliae, can mitigate individual or combined stress of NP and Pb in rice by examining fungus-soil-plant mechanisms using physiological assays, transcriptomics, metabolomics, and rhizosphere microbiome profiling. Rice seedlings were grown under eight treatments (individual or combined stress of Pb and NP, with or without M. anisopliae). Individual and combined Pb and NP stress reduced seedling growth, chlorophyll content, and hormonal levels, while increasing oxidative damage. Pb and NP interactions showed synergistic toxicity, causing severe growth suppression and lipid peroxidation, and repressing photosynthesis and hormone-related pathways. M anisopliae inoculation alleviated these effects and enhanced rice growth by reducing Pb uptake and translocation, restoring antioxidant and hormonal balance, and up-regulating pathways including flavonoid biosynthesis, ABC transporters, and hormone signaling. Pb measurements showed fungal inoculation restricted Pb uptake as a protective mechanism. M. anisopliae reshaped the soil bacterial community, enriching taxa associated with plant growth promotion and contaminant tolerance. These findings identify M. anisopliae seed inoculation as a strategy to mitigate Pb and NP phytotoxicity in rice by integrating contaminant uptake control with plant and rhizosphere reprogramming.}, } @article {pmid41645639, year = {2026}, author = {Toppila-Salmi, S and Reitsma, S and Hox, V and Gane, S and Gevaert, P and Maza-Solano, J and Helevä, A and Sulku, I and Santala, K and Kangasniemi, I and Klimek, L and Chaker, A and Karavelia, A and Rudenko, M and Pfaar, O and Van Gerven, L and Ariana, S and Schiappoli, M and Lundberg, M and Hagemann, J and Eguíluz-Gracia, I and Moreira, A}, title = {Comorbid Chronic Rhinosinusitis and Asthma: Shared Risk Factors and Treatment Implications-An EAACI Task Force Report.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.70237}, pmid = {41645639}, issn = {1398-9995}, support = {40211//European Academy of Allergy and Clinical Immunology (EAACI) under the EAACI (project Prevalence and predictive factors for comorbid CRS and asthma/ ; //Foundation of the Finnish Anti-Tuberculosis Association/ ; //Tampereen Tuberkuloosisäätiö/ ; //Allergy Research Foundation/ ; //State funding for university-level health research/ ; }, abstract = {Chronic rhinosinusitis (CRS) and asthma are prevalent conditions that often coexist. These diseases share common inflammatory mechanisms, such as T-helper cell 2 (T2)-high inflammation, driven by interleukin (IL)-4, IL-5, and IL-13 cytokines. The frequent comorbidity between CRS, especially CRS with nasal polyps (CRSwNP), and asthma exacerbates disease severity, impairs quality of life, and complicates treatment. Patients with NSAID-exacerbated respiratory disease (N-ERD) represent a severe phenotype of this disease, characterized by the coexistence of CRSwNP, asthma, and NSAID hypersensitivity, which poses unique therapeutic challenges. This EAACI Task Force explores the shared risk factors, including genetic predispositions, epithelial barrier dysfunction, microbiome dysbiosis, underlying CRS, and asthma. It also evaluates current therapeutic strategies such as biologics, aspirin therapy after desensitization (ATAD), and endoscopic sinus surgery (ESS). Biologics have shown their effectiveness and safety in the treatment of asthma and CRS. Dupilumab, mepolizumab, depemokimab, and omalizumab have emerged as transformative therapies, particularly for patients with severe type 2 inflammation. Tezepelulumab is effective for both T2-high and T2-low asthma and CRSwNP. Itepekimab has shown its effect in asthma and is under investigation for CRSwNP. Omalizumab is effective in allergic asthma and CRSwNP. ATAD provides an additional disease-modifying approach for N-ERD, though patient adherence and tolerability remain critical challenges. ESS significantly improves asthma control, reduces medication use, and enhances sinonasal outcomes, particularly in severe asthma cases; however, these patients often need recurring surgeries. Despite these advances, treatment outcomes vary based on individual phenotypes and endotypes, underscoring the need for personalized approaches. The report highlights gaps in the literature, such as the lack of head-to-head trials comparing biologics, ATAD, and surgery. Future research should focus on refining treatment algorithms, identifying biomarkers for treatment selection, and assessing long-term outcomes to optimize care for patients with CRS, asthma, and N-ERD.}, } @article {pmid41645608, year = {2026}, author = {Bohn, B and Tilves, C and Tanaka, T and Ferrucci, L and Chia, CW and Spira, A and Mueller, NT}, title = {Initiation of Proton Pump Inhibitors is Associated with Gut Microbiome Diversity and Composition: a new-user target trial emulation within the Baltimore Longitudinal Study of Aging.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwag026}, pmid = {41645608}, issn = {1476-6256}, } @article {pmid41645592, year = {2026}, author = {Sindelar, M and Kocurkova, A and Simek, M and Roudnicky, P and Ambrozova, G and Kubala, L and Turkova, K}, title = {Revisiting Hyaluronan Catabolism in Bacteroides: Pathway Conservation, Overlooked Proteins, and Predictive Accuracy.}, journal = {MicrobiologyOpen}, volume = {15}, number = {1}, pages = {e70227}, doi = {10.1002/mbo3.70227}, pmid = {41645592}, issn = {2045-8827}, support = {//Czech Academy of Sciences/ ; 25-16326S//Czech Science Foundation/ ; LX22NPO5104//Next Generation EU/ ; LM2023042//MEYS CR/ ; 90254//MEYS CR/ ; CZ.02.01.01/00/23_015/0008175//European Regional Development Fund-Project/ ; }, mesh = {*Hyaluronic Acid/metabolism ; *Bacteroides/metabolism/genetics ; *Bacterial Proteins/metabolism/genetics ; Proteomics ; *Metabolic Networks and Pathways/genetics ; Gastrointestinal Microbiome ; }, abstract = {The ability of gut microbes to degrade host- and diet-derived glycans is central to microbiome ecology and host interactions, yet predicting these functions in silico remains challenging. Hyaluronan (HA), a glycosaminoglycan (GAG) abundant in host tissues and dietary supplements, is depolymerized by specialized polysaccharide utilization loci (PULs) in Bacteroides. Here, we combined comparative protein analysis, functional assays, and quantitative proteomics to evaluate the reliability of sequence-based predictions of HA utilization. Clustering of more than 3900 PL8 and GH88 protein sequences from 54 Bacteroides species did not distinguish known HA degraders from nondegraders, underscoring the limited predictive power of these enzymes alone. Experimental validation in Bacteroides acidifaciens DSM 111135 and Bacteroides thetaiotaomicron DSM 2079 confirmed HA degradation, as HA-derived fragments were identified by liquid chromatography-mass spectrometry. Proteomic profiling revealed coordinated induction of both canonical GAG-specific PULs-encoded proteins and noncanonical accessory proteins (BT4410/BT4411) in response to HA in both species. Incorporating such noncanonical components into comparative frameworks may improve prediction of glycan utilization potential and help link microbial genomic content to ecological function in the gut.}, } @article {pmid41645591, year = {2026}, author = {Han, SJ and Wei, JL and Xu, QQ and Wei, XH and Shang, H}, title = {Association of Butyrate Supplementation with Cardiovascular Disease:A Narrative Review.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {3}, pages = {e70374}, doi = {10.1002/mnfr.70374}, pmid = {41645591}, issn = {1613-4133}, support = {82574739//National Natural Science Foundation of China/ ; 2024-JYB-JBZD-046//The Fundamental Research Funds for the Central Universities/ ; 2025M773867//China Postdoctoral Science Foundation/ ; }, mesh = {Humans ; *Cardiovascular Diseases/prevention & control ; *Butyrates/pharmacology/administration & dosage ; *Dietary Supplements ; Gastrointestinal Microbiome/drug effects ; Animals ; }, abstract = {Cardiovascular diseases (CVDs) have long been a significant source of the global disease burden and a leading cause of death and disability. In recent years, the precise microbiome modulation of the gut has made remarkable progress as a new strategy for treating CVDs, especially its production of short-chain fatty acids, the primary way the gut flora affects the organism. Butyrate, one of the critical metabolites of short-chain fatty acids, butyrate uniquely restores intestinal barrier function, suppresses systemic inflammation, promotes immune tolerance, and regulates energy metabolism while antagonizing the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) via the gut-heart axis. Preclinical studies consistently show that butyrate supplementation mitigates heart failure (HF), atherosclerosis, myocardial infarction, hypertrophic cardiomyopathy, hypertension, and cancer-related cardiac injury, and concurrently ameliorates metabolic syndrome, dyslipidaemia, and hyperglycaemia. However, clinical translation is currently hampered by a lack of large-scale human randomized controlled trials (RCTs) and an insufficient understanding of human dose-response relationships. This review synthesizes knowledge on butyrate's cardiovascular actions, details the underlying mechanisms, and highlights critical evidence gaps to inform future translational research.}, } @article {pmid41645327, year = {2026}, author = {Zubair, A and Alkahtani, AM and Shahani, MY and Afghan, N}, title = {Gut microbiome-based strategies for HIV prevention and therapy, current challenges and future prospects.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {11}, pmid = {41645327}, issn = {1757-4749}, abstract = {The gut microbiome has become a primary controller of host immunity as well as the pathogenesis of human immunodeficiency virus (HIV) infection. Commensal microbes in healthy persons keep the intestinal and other body barriers intact and regulate mucosal and systemic immune responses and generate metabolites, including short-chain fatty acids and indole derivatives that suppress inflammation and stimulate epithelial healing. These functions are impaired by HIV infection via depletion of gut CD4 + T cells, damage caused to epithelium, microbial translocation, and microbiota disruption. In this review article, we summarize recent studies suggesting that a balanced microbiome can mitigate HIV susceptibility and progression by preserving mucosal defenses, limiting systemic immune activation, and generating antiviral compounds. Other interventions, including probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT), have been trialed with mixed outcomes in most cases, showing small but significant changes in the gut microbial composition and/or inflammatory markers. Current evidence highlights the potential of microbiome-targeted strategies to support HIV management; however, substantial gaps remain. Future research should focus on defining protective microbial signatures, developing next-generation live biotherapeutics, exploring metabolite-based therapies, and conducting large, mechanistically driven clinical trials. Harnessing the microbiome's protective functions could offer novel approaches to reducing HIV transmission, mitigating inflammation, and improving immune reconstitution in infected individuals.}, } @article {pmid41645314, year = {2026}, author = {Lu, R and Zhang, Z and Cai, J and Zhao, G and Shen, W and Yang, Y and Jiang, Z and Hu, H}, title = {Veillonella, Neisseria, Prevotella, and Lachnoanaerobaculum enrichment in salivary microbiome predicts gallstone disease.}, journal = {European journal of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40001-026-03869-0}, pmid = {41645314}, issn = {2047-783X}, support = {81770625, 81770626//National Natural Science Foundation of China/ ; }, abstract = {INTRODUCTION: Gallstone disease (GSD) is a common hepatobiliary disorder influenced by bile composition, biliary drainage, and gallbladder motility. Emerging evidence suggests that oral microbiota may contribute to GSD development, but its role remains unclear. This study explores salivary microbiome alterations in GSD patients and their potential clinical relevance.

METHODS: This study enrolled 58 GSD patients and 10 age-matched healthy controls. Salivary microbiome profiles were characterized using high-resolution 16S rRNA amplicon sequencing. All participants underwent comprehensive clinical evaluations including physical examinations, oral health assessments, anthropometric measurements, and fasting venous blood sampling for serum biochemical analysis. A multi-dimensional approach was applied to investigate host-microbiome interactions and their potential role in GSD pathogenesis.

RESULTS: Comparative analysis revealed significant microbial divergence between GSD patients and healthy controls, characterized by increased α-diversity indices and distinct β-diversity clustering. The linear discriminant analysis effect size (LEfSe) analysis identified 65 differentially abundant taxonomic features across multiple phylogenetic levels, including 7 phyla, 9 classes, 11 orders, 16 families, and 22 genera, representing 550 operational taxonomic units (OTUs). Notably, Veillonella, Neisseria, Prevotella, and Lachnoanaerobaculum were markedly enriched in the GSD cohort. The developed eXtreme Gradient Boosting (XGBoost) diagnostic model demonstrated exceptional discriminatory capacity, achieving a mean AUC of 0.994 under rigorous fivefold cross-validation. Redundancy analysis (RDA) and Spearman correlation analysis showed strong associations between microbial community structure and key biochemical markers, including chenodeoxycholic acid (CDCA) and alkaline phosphatase (ALP). Functional prediction using PICRUSt2 indicated substantial metabolic pathway alterations in GSD patients, particularly enhanced activity in energy production, amino acid metabolism, and secondary metabolite biosynthesis.

CONCLUSIONS: Salivary microbiome dysbiosis in GSD patients demonstrated significant associations with disrupted bile acid homeostasis, suggesting a potential role of the oral microbiota in modulating lithogenic processes. The markedly altered microbial signatures may contribute to GSD pathogenesis, while the XGBoost-based diagnostic model shows considerable promise as a noninvasive tool for GSD detection.}, } @article {pmid41645302, year = {2026}, author = {Barrett, DE and Heintzman, LJ and Davidson, GR and Jackson, CR and Moore, MT}, title = {Barking up the right tree: ecological insights into the microbiome of bald cypress tree bark.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00862-2}, pmid = {41645302}, issn = {2524-6372}, abstract = {BACKGROUND: Trees and their associated microbes provide numerous ecosystem services including carbon sequestration, nutrient cycling and phytoremediation. Tree bark represents a large and seasonably stable habitat for microbial communities. However, the tree bark microbiome remains largely understudied, particularly for wetland tree species. In the Lower Mississippi River Basin, bald cypress (Taxodium distichum) are the predominant tree species in many wetlands, including lakes and streams connected to large agroecosystems dominated by row-crop agriculture. These water bodies are often managed for irrigation and drainage needs and are subject to agrochemical runoff from adjacent fields. Thus, we sought to understand how hydrology affects the bald cypress bark microbiome.

RESULTS: We collected 278 bark samples over six months from 18 trees located in three different lakes. Using 16S rRNA gene sequencing, we found that the bald cypress tree bark microbiome was largely consistent between trees within a lake as well as between different lakes, with a core microbiome that includes bacterial taxa that were present in over 95% of samples collected. Hydrology had a significant influence on microbiome structure, with different sections of bark having distinct bacterial communities depending on if the bark was submerged, just above the water, or dry. Water quality was significantly correlated with alpha diversity of wet bark, which was more diverse than dry bark and had higher relative abundances of bacteria that may be providing relevant ecosystem services such as denitrification, methane oxidation, and pollutant degradation.

CONCLUSIONS: Wetlands are important for nutrient cycling and water quality regulation. Our study provides insights into microbial dynamics of these ecosystems and how hydrology can impact the microbial communities present, which in turn may be impacting water quality. This work is the first to the describe the bark microbiome of a wetland tree species and lays the groundwork for future studies assessing the functional role of the microbiome in wetland ecosystem services.}, } @article {pmid41645294, year = {2026}, author = {Zhang, ZY and Wei, GF and Hou, LY and Zhang, GZ and Li, XD and Li, M and Meng, L and Wu, GY and Xu, J and Zhou, YX and Sun, C and Dong, LL}, title = {Effects of developmental stage-driven fungal community shifts on biomass and metabolite accumulation in Gastrodia elata.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00860-4}, pmid = {41645294}, issn = {2524-6372}, support = {CI2023E001TS03-04-01//grants from the Scientific and technological innovation project of China Academy of Chinese Medical Science/ ; 2024SF-ZDCYL-03-10//Shaanxi Province Key R&D Plan/ ; HJSYF2024(31)//Nuclear Technology R&D Program/ ; }, abstract = {BACKGROUND: Fungal communities play crucial roles in plant development and metabolite accumulation, especially in fully mycoheterotrophic medicinal plants like Gastrodia elata. While the importance of fungal symbiosis in G. elata is recognized, how fungal community dynamics evolve across its entire growth cycle and how they influence biomass and bioactive compound accumulation remain largely unclear.

RESULTS: High-throughput sequencing combined with multi-omics analyses revealed that developmental progression significantly shapes fungal diversity and composition, thereby influencing biomass and metabolite accumulation in G. elata. These effects are mediated by stage-specific selective recruitment and dynamic remodeling of fungal communities in both rhizome and rhizosphere compartments. Structural equation modeling indicated that developmental stage, fungal α-diversity, and community structure exert both direct and indirect effects on biomass and the accumulation of bioactive compounds. High-resolution association network analyses further identified key functional fungal groups, particularly wood and soil saprotrophs, as major contributors to seed stem biomass regulation. Notably, the symbiotic fungus Armillaria showed the strongest positive correlation with gastrodin accumulation, while wood saprotrophs and plant pathogens also significantly influenced its levels.

CONCLUSIONS: This study systematically elucidates the dynamic changes in fungal communities across different developmental stages of G. elata and their effects on biomass and bioactive metabolite accumulation. Our findings highlight the central role of microbe-plant-metabolite interactions in regulating biomass and bioactive metabolite production, offering valuable insight for optimizing the cultivation and quality of medicinal plants through microbiome-targeted strategies.}, } @article {pmid41645277, year = {2026}, author = {Ramírez, GA and Bar-Shalom, R and Perez, T and Epchtien, RE and Furlan, A and Romeo, R and Gavagnin, M and Garber, AI and Lalzar, M and Steindler, L}, title = {Diel transcriptional dynamics of a marine sponge and its microbiome in a natural environment.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {12}, pmid = {41645277}, issn = {2524-4671}, support = {GBMF9352//Gordon and Betty Moore Foundation/ ; 933/23//Israel Science Foundation/ ; }, } @article {pmid41645116, year = {2026}, author = {Wang, X and Long, T and Shen, L and Hu, Y and Zou, Y and Wang, Z and Yang, K and Dai, F and Song, L}, title = {Periodontal disease-associated oral and gut microbiome changes in female rheumatoid arthritis patients.}, journal = {BMC oral health}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12903-026-07831-8}, pmid = {41645116}, issn = {1472-6831}, support = {no. 82460196//the National Natural Science Foundation of China/ ; no. 20252BCG330024//the Key R&D Program of Jiangxi Province, China/ ; no. jxsq2023201045//the Double Thousand Talents Project of Jiangxi Province/ ; no. G/Y3034//the High-level and High-skilled Leading Talent Training Project of Jiangxi Province/ ; }, } @article {pmid41645099, year = {2026}, author = {Qiu, Y and Mo, F and Chen, Y and Lai, Y and Zhang, K and Huang, Z}, title = {Intersite differences in gut microbiome are associated with habitat quality in a limestone forest-dwelling langur.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04800-7}, pmid = {41645099}, issn = {1471-2180}, support = {2023GXNSFBA026045//Natural Science Foundation of Guangxi Zhuang Autonomous Region/ ; no.32170488//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Studying the compositional structure and function of the gut microbiome is essential for evaluating adaptability of wildlife to their environment. Given the high plasticity of the gut microbiome in primates, studying conspecific populations under different habitat quality can provide valuable insights for the conservation and management. To investigate intersite differences in composition and function of the gut microbiome of endangered François' langurs (Trachypithecus francoisi), we employed 16S rRNA and metagenomic sequencing.

RESULTS: The results showed that higher gut microbiota diversity of François' langurs was associated with higher habitat quality, possibly driven by the dietary diversity. In contrast, François' langurs inhabiting lower-quality habitats had a higher relative abundance of Bacillota and more enriched functional genes related to amino acid metabolism and metabolic pathways than those in higher-quality habitats, which support enhanced fiber degradation to meet energy demands. Additionally, the proportion of tetracycline-related ARGs (tetA(58)) was more abundant in lower-quality habitats, likely due to villagers applying livestock and poultry manure.

CONCLUSION: Our study concludes that intersite differences in gut microbiome are associated with habitat quality in the François' langurs, underscoring its role in habitat adaptation and necessity for physiological indicators to elucidate the mechanisms by which wildlife responds to human disturbance and ecological variability. In addition, we recommend prioritizing the restoration of native vegetation diversity in the langurs' habitats, which leverages their gut microbiota's adaptive potential to provide a suitable fundamental environment for the langurs' long-term survival.}, } @article {pmid41645047, year = {2026}, author = {Thalib, HI and Fatima, N and Fakruddin, FH and Ali, HH and Khan, S and Zubair, MTM and Pereira, M and Sayed Hassan, FE}, title = {Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut-Brain Interactions and Immune Pathways: A Narrative Review.}, journal = {Brain and behavior}, volume = {16}, number = {2}, pages = {e71254}, doi = {10.1002/brb3.71254}, pmid = {41645047}, issn = {2162-3279}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Multiple Sclerosis/immunology/microbiology/therapy/metabolism ; Animals ; *Dysbiosis/immunology ; *Brain-Gut Axis ; Probiotics ; Brain/immunology ; }, abstract = {PURPOSE: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by progressive disability. Emerging evidence has implicated gut microbiome dysbiosis, characterized by decreased short-chain fatty acids (SCFAs)-producing taxa and increased pro-inflammatory species, in disturbed immune signaling, T-helper17/T-regulatory cells imbalance, disturbed tryptophan metabolism, and disrupted integrity of the blood-brain barrier. In this review, we summarize the mechanistic and therapeutic insights from studies that have explored the gut microbiome in MS.

METHOD: We performed a literature search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov from database inception to January 2025; only English-language articles were included, comprising human MS cohorts and preclinical experimental autoimmune encephalomyelitis models. Of these, approximately 95 human and preclinical studies fulfilled the inclusion criteria. Evidence synthesis was narrative, without meta-analysis.

FINDING: There has been a consistent depletion of beneficial genera such as Faecalibacterium and Roseburia, expansion of Akkermansia muciniphila, and reduction in microbial metabolites such as butyrate, propionate, and neuroactive indole derivatives in MS patients across studies. These changes promote intestinal permeability, exaggerated pro-inflammatory cytokine responses, and microglial activation. The therapeutic approach of restoring microbial balance includes therapies such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Early trials have shown modest improvements in relapse rates, fatigue, immune profiles, and microbiome composition. Results across randomized studies are heterogeneous, with no significant clinical benefit in several. Pilot trials report modest reductions in relapse rate (RR ≈ 0.85) and fatigue (Cohen's d ≈ 0.3), but several double‑blind RCTs showed no significant benefit (p  >  0.05) in up to 40% of participants, highlighting variable effect sizes.

CONCLUSION: Interventions aimed at the microbiome are promising as adjunct approaches to the treatment of MS, acting principally through the restoration of SCFAs, immune modulation, and strengthening of the gut-brain axis. Larger, longer-term randomized trials are required to confirm clinical efficacy, define responder phenotypes, and inform personalized microbiome-based therapies.}, } @article {pmid41645037, year = {2026}, author = {Zhao, G and Mosby-Tourtellot, CA and Rosero, J and Schultz, AC and Khan, E and Elamrani, O and Ferraro, MJ and Kima, PE and Jones, MK}, title = {Induction of DNA-mediated immune responses by bacterial extracellular vesicles results in control of murine norovirus infection.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2624171}, doi = {10.1080/19490976.2026.2624171}, pmid = {41645037}, issn = {1949-0984}, mesh = {Animals ; *Extracellular Vesicles/immunology ; *Norovirus/immunology/physiology ; Mice ; *Caliciviridae Infections/immunology/virology ; Toll-Like Receptor 9/genetics/immunology ; Mice, Inbred C57BL ; Membrane Proteins/genetics/immunology ; Virus Replication ; Interferon-beta/immunology ; *Bacteria/immunology/genetics ; Interferon Type I/immunology ; Gastrointestinal Microbiome ; Mice, Knockout ; STING Protein ; }, abstract = {Commensal bacteria have been a centerpiece for understanding interkingdom impacts on viral replication. Multiple groups have investigated the roles commensal bacteria played in regulating enteric virus infection and it has been found that the mechanisms through which this regulation occurs varies between the viruses and bacteria explored. For noroviruses, commensal bacteria enhance or suppress viral infection in a region-dependent manner. Recently, it was found that the extracellular vesicles (EVs) produced by commensal bacteria can suppress norovirus infection. In this study, we used murine norovirus (MNV) to probe the immunological mechanisms induced by bacterial EVs. Global analysis of gene expression pointed to induction of cytosolic DNA pathways; thus, we evaluate the DNA content packaged within the bacterial EVs and DNA-sensing pathways that activate type I interferons (IFN), including STING and TLR9. Our results showed that loss of sting or tlr9, significantly decreased IFNβ production and recovered MNV replication in the presence of bEVs. Collectively, these data demonstrated bEVs of certain gram-negative bacteria can initiate antiviral DNA-mediated type I IFN production pathways and that these pathways are involved in the suppression of MNV replication. These findings expose novel mechanisms through which the native microbiota aids the host in controlling an enteric viral infection and offers a fresh perspective on interkingdom host‒microbiota interactions.}, } @article {pmid41645021, year = {2026}, author = {Lussac-Sorton, F and Narayana, JK and Wizla, N and Tatopoulos, A and Baravalle, M and Rotidis, L and Houdoin, V and Llerena, C and Reix, P and Sermet, I and Languepin, J and Charpentier, E and Lefranc, M and Alves Gomes, P and Bui, S and Beaufils, F and Berger, P and Chotirmall, SH and Delhaes, L and Enaud, R}, title = {Gut-lung microbial dynamics with lumacaftor/ivacaftor in children with cystic fibrosis: a prospective multicenter study.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {41645021}, issn = {1530-0447}, abstract = {BACKGROUND: CFTR modulators such as lumacaftor/ivacaftor (LUM/IVA) may reshape microbiota-mycobiota composition in the lungs and gut. While the gut-lung axis is established in other settings, little is known about its role following modulator therapy, particularly in the 2-11 age group.

METHODS: In a prospective national multicentre study, 116 children with cystic fibrosis (2-11 years) starting LUM/IVA were followed for 12 months. Stool and sputum were collected at baseline, 3, 6 and 12 months. Bacterial and fungal communities were profiled by 16S rRNA and ITS2 sequencing; diversity, dysbiosis indices, faecal and sputum calprotectin, and gut-lung microbial networks were analysed.

RESULTS: LUM/IVA was associated with increased bacterial diversity and compositional shifts in gut and lung microbiota, alongside a significant reduction in faecal calprotectin. Airway mycobiota diversity remained stable. Two lung microbiome response profiles emerged: "responders" (greater bacterial diversity gain) and "non-responders" (minimal change). Baseline gut and lung composition predicted these profiles with 81% accuracy in a random-forest model. Inter-organ microbial interactions peaked at 3 months after initiation and then diverged between profiles, indicating distinct gut-lung axis remodelling.

CONCLUSION: LUM/IVA influences gut-lung microbiota-mycobiota dynamics, with heterogeneous responses between paediatric patients. Identifying factors predictive of response is a key future challenge.

IMPACT: In 116 children aged 2-11, lumacaftor/ivacaftor reshaped gut and lung microbiota and reduced fecal calprotectin over 12 months. First pediatric multicenter study integrating bacterial and fungal profiling of stool and sputum with gut-lung network analyses; identifies two distinct lung microbiome response profiles. Baseline gut and lung composition predicted the response profile with approximately 81% accuracy. Highlights a 3-month interaction peak and baseline profiling as practical markers to guide monitoring and microbiome-informed precision care.}, } @article {pmid41644858, year = {2026}, author = {Vaghela, P and Dave, B and Dabhade, A and Deshmukh, R and Prajapati, B and Alsaidan, OA and Patel, S and Mehta, A and Singh, A and Dudhat, K}, title = {Redrawing the gut map: evolving probiotic approaches to microbiota modulation in inflammatory bowel disease.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {3}, pages = {51}, pmid = {41644858}, issn = {1572-9699}, mesh = {*Probiotics/therapeutic use ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/microbiology/therapy ; Dysbiosis/therapy ; }, abstract = {Inflammatory bowel disease (IBD), comprising Ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) that occurs due to several factors, including, but not limited to, gut microbiota dysbiosis, immune dysregulation, and environmental factors. Despite significant advances in IBD pharmacotherapy, patients often experience treatment failures due to suboptimal treatment responses, frequent relapses, and are also susceptible to developing several adverse effects (AEs), highlighting the need for developing alternative therapies. A growing body of evidence necessitates the importance of maintaining gut microbiome homeostasis, which is commonly disrupted in IBD. Probiotics have emerged as promising adjunctive IBD therapies due to their capacity to modulate immune responses, restore gut microbial balance, and preserve mucosal barrier integrity. Multiple probiotic strains, including Escherichia coli (E. coli) Nissle 1917, Lacticaseibacillus rhamnosus GG, Bifidobacterium longum (B. longum), Saccharomyces cerevisiae var. boulardii (S. boulardii), and combination formulations, such as VSL#3 (Lactobacillus, Bifidobacterium, and Streptococcus thermophilus), have demonstrated superior efficacy in inducing and maintaining remission in comparison with placebo and comparable efficacy with conventional treatments, such as mesalazine. While the efficacy of probiotics has been demonstrated in UC through several clinical studies, evidence supporting their use in CD remains inconsistent, with studies yielding mixed or inconclusive results. This highlights the necessity for additional carefully designed, large-scale studies specifically targeting CD patients to better understand the therapeutic potential of probiotics in a broader context. Finally, emerging innovations in genetic engineering and clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9 (CRISPR/Cas9) technology offer exciting prospects for the development of precision probiotics, which could possess both diagnostic and treatment benefits and further expand the clinical utility of probiotics in IBD treatment.}, } @article {pmid41644826, year = {2026}, author = {Zhang, X and Zhang, W and Cheng, Y and Zhang, M and Xie, J and Yang, S and Yang, Y and Zhang, Z and Bai, W and Kong, W}, title = {Characterization of spatio-temporal variations in carposphere microbial diversity of olive in Longnan, China.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {2}, pages = {76}, pmid = {41644826}, issn = {1573-0972}, support = {NWNU-LKZD2022-02//Key Scientific Research Project of Northwest Normal University/ ; 22YF7NA118//Key Research and Development Project of Gansu Province/ ; 24ZYQA039//Central Government Guides Local Science and Technology Development Funds/ ; }, mesh = {China ; *Bacteria/classification/genetics/isolation & purification ; *Olea/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Fungi/classification/genetics/isolation & purification ; Biodiversity ; Phylogeny ; Spatio-Temporal Analysis ; High-Throughput Nucleotide Sequencing ; Fruit/microbiology ; DNA, Bacterial/genetics ; Sequence Analysis, DNA ; }, abstract = {The fruit surface microbiome influences quality formation and disease occurrence, yet carposphere microbial diversity and functions remain poorly studied. This study employed 16S rRNA and ITS high-throughput sequencing technology to investigate the spatiotemporal variation patterns of the olive carposphere microbiome in Longnan City, Gansu Province, China, with respect to cultivars, maturity stages, and geographical locations. The results showed that the olive carposphere bacterial communities were dominated by Proteobacteria, and their abundance increased with fruit ripening. Methylobacterium-Methylorubrum showed significant enrichment at the mature stage, while Streptococcus served as a dominant genus across all geographical regions. For fungal communities, Ascomycota was the predominant phylum, while Nothophoma and Aureobasidium identified as the major genera. Diversity analyses revealed that both bacterial and fungal communities in the olive carposphere varied with cultivar, maturation stage, and geographical location. Among these factors, geographical location emerged as the most dominant driver, which implies that the environment and human activities play an important role in determining the carposphere microbiome. These findings enhance our understanding of the microbial diversity in olive carposphere, also provide valuable species information for the future use of microbial technology to modulate the fruit quality and prevent and control biological diseases.}, } @article {pmid41644796, year = {2026}, author = {Krukowski, H and Valkenburg, S and Vich Vila, A and Maciel, LF and Vázquez-Castellanos, JF and Gryp, T and Joossens, M and Van Biesen, W and Verbeke, F and Derrien, M and Huys, GRB and Glorieux, G and Raes, J}, title = {Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41644796}, issn = {2058-5276}, support = {860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 101149152//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; }, abstract = {Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study microbiome associations with estimated glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Intestinal transit time (ITT) and medications significantly explained microbiome variation, surpassing eGFR-related effects. Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios. This was consistent with community-wide saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down ITT. Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were covariate-independent markers for eGFR, but neither these nor previous microbial markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Nevertheless, our study adds insight into plausible ITT and nutrition-related effects, highlighting their potential in CKD interventions.}, } @article {pmid41644742, year = {2026}, author = {Ziogas, DC and Theocharopoulos, C and Martinos, A and Lyrarakis, G and Stefanou, D and Anastasopoulou, A and Gogas, H}, title = {Toward Microbiome-Informed Melanoma Care: The Gut Microbiota in Melanoma Evolution, Immunotherapy Response and Immune-Related Toxicity.}, journal = {Current oncology reports}, volume = {28}, number = {1}, pages = {10}, pmid = {41644742}, issn = {1534-6269}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Melanoma/immunology/therapy/microbiology/pathology ; *Immunotherapy/adverse effects/methods ; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome (GM) has emerged as a pivotal modulator of melanoma pathogenesis and progression through its influence on systemic inflammation, immune surveillance, and antitumor immunity. Inter-individual variability in GM composition may underlie differences in immune checkpoint inhibitor (ICI) responsiveness and the development of immune-related adverse events (irAEs). This review aims to synthesize current knowledge on the complex interplay between the GM, host immunity, and melanoma, emphasizing its relevance to disease development, therapeutic response, and toxicity.

RECENT FINDINGS: Both preclinical and clinical evidence have demonstrated that alterations in microbial diversity and composition can affect melanoma outcomes. Depletion or imbalance of specific microbial taxa has been linked to an increased risk of melanoma development or, conversely, to reduced tumor burden. In patients treated with ICIs, distinct taxonomic GM signatures have been correlated with therapeutic efficacy and the likelihood of developing irAEs. Emerging studies have also explored strategies to modulate the GM-including diet, antibiotics, probiotics, and fecal microbiota transplantation-to restore gut "eubiosis" and enhance antitumor immune responses. The intricate crosstalk between the gut microbiome, host immunity, and melanoma significantly influences disease biology and treatment outcomes. A deeper understanding of these interactions will be critical to the development of microbiome-informed, personalized approaches to melanoma management and immunotherapy optimization.}, } @article {pmid41644724, year = {2026}, author = {Polidoro, EE and Stosiek, N and Laman, JD and Palmer, CA and Kriesel, JD}, title = {Spinal fluid antibody profile against bacteria demonstrates intrathecal antibody production in demyelinating diseases.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {104}, number = {1}, pages = {41}, pmid = {41644724}, issn = {1432-1440}, mesh = {Humans ; Female ; *Antibodies, Bacterial/cerebrospinal fluid/immunology ; Male ; Adult ; Middle Aged ; *Demyelinating Diseases/immunology/cerebrospinal fluid/microbiology ; Immunoglobulin G/cerebrospinal fluid/blood ; *Bacteria/immunology ; Multiple Sclerosis/immunology/cerebrospinal fluid ; Enzyme-Linked Immunosorbent Assay ; Aged ; *Antibody Formation ; Young Adult ; }, abstract = {This study follows work establishing multiple sclerosis (MS) microbial candidates from RNA sequencing of human brain samples. A subsequent study demonstrated anti-microbial immune responses in cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD) and other neurologic diseases (OND). We aim to expand evidence for specific anti-microbial responses in CSF of patients with DD. CSF IgG ELISA assays were developed from 20 bacteria identified as MS microbial candidates. CSF responses from patients with DD (N = 16) and OND (N = 8) were determined using commercial CSF as positive and negative controls. CSF reactivity was expressed as ELISA Index (EI) values against each of the lysates. Antibody Index (AI) values were determined by comparing CSF reactivity and diluted serum samples with equivalent IgG concentrations. AI values > 1.5 were considered positive, 1.0-1.49 equivocal, and < 1.0 negative. Most samples from both groups displayed reactivity across all 20 lysates, with an overall rate of 87.8%. CSF EI values were highest against Haemophilus, Aggregatibacter, and Streptococcus, lowest against Veillonella, Fusobacterium, and Alistipes. Twenty-five percent of subjects with DD and 13% with OND had AI > 1.5 to at least one lysate. Clustering of AI values from four DD samples against Bacteroides and Lactobacillus was observed. This serological study shows reactivity against multiple bacteria in CSF from patients with primary DD including MS and OND. Elevated AI in four DD and one OND subject provides evidence for specific intrathecal antibody production in these patients. KEY MESSAGES: This study measured humoral immune responses in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis (MS) and other demyelinating diseases against 20 candidate bacteria previously identified by sequencing of diseased human brain tissue. The method described here involves diluting CSF to match the serum IgG concentrations, running an ELISA, and calculating an Antibody Index (AI). The methods described here are improved by directly measuring banked CSF and serum IgG concentrations in the laboratory. Several subjects with demyelinating diseases clustered strongly for responses against Bacteroides, Lactobacillus, Akkermansia, and Alistipes, found in the normal flora in the human gut and female genital tract.}, } @article {pmid41644412, year = {2026}, author = {Nisley, MJ and Burrough, ER and Spencer, JD and Mendoza, OF and Krishnan, HB and Gabler, NK}, title = {Dietary soybean-derived trypsin inhibitor protein reduces nursery pig performance and may exacerbate F18 enterotoxigenic Escherichia coli disease.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skag026}, pmid = {41644412}, issn = {1525-3163}, abstract = {Soybean-derived trypsin inhibitor proteins (TIU) impair amino acid bioavailability and increase exogenous and endogenous nitrogen flow to the hindgut, thereby attenuating pig growth performance. High protein diets potentiate proteolytic fermentation induced alterations to the gut microbiome, which may increase opportunistic enterotoxigenic Escherichia coli (ETEC) proliferation and exacerbate disease. We hypothesized that feeding high TIU diets to nursery pigs would reduce growth rates and exacerbate F18 ETEC disease. Two hundred and eighty-eight (5.42 ± 0.93 kg BW; Camborough 1050 × 337, [PIC, Hendersonville, TN]) newly weaned pigs were evenly allotted across two control rooms (CON) and two challenge rooms (ETEC). Pigs were allotted based on sex and α-(1,2) fucosyltransferase (FUT1) genotype, with both factors evenly distributed across all pens. Pens were randomly assigned to corn-soy diets consisting of 1.1, 2.4, or 4.2 TIU/mg, creating six treatments: CON1.1, CON2.4, CON4.2, ETEC1.1, ETEC2.4, and ETEC4.2 (8 pens/treatment). On day 10 (day post-infection [dpi] 0), pigs in the ETEC rooms were orally inoculated with 5 ml of 3.8 × 109 cfu/ml of an F18 ETEC culture. Pooled pen feces were assessed for dry matter (DM) on dpi 0, 3, 5, 7, 9, 11, 14, and 21. Pen growth performance, medical treatments, and mortality were assessed prior to infection (dpi -10 to 0) and post infection (dpi 0 to 28). On dpi 5 and 12, one pig/pen was sacrificed to assess ileal mucosal attachment of F18 ETEC via in situ hybridization. Pen was the experimental unit and data were analyzed for the interactive and main effects of diet and challenge. Increasing dietary TIU to 4.2 TIU/mg led to a 13-16% decrease in ADG compared to the 1.1 TIU/mg diets, regardless of the challenge (P = 0.014). A diet × challenge interaction was observed regarding mortality, with ETEC2.4 showing a 20.8% mortality rate compared to 0% in CON2.4 (P = 0.001). Similarly, 22.9% of ETEC2.4 pigs required antibiotic treatment compared with 0% of CON2.4 pigs (P = 0.001). Fecal DM from dpi 0-21 showed no interaction, but ETEC pens had lower fecal DM compared to CON pens from dpi 3-11 (P < 0.0001). On dpi 5, ileal F18 attachment was increased in ETEC versus CON pigs (3.7 × 10-3 vs 0.1 × 10-3 F18 copies/μm2, P < 0.0001). By dpi 12, ileal F18 attachment did not differ between challenge groups (P > 0.05), suggesting disease resolution. In conclusion, diets at or greater than 2.4 TIU/mg decreased pig growth and reduced livability in ETEC-infected nursery pigs.}, } @article {pmid41644129, year = {2026}, author = {Kreft, D and Hurka, S and Gurusinga, FF and Röthig, T and Vilcinskas, A and Tegtmeier, D}, title = {Towards Functional Fertilisers: Feed Composition Shapes Microbial Community Structure and Viability in Black Soldier Fly (Hermetia illucens) Frass.}, journal = {Environmental microbiology}, volume = {28}, number = {2}, pages = {e70249}, doi = {10.1111/1462-2920.70249}, pmid = {41644129}, issn = {1462-2920}, support = {FKZ 031B1274//German Federal Ministry of Research, Technology, and Space/ ; //Fraunhofer-Gesellschaft/ ; }, mesh = {Animals ; *Animal Feed/analysis/microbiology ; *Microbiota ; *Bacteria/classification/isolation & purification/genetics ; *Fertilizers/analysis/microbiology ; Larva/microbiology ; Fungi/isolation & purification/genetics/classification ; *Simuliidae/microbiology/growth & development ; *Diptera/microbiology ; Aquaculture ; }, abstract = {Black soldier fly larvae (BSFL) are increasingly valued as a sustainable protein source for aquaculture and can be reared on local industrial side streams, enhancing their environmental and economic benefits. The resulting frass-a byproduct of larval excreta and residual feed-shows promise as an organic fertiliser. In addition to its nutrient content, frass contains microbial communities that may enhance plant growth through phytohormone production, nitrogen fixation, and organic matter turnover. Yet, the roles of feed composition and thermal hygienisation in shaping these communities remain underexplored. This study examined the impact of five feed substrates, including industrial side streams and a control diet, on frass microbial composition, and assessed responses to thermal treatment. Feed nutrients were characterised, and microbial communities profiled using amplicon sequencing. Viable populations were quantified via culture-based methods, with bacterial isolates taxonomically classified. Feed type was the dominant factor influencing frass microbiota, with distinct communities reflecting substrate nutritional profiles. High-fibre diets promoted fungal diversity and abundance, while high-protein feeds enriched specific bacterial taxa. Thermal hygienisation had a heterogeneous effect on viable counts but minimal impact on overall community structure. These findings support microbiome-informed feed design to tailor frass microbial profiles for enhanced biofertiliser function in sustainable agriculture.}, } @article {pmid41644071, year = {2026}, author = {Ndjeambong, YC and Velmurugan, S and Patidar, P and Chouhan, V and Kundu, A and Balamurugan, A and Hussain, Z and Kumar, A}, title = {Rhizomicrobiome Diversity and Bioactive Bacterial Metabolomes of Cultivated and Wild Solanum Species Suppress Ralstonia pseudosolanacearum.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108354}, doi = {10.1016/j.micpath.2026.108354}, pmid = {41644071}, issn = {1096-1208}, abstract = {Bacterial wilt caused by Ralstonia pseudosolanacearum remains one of the most destructive diseases threatening eggplant production worldwide, as effective management options are limited, resistance in cultivated varieties is often unstable, and chemical control measures are largely ineffective and environmentally unsustainable. In this study, we profiled the rhizobacterial microbiomes of wilt-susceptible Solanum melongena and wilt-resistant S. torvum cultivated in contrasting soils from Cameroon and India representing non-endemic and endemic regions of bacterial wilt. A combined culture-dependent methodology together with 16S rRNA amplicon sequencing was used to elucidate the structure and functional attributes of the microbial communities. Soil origin was the principal factor influencing microbiome composition (PERMANOVA R[2] = 0.34, p = 0.001), followed by host genotype (R[2] = 0.21) and root niche (R[2] = 0.14). The wilt-resistant S. torvum consistently supported higher bacterial diversity and was enriched with core taxa, including Bacillus and Methanocella. Fourteen rhizobacterial isolates, mainly Bacillus spp., showed strong antagonistic activity against R. pseudosolanacearum. Metabolomic analyses using LC-QTOF-MS/MS and GC-MS indicated the production of lipopeptides and polyketides by Bacillus spp., while Pseudomonas plecoglossicida produced phenazine derivatives and indole-3-acetic acid. In greenhouse experiments, Bacillus cereus, B. velezensis, and Priestia megaterium significantly improved seed germination and seedling vigor at inoculum densities of 10[6]-10[7] CFU mL[-1]. Together, these results show that eggplant-associated rhizobacteria, particularly Bacillus spp. and P. plecoglossicida, contribute to bacterial wilt suppression and offer potential for sustainable disease management.}, } @article {pmid41643678, year = {2026}, author = {Wei, M and Yi, X and Lin, Z and Cai, J and Chen, S and Zhou, F and Cai, H and Lu, X and Tang, J and Shi, Y and Cui, L and Yang, L and Jing, X and Zeng, Y and Wu, R and Shu, T and Li, Y and Yang, F and He, Y and Zhao, Z and Yang, Y and Zhu, W and Jiang, Q and Zhang, W and Tan, X and Ma, Z and Fan, X and Ma, W and Li, S and Shu, W and Wei, H and Xiang, Z and Gilbert, JA and Gong, S and Wang, Z}, title = {Ketogenic diet alleviates septic lung injury via microbial gut-lung axis.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2026.01.005}, pmid = {41643678}, issn = {1932-7420}, abstract = {Sepsis is characterized by impaired immunity to infection, leading to multi-organ dysfunction, with the lung being the most vulnerable organ. Here, we show that ketogenic diet (KD) alleviates sepsis-induced lung injury through a microbial-gut-lung axis. KD alters the gut microbiota in mice and humans, enriching Limosilactobacillus reuteri and Lactiplantibacillus plantarum. Specific strains of these species produce a flavin-dependent monooxygenase (FMO) that converts oleic acid in KD into azelaic acid (AZA). During sepsis, AZA translocates to the lung, where it promotes neutrophil apoptosis and expands MerTK[+] alveolar macrophages (AMs) via PPAR-γ activation, enhancing efferocytosis and resolution of lung injury. In patients with sepsis, elevated AZA correlates with improved clinical outcomes, including survival rates, ventilation-free days (VFDs), and pulmonary function, along with increased MerTK[+] AMs and apoptotic neutrophils in patient lungs. These findings uncover a pathway of gut-lung crosstalk mediated by diet-microbiome interactions, highlighting the therapeutic potential of KD and microbiome modulation in sepsis.}, } @article {pmid41643502, year = {2026}, author = {Perrett, BM and Miliku, K and Moraes, TJ and Simons, E and Mandhane, P and Kebbe, M}, title = {Gut microbiota responses to complementary food sources differ by milk feeding type.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {58}, number = {}, pages = {106587}, doi = {10.1016/j.clnu.2026.106587}, pmid = {41643502}, issn = {1532-1983}, abstract = {BACKGROUND & AIMS: Early-life nutrition shapes host-microbe interactions with lasting consequences for health. While dietary patterns are known to influence the infant gut microbiome, the impact of solid food source (homemade, commercial, or mixed) has not been examined. Our aims were to determine how solid food source at 6 months relates to infant gut microbiome diversity and composition at 1 year, and whether relationships differ by milk feeding type..

METHODS: We conducted a secondary analysis within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Solid food source was assessed at 6 months, and stool samples at 1 year were profiled using 16S rRNA sequencing. Generalized linear models were used to assess alpha-diversity; permutational multivariate analysis of variance (PERMANOVA) was used to evaluate beta-diversity based on OTU-level Bray-Curtis dissimilarities; and Microbiome Multivariate Association with Linear Models 2 (MaAsLin2), using centered log-ratio normalization, was used to examine taxa-level associations, adjusting for relevant perinatal and dietary covariates. Effect modification by milk feeding type (human milk, formula, combination, or weaned) at 6 months and 1 year was examined. Benjamini-Hochberg correction was applied (p < 0.05; q < 0.25).

RESULTS: A total of 368 infants were included. At 6 months, most were mixed-fed (n = 154; 41.8 %), followed by homemade-fed (n = 143; 38.9 %) and commercially-fed (n = 71; 19.3 %). Solid food source explained only 0.53 % of gut microbiota variability. Differences were most pronounced in formula-fed infants: at 6 months, those given homemade or mixed foods showed higher abundances of Firmicutes, Turicibacteraceae, and Turicibacter compared with commercially fed infants. Within this group, mixed feeding was further linked to higher Eubacteriaceae and Lachnospiraceae (all q < 0.25). At 1 year, formula-fed infants who received homemade foods had higher microbial diversity (p = 0.028) but lower Shannon diversity (p = 0.041) than those receiving commercial foods, suggesting shifts in both community richness and evenness. No significant differences in gut microbiome diversity and composition were observed in the overall cohort or among infants receiving human milk or fully weaned (q > 0.25).

CONCLUSIONS: Solid food source is a previously under-investigated driver of infant microbiome variability, with effects contingent on milk feeding. Human milk may buffer against dietary choices, whereas formula-fed infants show heightened sensitivity to complementary food source, informing precision nutrition in early life.}, } @article {pmid41643413, year = {2026}, author = {Nunes, AT and de Almeida, DL and Faleiros, CA and Poleti, MD and de M Oliveira, EC and Moreira, FM and Gallo, SB and Fukumasu, H}, title = {Maternal chromium supplementation increases lamb weaning weight and modulates rumen microbiota.}, journal = {Animal : an international journal of animal bioscience}, volume = {20}, number = {2}, pages = {101755}, doi = {10.1016/j.animal.2026.101755}, pmid = {41643413}, issn = {1751-732X}, abstract = {Maternal nutrition during gestation can program offspring development and may influence the establishment of the rumen microbiome, with implications for growth and rumen health. However, the effects of maternal chromium (Cr) supplementation on offspring rumen microbial communities and performance in sheep remain poorly characterised. This study investigated the effects of maternal Cr supplementation during late gestation and early lactation on the offspring microbiome and performance in lambs. Fifteen pregnant ewes were assigned to two treatments in a randomised design: no Cr supplementation and 1.5 mg chromium propionate per ewe/day. Male Dorper × Santa Inês lambs (n = 19) were weaned at 80 d. They were provided creep feeding from 20 d to weaning, and finished in individual feedlot pens until slaughter at 132 d. The rumen microbiota of the offspring at slaughter was characterised. Feed intake, BW, daily gain, feed efficiency, and carcass yield were measured. Maternal Cr supplementation increased the weaning weight of lambs (P = 0.048), although no differences were observed in the feed intake, daily gain, or carcass weight. While the overall microbial diversity was unchanged, Cr increased Flexilinea (P = 0.042), SP3-e08 (P = 0.040) and U29-B03 (P = 0.037), genera linked to fibre degradation and volatile fatty acid modulation. Conversely, Cr reduced Streptococcus (P = 0.029), potentially lowering lactic acid accumulation and ruminal acidosis risk, and Oribacterium (P = 0.025) and Pseudobutyrivibrio (P = 0.008), genera involved in glycolysis and cell wall biosynthesis. In conclusion, supplementation with 1.5 mg chromium propionate during late gestation and early lactation increased lamb weaning weight and modulated rumen microbial taxa, suggesting potential improvements in nutrient utilisation and rumen stability.}, } @article {pmid41642554, year = {2026}, author = {Vuong, TTB and Le, TTV and Le, LGH and Le, TN and Do, MD}, title = {Analysis of the Facial Skin Bacterial Community in Vietnamese Individuals with Sensitive Skin and Clinical Relevance.}, journal = {Dermatology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41642554}, issn = {2193-8210}, abstract = {INTRODUCTION: Sensitive skin (SS) is a common clinical condition characterized by exaggerated sensory responses such as burning, stinging, itching, and irritation to otherwise nonpathological stimuli, most frequently affecting the face. The underlying mechanisms remain incompletely understood, particularly with regard to the role of the skin microbiome.

METHODS: This study investigated the facial skin microbiota in Vietnamese adults with SS and examined its associations with clinical symptoms and skin physiological parameters. A total of 75 participants were enrolled, including 45 with SS and 30 with nonsensitive skin (NSS). Clinical assessment included evaluation of subjective symptoms, symptom regularity, time of symptom onset, trigger factors, and objective measurements of skin pH, sebum, hydration, transepidermal water loss (TEWL), erythema, and melanin index. Bacterial communities were profiled using 16S rRNA gene sequencing targeting the V3-V4 region.

RESULTS: Participants with SS exhibited significantly higher erythema and TEWL across all sex and age subgroups, as well as elevated skin pH in female and middle-aged participants (p < 0.05). Alpha and beta diversity metrics did not differ significantly between SS and NSS groups. However, differential abundance analysis using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) identified 53 bacterial genera with significant compositional differences, indicating subtle community restructuring. A total of 32 genera, including Peredibacter, Enterobacter, and Marmoricola, were enriched in SS, whereas Streptococcus, Escherichia-Shigella, and Weissella were depleted. Correlation and stratified analyses further revealed genus-level associations with skin physiological parameters, clinical symptoms, anatomical locations, symptom regularity, and time since symptom onset.

CONCLUSIONS: SS is associated with subtle but distinct alterations in facial skin microbiome composition, in parallel with measurable changes in skin physiological parameters related to barrier function and reactivity. The results indicate associations between microbial composition, skin physiological parameters, and clinical characteristics in the SS phenotype, and offer a population-specific microbiome reference for Vietnamese facial skin.}, } @article {pmid41642539, year = {2026}, author = {Shenthilvel, RK and Umashankar, TA and Uvarajan, D and Mathuraj, M and Ravikumar, M}, title = {"Unfolding Parkinson's Disease Through the Microbiome-Gut-Brain Axis".}, journal = {Journal of molecular neuroscience : MN}, volume = {76}, number = {1}, pages = {25}, pmid = {41642539}, issn = {1559-1166}, mesh = {Humans ; *Parkinson Disease/microbiology/therapy/metabolism ; *Gastrointestinal Microbiome ; Animals ; *Brain/metabolism ; *Brain-Gut Axis ; }, abstract = {Parkinson's disease (PD) is a progressive and multifactorial neurodegenerative disorder primarily caused by the loss of dopaminergic neurons in the substantia nigra. This neuronal loss leads to characteristic motor symptoms such as tremors, rigidity, and slowness of movement. Although PD has long been regarded as a disorder originating in the brain, recent findings suggest that the gut-brain axis, the intricate communication network between the gastrointestinal tract and the central nervous system also plays an important role in the development and progression of PD. Interestingly, early non-motor symptoms such as constipation and other bowel irregularities often appear several years before the onset of motor symptoms, indicating that changes in gut function may precede and even contribute to neurodegeneration. The gut microbiota influences neuronal signaling, immune activity, and metabolic balance through neuroactive molecules such as neurotransmitters, short-chain fatty acids (SCFAs), and cytokines. In PD, microbial imbalance, intestinal barrier dysfunction, and chronic inflammation are closely linked to the misfolding and accumulation of α-synuclein (α-syn), which can spread from the gut to the brain through the vagus nerve in a prion-like manner. Current therapeutic approaches are increasingly exploring ways to restore gut microbial balance using probiotics, prebiotics, dietary interventions, fecal microbiota transplantation (FMT), and SCFA supplementation. These strategies not only aim to relieve symptoms but may also have the potential to slow disease progression. This review discusses the mechanisms through which the gut-brain axis contributes to PD, summarizes key clinical and preclinical findings, and highlights emerging gut-targeted therapeutic approaches.}, } @article {pmid41642392, year = {2026}, author = {Banerjee, A and Choudhury, A and Goswami, A}, title = {The gut-brain axis in arsenic-induced toxicity: mechanisms, consequences, and therapeutic perspectives.}, journal = {Metabolic brain disease}, volume = {41}, number = {1}, pages = {30}, pmid = {41642392}, issn = {1573-7365}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; Animals ; *Brain/drug effects/metabolism ; *Arsenic/toxicity ; Dysbiosis/chemically induced ; *Arsenic Poisoning/metabolism ; *Brain-Gut Axis/drug effects/physiology ; Oxidative Stress/drug effects ; }, abstract = {Chronic ingestion of arsenic frequently occurring in contaminated groundwater poses a serious dual threat to neurological health. Environmental toxicants present in groundwater are highly correlated with onset of neuropathological effects through complex gut-brain axis interactions. The systematic review of literature aims evaluate the neurobehavioural consequences and molecular outcome of a groundwater contaminant, arsenic with microbiota alteration involving animal studies and epidemiological data. Arsenic disrupts the gut microbiota, diminishing beneficial bacteria and promoting harmful strains, which in turn compromise gut barrier integrity, trigger inflammation and oxidative stress, leading to alteration in critical metabolic pathways involved in neurotransmitter production and mitochondrial function. Animal studies have shown that chronic exposure intensifies these effects, causing more pronounced microbial dysbiosis alongside worsened cognitive and behavioural deficits. Mechanistically, arsenic impairs neural signaling by elevating reactive oxygen species, disrupting synaptic and mitochondrial dynamics, and inducing neuroinflammation after its accumulation in brain tissues, while gut-derived neuroactive compounds exacerbate neuroinflammation and neuronal damage irrespective of significant arsenic deposition in the brain. Therapeutic strategies that reinforce gut health, such as targeted probiotic and prebiotic supplementation have demonstrated the ability to restore microbiome balance, strengthen barrier function, reduce neuroinflammatory markers and improve behavioural outcomes in experimental models. These microbiota-focused interventions, when combined with conventional measures like chelation to remove toxic metals and the deployment of water treatment infrastructure in affected regions, suggest a powerful integrated approach. By addressing both the source of contamination and the downstream biological consequences, this multimodal strategy holds significant promise for mitigating arsenic-induced neurotoxicity and protecting at-risk populations in affected communities.}, } @article {pmid41642353, year = {2026}, author = {Gholizadeh, P and Faghfuri, E}, title = {Reprogramming Gastric Cancer Therapy: A Microbiome-Guided Approach to Precision Oncology.}, journal = {Current microbiology}, volume = {83}, number = {3}, pages = {150}, pmid = {41642353}, issn = {1432-0991}, } @article {pmid41642241, year = {2026}, author = {Zheng, Y and Fang, X and Gao, J}, title = {Re-engineering insulin for oral delivery: structural modifications, advanced formulation strategies, and future directions.}, journal = {Drug delivery}, volume = {33}, number = {1}, pages = {2624192}, doi = {10.1080/10717544.2026.2624192}, pmid = {41642241}, issn = {1521-0464}, mesh = {Humans ; Administration, Oral ; *Insulin/administration & dosage/chemistry/pharmacokinetics ; *Hypoglycemic Agents/administration & dosage/chemistry/pharmacokinetics ; *Drug Delivery Systems/methods ; Animals ; Drug Carriers/chemistry ; Biological Availability ; Diabetes Mellitus/drug therapy ; }, abstract = {Oral insulin delivery represents a transformative approach to diabetes management, offering improved patient compliance and physiological insulin delivery patterns compared to subcutaneous injection. However, multiple gastrointestinal barriers, including enzymatic degradation, mucus entrapment, epithelial impermeability, and first-pass metabolism, have limited oral bioavailability to below 1% for unmodified insulin. This review comprehensively examines contemporary strategies to overcome these barriers. We analyze structural modifications of insulin, including PEGylation, lipidation, cyclization, and glycoengineering, which enhance stability while maintaining biological activity. The analysis extends to sophisticated formulation technologies incorporating nanocarriers (polymer-based, lipid-based, inorganic nanocarriers, and metal organic frameworks), biomimetic systems, and stimuli-responsive mechanisms for protection and delivery. A central focus is on absorption-enhancing strategies, which range from chemical permeation enhancers to precise biological mechanisms like receptor-mediated transcytosis and other active transport pathways. Emerging tools such as microbiome-based carriers and smart devices are also discussed. Despite significant progress in preclinical models, challenges remain in manufacturing scalability, inter-patient variability, long-term safety, and regulatory approval. Future directions emphasize hybrid delivery systems, digital health integration, and personalized formulations. Realizing clinically viable oral insulin requires continued multidisciplinary collaboration addressing biological, technological, and translational barriers to transform diabetes care.}, } @article {pmid41642221, year = {2026}, author = {Pavan, RR and Sullivan, MB and Tisza, MJ}, title = {CRESSENT: a bioinformatics toolkit to explore and improve ssDNA virus annotation.}, journal = {Microbial genomics}, volume = {12}, number = {2}, pages = {}, doi = {10.1099/mgen.0.001632}, pmid = {41642221}, issn = {2057-5858}, mesh = {*Computational Biology/methods ; Genome, Viral ; *DNA Viruses/genetics/classification ; *DNA, Single-Stranded/genetics ; Phylogeny ; Metagenomics/methods ; *Molecular Sequence Annotation/methods ; *Software ; }, abstract = {ssDNA viruses are important components of diverse ecosystems; however, it remains challenging to systematically identify and classify them. This is partly due to their broad host range and resulting genomic diversity, structure and rapid evolutionary rates. In addition, distinguishing genuine ssDNA genomes from contaminating sequences in metagenomic datasets (e.g. from commercial kits) has been an unresolved issue for years. Here, we present CRESSENT (CRESS-DNA Extended aNnotation Toolkit), a comprehensive and modular bioinformatic pipeline focused on ssDNA virus 'genome-to-analysis' and annotation. The pipeline integrates multiple functionalities organized into several modules: sequence dereplication, decontamination, phylogenetic analysis, motif discovery, stem-loop structure prediction and recombination detection. Each module can be used independently or in combination with others, allowing researchers to customize their analysis workflow. With this tool, researchers can comprehensively and systematically include ssDNA viruses in their viromics workflows and facilitate comparative genomic studies, which are often limited to dsDNA viruses, therefore leaving behind a crucial component of the microbiome community under study. Benchmarking analyses demonstrated that CRESSENT efficiently processes ssDNA virus datasets of varying scales, completing small family-level analyses within minutes and moderate comparative genomics studies within hours using standard computing resources. Its modular, parallelized design ensures scalability and low memory usage, making it accessible to research groups with diverse computational capacities.}, } @article {pmid41642002, year = {2026}, author = {Williams, A and Maros, A and France, MT and Ravel, J and Holm, JB}, title = {Not all vaginal microbiomes are equal: functional context shapes immune landscapes.}, journal = {mBio}, volume = {}, number = {}, pages = {e0364525}, doi = {10.1128/mbio.03645-25}, pmid = {41642002}, issn = {2150-7511}, abstract = {Taxonomic classification alone fails to capture the ecological and functional diversity of vaginal microbiomes, particularly those dominated by Gardnerella species. Using the expanded VIRGO2 gene catalog, we developed the vaginal inference of subspecies and typing algorithm (VISTA), a novel ortholog-based framework that defined metagenomic subspecies and 25 metagenomic community state types (mgCSTs), including six distinct Gardnerella-dominated profiles. The mgCSTs exhibit marked differences in species composition, functional gene content, transcriptional activity, and host immune responses. These findings reveal that Gardnerella predominance does not uniformly equate to dysbiosis and underscore the importance of functional context in shaping host-microbiome interactions. VISTA provides scalable classifiers and an interactive application to support mechanistic studies of vaginal microbiome function and its implications for reproductive health.IMPORTANCEThe vaginal microbiome plays a central role in reproductive and gynecologic health, yet its functional diversity and ecological organization remain poorly understood. Traditional 16S rRNA approaches provide only a partial view of this complexity, overlooking the strain-level variation that often determines microbial behavior and host outcomes. By applying metagenomic sequencing and scalable computational modeling, we developed the vaginal inference of subspecies and typing algorithm, a framework that defines gene-based subspecies and community state types across diverse populations. These classifications reveal new insights into the genomic and ecological foundations of vaginal community structure and offer a standardized resource for comparative and translational microbiome research. This work establishes the foundation for functionally informed diagnostics and precision interventions targeting women's reproductive health.}, } @article {pmid41641857, year = {2026}, author = {Marcinkowska, K and Wrzesińska-Krupa, B and Obrępalska-Stęplowska, A}, title = {Insights Into Sequences of Viral and Bacterial Origin in the Metatranscriptome of Centaurea cyanus L. Susceptible and Resistant to Acetolactate Synthase (ALS)-Inhibiting Herbicides.}, journal = {Environmental microbiology reports}, volume = {18}, number = {1}, pages = {e70287}, pmid = {41641857}, issn = {1758-2229}, support = {2020/04/X/NZ9/01767//National Science Centre/ ; }, mesh = {*Herbicides/pharmacology ; *Acetolactate Synthase/antagonists & inhibitors ; *Bacteria/genetics/classification/isolation & purification/drug effects ; *Herbicide Resistance ; *Centaurea/microbiology/virology ; Arylsulfonates/pharmacology ; Transcriptome ; Poland ; Plant Weeds/virology/microbiology ; *Plant Viruses/genetics/classification/isolation & purification ; Phylogeny ; }, abstract = {Cornflower (Centaurea cyanus L.) is a widespread weed in cereal crops and is commonly controlled with sulfonylurea herbicides. In Poland, populations of cornflower resistant to acetolactate synthase inhibiting herbicides, such as tribenuron-methyl, have been increasingly reported. Both target-site and non-target-site resistance mechanisms may contribute to this phenomenon. Plant-associated microorganisms are known to play essential roles in alleviating abiotic stress. Moreover, weeds are considered reservoirs of plant pathogenic viruses. Since bacteria and viruses associated with cornflower have not been analysed to date, data mining was undertaken to identify viral and bacterial sequences in metatranscriptome datasets obtained from plant biotypes that are both susceptible and highly resistant to tribenuron-methyl. Using MEGAN6 and Kraken2, taxonomic classification revealed the presence of sequences of two double-stranded RNA viruses belonging to the family Partitiviridae, which have not been described before. For bacterial sequences, 19 genera were identified, including Bacillus, Mesorhizobium and Acinetobacter, some of which are associated with plant growth promotion or xenobiotic degradation. Although the presence of partitiviruses was unrelated to herbicide resistance status, some bacterial genera (e.g., Rothia) were more abundant in resistant than in susceptible plants. These results suggest that those bacterial genera present in weeds may be involved in counteracting ALS-inhibiting herbicides.}, } @article {pmid41641785, year = {2026}, author = {Ma, R and An, H and Feng, Y}, title = {Two-sample Mendelian randomization study of gut microbiota and inflammatory proteins: Predictive, preventive, and personalized treatment for migraine.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01711}, pmid = {41641785}, issn = {1673-5374}, abstract = {The human gut microbiota is increasingly recognized as a significant factor in the pathogenesis of migraine, potentially via inflammatory pathways. Identifying specific human gut microbiota components associated with migraines, along with the investigation of particular inflammatory proteins, is essential for advancing primary prediction, targeted prevention, and personalized treatment strategies for migraines. We conducted a two-sample Mendelian randomization study using publicly available summary statistics from genome-wide association studies. Data for 473 human gut microbiota taxa were obtained from the Finnish national health survey conducted by the National Institute for Health and Welfare study (FINRISK, n = 5959 European participants). Genome-wide association study data (https://www.ebi.ac.uk/gwas/) for 91 circulating inflammatory proteins were obtained from 14,824 participants across 11 cohorts using the Olink Target 96 Inflammation panel. Migraine outcome data were obtained from the FinnGen R12 release, with cases defined using ICD-10 code G43. All genome-wide association study analyses were adjusted for sex, age, genotyping batch, and 10 genetic principal components to control population stratification (genomic inflation factors: 1.00-1.05). Inverse variance-weighted Mendelian randomization was the primary analysis method, with Mendelian randomization-Egger, weighted median, and mode-based methods as sensitivity analyses. Two-step Mendelian randomization mediation analysis quantified the proportion of the effects of human gut microbiota on migraine that are mediated through inflammatory proteins. Thirty-seven bacterial genera were found to be associated with migraine using the inverse variance-weighted method. Of these, 18 genera exhibited a negative association, while 19 genera demonstrated a positive association with migraine risk. Additionally, eight inflammatory proteins were found to increase the risk of migraine. Among human gut microbiota, four were observed to reduce inflammatory protein levels, whereas another four were associated with increased inflammatory protein levels. Additionally, five gut microbiota were identified to influence migraine through inflammatory proteins in both Mendelian randomization analyses. Specifically, Actinobacteria, Brachyspiraceae, CAG-269 sp001915995, and Paraglaciecola were found to affect migraine outcomes via inflammatory proteins, with mediation proportions of 12%, 19%, 15.5%, and 6.7%, respectively. Lawsonibacter sp002161175 was identified to influence migraine risk through Oncostatin-M and SLAM, with mediation proportions of 15.6% and 11.3%, respectively. Our study elucidated the role of specific human gut microbiota alterations in the pathogenesis of migraine and highlighted the mediating effects of inflammatory proteins. Targeting these particular human gut microbiota alterations offers a promising strategy for predictive, preventive, and personalized medicine in migraine management, resulting in substantial clinical advancements.}, } @article {pmid41641698, year = {2026}, author = {Aktary, Z and Sorg, K and Cucchiarini, A and Vesco, G and Noury, D and Zhang, R and Jourdain, T and Verga, D and Mahou, P and Olivier, N and Bohálová, N and Porubiaková, O and Brázda, V and Bouvier, M and Kwapisz, M and Clouet-d'Orval, B and Allers, T and Lestini, R and Mergny, JL and Guittat, L}, title = {Archaeal G-quadruplexes: a novel model for understanding unusual DNA/RNA structures across the tree of life.}, journal = {Nucleic acids research}, volume = {54}, number = {4}, pages = {}, pmid = {41641698}, issn = {1362-4962}, support = {ANR-20-CE12-0023//ANR/ ; ANR-11-EQPX-0029//ANR/ ; ANR-10-INBS-04//ANR/ ; ANR-22-CE12-0009-01//ANR/ ; }, mesh = {*G-Quadruplexes ; *DNA, Archaeal/chemistry/genetics ; *Haloferax volcanii/genetics ; *RNA, Archaeal/chemistry/genetics ; Thermococcus/genetics ; Genome, Archaeal ; Archaea/genetics ; Phylogeny ; Nucleic Acid Conformation ; }, abstract = {Archaea, a domain of microorganisms found in diverse environments, including the human microbiome, represent the closest known prokaryotic relatives of eukaryotes. This phylogenetic proximity positions them as a relevant model for investigating the evolutionary origins of nucleic acid secondary structures such as G-quadruplexes (G4s) which play regulatory roles in transcription and replication. Although G4s have been extensively studied in eukaryotes, their presence and function in archaea remain poorly characterized. In this study, a genome-wide analysis of the halophilic archaeon Haloferax volcanii identified over 5800 potential G4-forming sequences. Biophysical validation confirmed that many of these sequences adopt stable G4 conformations in vitro. Using G4-specific detection tools and super-resolution microscopy, G4 structures were visualized in vivo in both DNA and RNA across multiple growth phases. Comparable findings were observed in the thermophilic archaeon Thermococcus barophilus. Functional analysis using helicase-deficient H. volcanii strains further identified candidate enzymes involved in G4 resolution. These results establish H. volcanii as a tractable archaeal model for G4 biology.}, } @article {pmid41641501, year = {2026}, author = {Mei, S and Cao, Q and Huang, G and Chen, D and Kitts, DD and Chen, X}, title = {Polyphenol-Rich Coffee Leaf Extract Alleviates High-Fat Diet-Induced Intestinal Barrier Dysfunction through Modulation of Barrier Integrity, Enterohepatic Axis, and Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13455}, pmid = {41641501}, issn = {1520-5118}, abstract = {A polyphenol-rich extract (WEAC) from coffee leaf was previously shown to protect the epithelial barrier integrity. This study investigated the protective effects of WEAC in C57BL/6 mice fed a high-fat diet (HFD). WEAC supplementation (100-200 mg/kg·bw) reduced body weight and lowered TNF-α levels in serum, colon, liver, and brain in mice. WEAC improved mouse intestinal barrier integrity by upregulating the tight-junction protein and reducing intestinal d-lactic acid leakage. Liver histology revealed reduced lipid accumulation and ballooning degeneration, corresponding to decreased triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The WEAC intervention also decreased total bile acid levels and altered short-chain fatty acid profiles and key phytochemical metabolism. Furthermore, WEAC reduced the Firmicutes/Bacteroidetes ratio, increased the Parabacteroides, unclassified_Muribaculaceae, and Akkermansia abundance, and lowered the Blautia levels. Additionally, WEAC showed no adverse effects in mice fed a normal diet. Overall, WEAC mitigated HFD-induced intestinal barrier damage and enterohepatic function, reduced systemic inflammation, and stabilized the gut microbiome.}, } @article {pmid41641458, year = {2025}, author = {Bai, H and Xu, Y and Qu, S and Li, B and Wang, X}, title = {The influence of the maternal microbiome on offspring neurodevelopment: a critical review of associations, controversies, and challenges.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1737795}, pmid = {41641458}, issn = {1662-4548}, abstract = {The role of the maternal microbiome in offspring neurodevelopment has become a prominent topic in neuroscience, yet its true causal status is under intense scrutiny. This critical review moves beyond conventional deconstructions of popular hypotheses in the field (e.g., "prenatal programming" "windows of opportunity") to challenge a more fundamental premise. We systematically argue that the currently observed associations along the "microbiota-gut-brain axis" may reflect complex confounding, with macroscopic social factors such as socioeconomic status (SES) being the true underlying drivers. The core thesis of this paper is that the maternal microbiome is, to a great extent, a "biological imprint" of the mother's living environment, diet, and stress levels-a highly sensitive "proxy" indicator acting as a biological mediator heavily shaped by the environment, rather than solely as an independent driver. By integrating evidence from social epidemiology, we contend that positioning the microbiome alongside factors like SES in a "flattened" network model is misleading. Instead, we propose a Hierarchical Causal Model where socioeconomic factors act as top-level "master regulators," systematically shaping all downstream biological processes, including the microbiome. Through a critical analysis of interventions such as Fecal Microbiota Transplantation (FMT) and vaginal seeding, this review further exposes the translational predicaments that arise from neglecting this hierarchical structure. Ultimately, this review advocates for a paradigm shift: from searching for a single "microbial panacea" to understanding the microbiome's true position within the socio-biological system, and proposes a conceptual framework for future research that is more aligned with real-world complexity and endowed with greater sociological imagination.}, } @article {pmid41641369, year = {2026}, author = {Wang, N and Luo, L and Yang, X}, title = {The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10876}, pmid = {41641369}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.}, } @article {pmid41641367, year = {2026}, author = {Chapman, JA and Frey, AM and Dueñas, ME and Palmer, JM and Masi, AC and Embleton, ND and Trost, M and Berrington, JE and Stewart, CJ}, title = {Optimising the induction of inflammation within preterm infant-derived intestinal epithelial organoids.}, journal = {Npj gut and liver}, volume = {3}, number = {1}, pages = {5}, pmid = {41641367}, issn = {3004-9806}, abstract = {Preterm infants born <32 weeks gestation have abnormal microbial colonisation and dysregulated inflammation within the gut. Preterm infant-derived intestinal organoids (PIOs) represent a valuable model for investigating gut microbiome-host interactions and inflammatory responses. We optimised an inflammation model in PIO monolayers incubated within an anaerobic co-culture system that recreates the physiological oxygen gradient of the intestinal epithelium. We trialled multiple stimuli, including live and heat-killed pathobiont consortia, lipopolysaccharide (LPS) and flagellin. We found that a combination of apical LPS and basolateral flagellin, incubated for 3 h, elicited the most robust response. This was characterised by enhanced pro-inflammatory cytokine secretion, the potential for chemokine-driven immune recruitment, TNFα and IL17C pathway signalling, shifts from NF-κB to AP-1-mediated responses, and signs of tissue remodelling. This provides a framework for appropriate study design to disentangle the impacts of microbiome-host interactions in health and disease using intestinal organoids.}, } @article {pmid41641316, year = {2026}, author = {Zhang, X and Wang, J and He, Y and Xiao, X and Fan, J and Ma, X}, title = {Mucosal-associated invariant T cells and the gut-kidney axis: a review.}, journal = {Clinical kidney journal}, volume = {19}, number = {2}, pages = {sfaf366}, pmid = {41641316}, issn = {2048-8505}, abstract = {Mucosal-associated invariant T (MAIT) cells are a distinct subset of innate-like lymphocytes that bridge microbial homeostasis and tissue immunity. These evolutionarily conserved cells are activated via the recognition of microbial metabolites presented by the MR1 molecule and establish stable residency in the kidney, where they profoundly influence local immune-metabolic processes. There is growing interest in the robust regulatory capacities of MAIT cells in renal physiology and pathology. This review systematically delineates their paradoxical roles in kidney diseases. Under specific conditions, they exert protective functions by suppressing inflammation and maintaining tissue homeostasis. Conversely, in distinct microenvironments, they adopt a pro-inflammatory phenotype, exacerbating pathological progression through the release of inflammatory cytokines and cytotoxic effector functions. The gut-kidney axis serves as a critical regulatory hub, wherein dysbiosis-derived signals can significantly amplify the renal impact of MAIT cells. Focusing on clinical translation, we provide an in-depth exploration of innovative strategies targeting MAIT cells, including adoptive cell therapy, receptor-targeting agents, and microbiome reconstruction. These approaches position MAIT cells as promising therapeutic targets for a new generation of immune-mediated kidney diseases.}, } @article {pmid41641314, year = {2026}, author = {Heneberg, P and Heneberg Šimčíková, D}, title = {Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps.}, journal = {Clinical kidney journal}, volume = {19}, number = {2}, pages = {sfaf380}, pmid = {41641314}, issn = {2048-8505}, abstract = {Amino acid metabolism is closely linked with kidney physiology and pathology. In acute kidney injury, chronic kidney disease, diabetic kidney disease, and autosomal dominant polycystic kidney disease, disturbances in the branched-chain amino acids, tryptophan, glutamine, taurine, and sulfur amino acids pathways are consistently observed. Specific metabolites such as D-serine, kynurenine intermediates, and branched-chain keto acids are associated with disease progression. Taurine and indoxyl sulfate have also been proposed as therapeutic targets. At the nephron level, transporters and enzymes controlling amino acid flux influence nitrogen balance, oxidative stress, fibrosis, inflammation, and tubular injury. In chronic kidney disease, impaired amino acid handling contributes to protein-energy wasting, altered muscle metabolism, and systemic complications. In autosomal dominant polycystic kidney disease, cyst fluid metabolomics has revealed alterations in tryptophan and polyamine metabolism. The use of nutritional interventions, microbiome modulation, and selective supplementation as therapeutic strategies is being explored, although clinical trial evidence remains limited. Several key issues remain unresolved, including the need for isotope tracer studies to define renal amino acid kinetics in humans, the rigorous validation of metabolite biomarkers across diverse populations, the integration of diet and microbiome-derived metabolites into mechanistic frameworks, and the systematic evaluation of sex-specific differences. Longitudinal studies are scarce, thus restricting predictive power and therapeutic translation. Further mechanistic clarification may support the development of biomarkers and targeted therapies.}, } @article {pmid41641227, year = {2026}, author = {Tajdari, M and Abolghasemi, S and Khanniri, E and Bayanati, M and Hakimimofrad, R and Mahboubi-Rabbani, M}, title = {A Comprehensive Review of Acne Treatments: Unpacking the Chemical Structures and Effective Bioactive Compounds.}, journal = {Health science reports}, volume = {9}, number = {2}, pages = {e71803}, pmid = {41641227}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: Acne vulgaris is a frequent skin disorder, affecting a large part of the population worldwide, and strongly influencing not only the physical but also the mental aspects of health. The choice of therapy for acne vulgaris is a very difficult one because the multifactorial causality of the disease and interindividual variability in response to treatment should be considered. This article aims to provide a comprehensive review of the drugs used in the treatment of acn\e vulgaris, along with their chemical structure.

METHODS: A comprehensive search of relevant databases (PubMed, Google Scholar, Web of Science, and Scopus) was conducted using keywords such as "acne vulgaris", "chemical structure", "mode of action", and "structure-activity relationship". We reviewed articles published up to 2025. The authors reviewed articles that discussed the chemical structure and structure-activity relationships of drugs used in the treatment of acne vulgaris. In addition, articles on acne vulgaris pharmacotherapy were also reviewed.

RESULTS: In this review, all the current modalities for the management of acne vulgaris are presented and grouped according to their chemical nature, including topical applications and systemic administration. In this light, we go further into the mechanism of action of each treatment, its efficacy and safety, and possible side effects. New therapeutic agents targeting the skin microbiome, inflammation, and hormonal imbalance are also a focus. We finally propose one step for choosing an optimum therapy based on the subject's constitution, the severity of post-acne scarring, and associated comorbidities.

CONCLUSION: The present review would benefit general physicians in adapting their management to treat zits and pimples for the improvement of their patients, with particular importance given to the knowledge of the chemical structures of various drugs.}, } @article {pmid41641220, year = {2026}, author = {Huang, YY and Li, CY and Li, Y and Fang, H and Ke, XY}, title = {Characteristics and functions of the gut microbiome in monozygotic twins with autism spectrum disorders of varying severity.}, journal = {World journal of psychiatry}, volume = {16}, number = {2}, pages = {111012}, pmid = {41641220}, issn = {2220-3206}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by pronounced behavioral heterogeneity and individual variability. Growing evidence indicates a strong association between gut microbiota and ASD; however, differences in microbial functions across varying levels of ASD severity remain poorly understood. Monozygotic twins (MZs) provide an appropriate model for examining the influence of nonshared environmental factors in ASD.

AIM: To investigate the effects of the gut microbiome in MZs with ASD using 16S ribosomal RNA sequencing.

METHODS: Participants were recruited from the Chinese MZs with autism spectrum disorder (MZCo-ASD) cohort and stratified into mild MZCo-ASD and severe MZCo-ASD (MZCo-ASD-H) groups based on their Childhood Autism Rating Scale scores. Fecal samples were collected and analyzed using 16S ribosomal RNA sequencing.

RESULTS: Although overall microbial diversity did not differ significantly between the groups, gut microbiota composition was notably altered. At the genus level, Por phyromonas was significantly enriched in the MZCo-ASD-H group. Clusters of Orthologous Groups analysis revealed decreased expression of key genes in the MZCo-ASD-H group, including fructose-1,6-bisphosphatase, membrane-bound lytic murein transglycosylase, PasI (part of the RatAB toxin-antitoxin system), HmoA, and a glycoside hydrolase family 25 domain-containing protein. Kyoto Encyclopedia of Genes and Genomes Orthology analysis showed that msmF (K10118) and msmG (K10119), involved in oligosaccharide transport, were significantly downregulated in the MZCo-ASD-H group, suggesting a reduced microbial capacity for prebiotic carbohydrate utilization.

CONCLUSION: Despite similar overall diversity, children with severe ASD exhibited distinct gut microbiota structures and functional impairments. The enrichment of Porphyromonas, along with the reduced expression of genes involved in carbohydrate metabolism and stress responses in the high-severity group, suggests an association between gut microbial dysregulation and ASD severity. These findings provide new insights into microbiota-related mechanisms underlying ASD and highlight potential functional targets for intervention.}, } @article {pmid41641127, year = {2025}, author = {Rogalidou, M}, title = {Clostridioides difficile infection in pediatric inflammatory bowel disease: current understanding and clinical challenges.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1753289}, pmid = {41641127}, issn = {2296-2360}, abstract = {Clostridioides difficile infection (CDI) represents a significant and increasingly recognized complication in children with inflammatory bowel disease (IBD), contributing to prolonged hospitalization and risk of adverse outcomes. Children with IBD are particularly susceptible due to frequent antibiotic exposure, healthcare system contact, immunosuppressive therapy, and underlying gut dysbiosis, all of which promote colonization and toxin-mediated intestinal injury. Distinguishing CDI from an IBD flare is challenging, as gastrointestinal symptoms and systemic inflammation overlap, and asymptomatic toxigenic colonization is common. Management recommendations for pediatric IBD-associated CDI are largely extrapolated from adult studies, with prompt initiation of targeted antibiotics being critical. Immunosuppressive therapy is generally continued, with escalation considered if diarrhea persists despite CDI-directed therapy. Fecal microbiota transplantation (FMT) has emerged as a safe and promising option for recurrent CDI in children with IBD, although careful patient selection, donor choice, and timing remain crucial. Key challenges persist in differentiating true CDI from IBD flares, understanding the clinical impact of asymptomatic colonization, and optimizing microbiome-targeted interventions. Future research should prioritize biomarker-driven diagnosis, individualized therapeutic strategies, and longitudinal evaluation of microbiome-based treatments to improve outcomes in pediatric patients with concurrent CDI and IBD.}, } @article {pmid41640962, year = {2026}, author = {Goyal, MK and Chowdhary, R and Vohra, C and Patel, M and Kalra, S and Mehta, M and McNulty, R and Goyal, K and Vuthaluru, AR and Goyal, O}, title = {Current management strategies for sarcopenia and frailty in cirrhosis: Missing link in transplant candidacy.}, journal = {World journal of hepatology}, volume = {18}, number = {1}, pages = {115048}, pmid = {41640962}, issn = {1948-5182}, abstract = {Sarcopenia and frailty are pervasive, interrelated syndromes in cirrhosis that worsen morbidity, quality of life, transplantation waitlist outcomes, and post-transplant survival. This review synthesized contemporary evidence on definitions, epidemiology, mechanisms, diagnosis, prognostic impact, and management with an emphasis on implementable strategies in hepatology practice. Sarcopenia affects 40%-70% of patients with cirrhosis, and frailty affects 20%-50% of patients with cirrhosis with variations across populations and definitions. Mechanistic drivers include hyperammonemia, systemic inflammation, endocrine disturbances, malnutrition and accelerated starvation, gut-liver-muscle axis alterations, mammalian target of rapamycin inhibition, and inactivity. Diagnosis spans simple bedside tests such as handgrip strength, chair stands, gait speed, and the Liver Frailty Index as well as imaging modalities including computed tomography-based skeletal muscle index, dual energy X-ray absorptiometry, magnetic resonance imaging, and bioimpedance. Both sarcopenia and frailty independently predict hepatic decompensation, hospitalizations, waitlist dropout, and mortality, providing additive prognostic value beyond model for end-stage liver disease (MELD)/MELD-Na, and they are associated with longer intensive care unit and hospital stays and worse post-transplant outcomes. Management requires a multimodal approach: Optimization of cirrhosis complications and ammonia-lowering therapy; adequate nutrition with 1.2-1.5 g/kg/day protein and a late-evening snack; structured aerobic and resistance exercise programs; cautious use of testosterone in hypogonadal males; and emerging therapies such as beta-hydroxy-beta-methylbutyrate, vitamin D, L-carnitine, microbiome modulation, and myostatin inhibitors. Routine screening and multidisciplinary prehabilitation should be embedded in standard care pathways, and incorporation of sarcopenia and frailty metrics alongside MELD may refine risk stratification, enhance transplant allocation, and improve long-term outcomes.}, } @article {pmid41640922, year = {2026}, author = {Iturbe Cordero, AA and Jaramillo, AP and Vasquez, J}, title = {Perioperative Antimicrobial Prophylaxis for Invasive Dental Procedures: A Systematic Review and Random-Effects Meta-Analysis of Randomized and Placebo-Controlled Studies.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e100755}, pmid = {41640922}, issn = {2168-8184}, abstract = {Prophylactic antimicrobials are frequently administered before invasive dental procedures (including implant placement and extractions) to reduce early infectious complications and procedure-related bacteremia; however, clinical benefit remains debated and must be balanced against ecological disruption and antimicrobial resistance. Evidence from experimental work indicates that even a single prophylactic dose of amoxicillin may transiently perturb the oral microbiome and select resistant strains. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review was conducted. PubMed, Embase, and Cochrane databases were searched. Screening identified 10 randomized placebo-controlled/comparator trials (486 records; 289 duplicates removed; 197 screened; 72 full texts reviewed) for qualitative synthesis and meta-analysis. Included studies evaluated perioperative prophylaxis (systemic antibiotics and/or local antiseptic prophylaxis) versus placebo or no prophylaxis in invasive dental procedures. Outcomes were harmonized across studies as early procedure-related infectious outcomes and/or bacteremia-related endpoints, with secondary assessment of postoperative morbidity indicators (e.g., pain/analgesic use where available). Meta-analysis was performed in Review Manager (RevMan) version 5.4 (2020; The Cochrane Collaboration, London, United Kingdom), using an inverse-variance random-effects model. Across all invasive dental procedures (~1,950 participants pooled), prophylaxis did not demonstrate a statistically significant overall reduction in the primary pooled endpoint (MD -0.12, 95%CI -0.31 to 0.07; random-effects; I[2] ≈ 99%). In the dental-surgery subgroup, the pooled effect similarly crossed the null (MD -0.17, 95%CI -0.45 to 0.11; I[2] ≈ 99%). Individual trials showed marked reductions in post-extraction bacteremia surrogates with chlorhexidine mouthwash prophylaxis and with intravenous amoxicillin-clavulanate in extraction settings, whereas in uncomplicated extractions among well-controlled type 2 diabetes, antibiotics did not reduce postoperative complications and were associated with greater analgesic consumption. Implant trials reported low event rates and did not consistently demonstrate clinically meaningful superiority of routine prophylaxis. Funnel plot inspection suggested possible small-study effects influenced by outliers, but interpretation was constrained by extreme between-study heterogeneity. In this pooled analysis of randomized and placebo-controlled studies spanning heterogeneous invasive dental procedures, routine prophylactic antimicrobial strategies did not yield a consistent overall benefit on early infectious/bacteremia-related outcomes, and secondary postoperative morbidity outcomes showed no clear improvement. In parallel, microbiological evidence indicates that single-dose prophylaxis can promote short-term ecological disturbance and selection of resistant oral flora. Future trials should standardize endpoints (distinguishing clinical infection/implant failure from surrogate bacteremia measures), stratify by baseline risk, and prioritize antimicrobial stewardship to identify the limited patient subsets most likely to benefit.}, } @article {pmid41640815, year = {2026}, author = {de Souza Alves, CC and de Castro, SBR and Brugiolo, ASS}, title = {Editorial: Novel therapeutic targets in autoimmune diseases: intestinal microbiota and adaptive immunity regulation.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1779062}, doi = {10.3389/fimmu.2026.1779062}, pmid = {41640815}, issn = {1664-3224}, } @article {pmid41640761, year = {2025}, author = {Fosso, E and Gizzi, G and Tartaglia, M and Prigioniero, A and Ranauda, MA and Maisto, M and Labella-Ortega, M and Zuzolo, D and Guarino, C}, title = {Management affects the diversity and functions of root and leaf-associated microbiomes: implications for olive resilience.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1699667}, pmid = {41640761}, issn = {1664-462X}, abstract = {This study explores the impact of organic, conventional, and traditional agricultural management on the aboveground and belowground microbiomes of Olea europaea L. cv. Ortice, a cultivar widely cultivated in southern Italy's agricultural landscape. Through metabarcoding analyses (16S rRNA and ITS), we assessed the influence of farming approaches on the microbiome traits of the olive holobiont. Our findings demonstrate that agricultural management practices significantly shape microbiome composition both aboveground and belowground. The conventional management was associated with the highest number of microbial biomarkers aboveground, mainly belonging to Rhizobiaceae and Rhodocyclaceae families. Instead, Fusarium (family Nectriaceae) was the most abundant taxon under organic treatment. Regarding root-associated microbiome, organic management supported a greater number of microbial biomarkers, including the bacterial genera Actinophytocola and Streptomyces, both known for their roles in promoting plant health and protecting against pathogens. In traditional systems, biomarkers included taxa from the order Burkholderiales and the species Nocardioides islandensis. Functional analysis of the aboveground fungal community revealed a higher capacity for endophytic interactions in traditional management, predominantly involving known pathogenic species such as Alternaria alternata, Aureobasidium spp., and Cladosporium spp. Similarly, traditional management was associated with significant enrichment of phototrophic functions belowground, mainly attributed to the bacterium Rhodopseudomonas palustris. Conversely, the potential for endophytic interactions was significantly greater under conventional management and was primarily linked to fungi within the class Sordariomycetes. Management practices shape distinct microbial communities both aboveground and belowground of olive groves, potentially influencing the resilience of Mediterranean agroecosystems and underscoring the importance of sustainable strategies.}, } @article {pmid41640760, year = {2025}, author = {Zhang, C and Yang, L and Zhang, X and Zhao, Y and Tang, J and Cheng, Z and Cao, Y and Wu, S and Li, G and Yang, L and Wei, K}, title = {Regional climate variation structures the phyllosphere microbiome of flue-cured tobacco.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1733198}, pmid = {41640760}, issn = {1664-462X}, abstract = {INTRODUCTION: Climate change poses major challenges to agriculture, with phyllosphere microbiota playing a key but poorly understood role in plant adaptation.

METHODS: We examined structural and functional responses of the phyllosphere microbiome in flue-cured tobacco (Nicotiana tabacum L.) across climatic gradients, using multi-regional sampling, high-throughput sequencing (16S rRNA/ITS), and functional prediction (PICRUSt2).

RESULTS: Leaf starch, total sugar, and reducing sugar contents varied significantly (26.87-32.25%, 14.24-16.74%, and 9.96-11.26%, respectively). Bacterial communities were primarily shaped by precipitation (41.7% variance explained), whereas fungal communities were mainly driven by temperature (27.3%). Microbial networks showed climate-adaptive patterns: complex, cooperative networks (85.99% positive edges) in high-precipitation areas versus simplified, drought-tolerant networks (Nodes: 93, Edges: 1124) dominated by Sphingomonas (86.50%) and Methylobacterium (10.24%) in arid regions. Metabolic potential shifted along the gradient: Communities in low-precipitation areas were enriched with genes potentially encoding starch-degrading enzymes (e.g., α-amylase), while those in high-precipitation areas showed enhanced potential for sucrose synthesis (e.g., via sucrose synthase).

DISCUSSION: This study reveals the adaptive strategies of phyllosphere microbial communities in response to climate variations. Under low-rainfall conditions, community metabolism shifts toward starch degradation, which may aid host osmoregulation. In contrast, under humid conditions, dominant taxa such as Sphingomonas and Methylobacterium collaboratively enhance sucrose synthesis. This metabolic reprogramming aligns with structural changes in microbial networks: transitioning from complex, cooperative networks in humid regions to simplified, stress-tolerant networks in low-rainfall areas. Key metabolic functions are primarily contributed by low-abundance taxa, suggesting the vital role of the rare biosphere in maintaining functional redundancy. Based on these findings, we propose that microbial communities may enhance adaptability by retaining core metabolic functions, such as starch degradation, within rare taxa when facing drought or temperature fluctuations. This study provides a theoretical framework for improving crop climate resilience through microbiome management.}, } @article {pmid41640612, year = {2026}, author = {Liu, ZX and Liu, XY and Tan, WW and Zhang, WB and Zhang, YL and Zheng, L and Dai, YC}, title = {Characteristics of gut microbiota and metabolites in patients with ulcerative colitis with fatigue.}, journal = {World journal of gastroenterology}, volume = {32}, number = {3}, pages = {115264}, pmid = {41640612}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics/physiology ; *Colitis, Ulcerative/microbiology/complications/metabolism ; Male ; Female ; Adult ; Feces/microbiology ; Middle Aged ; *Fatigue/microbiology/etiology/metabolism ; Metabolomics ; RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Bacteria/isolation & purification/classification/genetics ; Quality of Life ; Young Adult ; Dysbiosis/microbiology ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease. The gut microbiome undergoes significant changes in UC. Fatigue is a highly prevalent and debilitating extraintestinal symptom of UC, which negatively affects quality of life. However, its relationship with gut microbes and metabolites remains unclear.

AIM: To assess the gut microbiota and metabolomic characteristics of patients with UC with fatigue (HUCF).

METHODS: A total of 120 participants were recruited and divided into four groups (n = 30 per group) based on the diagnosis of UC and Fatigue Scale-14 scores: HUCF, UC without fatigue (HUCN), healthy with fatigue (HHF), and healthy without fatigue (HHN). Fresh stool samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis.

RESULTS: Metabolomic analysis revealed significant differences among the four groups (principal component analysis/partial least squares discriminant analysis, P = 0.001), with differential expression of metabolites such as linoleoyl ethanolamide, arachidonoyl ethanolamide, glycocholic acid, and thromboxane (TX). Notably, TX was detected only in the HUCF group. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed alterations in eicosanoid, tryptophan, and tyrosine metabolism in the HUCF group. Microbial richness and diversity were significantly lower in the HUCF group than in the other three groups. The HUCF group showed enrichment of Hyphomicrobiales, Brucella, Eisenbergiella, Pediococcus, and Sellimonas. The HUCN group showed enrichment of Campylobacter-related taxa. The HHF group showed enrichment of Fusobacterium, Desulfovibrionaceae, and Bilophila. The HHN group showed enrichment of beneficial genera such as Adlercreutzia. Notably, Anaerococcus, a beneficial genus, was enriched in the HUCF group. Correlation analysis indicated that specific microbes (e.g., Faecalibacterium and Escherichia-Shigella) were associated with the severity of UC and fatigue.

CONCLUSION: Patients with HUCF exhibit a distinct gut microbial structure and metabolomic profile. The pro-inflammatory metabolite TX and the genus Anaerococcus are uniquely enriched in patients with HUCF, suggesting their potential roles in the development of HUCF. These findings provide novel insights and a theoretical basis for improving the clinical management of HUCF.}, } @article {pmid41640608, year = {2026}, author = {Velikova, T and Ali, H and Batselova, H and Chervenkov, L and Miteva, D and Peruhova, M and Gulinac, M and Tomov, L and Mitova-Mineva, Y and Velev, V}, title = {Interplay between viral infections and gut microbiota dysbiosis: Mechanisms and therapeutic potential.}, journal = {World journal of gastroenterology}, volume = {32}, number = {3}, pages = {112437}, pmid = {41640608}, issn = {2219-2840}, mesh = {Humans ; *Dysbiosis/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *COVID-19/immunology/microbiology/complications/therapy ; SARS-CoV-2 ; Prebiotics/administration & dosage ; *Virus Diseases/immunology/microbiology/therapy ; Animals ; }, abstract = {Viral infections, particularly those triggered by emerging pathogens like severe acute respiratory syndrome coronavirus 2, are increasingly recognized for their profound impact on the gut microbiota, causing dysbiosis, a condition characterized by an imbalance in microbial communities. Recent studies suggest that alterations in gut microbiota can influence disease progression, immune responses, and clinical outcomes. The bidirectional relationship between the gut microbiota and the host immune system is crucial in shaping responses to infection. Furthermore, dysbiosis has been linked to exacerbated inflammation, impaired mucosal barrier function, and altered drug metabolism, thereby complicating both disease pathogenesis and treatment efficacy. This review examines the interplay between viral infections and gut microbiota dysbiosis, with a focus on the underlying mechanisms and potential therapeutic strategies to modulate host immunity. We also evaluate the potential of microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, as therapeutic strategies for restoring microbial balance and mitigating the severity of infections. The paper underscores the need for further research to optimize microbiota-targeted therapies and integrate them into clinical practice, offering a comprehensive approach to managing dysbiosis in viral infectious diseases.}, } @article {pmid41640423, year = {2026}, author = {Sola-Leyva, A and Pérez-Prieto, I and Canha-Gouveia, A and Salas-Espejo, E and Molina, NM and Vargas, E and Apostolov, A and Pathare, ADS and Vela-Moreno, S and Ruiz-Durán, S and Romero, B and Sánchez, R and Castilla-Alcalá, JA and Saare, M and Acharya, G and Salumets, A and Altmäe, S}, title = {Comprehensive 16S rRNA gene sequencing and meta-transcriptomic analyses of the female reproductive tract microbiota: two molecular profiles with different messages.}, journal = {Human reproduction open}, volume = {2026}, number = {1}, pages = {hoag001}, pmid = {41640423}, issn = {2399-3529}, abstract = {STUDY QUESTION: Does the analysis of endometrial microbes provide the same information when using DNA or RNA sequencing-based techniques?

SUMMARY ANSWER: DNA vs RNA-based microbial analysis techniques demonstrated significant microbial compositional differences and lack of transcriptionally active lactobacilli in the endometrium.

WHAT IS KNOWN ALREADY: Our understanding of the endometrial microbiome is primarily based on DNA-based 16S rRNA gene profiling, but DNA detection does not imply the presence of living microbes. While this method is cost-effective and widely used, it has notable limitations, including the underestimation of microbial diversity, abundance, and functionality, as well as limited species-level resolution. While the microbiome reflects DNA-based characterization, the microbiota more precisely captures metabolically active communities. In this context, meta-transcriptomic analysis, an RNA-based approach, addresses these shortcomings by capturing functional transcripts that are actively expressed in living microbes.

STUDY DESIGN SIZE DURATION: This cross-sectional study consisted of 49 reproductive-aged women (27-42 years old) who were receiving ART. By simultaneously analysing the microbial composition and gene expression within female reproductive tract samples, we sought to provide a more comprehensive understanding of the microbiota and functional potential of these samples.

Vaginal swabs, endometrial brushing, and endometrial biopsy samples were collected from 49 participants during the mid-secretory phase of their menstrual cycle, 6-9 days after the luteinizing hormone surge for parallel 16S rRNA gene sequencing and meta-transcriptome analyses. For DNA-based analysis, the 16S rRNA gene V4 region was sequenced. For RNA-based analysis, total RNA was extracted followed by ribosomal RNA depletion. Strand-specific total RNA sequencing libraries were prepared and sequenced. Taxonomy was assigned by using Kraken2 (v2.2.1), and Bracken (v2.7).

Our findings suggest that in low-microbial-biomass environments such as the endometrium, the correlation between 16S rRNA gene sequencing and meta-transcriptomics is relatively weak. This highlights the limitations of microbial analysis of low-microbial-biomass samples. Alternatively, microbial functions and genome activity may be tissue-specific and dependent on the host tissue environment. Moreover, RNA-based analysis provides higher resolution in detecting certain pathogens, even within the endometrium.

LARGE SCALE DATA: The data presented in the study are deposited in the NCBI SRA Database, accession number PRJNA1247240.

High levels of host RNA and the low abundance of microbial reads in the endometrium complicate microbial identification. Our findings indicate that RNA-seq enables precise profiling of the vaginal microbiome and, in cases of dysbiosis, reveals higher pathogen activity than DNA-based approaches. However, the limited sample size restricts the generalization of these conclusions.

Contrary to the general belief of the dominance of Lactobacillus in the human endometrium, our study suggests that the endometrial microenvironment may be harbouring DNA fragments and/or cells of lactobacilli originating from the lower reproductive tract. Our study results indicate a need to re-consider/re-analyse the endometrial microbiome in health and disease.

This work was supported by the projects Endo-Map PID2021-127280OB-I00, ROSY CNS2022-135999, and ENDORE SAF2017-87526-R funded by MICIU/AEI/10.13039/501100011033 and by FEDER, EU. This work was also supported by the Estonian Research Council grants (PSG1082 and PRG1076), Swedish Research Council grant no. 2024-02530 and Novo Nordisk Foundation grant no. NNF24OC0092384. Additionally, A.S.L. and I.P.P. acknowledge Becas Fundación Ramón Areces para Estudios Postdoctorales-Convocatorias XXXV and XXXVI, para Ampliación de Estudios en el Extranjero en Ciencias de la Vida y de la Materia. A.S. is supported by Horizon Europe (NESTOR, grant no. 101120075) and the Ministry of Education and Research Centres of Excellence grant TK214 name of CoE. All the authors declare no conflict of interest.}, } @article {pmid41640411, year = {2025}, author = {Fernández-Pastrana, VM and Mora, MR and González-Reguero, D and Probanza, A and Iglesias, DP and Gómez, PAJ}, title = {Use of PGPB in bio-fertilisation: preserving the soil microbiome and enhancing field production of alfalfa.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1735729}, pmid = {41640411}, issn = {1664-302X}, abstract = {Sustainable fodder production requires fertilisers that increase yield without compromising soil ecology. We tested whether a humic-rich biofertiliser derived from valorised horticultural waste (ORGAON® PK) could be enhanced with two genomically screened plant-growth-promoting bacteria (PGPB) in a field trial with Medicago sativa. The crude residue substantially increased biomass, and the addition of Bacillus sp. C1 or Pseudomonas sp. C2 further redirected these gains towards improved fibre digestibility or greater protein and energy content. Soil microbial diversity was maintained, although community composition shifted towards taxa involved in organic-matter degradation and nitrification. Both inoculants persisted without displacing dominant native genera, and biofertilised soils showed reduced susceptibility to β-lactam antibiotics. Overall, pairing OPK with targeted PGPB enhanced forage yield and quality while supporting microbiome resilience, highlighting a promising One-Health-aligned alternative to mineral fertilisers. Multi-season trials are now needed to validate broader applicability.}, } @article {pmid41640410, year = {2025}, author = {Wang, X and Cheng, Y and Huang, J and Xu, F and Jiang, J and Nalinratana, N and Jin, L and Xue, Y}, title = {Engineered probiotics for inflammatory bowel disease therapy: mechanisms, delivery strategies, and precision medicine.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1696524}, pmid = {41640410}, issn = {1664-302X}, abstract = {Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is a prevalent chronic gastrointestinal disorder. Conventional therapies are often limited by adverse effects and suboptimal long-term efficacy. Probiotics have emerged as promising therapeutic alternatives for IBD because of their ability to modulate the gut microbiota, reinforce intestinal barrier integrity, and regulate immune responses. However, their clinical translation is hampered by challenges within the harsh gastrointestinal milieu, including low viability, poor colonization, and insufficient target specificity. This review focuses on the engineering of probiotics designed to overcome these limitations for IBD management. We outline the therapeutic potential and mechanisms of action of probiotics in IBD, with a critical emphasis on discrepancies between preclinical and clinical observations. We subsequently discuss the drawbacks of conventional probiotic therapies, highlighting gaps between in vitro efficacy and in vivo performance. We then highlight cutting-edge engineering strategies, encompassing advanced encapsulation techniques, genetic engineering approaches, novel delivery systems, and molecular-targeting modifications, with quantitative comparisons of their advantages, limitations, and translational potential. The application of these engineered probiotics specifically in UC and CD treatment is explored, with detailed analyses of preclinical models and clinical trials. We also address personalized interventions tailored to individual gut microbiome profiles. Despite significant promise, critical challenges remain, including long-term safety, stability, and accurate prediction of therapeutic responses for engineered probiotics in IBD. Nevertheless, with ongoing advancements in gene editing, synthetic biology, and microbial safety engineering, engineered probiotics represent a promising direction in IBD therapy that will enable more precise, effective, and personalized treatment modalities, provided that safety, reproducibility, and regulatory compliance are prioritized.}, } @article {pmid41640408, year = {2025}, author = {Sun, G and Zou, Q and Wang, B}, title = {The interplay of carbon and nitrogen cycling driven by watershed microorganisms.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1696238}, pmid = {41640408}, issn = {1664-302X}, abstract = {Microorganisms play central roles in regulating carbon and nitrogen cycling across watersheds, driving processes such as organic matter decomposition, primary production, nitrification, and denitrification. Rapid advances in high-throughput sequencing and environmental monitoring have enabled unprecedented insights into the taxonomic diversity and functional capacities of microbial communities under global change. In this review, we synthesize findings from studies published in recent years to evaluate how hydrological connectivity, redox gradients, temperature shifts, and nutrient loading shape microbial metabolism across rivers, lakes, wetlands, and coastal interfaces. We further summarize emerging evidence on how antibiotic resistance genes (ARGs) propagate through these ecosystems and influence microbial functions. The integration of multi-omics technologies including metagenomics, metatranscriptomics, combined with ecological and biogeochemical modeling provides new opportunities to quantify microbe-mediated carbon sequestration and nitrogen transformation. Finally, we discuss current knowledge gaps, including the limited understanding of ARG-driven community restructuring and the insufficient mechanistic resolution of microbe-environment interactions under future climate scenarios. This review highlights the need for cross-scale, data-integrated frameworks to better predict how microbial processes regulate watershed-level biogeochemical cycles in a rapidly changing world.}, } @article {pmid41640388, year = {2026}, author = {Li, S and Li, W and Zhang, X and Zhou, H and Zhan, J}, title = {Harnessing Population Genomics, Gut Microbiota, and Environmental DNA Surveillance for the Conservation of Chinese Spotted Seals in a Changing World.}, journal = {Ecology and evolution}, volume = {16}, number = {2}, pages = {e72952}, pmid = {41640388}, issn = {2045-7758}, abstract = {The triple planetary crisis-encompassing climate change, biodiversity loss, and pollution-poses escalating threats to Earth's systems, particularly impacting marine mammals. The spotted seal (Phoca largha Pallas 1811), currently recognized as the only pinniped species known to breed in China, holds the status of a National Grade I protected species in China. To elucidate the genetic diversity of Chinese spotted seal populations and provide scientific foundations for their conservation and management, this review systematically summarized the fundamental biological characteristics and documented migration routes of spotted seal populations in China, with particular emphasis on reviewing molecular-level research advancements regarding population genetic structure. Early studies primarily employed molecular markers such as microsatellite DNA and mitochondrial DNA (mtDNA), revealing relatively low genetic diversity levels within Chinese spotted seal populations. In recent years, rapid developments in omics technologies have enabled comprehensive investigations into both genomic compositions, as well as gut microbial community diversity and functional profiles of this species. Furthermore, this review critically examined current research limitations and challenges while proposing the potential advantages and developmental trends of environmental DNA (eDNA) technology in future population studies. These technological and strategic advancements are anticipated to significantly enhance survey efficiency and conservation effectiveness for Chinese spotted seal populations.}, } @article {pmid41640304, year = {2026}, author = {Hart, DW and Ng, AS and Gazińska, P and Goldin, R and Gopal, P and O'Dell, N and Zargar, A and Pytowski, L and Montazid, S and Bardella, C and East, JE and Tomlinson, IP and Koch, N and Bennett, NC and Irshad, S}, title = {Characterisation of bacteria-induced colitis and its modulation by probiotics in naked mole rats: a new mammalian model for acute inflammatory disease.}, journal = {The Journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1002/path.70034}, pmid = {41640304}, issn = {1096-9896}, support = {DST-NRF (GUN 64756)//Department of Science and Technology-National Research Foundation/ ; //The National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC)/ ; }, abstract = {Enteropathogenic bacteria are a major cause of morbidity and mortality globally. While mouse models have been indispensable in advancing our understanding of infectious enteric diseases, key differences in intestinal microbiota and immunobiology between mice and humans underscore the need for alternative mammalian models that better recapitulate human disease states. The naked mole rat (NMR), the longest-lived rodent and a model of healthy ageing, presents a unique opportunity. It possesses an exceptionally robust intestinal barrier, an abundance of goblet cells, a thicker mucin layer, and reduced gut permeability compared to mice. Additionally, the NMR gut microbiome exhibits compositional and functional features shared with human centenarians and traditional-lifestyle populations (e.g. Hadza hunter-gatherers), including an enrichment of health-associated taxa and metabolic pathways. Here, we leverage this model to show that systemic Citrobacter braakii infection is associated with colonic inflammation and epithelial injury that closely mimics human haemorrhagic colitis. Infected NMRs develop mucosal erosions, ulcerations, depletion of goblet cells, expansion of proliferative compartments, and active inflammation in the lamina propria. Without intervention, systemic inflammation associated with sepsis ensues and results in high mortality. Furthermore, we demonstrate the utility of this model for therapeutic testing by showing a strong effect of a probiotic cocktail comprising lactobacilli, bifidobacteria, streptococci, and enterococci. Treatment with this cocktail promoted mucosal healing, restored intestinal homeostasis, and exerted an anti-inflammatory effect. Taken together, we establish the NMR as a translatable model for investigating disease mechanisms in infectious colitis, including disruptions in mucosal barrier permeability, gut microbial ecology, and local and systemic immune regulation, as well as for testing functional probiotic strains as potential therapeutics. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid41639970, year = {2026}, author = {Hey, JC and Saalfrank, J and Rasamoelina, T and Razafindrakoto, AR and Razafindralava, M and Rajaoniarivo, VG and Kutz, JM and Ratefiarisoa, S and Thye, T and Kislaya, I and Graspeuntner, S and Rakotomalala, Z and Randrianasolo, BS and Rakotomalala, RS and Marchese, V and Rakotozandrindrainy, R and Koecher-Andrianarimanana, D and Rausche, P and Remkes, A and May, J and Hoekstra, PT and van Dam, GJ and Corstjens, PLAM and Gheit, T and Rakotoarivelo, RA and Bang, C and Fusco, D}, title = {The vaginal microbiota of adult Malagasy women of reproductive age in the Marovoay district: first characterization and exploration of associations with human papillomavirus and Schistosoma haematobium infections.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiag065}, pmid = {41639970}, issn = {1537-6613}, abstract = {BACKGROUND: The vaginal microbiome plays an important role for women's health. Changes in its composition have been associated with several sexually transmitted infections, including human papillomavirus (HPV) or parasitic infections such as Schistosoma haematobium (Sh). In Madagascar, gynaecological conditions such as chronic manifestations of Sh infections (female genital schistosomiasis, FGS), HPV infections, and cervical cancer are highly prevalent; however, data on the interplay between these conditions and the vaginal microbiota (VM) is still scarce. Additionally, the majority of data originates from the Global North, generating a biased understanding of "healthy" VM across different geographical and social contexts. The objective of our study was to characterize for the first time the VM of adult women of reproductive age in Madagascar and to describe the variability of the vaginal environment in presence of three conditions affecting the urogenital tract.

METHODS AND RESULTS: We characterized the VM of 443 participants, identifying the five community state types (CSTs I - V) with CST IV (57.1 %, diverse) and CST III (34.1 %, Lactobacillus iners-dominated) as the most prevalent. CSTs were associated with previous antibiotics usage, while variability in the alpha and beta diversity was associated with dietary behaviour and previous antibiotics usage. Differential abundance analysis showed variations among specific taxa in HPV- and FGS-positive participants.

CONCLUSION: With this first study of the VM in Madagascar we contribute to a broader understanding of vaginal health as well as narrowing the gap of VM research in sub-Saharan Africa by enriching microbiota databases.}, } @article {pmid41639557, year = {2026}, author = {Aran, K}, title = {What my cave stay taught me about sensors.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {41639557}, issn = {1476-4687}, } @article {pmid41639421, year = {2026}, author = {Tashiro, H and Kuwahara, Y and Kurihara, Y and Konomi, Y and Takahashi, K}, title = {Distinct gut microbiome signatures associated with sedentary behavior improvement following rehabilitation in chronic obstructive pulmonary disease patients with higher functional exercise capacity.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-38360-7}, pmid = {41639421}, issn = {2045-2322}, support = {20K17184, 23K15210//Japan Society for the Promotion of Science/ ; 22K11370, 25K14535//Japan Society for the Promotion of Science/ ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is associated with reduced functional exercise capacity and increased sedentary behavior, both of which worsen prognosis. Although rehabilitation is a standard intervention, its impact on physical activity and gut microbiota remains incompletely understood. The present study enrolled 37 stable COPD patients and based on 6-min walk distance (6MWD), patients were classified into higher and lower functional exercise capacity. Physical activity was monitored using a tri-axial accelerometer, and gut microbiome composition was analyzed via 16S rRNA sequencing before and after a 12-week, home-based, rehabilitation program. At baseline, the higher functional exercise capacity group had significantly greater lower limb muscle mass, phase angle, and time spent in moderate-to-vigorous activity than the lower functional exercise capacity group. Rehabilitation did not significantly improve 6MWD or muscle mass in either group. However, sedentary time decreased significantly in the higher functional exercise capacity group, whereas it increased in the lower group. Gut microbiome profiles differed between the two groups at baseline and showed distinct changes after rehabilitation. Notably, the family level for Enterococcaceae decreased post-intervention only in the higher functional exercise capacity group. In COPD patients with higher functional exercise capacity, distinct changes in the gut microbiota were observed among participants whose sedentary time decreased.}, } @article {pmid41639396, year = {2026}, author = {Weber, D and Tariq, M and Hazenberg, M and Poeck, H and Malard, F}, title = {Microbiome, GvHD, and immune reconstitution in allogeneic hematopoietic cell transplantation.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {41639396}, issn = {1476-5365}, abstract = {The gut microbiota has emerged as a critical factor influencing outcomes following allogeneic hematopoietic cell transplantation (alloHCT). Notably, disruptions to the intestinal microbiome-referred to as dysbiosis-have been strongly linked to the development of acute graft-versus-host disease (aGVHD). The gut microbiome interacts closely with the host immune system, influencing both immune reconstitution and alloHCT complications. As a result, microbiome-targeted strategies are being investigated to improve outcomes and include antibiotic stewardship, prebiotic and diet intervention, probiotics including fecal microbiota transfer (FMT) and postbiotics. These approaches are being investigated not only as a therapeutic intervention in particular for aGVHD, but also as preventive strategies.}, } @article {pmid41639095, year = {2026}, author = {Walusimbi, B and Lawson, MA and Bancroft, AJ and Nassuuna, J and Trivedi, DK and Taylor, G and Sanya, RE and Webb, EL and Kateete, DP and Grencis, RK and Elliott, AM}, title = {The gut microbiome and metabolome associate with Schistosoma mansoni infection and cardiovascular disease risk in Uganda.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68983-3}, pmid = {41639095}, issn = {2041-1723}, support = {R120442//Royal Society/ ; NIHR134531//DH | National Institute for Health Research (NIHR)/ ; Z10661/Z/18/Z//Wellcome Trust (Wellcome)/ ; 088785/Z/09/Z//Wellcome Trust (Wellcome)/ ; 095778/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Helminth infections are consistently associated with reduced cardiovascular disease (CVD) risk, yet the biological mechanisms underlying this relationship remain unclear. The gut microbiome and metabolome are key regulators of cardiometabolic health and may mediate infection-associated effects on host physiology. Here we show that Schistosoma mansoni infection associates with distinct gut microbial and metabolic profiles linked to CVD risk in people living in Uganda. In a cross-sectional study of 209 individuals living in communities with contrasting S. mansoni endemicity, we profile the gut microbiome using 16S rRNA gene sequencing and the faecal metabolome using liquid chromatography-mass spectrometry. S. mansoni infection associates with increased gut microbial diversity and distinct taxonomic signatures, including enrichment of taxa such as Treponema and depletion of Prevotella and Streptococcus. Several infection-associated microbial taxa statistically mediate the relationships between S. mansoni infection and cardiovascular disease risk. Faecal metabolomic profiling identifies infection-associated metabolites, and integrative analyses showed linked microbe-metabolite networks associated with cardiovascular risk.These findings identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk in Uganda. Although causality cannot be inferred, this work provides insight into host-parasite-microbiome interactions and highlights microbial and metabolic pathways relevant to cardiometabolic health.}, } @article {pmid41638512, year = {2026}, author = {Yan, Q and Yuan, S and Mou, W and Liu, J and Yu, Z and Li, Y and Zhang, Z}, title = {The blood microbial community signatures in patients with acute ischemic stroke.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108322}, doi = {10.1016/j.micpath.2026.108322}, pmid = {41638512}, issn = {1096-1208}, abstract = {BACKGROUND: While systemic inflammation and metabolic dysregulation contribute to acute ischemic stroke (AIS)development, the function of the peripheral blood microbiome, which reflects systemic states, remains unclear. This study aimed to characterize these blood microbial signatures and define their clinical relevance in AIS.

METHODS: Blood microbiome profiles from 61 AIS patients and 54 controls were analyzed by 16S rRNA sequencing. Patients were stratified by baseline NIHSS scores and followed for 3-month outcomes to assess prognostic microbial signatures.

RESULTS: AIS patients exhibited a distinct blood microbiota profile compared to controls, characterized by reduced richness and significant structural changes. These alternations included a reduction of key commensal bacteria, such as Akkermansia, and an increase in opportunistic taxa like Meiothermus. Crucially, these microbial dysregulations were strongly correlated with host metabolic parameters, including blood glucose, homocysteine, and lipid levels. However, classification models based on the blood microbial signature failed to predict disease severity and 3-month neurological outcomes. In contrast, alterations in the blood microbiome demonstrated potential as an indicator of AIS severity (AUC = 0.733).

CONCLUSION: Our findings reveal that the blood microbiome in AIS is highly dysregulated, reflecting the host's systemic metabolic health. This strong association suggests circulating microbial signatures could play a role in stroke's pathophysiology, potentially influencing metabolic and inflammatory processes. As a result, analyzing these signatures could lead to the development of minimally invasive biomarkers for disease assessment and may also reveal novel therapeutic targets for managing systemic dysfunction in stroke patients.}, } @article {pmid41638450, year = {2026}, author = {Nogueira, LM and Meurer, EC and Pileggi, M}, title = {Modulation of Clostridioides difficile virulence by metabolites derived from probiotic consortia and genetically edited strains.}, journal = {Biotechnology advances}, volume = {88}, number = {}, pages = {108818}, doi = {10.1016/j.biotechadv.2026.108818}, pmid = {41638450}, issn = {1873-1899}, abstract = {Clostridioides difficile infection (CDI) continues to pose a significant clinical and biotechnological challenge, primarily driven by antimicrobial resistance and frequent recurrence. Emerging strategies are shifting the therapeutic focus from pathobiont eradication to virulence suppression, achieved by targeting the key metabolic and regulatory networks that underpin C. difficile pathogenicity in the gut. This review synthesizes multi-omic data demonstrating that a synergistic approach-restoring secondary bile acid metabolism (through the bai operon), boosting short-chain fatty acid (SCFA) production, and disrupting quorum-sensing systems (e.g., luxS, agr)-can collectively suppress toxin expression, biofilm formation, and spore germination. We further examine how synthetic biology and metabolic engineering are paving the way for next-generation solutions, including engineered probiotics, designer microbial consortia, and live biotherapeutic products endowed with programmable quorum quenching capabilities and optimized metabolic outputs. The integration of genomics, transcriptomics, proteomics, and metabolomics, with computational modeling, now enables the predictive design and industrially scalable production of these microbiome-based interventions. Together, these advances mark a pivotal transition from empirical probiotic use to the era of precision, mechanism-driven microbiome therapeutics designed to achieve durable control of CDI recurrence.}, } @article {pmid41638261, year = {2026}, author = {Bröker, BM and Bachert, C}, title = {Microbial influences on chronic rhinosinusitis.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2026.01.019}, pmid = {41638261}, issn = {1097-6825}, abstract = {The nasal microbiome is altered in chronic rhinosinusitis (CRS), characterized by increased bacterial density and higher relative abundance of Staphylococcus aureus compared to healthy adults. This review examines determinants of S. aureus nasal colonization, focusing on immune control and its evasion by the bacteria. CRS and asthma share pathomechanisms of chronic airway inflammation and often co-occur. In both conditions, many patients are sensitized to secreted factors of S. aureus - enterotoxins (SE) and serine protease-like proteins (Spls) - and produce specific IgE, which influences the disease course. Therefore, we propose to incorporate S. aureus-specific IgE measurements into the routine diagnostic evaluation of CRS and asthma.}, } @article {pmid41533436, year = {2026}, author = {Cox, IJ and Lauridsen, MM and Le Guennec, A and Fagan, A and Heitmann, GG and Lukose, T and Verna, EC and Bajaj, JS}, title = {Serum and Urinary Metabolomics Reflect the Early Stages of De Novo Metabolic Syndrome After Liver Transplant: A 2-Center Longitudinal Study.}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000000968}, pmid = {41533436}, issn = {2155-384X}, support = {R21TR003095/TR/NCATS NIH HHS/United States ; 1I01CX002472, 2I01CX001076//U.S. Department of Veterans Affairs/ ; }, abstract = {INTRODUCTION: Liver transplantation (LT) recipients are at high risk of developing de novo metabolic syndrome (MetS), which contributes to cardiovascular and cerebrovascular morbidity. This study investigated serum and urinary metabolic changes after LT to identify microbial and metabolic markers associated with MetS development.

METHODS: We conducted a prospective, 2-center longitudinal study with biospecimen collection pre-LT and at 6 months, 1 year, and 2-9 years post-LT. Nuclear magnetic resonance spectroscopy was used to characterize serum and urine metabolomic profiles from 73 to 44 patients, respectively. MetS was defined as body mass index >30 kg/m 2 plus at least 1 additional metabolic abnormality.

RESULTS: MetS prevalence increased from 11% pre-LT to 36% post-LT. Post-LT, serum metabolite profiles showed increased phosphocholines and lipid-CH 3 (low density lipoprotein), whereas urine profiles demonstrated higher levels of trimethylamine- N -oxide (TMAO) and phenylacetylglutamine. Patients who developed or had persistent MetS exhibited smaller increases in serum phosphocholines and lipid-CH 3 but greater elevations in urinary TMAO levels compared with patients who remained MetS-free.

DISCUSSION: LT is followed by distinct metabolic shifts reflecting changes in both hepatic lipid metabolism and gut-liver microbial cometabolism. Elevated urinary TMAO, together with reduced serum phosphocholine and lipid-CH 3 responses, characterize patients who develop post-LT MetS and may serve as early biomarkers of cardiometabolic risk in LT recipients.}, } @article {pmid41513932, year = {2026}, author = {Ruiz-Ruiz, S and Piquer-Esteban, S and Pérez-Rocher, B and Pérez-Brocal, V and Arnau, V and Artacho, A and Diaz, W and Jiménez-Hernández, N and Pons, J and Castro, JA and Moya, A}, title = {Lifetime existence of a core of mutualistic symbionts and functionally uncoupled taxa in the gut of a Mediterranean cohort.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4921}, pmid = {41513932}, issn = {2045-2322}, support = {grant number CD15/00067//the Carlos III Health Institute (ISCIII)/ ; project number PMPTA23/00001//the Carlos III Health Institute (ISCIII)/ ; grant Conselleria d´Educació, Cultura, Universitats i Ocupació, cofinançat per la Unió Europea FSE+ 2021-2027, ACIF/2021/341//ACIF fellowship from the Generalitat Valenciana/ ; grant number FPU20/05756//Spanish Ministry of Universities, Vocational Training ans Sports/ ; project number PID2019-105969GB-I00 funding by MICIU/AEI/10.13039/501100011033//the Spanish Ministry of Science and Innovation and Universities/ ; project number SAF2015-65878-R funding by MICIU/AEI/10.13039/501100011033/ and by FEDER Una manera de hacer Europa//the Ministry of Science, Innovation and Universities/ ; project number CIPROM/2021/042//Conselleria d´Educació, Cultura, Universitats i Ocupació/ ; }, abstract = {UNLABELLED: While a proportion of the microbiota plays a beneficial role, there is no conclusive evidence that the entire microbiome is mutualistic. Here, we have studied the intestinal microbiota of three healthy age groups from the Valencian Region (Spain). We have periodically obtained stool samples to determine the 16S rRNA gene amplicons, metagenomes, and metatranscriptomes, and we have observed that the microbiota’s stability differs with age, being less stable in infants. Regarding analyses of the conserved microbiota across the three age groups throughout the study period, shared genera account for about 60%. In addition, we identified a core of microbial taxa present in all individuals, which could represent mutualistic symbionts. Finally, in a previous study, we detected that tryptophan and indole production by intestinal bacteria decreases substantially with host age. Metagenomics and metatranscriptomics analyses show that tryptophanase mRNA synthesis in the genus Akkermansia is approximately 10 times lower in adults and the elderly than in children, consistent with this enzyme’s low levels or absence in these groups. Consequently, this supports the hypothesis that an uncoupling might occur between some microbiota taxa and the human host at older ages.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-35033-3.}, } @article {pmid41647444, year = {2025}, author = {Follestad, P and Filbin, P and Thompson, B and Dobner, P and Jaffe, A and Perlmutter, A and Zwickey, H}, title = {Gut-Mind Interactions in Psychedelic Healing: A Case Study Assessing the Effects of Huachuma and Ayahuasca on the Mind and Microbiome.}, journal = {Journal of restorative medicine}, volume = {15}, number = {}, pages = {63-79}, pmid = {41647444}, issn = {2330-2941}, abstract = {BACKGROUND: Psychedelic plant medicines such as Ayahuasca and Huachuma (San Pedro cactus) are gaining scientific attention for their potential to improve mental health. However, the interplay between these traditional medicines, the gut microbiome, and mental health outcomes remains underexplored.

OBJECTIVE: The main objectives of this study are to investigate the effects of Ayahuasca and Huachuma ceremonies on the gut microbiome, depression, and subjective connectedness in a single patient and to generate hypotheses for future studies.

CASE: A 35-year-old female with prior psychedelic experience participated in separate Ayahuasca and Huachuma ceremonies. Qualitative data were collected through patient interviews. Quantitative data included stool samples collected before and after each ceremony for microbiome analysis, as well as survey data using the Hamilton Depression Rating Scale (HAM-D) and Watts Connectedness Scale (WCS) administered pre- and post-ceremony.

RESULTS: Both ceremonies resulted in substantial reductions in depression scores (HAM-D decreased: Ayahuasca from 18 to 6; Huachuma from 12 to 2) and connectedness scores (WCS increased: Ayahuasca from 62.3% to 95.37%; Huachuma from 58.32% to 84.65%). Although Ayahuasca and Huachuma induced different gut microbial composition shifts, reductions in pro-inflammatory taxa, normalization of inflammation-linked bacterial species, and increases in beneficial butyrate-producing bacterial species were observed for both. These microbial shifts aligned with improved subjective mental health and reduced inflammation. Qualitative interviews revealed distinct archetypal experiences with each medicine, informing personalized therapeutic approaches.

CONCLUSION: This hypothesis-generating case study illustrates a potential link between psychedelic-induced microbiome changes and improvements in mental health which may contribute to reduced inflammation and sustained antidepressant effects via the microbiota-gut-brain axis.}, } @article {pmid41638211, year = {2026}, author = {Blackmer-Raynolds, L and Lipson, LD and Kozlov, A and Yang, A and Hill, EJ and Sampson, MM and Hamilton, AM and Fraccaroli, I and Kelly, SD and Chopra, P and Chang, J and Sloan, SA and Sampson, TR}, title = {Indigenous gut microbes modulate neural cell state and neurodegenerative disease susceptibility.}, journal = {Cell systems}, volume = {}, number = {}, pages = {101481}, doi = {10.1016/j.cels.2025.101481}, pmid = {41638211}, issn = {2405-4720}, abstract = {The native microbiome influences numerous host processes, including neurological function. However, its impacts on diverse brain cell types remain poorly understood. Here, we performed single-nucleus RNA sequencing on the hippocampus of wild-type, germ-free mice, revealing the microbiome-dependent transcriptional landscape across all major neural cell types. We found conserved impacts on key adaptive immune and neurodegenerative transcriptional pathways. Mono-colonization with select indigenous microbes identified organism-specific effects on brain myeloid cell transcriptional state. Escherichia coli colonization induced a distinct myeloid cell activation state, increased brain-resident CD8[+] T cells, and shaped amyloid phagocytic capacity, suggesting heightened disease susceptibility. Finally, E. coli-exposed 5xFAD mice displayed exacerbated cognitive decline and amyloid pathology, demonstrating the sufficiency of intestinal E. coli to worsen Alzheimer's disease-relevant outcomes. Together, these results emphasize the broad, species-specific, microbiome-dependent consequences on neural cell states and highlight the capacity of specific microbes to modulate disease susceptibility.}, } @article {pmid41638193, year = {2026}, author = {Costa, PCTD and Magnani, M and Martins, VJB and Moraes, RCS and Silva-Luis, CC and Rodrigues, JMA and Cabral, L and Noronha, MF and Vitalis, O and Chikh, K and Godet, M and Vidal, H and de Brito Alves, JL}, title = {Multicomponent intervention improves gut microbiome and cardiac autonomic function in childhood obesity.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpheart.00769.2025}, pmid = {41638193}, issn = {1522-1539}, support = {41903.612.28794.22092020//Fundação de Apoio à Pesquisa do Estado da Paraíba (FAPESQ)/ ; 88881.711922/2022//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; }, abstract = {Childhood obesity is associated with gut microbiome dysbiosis, inflammation, and early cardiac autonomic dysfunction. Lifestyle interventions integrating physical activity and dietary modification represent a primary strategy to mitigate cardiometabolic risk during childhood. This longitudinal intervention study investigated cardiovascular, autonomic, inflammatory, metabolic, and gut microbiome-related outcomes before and after a 4-month program combining structured physical exercise with food and nutrition education in 51 children with obesity aged 7 to 10 years. The intervention promoted favorable dietary changes, including reduced intake of saturated fatty acids (SFA), sodium, and total energy. These modifications were accompanied by a reduction in body fat percentage and systemic inflammation, evidenced by lower circulating interleukin-17A (IL-17A) and tumor necrosis factor-alpha (TNF-α) levels. Improvements in biochemical profiles were observed, including increased albumin and high-density lipoprotein cholesterol (HDL-c), and reduced serum triglyceride and urea levels. Metabolomic analyses revealed beneficial shifts in circulating phosphatidylethanolamines, phosphatidylglycerols, choline, and branched-chain amino acids (BCAA). Cardiovascular assessments demonstrated significant reductions in systolic and diastolic blood pressure and improvements in heart rate variability, indicating enhanced cardiac autonomic modulation. Gut microbiota analyses showed no differences in alpha or beta diversity; however, Bray-Curtis volatility analyses identified significant within-subject compositional shifts. Exploratory multivariate analyses suggested potential associations between specific gut taxa (e.g., Ligilactobacillus, Streptococcus, Roseburia), circulating metabolites, and cardiovascular autonomic indices, supporting the existence of microbiota-metabolite-heart interactions. In summary, a 4-month multicomponent lifestyle intervention improved cardiovascular autonomic function, inflammatory status, and cardiometabolic profiles in children with obesity. These findings highlight the cardiovascular benefits of early lifestyle modification and support integrative approaches targeting autonomic and metabolic pathways in pediatric obesity.}, } @article {pmid41638192, year = {2026}, author = {Ding, N and Wu, H and Hua, Y and Hua, R and Li, B and Xie, Y and Xiong, Y and Bai, T and Shi, X and Shen, T and Liu, P and Liu, J and Yang, X and Xu, Y and Meng, Z and Lan, B and Zhou, J and Liu, B and Shyy, JY and Yuan, Z and Wu, Y and Li, T}, title = {Gut microbiota-derived isovaleric acid alleviates atrial fibrillation by suppressing GSDME-dependent pyroptosis.}, journal = {Cell metabolism}, volume = {38}, number = {2}, pages = {370-387.e10}, doi = {10.1016/j.cmet.2025.12.017}, pmid = {41638192}, issn = {1932-7420}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Pyroptosis/drug effects ; *Atrial Fibrillation/metabolism/microbiology/pathology ; *Pentanoic Acids/metabolism/pharmacology ; Mice ; Humans ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism ; Male ; Ruminococcus/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Hemiterpenes ; }, abstract = {Atrial fibrillation (AF), a common and clinically significant cardiac rhythm disturbance, is associated with gut microbial dysbiosis. However, the precise role of the microbiota and associated metabolism in this condition remain unclear. Through integrated analysis of clinical cohorts and multiple animal models, we identified an intestinal symbiont, Ruminococcus gnavus (R. gnavus), which suppresses the occurrence of AF and atrial fibrosis by producing the leucine-derived branched-chain fatty acid isovaleric acid (IVA). R. gnavus colonization or exogenous IVA supplementation reduced AF susceptibility and improved fibrosis-driven atrial remodeling. Mechanistically, R. gnavus metabolizes dietary leucine into IVA through its unique enzyme 2-oxoisovalerate ferredoxin reductase γ-subunit (vorC). Microbiome-derived IVA activates G protein-coupled receptor 109A (GPR109A) on atrial cardiomyocytes, inhibiting interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling activation and blocking gasdermin E (GSDME)-mediated pyroptosis through a STAT3-GSDME feedforward circuit. These results reveal that the microbial metabolism of dietary leucine and the production of IVA play pivotal roles in preventing AF onset and progression.}, } @article {pmid41637999, year = {2026}, author = {Horvath, A and Haller, R and Schmid-Zalaudek, K and Goswami, N and Wagner-Skacel, J and Habisch, H and Madl, T and Stadlbauer, V}, title = {The beneficial effect of a multispecies probiotic intervention on quality of sleep - a randomized, double-blinded, placebo-controlled study.}, journal = {Journal of psychiatric research}, volume = {195}, number = {}, pages = {244-256}, doi = {10.1016/j.jpsychires.2026.01.040}, pmid = {41637999}, issn = {1879-1379}, abstract = {STUDY OBJECTIVES: Sleep disorders are common and impair performance and health. The intestinal microbiome regulates human chronobiology. Microbiome modulation through probiotic intervention might therefore harbor the potential to treat sleep disorders. We tested this hypothesis in a randomized, double-blind, placebo-controlled study.

METHODS: We randomized 130 volunteers with self-reported impaired quality of sleep (PSQI>5) in a 1:1 ratio to a 28-day intervention with either a multispecies probiotic (OMNiBiOTiC® STRESS Repair) or a placebo. Participants completed validated questionnaires to estimate quality of sleep, quality of life and perceived stress, and collected stool samples for 16S rRNA sequencing before and after the intervention. Ninety-four participants finished the study and were included in the analysis.

RESULTS: Baseline characteristics were similar between the probiotic group (n = 50; 88.6 % female, 41.2 ± 10.6 years old) and the placebo group (n = 44; 88.0 % female, 40.1 ± 10.7 years old), including the initial PSQI score (10.1 ± 2.7 vs. 10.5 ± 2.6). The probiotic intervention led to an improved sleep efficiency and latency, and thereby improved quality of sleep beyond an observable placebo effect (6.8 ± 2.9 vs. 7.7 ± 3.1; p = 0.036, probiotic and placebo group, respectively). Probiotic bacteria were partially recovered in the microbiome, causing a slight shift in beta diversity in the probiotic group. The intervention did not influence quality of life or perceived stress.

CONCLUSIONS: In conclusion, this well-powered RCT shows that the intervention with a multispecies probiotic improved quality of sleep beyond the effect of a placebo intervention, and that the modulation of the microbiome may therefore be of clinical benefit in alleviating sleep disturbances.}, } @article {pmid41637678, year = {2026}, author = {Eriksen, E and Graff, P and Afanou, AK}, title = {Bacterial Communities as Modulators of Innate Immune Signalling: An In Vitro Perspective on Toll-Like Receptor Activation.}, journal = {Environmental microbiology reports}, volume = {18}, number = {1}, pages = {e70289}, doi = {10.1111/1758-2229.70289}, pmid = {41637678}, issn = {1758-2229}, support = {//National institute of occupational health, Oslo (STAMI)/ ; //IVAR-IKS/ ; //The federation of Norwegian Industries/ ; //Norwegian Union of Municipal and General Employees (NUMEG)/ ; }, mesh = {*Immunity, Innate ; *Bacteria/classification/genetics/isolation & purification/immunology ; *Toll-Like Receptors/immunology/genetics/metabolism ; Humans ; *Microbiota/immunology ; Signal Transduction ; Dust/analysis ; }, abstract = {Investigating the work-environmental microbiome is critical for assessing occupational risk associated with exposure to microorganisms. The present study examined the bacterial composition of inhalable dust from waste sorting plants and explored their potential to induce Toll-like receptors (TLR) in vitro, thereby providing insights into the immunomodulatory potential of complex microbial communities from occupational settings. These findings highlight how few dominant bacterial species shape the immune activation properties of the overall bacterial community, where less abundant taxa play a crucial role in immune modulation through TLR activation. The strong association between TLR activation and rare yet highly inductive bacterial taxa demonstrates their potential immunological significance, suggesting that even low-abundant microbes may have a disproportionate impact on immune responses and occupational health outcomes.}, } @article {pmid41637499, year = {2026}, author = {Stief, P and Niggemann, J and Bligh, M and Buck-Wiese, H and Wünsch, U and Steinke, M and Hehemann, JH and Glud, RN}, title = {Hydrostatic pressure induces strong leakage of dissolved organic matter from "marine snow" particles.}, journal = {Science advances}, volume = {12}, number = {6}, pages = {eaec5677}, pmid = {41637499}, issn = {2375-2548}, abstract = {Marine snow forms at the ocean surface, sinks to depth, and ultimately enables carbon sequestration in the seabed. Fast-sinking marine snow particles, such as diatom aggregates, encounter a rapid increase in hydrostatic pressure during their descent. Using incubations in rotating pressure tanks, we found that pressure levels corresponding to 2- to 6-kilometer water depth induce leakage of dissolved organic matter (DOM) from diatom aggregates equivalent to ~50% of their initial carbon contents. The leaked DOM proved to be diatom-derived and changed the amount and composition of DOM in the surrounding seawater substantially. Ultrahigh-resolution mass spectrometry, high protein-like fluorescence, and low carbon:nitrogen ratios classified the leaked DOM as labile. The bioavailability of leaked DOM was demonstrated by its rapid utilization by a pelagic microbial community, leaving mainly recalcitrant DOM behind. Pressure-induced DOM leakage likely weakens the gravitational "biological carbon pump" and supplies labile DOM to the pelagic microbiome of the deep ocean.}, } @article {pmid41637186, year = {2026}, author = {Xu, X and Sun, T and Qing, X and Liu, S and Yang, P and Dong, M and Liu, J and Ren, Y and Shen, Q and Scheu, S and Li, R and Kowalchuk, GA and Krashevska, V}, title = {Meloidogyne nematodes reprogram rhizosphere metabolism to suppress antagonistic microbiota and enable bacterial pathogen co-infection.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116949}, doi = {10.1016/j.celrep.2026.116949}, pmid = {41637186}, issn = {2211-1247}, abstract = {Root-knot nematodes cause substantial crop losses by compromising plant immunity and facilitating invasion by soil-borne bacterial pathogens, yet the mechanisms underlying nematode-facilitated co-infection remain poorly understood. Here, we quantify the global prevalence of nematode-pathogen co-infection and integrate multi-omic analyses across greenhouse and in vitro experiments. We show that nematode invasion activates plant defense gene expression but concurrently disrupts rhizosphere homeostasis, resulting in microbiome dysbiosis that overrides host resistance. Meloidogyne invasion induces pronounced metabolic reprogramming, characterized by depletion of tomatidine and accumulation of carbohydrate metabolites such as galactose. These shifts selectively suppress Streptomyces-dominated antagonistic microbiota while enriching Acidovorax, which exhibits nutritional synergy with Ralstonia. Using synthetic microbial community transplantation, we demonstrate a functional transition from pathogen-suppressive to pathogen-permissive bacteriomes following nematode invasion. Together, our findings reveal how nematodes and bacterial pathogens cooperatively subvert plant-microbe metabolic signaling to undermine rhizosphere immunity, highlighting actionable targets for microbiome-based disease control.}, } @article {pmid41636526, year = {2026}, author = {Dove, AS and Abdelsattar, AS and Abutaleb, NS and Seleem, MN}, title = {Identification of the cannabinoid receptor 1 antagonist, ibipinabant, as a potent inhibitor of Neisseria gonorrhoeae.}, journal = {Antimicrobial agents and chemotherapy}, volume = {}, number = {}, pages = {e0123125}, doi = {10.1128/aac.01231-25}, pmid = {41636526}, issn = {1098-6596}, abstract = {Neisseria gonorrhoeae, the causative agent of the second-most prevalent sexually transmitted bacterial disease globally, has been classified as an urgent threat to public health and a high-priority pathogen. Concerningly, N. gonorrhoeae has developed resistance to nearly all FDA-approved drugs. Currently, no approved oral therapies exist, with parenteral administration of ceftriaxone as the only available FDA-approved treatment option for multidrug-resistant gonococcal infections. Yet, ceftriaxone-resistant isolates have now been identified globally, further highlighting the urgent need for the development of novel antibacterial agents. In a screen of 2,528 small molecules targeting G-protein-coupled receptors and related signaling pathways, ibipinabant, a potent cannabinoid receptor 1 antagonist, was identified as having the most potent anti-gonococcal activity. Ibipinabant demonstrated potent activity against a panel of 20 N. gonorrhoeae isolates, without inhibiting some representative Lactobacillus species of the vaginal microbiome. A time-kill assay revealed that ibipinabant is bactericidal, clearing the burden of N. gonorrhoeae (below the limit of detection) within 12 h. Ibipinabant was also able to clear the intracellular burden of N. gonorrhoeae inside human endocervical cells more effectively than the drug of choice, ceftriaxone. This drug was non-toxic against multiple cell lines and did not induce hemolysis of human red blood cells. Finally, in the in vivo mouse model of N. gonorrhoeae genital tract infection, ibipinabant showed a significant reduction (>95%) in the gonococcal burden after 2 days of treatment. Altogether, these results indicate that ibipinabant is a promising candidate for drug repurposing as a novel antimicrobial against multidrug-resistant N. gonorrhoeae.}, } @article {pmid41636510, year = {2026}, author = {Anne Hallowell, H and Malogan, J and Suez, J}, title = {Tools and approaches to study the human gut virome: from the bench to bioinformatics.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0100225}, doi = {10.1128/msystems.01002-25}, pmid = {41636510}, issn = {2379-5077}, abstract = {The human gastrointestinal tract is home to a diverse community of microorganisms from all domains of life, collectively referred to as the gut microbiome. While gut bacteria have been studied extensively in relation to human host health and physiology, other constituents remain underexplored. This includes the gut virome, the collection of bacteriophages, eukaryotic viruses, and other mobile genetic elements present in the intestine. Like gut bacteria, the gut virome has been causatively linked to human health and disease. However, the gut virome is substantially more difficult to characterize, given its high diversity and complexity, as well as multiple challenges related to in vitro cultivation and in silico detection and annotation. In this mini-review, we describe various methodologies for examining the gut virome using both culture-dependent and culture-independent tools. We highlight in vitro and in vivo approaches to cultivate viruses and characterize viral-bacterial host dynamics, as well as high-throughput screens to interrogate these relationships. We also outline a general workflow for identifying and characterizing uncultivated viral genomes from fecal metagenomes, along with several key considerations throughout the process. More broadly, we aim to highlight the opportunities to synergize and streamline wet- and dry-lab techniques to robustly and comprehensively interrogate the human gut virome.}, } @article {pmid41636504, year = {2026}, author = {Mahooti, M and Safaei, F and Mousavian, Z and Samimiazad, A and Bakhtiyarizadeh, M and Emadi, A and Babae, L and Hassani, FS and Eskandari, A and Azman, EM and Zare, D}, title = {Potential of yeast probiotics as immunomodulators: a new frontier in cancer management.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/17460913.2026.2624283}, pmid = {41636504}, issn = {1746-0921}, abstract = {Probiotic yeasts have attracted attention for immunological and functional advantages. They alter inflammatory pathways through immune system induction activities, mitigating some cancer-related immune system pathways, and can be an option in treating inflammation-related diseases such as cancer. Current research has directed to survey mechanisms behind the anti-cancer effects of this genus. It has been demonstrated how probiotic yeasts can be used in managing cancer incidence alone or with other current cancer therapies. This could be possible through their potential in suppression of tumor progression by up-regulating apoptosis, activating immune cells, secreting cytokines, managing inflammation by gut microbiome improvement, and helping short-chain fatty acids production. Recent studies have focused on this genus due to its characteristics, ranging from their capacity to survive in the human gastrointestinal tract, resistance to antibiotics, and lack the ability to transfer genetic elements such as antibiotic resistance genes to pathogenic microorganisms. This review surveys anti-cancer potential of probiotic yeasts through their distinct effects, such as managing inflammation and modulating the immune system, and summarizes current studies of probiotic yeasts. The literature search was conducted from 2000 to 2025, with 2% of reviewed studies before 2000. The databases used were PubMed, Scopus, and Web of Science.}, } @article {pmid41636495, year = {2026}, author = {Kopp, OS and Morandi, SC and Kreuzer, M and Uldry, A-C and Eldridge, N and Zinkernagel, MS and Zysset-Burri, DC}, title = {Impact of contact lenses on the ocular surface microbiome, tear proteome, and dry eye disease.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0226425}, doi = {10.1128/spectrum.02264-25}, pmid = {41636495}, issn = {2165-0497}, abstract = {Although contact lens wear is widespread and known to affect the ocular surface, its impact on the ocular surface microbiome (OSM) remains poorly understood, with existing studies reporting conflicting findings. Additionally, the relationship between contact lens wear, tear proteome, and dry eye disease (DED) is unclear. In this study, we aimed to characterize the OSM (via whole-metagenome shotgun sequencing) and the tear proteome of 25 contact lens wearers and 23 age- and sex-matched controls. The dominant phyla were Actinobacteria, Proteobacteria, and Firmicutes, with Cutibacterium acnes being the most abundant species. No significant differences in microbial composition, diversity, or tear proteome were observed between contact lens wearers and controls. DED parameters (tear breakup time, Schirmer's test, tear osmolarity, and Ocular Surface Disease Index [OSDI]) also showed no significant differences, although contact lens wearers reported a trend toward higher subjective symptoms (OSDI). Sex-stratified analysis revealed a marginal difference in microbial beta diversity between male contact lens wearers and male controls, along with increased tear production in male contact lens wearers. Female contact lens wearers reported a higher OSDI compared to female controls. These findings suggest that contact lens wear does not significantly alter the OSM or tear proteome in healthy individuals, although sex-specific responses may warrant further investigation.IMPORTANCEContact lenses are worn by millions of people, yet the scientific literature contains conflicting reports about their impact on the microbial communities that are naturally present on the eye surface. This study addresses these knowledge gaps by examining both the eye microbiome and tear proteins using advanced sequencing and linking them to dry eye symptoms. Understanding the relationship between contact lens wear, natural eye bacteria, and tear composition is essential for resolving contradictory findings in the field. Additionally, identifying potential sex-specific differences in how individuals respond to contact lens wear could lead to more personalized approaches to contact lens management.}, } @article {pmid41636304, year = {2026}, author = {Brown, LP and Marizzi, A and Borrego, CM and Gionchetta, G and Zhengzheng, Z and Carneiro, RB and Gago-Ferrero, P and Matamoros, V and Subirats, J}, title = {Metagenomic Assessment of Full-Scale Wastewater Treatment Plants Identifies Sentinel Antibiotic Resistance Gene Families for Monitoring Reclaimed Wastewater and Treated Sludge.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c13541}, pmid = {41636304}, issn = {1520-5851}, abstract = {The new European (EU) regulation on water reuse explicitly incorporates antimicrobial resistance (AMR) into routine monitoring and risk management, creating an urgent need to define target antibiotic resistance genes (ARGs) for reclaimed irrigation water and agricultural sludge. However, existing global data largely focus on secondary effluents, providing little actionable evidence for reuse-oriented systems. Here, we present the first integrated framework combining targeted antibiotic residue analysis with shotgun metagenomics of the resistome, mobilome, and microbiome across full-scale reuse-oriented wastewater treatment plants (WWTPs) in Southern Europe to identify sentinel antibiotic resistance families for monitoring. Reclaimed effluents exhibited lower AMR exposure levels than those typically reported for secondary effluents (<0.5 ARGs/cell), while mobile genetic element (MGE) abundances were comparable to secondary effluents (1-2 MGEs/cell). Effluent communities differed by WWTP configuration: membrane bioreactor combined with ultrafiltration favored nutrient-removal/oxidative-stress taxa and reduced transferable MGEs, whereas plants relying on physical separation (sand filtration or reverse osmosis) retained fecal-associated taxa and MGEs. Specific clinically relevant ARGs persisted after treatments, including aadA and aph(3'')-Ibs (resistance to aminoglycosides), ermB and mphA (resistance to macrolides), and blaOXA-129 (resistance to beta-lactams), which we identify as sentinel markers for monitoring reclaimed water and sludge. We advance a generalizable two-step framework, metagenomic discovery to identify sentinel markers, followed by targeted assays for streamlined surveillance, that provides the first operational blueprint for integrating AMR into water reuse management under the EU regulation.}, } @article {pmid41636271, year = {2026}, author = {Sung, HH and Chalamalasetty, N and Alzainal, A and Liu, H and Wang, L and Arikita, PC and Wei, ICX and Wang, HL and van den Bosch, MHJ and Caird, MS and van der Kraan, PM and Kozloff, KM and Davidson, EB}, title = {The Role of Wnt Signaling in Age-Related Alveolar Bone Loss and Regeneration.}, journal = {Journal of periodontal research}, volume = {}, number = {}, pages = {}, doi = {10.1111/jre.70085}, pmid = {41636271}, issn = {1600-0765}, support = {5K08DE030116/DE/NIDCR NIH HHS/United States ; P30AR069620/NH/NIH HHS/United States ; R21AR075197/AR/NIAMS NIH HHS/United States ; }, abstract = {The periodontium is a uniquely dynamic tissue system requiring precise signaling for lifelong adaptation. The canonical Wnt/β-catenin pathway is a master regulator of bone homeostasis; however, its role in the specialized environment of the alveolar bone-marked by rapid turnover, complex mechanical forces, and exposure to the oral microbiome-remains incompletely understood, particularly in the context of aging. This review critically synthesizes evidence on Wnt signaling in alveolar bone remodeling, with a focus on age-related dysregulation, contrasting established paradigms from long bone biology with emerging oral-tissue-specific data. Wnt/β-catenin signaling is essential for periodontal homeostasis, orchestrating osteoblastogenesis and mechanotransduction. Its activity is compartment-specific within the periodontium and is potently suppressed in pathology. Key mechanisms of age-related decline include the upregulation of Wnt antagonists (e.g., sclerostin, DKK1), cellular senescence, altered FoxO-Wnt crosstalk under oxidative stress, and impaired mechanosensing. These changes converge to disrupt regenerative capacity, tipping the balance toward net alveolar bone loss. Therapeutically, sclerostin inhibition demonstrates robust preclinical efficacy in rescuing bone loss in models of periodontitis and estrogen deficiency. However, the potential cardiovascular risks of systemic Wnt activation suggest that redirecting efforts toward localized delivery strategies could be a promising alternative. Aging induces a multifaceted suppression of regenerative Wnt signaling in the periodontium. Modulating the Wnt pathway shows great potential for oral bone regeneration. However, significant challenges exist, especially in designing local delivery systems that are both safe and effective. Overcoming these hurdles is crucial for successful clinical applications. Future research must bridge the gap between skeletal biology and direct oral-specific investigations to enable targeted therapies that preserve periodontal health in an aging population.}, } @article {pmid41636127, year = {2026}, author = {Silva-Luis, CC and Trindade da Costa, PC and Baccin Martins, VJ and de Brito Alves, JL}, title = {The influence of ultra-processed foods on gut microbiome and inflammatory markers in schoolchildren from Northeastern Brazil.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70369}, pmid = {41636127}, issn = {1536-4801}, support = {#41903.612.28794.22092020//Paraíba State Research Foundation/ ; //CAPES/ ; }, abstract = {OBJECTIVE: This study investigated the relationship between the consumption of ultra-processed foods (UPF), dietary profile, and inflammation on the intestinal microbiome in children.

METHODS: A cross-sectional study was conducted using data from a community-based controlled trial involving 82 children aged 7-11 years enrolled in public schools in João Pessoa, Paraíba, Brazil. The gut microbiome was assessed by 16S rRNA gene sequencing. Dietary intake was assessed by a 24-h food recall and UPF intake was estimated using the NOVA system. Anthropometry, socio-economic variables, and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were also assessed.

RESULTS: Children in the third tertile (higher consumption of UPF) had a higher intake of calories from UPF (p < 0.01), trans-fatty acids (p = 0.01), thiamine (p = 0.02), while the intake of protein (p = 0.01), and copper (p = 0.04) was lower. Children in the third tertile had lower abundance of Ruminococcaceae (p = 0.04) and Barnesiellaceae (p = 0.02) and higher abundance of the Monoglobaceae and Erysipelotrichaceae (p = 0.04). Several bacterial genera showed significant correlations with inflammatory cytokines. Dorea and Subdoligranulum were associated with IL-17A and IL-10; Agathobacter with IL-6, IL-10, and IFN-γ; Faecalibacterium with IL-10, IFN-γ, and TNF-α; Fusicatenibacter and Bifidobacterium with IL-10; and Roseburia with TNF-α (all q < 0.05).

CONCLUSIONS: A high UPF intake was associated with a poorer-quality diet and changes in the composition of the gut microbiome, suggesting potential interactions between diet, microbial communities, and immune responses.}, } @article {pmid41636025, year = {2026}, author = {Shi, H and Shi, F and Wagle, R and Gonzalez-Gonzalez, MA and Mell, B and Oliver, B and Zhu, T and Joe, B and Durgan, DJ}, title = {Bacterial Extracellular Vesicles Mediate Microbiota-Host Communication to Regulate Blood Pressure in Male Rats.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1161/HYPERTENSIONAHA.125.25962}, pmid = {41636025}, issn = {1524-4563}, abstract = {BACKGROUND: Altered gut microbiota composition has been implicated in the development of hypertension. Evidence suggests bacterial products and metabolites can enter circulation, act on peripheral tissues, and modulate blood pressure (BP). We identified extracellular vesicles (EVs) of bacterial origin (bacterial extracellular vesicles [bEVs]) in the circulation of spontaneously hypertensive stroke-prone rats (SHRSP). We hypothesized that bEVs mediate communication between microbiota and the host, and that bEVs from SHRSP microbiota contain unique cargo that promotes hypertension.

METHODS: EVs were isolated from plasma and cecal content of SHRSP and Wistar-Kyoto (WKY) rats. Multiomics analysis, including 16S rRNA sequencing, small RNA sequencing, lipidomics, and proteomics were performed to assess the cargo of bEVs. BEVs from WKY and SHRSP were transplanted by oral gavage to WKY and SHRSP recipients, and the effects on BP and sympathetic activity were monitored. The potential role of bEVs on BP was also evaluated in Dahl S and obstructive sleep apnea models of hypertension.

RESULTS: Significant differences were observed in WKY and SHRSP bEV cargo, including small RNAs, proteins, and PAMPs (pathogen-associated molecular patterns). Transplantation of SHRSP bEVs to WKY rats increased renal sympathetic nerve activity and elevated BP. Moreover, we showed that bEVs influence BP regulation in Dahl S and obstructive sleep apnea-induced hypertension.

CONCLUSIONS: Our findings position bEVs as critical mediators of microbiota-host communication in BP regulation and demonstrate that bEVs from the altered SHRSP microbiota promote hypertension. Our findings shed new light on the role of bEVs in hypertension pathogenesis and offer new perspectives for diagnostics and therapeutic interventions.}, } @article {pmid41636006, year = {2026}, author = {Parkinson, H}, title = {Adult and perimenopausal acne and the nurse's role in management.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {35}, number = {3}, pages = {145-152}, doi = {10.12968/bjon.2025.0559}, pmid = {41636006}, issn = {2052-2819}, mesh = {Humans ; *Acne Vulgaris/nursing/epidemiology/therapy/diagnosis ; Female ; Adult ; *Perimenopause ; *Nurse's Role ; }, abstract = {Adult female acne is increasingly recognised as a chronic inflammatory skin disorder affecting women well beyond adolescence. Hormonal fluctuation, inflammatory signalling, skin barrier impairment, and microbiome shifts contribute to its development and persistence. Perimenopause and menopause introduce further complexity due to declining oestrogen levels and relative androgen excess. This article provides an evidence-based overview of adult and menopausal acne, integrating epidemiology, underlying mechanisms, clinical presentation, assessment, management, and the crucial role nurses play in patient education, continuity of care, and multidisciplinary referral.}, } @article {pmid41635787, year = {2025}, author = {Marchetti, L and Rebucci, R and Cremonesi, P and Biscarini, F and Castiglioni, B and Lanzoni, D and Monteiro, A and Manaig, YJY and Bontempo, V}, title = {Potentiated zinc and monovalent copper oxide as dietary supplements for weanling piglets: effects on systemic and mucosal immunity, gut permeability, and fecal microbiota composition.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1647844}, pmid = {41635787}, issn = {2297-1769}, abstract = {This study examines the potential of modulating gut health parameters in piglets by varying zinc/copper ratios administered through specialty oxide sources. A total of 84 piglets were selected after weaning and divided into four experimental treatment groups; the trial lasted 28 days. During the initial phase (1-14 d), the positive control (PC) received 2500 ppm of zinc, provided as conventional zinc oxide. In parallel, three additional treatment groups were formed, in which copper (Cu) and zinc (Zn) were supplemented using potentiated zinc oxide (Pot-ZnO) and monovalent copper oxide (Cu2O), at both European and Non-European recommended inclusion levels: EU (120 ppm of Zn; 140 ppm of Cu), Non-EU[+] (300 ppm of Zn; 200 ppm of Cu), and Non-EU[-] (300 ppm of Zn; 140 ppm of Cu). Lower Zn/Cu ratios characterized the second phase (15-28 d). Growth performance and fecal score were monitored throughout the trial. Blood samples were collected on days 1 and 14 from one subject per replicate to assess serum proinflammatory cytokines, immunoglobulins, and biomarkers of intestinal permeability. On day 28, one subject per replicate was slaughtered to obtain jejunal mucosa for the determination of jejunal secretory immunoglobulin A (sIgA) and alkaline phosphatase. Fecal samples collected on days 14 and 28 were used to analyze Zn and Cu content and to evaluate microbiota composition. A better fecal score was detected on day 4 in PC group compared to EU (p < 0.01). Serum immunoglobulin A increased in Non-EU[-] vs. PC group (p < 0.05) at day 14. Serum diamine oxidase decreased in the PC and Non-EU[+] groups vs. Non-EU[-] group (p < 0.05) at day 14. sIgA increased in PC vs. Non-EU[-] group (p < 0.01) at day 28. Zn was higher in PC fecal samples (p < 0.01), whereas fecal Cu increased in EU and Non-EU[+] treatments at day 14 (p < 0.05). Analysis of fecal microbiota performed at day 14 showed decreased. Observed, Shannon, and Simpson metrics in the Non-EU[-] group compared to the EU group (p < 0.05). Beta diversity highlighted a significant separation among groups at day 14 (p < 0.01). Differential abundance analysis revealed notable changes in genera composition among PC and EU groups at day 14 (p < 0.05). In conclusion, balanced Pot-ZnO and Cu2O administered at inclusion levels compliant with European levels of inclusion (EU) represent a valid strategy to enhance gut health of piglets during the first two weeks after weaning.}, } @article {pmid41635752, year = {2025}, author = {Shaw, D and Edwards, WJS and Thompson, GS and Kolisko, M and Gentekaki, E and Tsaousis, AD}, title = {Microbial and metabolic signatures among Blastocystis subtypes ST1-ST9 in xenic cultures.}, journal = {Current research in parasitology & vector-borne diseases}, volume = {8}, number = {}, pages = {100317}, pmid = {41635752}, issn = {2667-114X}, abstract = {Blastocystis is the most prevalent intestinal protist in humans, yet its role in gut health remains poorly understood. Increasing evidence suggests subtype-specific interactions with the gut microbiome and metabolome may underlie its variable associations with health and disease. In this pilot study, we performed an integrated analysis of the microbiota and metabolite profiles of nine Blastocystis subtypes (ST1-ST9) grown in vitro using xenic cultures. Using 16S rRNA amplicon sequencing and proton nuclear magnetic resonance ([1]H-NMR) metabolomics, we characterised the microbial communities and extracellular metabolites across subtypes. ST3 exhibited the most distinct microbiome and metabolomic profile, characterised by a significant enrichment of short-chain fatty acids (SCFAs) and amino-acid derivatives. Benzoate, a known antimicrobial, was uniquely downregulated in ST3. Linear discriminant analysis identified several bacterial genera, such as Methanobrevibacter and Enterobacter, as biomarkers for ST3. Correlations between key metabolites and microbial taxa suggest potential syntrophic interactions. These findings suggest that individual Blastocystis subtypes establish distinct microenvironments in vitro, with implications for their ecological roles in vivo. Our study provides a foundational framework for understanding subtype-specific biology and offers a platform for improving culture conditions and investigating host-microbe interactions.}, } @article {pmid41635632, year = {2026}, author = {Szudzik, M and Sureda, A and Barone, M}, title = {Editorial: The role of gut microbiome metabolites in cardiometabolic disorders.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1759753}, pmid = {41635632}, issn = {2296-861X}, } @article {pmid41635321, year = {2026}, author = {Ozturk, SZ and Aydin, B and Cifcibasi, E}, title = {Antibiotic Resistance Genes in the Subgingival Microbiome in Periodontitis: A Scoping Review of Prevalence, Mobility, and Future Directions.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e100685}, pmid = {41635321}, issn = {2168-8184}, abstract = {The objective of the study is to evaluate the prevalence, diversity, and mobility of antibiotic-resistant species and resistance genes within the subgingival microbiome of patients with periodontitis. A systematic scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Five electronic databases were searched for studies published between January 2020 and December 2025 that used molecular techniques (shotgun metagenomics, PCR/qPCR, 16S + PCR) to detect antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in the subgingival plaque of patients with clinically diagnosed periodontitis. Only peer-reviewed articles presenting original data were included; reviews, animal studies, and investigations lacking clear methodological details were excluded. Data extraction included study design, sample size, identified ARGs, associated MGEs, and clinical context. Nine eligible studies involving over 900 subgingival samples were identified. A core resistome was consistently identified across all cohorts, predominantly comprising tetracycline genes (tetM, tetQ, tet32) and macrolide-lincosamide determinants (ermB, ermF, msrD), as well as β-lactamase genes such as cfxA. Sites affected by periodontitis showed higher abundance of these ARGs than healthy controls. Mobile elements, especially Tn916-family conjugative transposons, were often associated with macrolide resistance genes, suggesting potential for horizontal transfer. Methodological differences prevented meta-analysis, and no study compared results based on the 2017 stage/grade classification of periodontitis. The subgingival resistome in periodontitis features a consistent set of tetracycline, macrolide, and β-lactam resistance genes that are increased in disease and frequently associated with mobile transposons. Currently, the evidence remains primarily descriptive; future research should include standardized antibiotic washout periods, longitudinal follow-up, stage/grade stratification, and integrated multi-omics approaches to evaluate functional activity and guide personalized antimicrobial therapies.}, } @article {pmid41635082, year = {2026}, author = {Zhang, F and Zheng, J and Xie, X and Tang, M and Li, H and Zuo, L and Zheng, L and Liu, H and Huang, J and Mei, Z and Chen, XL}, title = {Endophyte-engineered plant immunity: A post-GMO strategy for programmable crop defense.}, journal = {Molecular plant}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molp.2026.01.015}, pmid = {41635082}, issn = {1752-9867}, abstract = {Plant disease control is trapped in a constant evolutionary competition between plants and pathogens. Pathogens evolve faster than we can breed resistance genes or register new fungicides (Singh et al., 2023). Notably, plants employ multiple immune strategies, including both disease resistance and tolerance, to protect their health (Tang et al., 2025), enriching the contextual understanding of plant defense mechanisms. Transgenic crops, while powerful, remain facing regulatory and public acceptance challenges in many regions, with regulatory timelines varying across global frameworks-extending 8-12 years in some Western countries, while China has established a structured evaluation system that balances safety and efficiency (Liang et al., 2022, 2025). Meanwhile, chemical control faces an accelerating loss of efficacy due to resistance and is increasingly incompatible with climate-smart and biodiversity-friendly farming mandates. We argue that it is time to decouple crop immunity from plant genetics altogether and outsource it to an editable, transient, and regulation-resilient microbial layer: the endophyte microbiome.}, } @article {pmid41635070, year = {2026}, author = {Lee, JW and Cho, HS and Cha, HE and Seo, J and Lim, SK}, title = {Development of real-time PCR and droplet digital PCR assays for the simultaneous quantification of bacterial and human mitochondrial DNA for forensic analysis.}, journal = {Journal of forensic sciences}, volume = {}, number = {}, pages = {}, doi = {10.1111/1556-4029.70276}, pmid = {41635070}, issn = {1556-4029}, support = {PR10-01-000-21//Korean National Police Agency/ ; 2020R1A6C101A191//Ministry of Education/ ; }, abstract = {Forensic evidence recovered from crime scenes often contains a mixture of human and bacterial DNA. Although short tandem repeat (STR) profiling of genomic DNA (gDNA) is widely used for human identification, its effectiveness can be limited in cases involving highly degraded DNA. In such cases, human mitochondrial DNA (mtDNA) and microbiome analysis may serve as alternative methods. In this study, we developed a multiplex quantification assay targeting the bacterial 16S rRNA V7 region and the human mitochondrial NADH-dehydrogenase subunit 5 (ND5) gene. Quantification was performed using TaqMan-based real-time PCR (Human-Bacteria qPCR; HBQ) and droplet digital PCR (Human-Bacteria ddPCR; HBD). Optimal primer and probe concentrations were at 7 μM for the HBQ assay, and 5 μM bacterial primer set, 7 μM human mtDNA primer set, and 700 nM probes for the HBD assay. Sensitivity testing showed that the HBQ assay detected all DNA samples-except G147A-down to 20 fg, while the HBD assay detected both bacterial and human DNA at 20 fg, demonstrating higher analytical sensitivity than the real-time PCR method. Moreover, mock forensic samples were analyzed to confirm the assay applicability, and PCR inhibitor tolerance tests using humic acid and tannic acid were conducted to further validate their performance. Furthermore, the HBQ and HBD assays may be used in quality control processes for samples potentially affected by bacterial DNA or human mtDNA contamination and could also be applied to other fields such as food safety, environmental science, and biological research involving microbial DNA and human mtDNA.}, } @article {pmid41634889, year = {2026}, author = {Qin, Y and Zhu, X and Zheng, Y and Wang, K and Liao, K and Ye, X and Zhang, H and Yang, J and Wei, HL and Yang, X}, title = {Host genetic regulation of xylem-resident Pseudomonas enhances cucumber growth.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02308-2}, pmid = {41634889}, issn = {2049-2618}, support = {32102381//National Natural Science Foundation of China/ ; 32172606//National Natural Science Foundation of China/ ; 2021YFF1000100//National Key Research and Development Program of China/ ; CAAS-ASTIP-2025-IVF//Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences/ ; }, abstract = {BACKGROUND: Although endophytic microorganisms play a critical role in plant growth and stress resilience, the genetic basis underlying host selection of beneficial microbiota-particularly within the xylem-remains poorly understood. Cucumber (Cucumis sativus), as a crop model with a well-developed system for studying vascular biology, offers a valuable system to investigate the host genetic determinants of xylem microbiome assembly.

RESULTS: By conducting population-level microbiome profiling across 109 cucumber accessions, we identified a conserved xylem microbiota dominated by Proteobacteria. Within this community, 20 core amplicon sequence variants (ASVs) were consistently present in xylem sap. Genome-wide association mapping identified a host genetic locus, CsXPR1, which encodes a tetratricopeptide repeat protein that regulates the abundance of the dominant xylem-colonized Pseudomonas ASV_4. Colonization patterns of ASV_4 varied across host genotypes and were correlated with CsXPR1 expression levels, suggesting a precision genetic regulation of bacterial entry into vascular tissues. Pseudomonas fulva strain 220, with 97% 16S rRNA gene identity with ASV_4, could colonize in cucumber xylem by inoculation of either roots or leaves. Genome analysis and plate assays revealed the biosynthesis of indole-3-acetic acid (IAA), solubilization of phosphate, and a range of plant beneficial traits in strain 220. Inoculation with strain 220 significantly enhanced growth in cucumber, but only in CsXPR1 haplotype that exhibited high gene expression and higher recruitment capacity of the strain. These benefits included notable increases in plant height (38%), stem diameter (36%), leaf area (61%), fresh and dry weight (51% and 85%, respectively), and a 4.57-fold increase in 4-methyleneglutamine content within the xylem sap.

CONCLUSION: Our findings reveal a complete "gene-to-function" pathway where the host gene CsXPR1 mediates a genotype-dependent growth promotion. It achieves this by regulating the xylem colonization of a beneficial bacterium, Pseudomonas fulva, which in turn enhances plant growth by enriching the xylem sap with the key metabolite 4-methyleneglutamine. Video Abstract.}, } @article {pmid41634852, year = {2026}, author = {Yan, A and Li, X and Cheng, J and Cheng, Y and Gebeyew, K and Tan, Z and Kang, J and He, Z}, title = {The developmental trajectory and maturation of the Hulunbuir sheep (Ovis aries) microbiome.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {10}, pmid = {41634852}, issn = {2524-4671}, support = {32350410422//National Natural Science Foundation of China/ ; 2022JJ10054//Natural Science Foundation of Hunan Province of China/ ; 32350410422//the National Natural Science Foundation of China/ ; 32302783//Natural Science Foundation of China/ ; }, abstract = {The rumen microbiota plays a pivotal role in the growth performance of host animals, primarily due to its ability to ferment ingested feed. Hulunbuir sheep exhibited a slow growth rate compared to other local breeds. A deeper comprehension of the development of the rumen bacteria community in Hulunbuir sheep can offer insights into the factors contributing to their slow growth rate. This study utilized metagenomic analysis of rumen content samples from Hulunbuir sheep to investigate the patterns of microbial growth and their relationship with the ADG. The results of the PCoA and enterotype analyses demonstrated that the ruminal bacterial community developed distinct characteristics following weaning. The dominant bacterial phyla in the rumen of Hulunbuir sheep, Bacteroidetes and Firmicutes, exhibited a significant age-related change. At the genus level, while the abundance of dominant bacterial genera changed with the growth of Hulunbuir sheep, Prevotella consistently maintained a high abundance across all age time points. We then examined the effects of age on microbial function by analyzing carbohydrate-metabolizing enzymes and protein-metabolizing peptidases. The abundance of carbohydrate-metabolizing enzymes decreased with growth, while peptidases showed opposite dynamics. Under the current feeding conditions correlation analysis showed that the abundances of Firm-04, CAG-83, and GCA-900,199,385 were negatively correlated with ADG (R<-0.4, p < 0.05), while the abundance of Ga6A1 was positively correlated with ADG (R > 0.5, p < 0.05). In addition, we found 67 MAGs related to ADG, which are capable of secreting carbohydrates-metabolizing enzymes and peptidase. This study uncovers the temporal dynamics of rumen microbiota development during the early to late fattening phase and identifies microbes associated with ADG, which could inform strategies to improve growth and production efficiency.}, } @article {pmid41634835, year = {2026}, author = {Vayena, E and Ataman, M and Hatzimanikatis, V}, title = {In silico analysis and comparison of the metabolic capabilities of different organisms by reducing metabolic complexity.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02299-0}, pmid = {41634835}, issn = {2049-2618}, support = {200021_188623//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {BACKGROUND: Understanding how metabolic capabilities diverge across microbial species is essential for deciphering community function, ecological interactions, and the design of synthetic microbiomes. Despite shared core pathways, microbial phenotypes can differ markedly due to evolutionary adaptations and metabolic specialization. Genome-scale metabolic models (GEMs) provide a systems-level framework to explore these differences; however, their complexity hinders direct comparison.

RESULTS: We introduce NIS (Neidhardt-Ingraham-Schaechter), a computational workflow that integrates the redGEM, lumpGEM, and redGEMX algorithms to systematically reduce genome-scale models into biologically interpretable modules. This approach enables direct, quantitative comparison of fueling pathways, biomass biosynthetic routes, and environmental exchange processes while retaining essential metabolic information. We first demonstrate the utility of NIS by analyzing Escherichia coli and Saccharomyces cerevisiae, which revealed both conserved and divergent strategies in central metabolism, biosynthetic cost, and substrate utilization. We then applied NIS to the core honeybee gut microbiome, uncovering distinct metabolic traits, functional redundancy, and complementarity that help explain auxotrophy, cross-feeding interactions, and microbial coexistence.

CONCLUSIONS: NIS provides an automated, scalable, and reproducible framework for dissecting microbial metabolic networks beyond gene content or taxonomy. By linking metabolism to ecological function, NIS offers new opportunities to interpret microbial community dynamics and to support the rational design of microbiomes in health, agriculture, and environmental applications. Video Abstract.}, } @article {pmid41634815, year = {2026}, author = {Hao, X and Wang, X and Wang, X and Wang, C and Li, C and Lu, Y and Cheng, Q and Chen, Z and Zhu, L and Li, C and Shen, X}, title = {Synthetic community derived from the root core microbes of a desert shrub Caragana korshinskii enhances wheat drought tolerance.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-026-02350-8}, pmid = {41634815}, issn = {2049-2618}, abstract = {BACKGROUND: Drought, intensified by climate change, poses a mounting threat to global food security by severely constraining crop productivity. While microbial inoculants offer promise for drought tolerance, their poor adaptability remains insufficient for extremely water-deficient environments. Desert plants host unique drought-adapted microbiomes that remain largely unexplored for agricultural applications.

RESULTS: Here, we investigated the microbial community of the desert shrub Caragana korshinskii and identified a core set of drought-responsive strains. A synthetic microbial community (SynCom) derived from these strains significantly improved wheat growth under drought stress. Metagenomic analyses revealed that microbial functions related to biofilm formation, quorum sensing, and carbon metabolism were enriched, with Pseudomonas identified as a key functional taxon. Guided by inter-strain interactions in biofilm assembly, we streamlined the consortium into a five-member synthetic community, where quorum-sensing signals promoted community-wide biofilm formation. Community biofilm production improved strain colonization and conferred greater drought tolerance compared to monocultures. In plants, mechanistic investigations indicated that the simplified SynCom inoculation universally upregulated MAPK and jasmonic acid signaling pathways. Furthermore, carbohydrate metabolic pathways such as starch and sucrose metabolism were specifically activated, suggesting a multi-level mechanism underlying SynCom-mediated drought tolerance.

CONCLUSIONS: These findings demonstrate that SynCom constructed on the endophytic flora of desert plants can significantly enhance crop drought tolerance. Our work highlights the pivotal role of community biofilm synthesis in facilitating root colonization and activating a multidimensional drought tolerance network in plants. This study not only gives an ecological perspective on desert microbiome adaptations but also offers a strategic framework for developing effective microbial inoculants for arid-region agriculture. Video Abstract.}, } @article {pmid41634734, year = {2026}, author = {Hou, X and Guan, X and Qin, X and Guo, HD}, title = {Exploring the basis of Traditional Chinese Medicine in treating cardiovascular disease: insights into the microbiota-gut-heart axis.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {63}, pmid = {41634734}, issn = {1749-8546}, support = {82174120//National Natural Science Foundation of China/ ; 2024PT005//Traditional Chinese Medicine Research Project of Shanghai Municipal Health Commission/ ; 22XD1423400//Program of Shanghai Academic Research Leader/ ; }, abstract = {Despite being widely used to treat cardiovascular disease (CVD), there are still limitations of Traditional Chinese Medicine (TCM) for their widespread use due to undetermined pharmacological mechanisms. The emerging area of "pharmacomicrobiology" facilitates the pursuing of the complex interactions between TCM and gut microbiome as the gut microbiota influences TCM bioavailability and efficacy, vice versa TCM affects the microbial composition and function. Furthermore, research over the past decades has proved that gut dysbiosis and diverse microbial metabolites intimately related to the onset and progression of CVD. Herein, we summarize latest understanding of the TCM-gut-heart axis in CVD, with an emphasis on describing microbial changes and the associated mechanisms in CVD, elaborating the role of gut microbiota in metabolizing TCM, and how TCM can be used to treat CVD through affecting the gut microbiota. We further highlight the challenges and future directions that target TCM-gut-heart axis in prospects for personalized medicine in CVD, thus to present novel insights for developing new therapeutic approaches.}, } @article {pmid41634709, year = {2026}, author = {Dhakad, P and Newman, D and Obbard, DJ}, title = {Transcriptomic analysis of non-model Drosophilidae reveals novel AMP candidates.}, journal = {BMC biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12915-026-02535-5}, pmid = {41634709}, issn = {1741-7007}, support = {BB/T007516/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Drosophila melanogaster has been a valuable model for dissecting the molecular architecture of innate immunity. However, the family Drosophilidae encompasses over 4000 species, spanning deep evolutionary divergences and diverse ecologies. Here, we use immune challenge with the Gram-negative pathogen Providencia rettgeri to investigate the conservation and evolution of immune responses in three non-model drosophilid species that diverged from D. melanogaster over 45 million years ago-Hirtodrosophila cameraria, H. confusa, and Scaptodrosophila deflexa.

RESULTS: We find that all three species retain a core set of immune signaling and recognition genes, but exhibit substantial variation in effector gene content and inducibility. In particular, Scaptodrosophila deflexa lacks orthologs of multiple antimicrobial peptides (AMPs) known from D. melanogaster, including DptA, AttA, and AttC, and shows little transcriptional response to bacterial challenge with Providencia rettgeri. In contrast, both of the Hirtodrosophila species exhibit substantial transcriptional responses, including strong induction of canonical Imd pathway genes. Microbiome profiling of our samples revealed higher Providencia abundance in H. cameraria, and high levels of the defensive symbiont Spiroplasma in S. deflexa-potentially explaining differences in infection outcome. Our combined annotation and expression analysis of these species also allowed us to identify 20 novel AMP-like candidates, many with structural features like known AMPs.

CONCLUSIONS: Our study demonstrates the feasibility of functional immune analyses in non-model Drosophila species and reveals striking lineage-specific differences in immune gene repertoire and expression. These findings highlight the importance of non-model, wild-derived samples for uncovering novel immune effectors and understanding evolutionary forces shaping insect immunity.}, } @article {pmid41634704, year = {2026}, author = {Bao, L and Jin, L and Yang, Y and Zhao, Y and Wu, K and Shan, R and Liu, Y and Han, Y and Shang, S and Zhang, N and Hu, X and Fu, Y and Zhao, C and Jiang, H and Bian, W}, title = {Hexadecanamide alleviates experimental colitis in mice and modifies the gut microbiome.}, journal = {BMC biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12915-026-02530-w}, pmid = {41634704}, issn = {1741-7007}, abstract = {BACKGROUND: Hexadecanamide (HEX) has been recognized for its significant anti-inflammatory properties. However, its specific role and underlying mechanisms in the context of colitis remain poorly understood.

RESULTS: Herein, we first determined the effect of oral HEX on DSS-induced colitis in mice. Our results showed that HEX alleviated DSS-induced colitis in mice, which was related to the improvement of intestinal barrier integrity and the reduction of colonic inflammatory responses. Interestingly, HEX suppressed the initiation of DSS-induced ferroptosis. In detail, HEX inhibited autophagy and ferritinophagy, which subsequently blocked lipid peroxidation. 16S rRNA sequencing revealed that HEX intervention regulated the gut microbial composition, characterized by an increased relative abundance of Actinobacteriota and Patescibacteria and a decreased the relative abundance of Firmicutes. To validate these findings, fecal microbiota transplantation (FMT) was performed in DSS-treated mice. The microbiota derived from HEX-treated mice exhibited greater efficacy in alleviating colitis compared to that from control-treated mice, as evidenced by prominent anti-inflammatory effects and colonic barrier repair, and consistent alterations in the gut microbial community, which were further confirmed by FMT.

CONCLUSIONS: Overall, our findings suggest that HEX markedly ameliorates DSS-induced colitis by limiting inflammation, improving barrier integrity and regulating gut microbial composition. These results highlight the critical role of HEX in maintaining intestinal homeostasis and suggest its potential as a novel preventive and therapeutic strategy.}, } @article {pmid41634580, year = {2026}, author = {Gong, X and Chen, B and Yang, L and Zhang, Y and Chang, S and Yang, T and Chen, Y and Zhu, Y and Wang, Z and He, X and Xue, L}, title = {Location and growth period influence the bioactive compounds of Angelica sinensis (Oliv.) diels: multi-omics insights.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08135-3}, pmid = {41634580}, issn = {1471-2229}, support = {24JRRA1134; 2024YQ-04//the Natural Science Foundation of Gansu Province of China; the Outstanding Youth Fund of the Gansu Academy of Sciences/ ; 22ZSCQ037//Intellectual Property Plan Project Gansu Province of China/ ; 24JRRA1137; 2024QN-13//the Science and Technology Program of Gansu Province of China; the Young Scientists Fund Project of Gansu Academy of Sciences/ ; }, } @article {pmid41634542, year = {2026}, author = {Sun, M and Wei, J and Wang, M and Xu, H and Ma, W and Wang, Y}, title = {Research on the process of synergistic degradation of corn straw by probiotics-enzymes based on microbiome and metabolomics.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04776-4}, pmid = {41634542}, issn = {1471-2180}, support = {CARS-39-27//National Wool Sheep Industry Technology System/ ; jytms20231736//Liaoning Provincial Department of Education General Project/ ; 2024010768-JH3/107, 2024012131-JH4/4800//Liaoning Provincial Natural Science Foundation Project/ ; S202410160014//College Student Innovation Project/ ; }, } @article {pmid41634282, year = {2026}, author = {Yamaguchi, K and Sekido, K and Kobayashi, E and Ogura, K and Nishiyama, M and Konno, K and Tanaka, R and Hamana, H and Kishi, H and Sasaki, SI and Susukida, T and Hayakawa, Y}, title = {Juzentaihoto modulates gut microbiota and potentiates the anti-tumor effect of anti-PD-1 antibody in an immunogenic mouse melanoma model.}, journal = {Journal of natural medicines}, volume = {}, number = {}, pages = {}, pmid = {41634282}, issn = {1861-0293}, support = {N/A//Tsumura and Company/ ; }, } @article {pmid41634153, year = {2026}, author = {Li, N and Li, G and Huang, X and Ma, L and Wang, D and Luo, Y and Cao, X and Zhu, Y and Mu, J and An, R and Zhao, J and Wang, Y and Yang, C and Chen, H and Xu, Y and Jiang, L and Luo, M and Li, X and Dong, Y and Chen, X and Hochholdinger, F and Jiang, Y and Reif, JC and Wang, D and Zhang, Y and Bai, Y and Yu, P}, title = {Large-scale multi-omics unveils host-microbiome interactions driving root development and nitrogen acquisition.}, journal = {Nature plants}, volume = {}, number = {}, pages = {}, pmid = {41634153}, issn = {2055-0278}, support = {444755415//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 2022YFD1900705//National Science Foundation of China | Key Programme/ ; }, abstract = {The rhizosphere microbiome plays a crucial role in determining plant performance and fitness. Nevertheless, regulatory mechanisms linking host genetic variation, root gene regulation and microbiome assembly-and their collective influence on plant nutritional traits-remain poorly understood. Here we generated and integrated 1,341 paired datasets, including root transcriptomes, rhizosphere bacterial 16S rRNA profiles and root ionomes, across 175 resequenced Brassica napus ecotypes grown at two contrasting field sites. We identified 203 highly heritable bacterial amplicon sequence variants (ASVs), many of which were significantly associated with root nitrogen (N) levels. Host transcriptome-wide gene expression and these microbial features together explained up to 45% of natural variation in N uptake while genome-wide association analyses revealed host loci regulating ASV abundance, many of which were under the control of eQTL hotspots linked to carbon and N metabolism. Isolate-level inoculation, whole-genome sequencing, metabolite profiling and confocal imaging demonstrated that the dominant, genetically regulated bacterial genus Sphingopyxis modulates auxin biosynthesis and promotes lateral root development to enhance N acquisition under stress. This study therefore identifies Sphingopyxis as a functionally relevant taxon with potential for microbiome-assisted breeding of nutrient-efficient crops.}, } @article {pmid41634036, year = {2026}, author = {Huang, L and Pu, YT and Zhao, YH and Sun, XY and Zhu, Y and Lu, YP and Leng, HX and Feng, J and Jin, LR and Sun, KP}, title = {Diet and environmental factors jointly drive the gut microbiome, resistome, and virulome of urban bats.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00930-y}, pmid = {41634036}, issn = {2055-5008}, support = {32430066//National Natural Science Foundation of China/ ; 32171525//National Natural Science Foundation of China,China/ ; }, abstract = {The coexistence and horizontal transfer of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) carried by urban wildlife represent an emerging form of biological pollution, constituting a significant threat to public health. We employed meta-omic approaches to evaluate the effects of host traits (sex, age, etc.), environmental factors (including geographical location and time), and diet (including food composition and antibiotic residues) on the bacterial, ARG, and VFG profiles of Vespertilio sinensis, an urban-dwelling bat. Our results demonstrate that the feces of V. sinensis harbor diverse ARGs and VFGs, but their genomic evidence for horizontal mobility in bacterial communities is limited. Notably, environmental changes over time and across geographical locations are associated with the ARG and VFG profiles, potentially due to the influence of pollutants in specific habitats. Dietary factors are associated with their dynamics through the microbiome, with antibiotic residues exerting selective pressure on ARG profiles. No significant impacts of sex, age, body size, and reproductive status on the gut microbiota, resistome, or virulome were observed. This study provides valuable insights into the ecological drivers of the gut microbiome, resistome, and virulome in bats, thereby contributing to our understanding of the public health risks associated with urban wildlife.}, } @article {pmid41633818, year = {2026}, author = {Giangrazi, F and Sugrue, JA and Sularea, VM and Brugman, AAI and Horan, M and Wingfield, M and Crosby, DA and Glover, LE and O'Farrelly, C}, title = {Contribution of endometrial microbiome to inflammation-mediated infertility in women undergoing ART.}, journal = {Human reproduction (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/humrep/deaf252}, pmid = {41633818}, issn = {1460-2350}, support = {15692//Fertility Innovation from Merck KGaA/ ; }, abstract = {STUDY QUESTION: Is the endometrial microbiome altered in women who fail to get pregnant after ART and do microbial-derived metabolites influence endometrial cellular mechanisms important for embryo implantation?

SUMMARY ANSWER: The endometrial microbiome in women who fail to get pregnant after ART is more diverse and has fewer lactobacilli species than the endometrial microbiomes of women who become pregnant; the short-chain fatty acid butyrate, a common metabolite found in the presence of increased microbial diversity, diminishes endometrial epithelial barrier function and increases the expression of inflammatory markers.

WHAT IS KNOWN ALREADY: Shifts in the endometrial microbial community structure have been linked to fertility and pregnancy complications although the underlying mechanisms are poorly understood. Microbial metabolites at other mucosal surfaces, such as the gut, act as important modulators of immune and barrier function, particularly in epithelial cells. Effects of changes in local bacterial microbial populations on fertility, and how their metabolites might influence endometrial cell function have not been explored.

STUDY DESIGN, SIZE, DURATION: In this prospective longitudinal study of ART outcomes, 29 nulliparous women with unexplained infertility were recruited between October 2016 and February 2018. Endometrial tissue samples were taken for microbiome analysis and endometrial transcriptomics prior to ART. For primary cell culture studies, endometrial biopsies were obtained from fertile women of reproductive age undergoing laparoscopic surgical investigation between February 2021 and September 2023. In vitro models of implantation were established using endometrial cell lines and primary endometrial stromal cells.

Microbiome 16S sequencing analysis was performed on bacterial DNA isolated from endometrial biopsies and correlated with receptivity markers. Endometrial RNA sequencing data from women undergoing ART were used to analyse differential gene expression of receptivity and decidualization markers in women who had a positive or negative ART cycle outcome. In vitro models, using both established endometrial cell lines and primary human endometrial epithelial cells and stromal cells, were developed to investigate the effects of microbial-derived metabolites. An in vitro model of peri-implantation was used to test the effect of butyrate on endometrial epithelial receptivity and stromal cell decidualization.

Endometrial microbiome 16S sequencing revealed a lower abundance of Lactobacillus spp. and significantly higher abundance of pathogenic species such as Prevotella spp. and Corynebacterium spp. in women who did not become pregnant after ART. Endometrial microbiota from women who had positive ART outcomes showed significantly lower diversity indices. Intriguingly, analysis of endometrial RNA sequencing data from women with unexplained infertility undergoing ART showed that negative ART outcomes were associated with higher levels of some receptivity and decidualization markers in their endometrial tissue. Butyrate, but not lactate or acetate, also increased some markers of epithelial receptivity and stromal decidualization. Butyrate exposure also activated defence mechanisms in cultured endometrial epithelial cells by inducing expression of antimicrobial peptide(s) and inflammation markers, as well as impairing the barrier integrity of endometrial epithelial cell monolayers.

LARGE SCALE DATA: The RNA-seq data used for the study can be found in GEO database, GEO ID GSE144895. The data for the 16S sequencing can be accessed in SRA BioProject number PRJNA1338067.

Limitations of our study include the cohort size and technical challenges that precluded absolute butyrate measurement in endometrial tissue biopsies. Biopsy collection from women undergoing gynaecological investigation varied in menstrual cycle staging and fertility diagnoses, which may contribute to the variability between responses obtained from in vitro stimulations. The transferred embryos were not genetically tested, but were all of good or top quality.

Our findings indicate that the endometrial microbiome is altered in women who fail to become pregnant after ART, and that the microbial-derived metabolite butyrate can induce inflammation and impair endometrial epithelial barrier function and drive increased gene expression levels of markers for epithelial receptivity and stromal decidualization in in vitro models of peri-implantation. Endometrial microbial dysbiosis and higher expression of receptivity markers were found in women who failed to establish pregnancy post-ART. Negative ART outcomes in this cohort were found to correlate with the presence of a wider, more diverse microbial community that includes Prevotella spp., which is among the butyrate-producing bacteria. Further investigation of the microbial metabolome in healthy endometrium would help clarify the physiological role of butyrate and other bacterial metabolites in endometrial function.

This research was supported by the Grant for Fertility Innovation from Merck KGaA, grant award number 15692. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

TRIAL REGISTRATION NUMBER: N/A.}, } @article {pmid41633775, year = {2026}, author = {Kang, KS and Choi, GH and Kim, YJ and Lee, WS and Lee, DE and Kim, MY and Yoon, H and Lee, DH}, title = {Analysis of gut microbiota in super donors for fecal microbiota transplantation and isolated gut commensal bacteria of inhibition against Clostridioides difficile.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2025.00179}, pmid = {41633775}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is increasingly recognized as an alternative to antibiotics for treating recurrent Clostridioides difficile infection. The success of FMT heavily depends on the appropriate selection of donors, encompassing factors such as diet patterns, lifestyle, environmental exposures, and intestinal microbiota diversity.

METHODS: A potential super donor was identified from 5 healthy adults and provided stool samples periodically over 2 years (2021-2022). The samples underwent 16S rRNA sequencing via the Illumina MiSeq platform, and microbial diversity was analyzed using QIIME 2 in comparison with 152 healthy individuals.

RESULTS: The stool microbiome composition of the potential super donor remained stable without significant changes over a 2-year period. Both alpha and beta diversity analyses revealed significant differences between the super donor and the 152 healthy individuals. The super donor exhibited significantly higher microbial diversity based on alpha diversity metrics (P< 0.0001) and distinct compositional profiles as shown by beta diversity. Linear discriminant analysis effect size (LEfSe) analysis indicated that Faecalibacterium and Prevotella strains comprised a significant proportion, with notable differences in relative abundance patterns (P< 0.05). Furthermore, 7 bacterial species were isolated from the super donor, all of which demonstrated inhibitory effects on the growth of C. difficile in vitro.

CONCLUSIONS: These findings suggest that selecting donors with specific microbiota profiles, particularly those exhibiting higher microbial diversity, may potentially contribute to the inhibition of C. difficile, and further clinical studies are warranted to validate these findings.}, } @article {pmid41633616, year = {2026}, author = {You, ZB and Cao, P and Yao, ST and Luo, ZM}, title = {Mendelian Randomization Analysis Uncovers the Causal Link Between Gut Microbiota and Cerebrovascular Diseases.}, journal = {Neurology India}, volume = {74}, number = {Suppl 1}, pages = {S9-S20}, doi = {10.4103/neurol-india.Neurol-India-D-24-00850}, pmid = {41633616}, issn = {1998-4022}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Mendelian Randomization Analysis ; *Cerebrovascular Disorders/microbiology/genetics ; }, abstract = {The intestinal microbiome represents the most extensive microbial community within the human body, significantly influencing neurodevelopment, aging, maintenance of normal physiological functions, and brain disorders, including ischemic stroke. Emerging research indicates that the gut microbiome might affect cerebrovascular health via multiple mechanisms. However, since many of these studies are observational, establishing a direct causal link remains challenging. Mendelian randomization, leveraging genetic variations, provides a novel approach to evaluate causality. We reviewed recent studies employing Mendelian randomization to investigate the potential causal associations between the gut microbiome and cerebrovascular diseases. Our analysis synthesizes findings from Mendelian randomization studies that connect specific gut microbial compositions with cerebrovascular conditions such as stroke and its subtypes, aneurysms, atherosclerosis, and cerebral small vessel disease. This aims to offer a more definitive framework for understanding the causal relationship between the gut microbiome and cerebrovascular health.}, } @article {pmid41633513, year = {2026}, author = {Broadribb, M and Rogers, A and Thomas, T and Micaroni, V and Strano, F and Bell, J}, title = {Differing temperature regimes have no impact on the heat stress response of shallow and upper-mesophotic populations of a temperate calcareous sponge.}, journal = {Proceedings. Biological sciences}, volume = {293}, number = {2064}, pages = {}, doi = {10.1098/rspb.2025.1103}, pmid = {41633513}, issn = {1471-2954}, support = {//Southern Fiordland Initiative/ ; //George Mason Charitable Trust/ ; //NZ Department of Conservation/ ; //Victoria University of Wellington/ ; //Royal Society Te Apārangi/ ; }, mesh = {Animals ; *Porifera/physiology/microbiology ; *Heat-Shock Response ; *Hot Temperature ; Climate Change ; Temperature ; Ecosystem ; }, abstract = {Marine heatwaves (MHWs) are increasing in intensity and frequency globally owing to anthropogenic climate change. Temperate mesophotic ecosystems (TMEs; 30-150 m) are light-dependent habitats that generally experience cooler and more stable temperatures than adjacent shallow zones, potentially leading to intraspecific differences in thermal tolerance between shallow and mesophotic populations. Sponges, often the dominant benthic organisms in TMEs, show varied responses to thermal stress. We hypothesized that shallow-water sponges may be more resilient to heat stress than conspecifics from upper-mesophotic depths. To test this, we exposed Rowella lancifera sponges from one shallow and one upper-mesophotic population to a simulated MHW and measured respiration, buoyant weight, mortality and microbial community composition. Temperature records from the preceding year confirmed cooler, more stable conditions at upper-mesophotic depths. Sponges displayed strong stress responses under MHW exposure, resulting in high mortality, but responses did not differ between depths. Elevated respiration rates also coincided with microbial community shifts. Overall, our results indicate that a 1°C increase above previous MHW peaks could cause widespread mortality in R. lancifera.}, } @article {pmid41633490, year = {2026}, author = {Kelly, MS and Huang, CY and Kim, M and Haghnazari, D and Baig, A and Sun, Y and Lenneman, BR and Tisza, MJ and Cunningham, A and Gold, D and Phipatanakul, W and Lai, PS}, title = {Nasal microbiome and phageome profiles are associated with prospective respiratory viral infection risk in school-aged children.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2026.01.017}, pmid = {41633490}, issn = {1097-6825}, abstract = {BACKGROUND: Respiratory viral infections are common and can trigger asthma exacerbations in children. The roles of the nasal microbiome and phageome (viruses that infect microbes) are not well understood.

OBJECTIVE: To characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-aged children with asthma.

METHODS: We performed metagenomic sequencing and RT-qPCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely three times over one year. Surveys on parent-reported cold and asthma symptoms were administered routinely every two months. We evaluated multi-kingdom changes to the nasal microbiome during infection. A sPLS-DA model identified microbial signatures associated with prospective viral infection risk.

RESULTS: Respiratory viruses were identified in 124 (33%) samples, with rhinovirus most prevalent. Cold and asthma symptoms within the prior 14 days had a sensitivity of 79% and 59%, respectively, for RT-qPCR-confirmed infection. Respiratory viral infection increased asthma symptoms and was accompanied by loss of nasal bacterial diversity and a reproducible bloom of pathobionts with no change in the mycobiome or phageome. A baseline bacteriome-dominated profile was protective (adjusted OR 0.41 [95% CI, 0.25 - 0.67]; P < 0.001), whereas phageome profiles increased risk (adjusted OR 3.74 [1.85 - 7.55]; P < 0.001) of viral infection. Specific phages inversely correlated with Staphylococcus epidermidis abundance, the most protective commensal against infection risk.

CONCLUSION: The nasal microbiome and phageome exert opposing influences on respiratory viral infection risk, highlighting their potential roles in modulating susceptibility to viral infections.}, } @article {pmid41633474, year = {2026}, author = {Cazzola, M and Maniscalco, M and Matera, MG and Rogliani, P}, title = {The importance of biomarkers in the treatable-trait approach to chronic airway diseases.}, journal = {Pulmonary pharmacology & therapeutics}, volume = {92}, number = {}, pages = {102410}, doi = {10.1016/j.pupt.2026.102410}, pmid = {41633474}, issn = {1522-9629}, abstract = {Chronic airway diseases (CAD), including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and cystic fibrosis, are increasingly recognized as heterogeneous and overlapping syndromes that share treatable biological and clinical characteristics. The Treatable Traits (TT) approach is a precision medicine framework that transcends diagnostic labels. It identifies and targets modifiable pulmonary, extrapulmonary, and behavioral characteristics in each patient. Biomarkers are central to this paradigm, translating latent endotypes into measurable traits that inform diagnosis, treatment selection, and longitudinal monitoring. This review synthesizes contemporary evidence on the role of biomarkers in implementing the TT model across CAD. Peripheral and airway biomarkers, including blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and sputum cell profiles, enable the identification of type 2 inflammatory traits and the prediction of corticosteroid or biologic responsiveness. Imaging and quantitative computed tomography metrics extend trait definition to structural and functional domains. Meanwhile, multi-omic and microbiome signatures reveal the molecular endotypes that underpin disease heterogeneity. Canonical examples include BEC predicting the benefit of inhaled corticosteroids in COPD and FeNO indicating steroid responsiveness in asthma. Additionally, emerging data suggest that rapid trait identification during acute exacerbations may facilitate targeted biologic therapy, extending precision care into acute management contexts. Integrating biomarker-guided assessment with individualized therapy redefines the management of CAD by offering a pathway toward biologically precise, dynamically adaptive care. Continued research should focus on standardizing biomarker thresholds, validating composite panels, and translating omic and imaging discoveries into routine clinical tools to optimize outcomes across the chronic airway disease spectrum.}, } @article {pmid41633255, year = {2026}, author = {Oh, EY and Suh, SH and Byeon, S and Lee, J and Lee, YH and Choi, SK}, title = {Liraglutide alters gut microbiota and improves endothelium-dependent relaxation in db/db mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {196}, number = {}, pages = {119042}, doi = {10.1016/j.biopha.2026.119042}, pmid = {41633255}, issn = {1950-6007}, abstract = {Endothelial dysfunction is a hallmark of type 2 diabetes mellitus (T2DM) and a major contributor to cardiovascular complications. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemic control and cardiovascular outcomes, the mechanisms linking GLP-1RA therapy, gut microbiome modulation, and endothelial function remain incompletely understood. In this study, we investigated whether the GLP-1RA liraglutide improves endothelial dysfunction in T2DM through microbiome-associated mechanisms that support vascular homeostasis. Male db/db mice and non-diabetic controls were treated with liraglutide (300 μg/kg/day, intraperitoneally) or saline for two weeks. Vascular function was assessed in mesenteric resistance arteries using wire myography. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose with or without liraglutide or the short chain fatty acid (SCFA), butyrate. Endothelial nitric oxide (NO) signaling was evaluated by eNOS (at Ser1177) phosphorylation and nitrite production. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Liraglutide significantly improved endothelium-dependent relaxation in db/db mice and restored high glucose-induced impairment of eNOS phosphorylation and NO production in HUVECs. In vivo, diabetes was associated with marked gut dysbiosis characterized by reduced alpha diversity and depletion of SCFA-producing taxa. Liraglutide treatment substantially restored microbial diversity and enriched beneficial genera, including Lachnospiraceae and Lactobacillus. Consistently, low-dose butyrate modestly enhanced NO production in endothelial cells. These findings support the concept of a GLP-1RA-microbiome-vascular axis, in which liraglutide-associated remodeling of the gut microbiota may contribute to improved endothelial NO signaling and vascular function in diabetes.}, } @article {pmid41633172, year = {2026}, author = {Chen, Y and Zhu, R and Liu, F and Zhang, X and Li, S and Gu, L and Shu, J}, title = {Deciphering the impacts of multi-source materials on semi-continuous anaerobic digestion of food waste: performance enhancement and mechanism analysis.}, journal = {Journal of environmental management}, volume = {400}, number = {}, pages = {128824}, doi = {10.1016/j.jenvman.2026.128824}, pmid = {41633172}, issn = {1095-8630}, abstract = {Anaerobic digestion is a promising technology for food waste valorization, enabling resource recovery and renewable energy production. However, while exogenous material supplementation improves digestion performance, the mechanisms governing semi-continuous operation remain unclear. Via 120-day semi-continuous experiments, this study assessed the impacts of iron-based composites (Fe + C, Fe2O3, and Fe3O4) and granular activated carbon (GAC) on system efficiency. Results showed that exogenous materials significantly enhanced biogas production (up to 808.1 ± 66.0 mL/g VS in mesophilic anaerobic digestion + Fe2O3 reactor) (MAD + Fe2O3), improved organic degradation (VS removal: 82.7 ± 0.7%), and mitigated volatile fatty acid (VFA) inhibition (reduced from 5000 to 2800 mg/L). Notably, iron-based materials exerted selective regulatory effects: Fe and Fe3O4 boosted hydrogenotrophic methanogen metabolism, while Fe2O3 enhanced hydrolase activity and upregulated tricarboxylic acid (TCA) cycle-related genes. Microbial analysis uncovered a dual enhancement mechanism: 1) enrichment of hydrogenotrophic methanogens (Methanobacterium) and acetoclastic methanogens (Methanosarcina/Methanosaeta) and 2) upregulation of critical metabolic genes, including pyc (pyruvate carboxylase) and acs (acetyl-CoA synthetase). Intriguingly, direct interspecies electron transfer (DIET) contributed insignificantly, challenging the common assumption of DIET-dominated enhancement. This work clarifies how exogenous materials orchestrate methanogenic pathways via microbe-material coupling, and bridges the knowledge gap between material-enhanced performance and functional microbiome in semi-continuous anaerobic digestion, providing a theoretical basis for optimizing energy-efficient treatment systems.}, } @article {pmid41633137, year = {2026}, author = {Zhang, FY and Shu-Kui, D and Wang, LL and Ma, YT and Wu, MZ and Yuan, HM and Yang, JN and Zhang, Y and Zhang, GA and Zhao, J and Liu, C and Guan, DW and Zhao, R}, title = {Metagenomic profiling reveals lung multi-kingdom microbes as forensic markers for aquatic corpses investigation.}, journal = {Forensic science international. Genetics}, volume = {83}, number = {}, pages = {103435}, doi = {10.1016/j.fsigen.2026.103435}, pmid = {41633137}, issn = {1878-0326}, abstract = {The forensic investigation of corpses recovered from aquatic environments presents a major practical challenge. Recent studies have demonstrated that the bacterial community in the lung serves as a valuable indicator for diagnosing drowning, determining the drowning medium and estimating postmortem submersion interval (PMSI). However, the application and significance of lung multi-kingdom microbiome (archaea, eukaryota, and viruses) remains inadequately characterized. Meanwhile, the insufficient sequencing depth of commonly employed techniques, such as amplicon sequencing, restricts our understanding of microbial communities. In this study, we characterized the postmortem lung microbiome of mice submerged in water for up to 10 days using metagenomic sequencing, and subsequently validated the potential microbial biomarkers in both murine and human forensic specimens via qPCR. Integrated analyses were conducted followed by the confirmation of significant lung bacterial communities for drowning diagnosis, inference of drowning site, and estimation of the PMSI. Our findings revealed that bacteria constituted the predominant component of the lung microbiome in submerged murine carcasses, with eukaryota serving as the secondary dominant taxa. Seventeen bacterial and nine eukaryotic features at the species level were identified as potential biomarkers for drowning diagnosis. By detecting the specific molecular markers for Aeromonas species in both murine and human samples, the positive detection of Aeromonas species, particularly Aeromonas hydrophila, provides solid evidence for drowning diagnosis. Additionally, 14 and 17 bacterial species were identified as biomarkers for the inference of drowning site and estimation of PMSI, respectively. Based on the identified potential biomarkers, robust forensic models were constructed using the random forest (RF) algorithm. The accuracy of the bacterial model for drowning diagnosis was 89.29 %, while the accuracy of the eukaryotic model was 87.5 %. For the inference of the drowning site, the bacterial model achieved an accuracy of 100 %. Furthermore, the estimation of the PMSI yielded a mean absolute error of 0.66 ± 0.097 days. Collectively, our findings revealed that the selected 17 bacterial and 9 eukaryotic features in the lungs, particularly Aeromonas hydrophila, are beneficial for drowning diagnosis. Additionally, the other selected bacterial species contribute to the estimation of the drowning site and PMSI, thereby providing more comprehensive and refined information for accurate forensic investigations of corpses recovered from aquatic environments.}, } @article {pmid41633028, year = {2026}, author = {Xue, L and Zhao, W and Wang, C and Ma, Y and Tian, J and Yang, L and Ma, L and Jiang, Q and Chen, Y and Tian, X and Ji, X and Zhang, J and Gu, Y}, title = {Integrating multi-omics to characterize the dynamics of rumen microorganisms and metabolites in Angus cattle at different growth stages.}, journal = {Research in veterinary science}, volume = {203}, number = {}, pages = {106092}, doi = {10.1016/j.rvsc.2026.106092}, pmid = {41633028}, issn = {1532-2661}, abstract = {The development of the bovine rumen microbiome is crucial for growth, yet the dynamic interactions between the microbiome and metabolome during key growth stages remain poorly understood. This study aims to integrate metagenomics and metabolomics approaches to decipher the stage-specific patterns of rumen microbial community and metabolite changes in castrated Angus cattle at three critical growth stages (6, 12, and 18 months of age), and to elucidate their associations with host growth performance. We collected rumen fluid samples from 24 Angus steers (8 per age group) reared under standardized conditions and performed metagenomic and non-targeted metabolomic analyses. Integrated analysis revealed distinct rumen ecosystem succession patterns: multiple species represented by Prevotella_sp._ne3005 dominated at 6 months, Fibrobacter_succinogenes showed significantly increased abundance at 12 months, and Methanobrevibacter_millerae exhibited the most pronounced enrichment at 18 months. Concurrently, key metabolites 12,13-Dihydroxyoleic Acid, Delta-12-Pgj2, and Cortisol exhibited a significant positive correlation with age. Further Pearson correlation analysis revealed strong correlations between the 18-month-enriched characteristic microorganism Methanobrevibacter_millerae and key metabolites (12,13-Dihydroxyoleic Acid, Delta-12-Pgj2, and Cortisol) as well as higher body weight. This study delineates a dynamic map of synergistic interactions between the rumen microbiome and metabolome, confirming their close association with host growth performance. This work provides a systematic multi-omics framework for understanding rumen development in ruminants and identifies potential targets for optimizing beef cattle production performance through microbial or metabolic interventions.}, } @article {pmid41632629, year = {2026}, author = {Runaas, L and Fank, S and Palen, K and Szabo, A and Rein, L and Ying, G and Salzman, N and Samanas, L and Abedin, SM and Chhabra, S and Hamadani, M and Longo, W and Shah, NN and Haber, J and Gradissimo, A and Waters, NR and Peled, JU and Johnson, B and Kearl, T and Drobyski, WR}, title = {TIDRAKIZUMAB FOR THE PROPHYLAXIS OF GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2025019065}, pmid = {41632629}, issn = {2473-9537}, abstract = {We conducted a phase 1-2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tildrakizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease (GVHD) prophylaxis. Fifty patients were enrolled between March 2020 and June 2023 with a median age of 56 (range 19-64). All patients received myeloablative busulfan-based conditioning and were transplanted with HLA-matched related or unrelated peripheral blood stem cell grafts. Patients were treated with tildrakizumab on an extended subcutaneous administration schedule for five doses which was well tolerated. The cumulative incidences of grades II-IV and III-IV acute graft versus host disease were 14% (95% CI 7-28) and 4% (95% CI 1-16) at day 100, respectively. The incidence of chronic GVHD requiring systemic immune suppression was 52.7% (95% CI 40.4-68.9) at twelve months. The one-year probabilities of overall, disease-free, and GVHD-free relapse-free survival were 80% (95% CI 70-92), 78% (95% CI 67-90), and 19.3% (90% CI 11.8-31.4), respectively. Pharmacokinetic analysis revealed that the half-life of tildrakizumab approximated 28 days without formation of detectable anti-tildrakizumab neutralizing antibodies. Comparative examination of fecal microbial composition in tildrakizumab and a similarly transplanted cohort treated with tocilizumab prophylaxis demonstrated that both cytokine blockade strategies had a low frequency of enterococcal dominance. We conclude that tildrakizumab resulted in a low incidence of acute GVHD and attenuation of microbiome dominance with potentially pathogenic organisms but did not mitigate the emergence of chronic GVHD as administered on this dosing schedule. NCT04112810.}, } @article {pmid41632533, year = {2026}, author = {Cho, JM and Park, SK and Satheesh Babu, AK and Mookherjee, S and Hansen, M and Petersen, C and Zhong, Y and Jalili, T and Robeson, MS and Whankade, UD and Anandh Babu, PV and Symons, JD}, title = {Late-in-life treadmill-training mitigates gut microbiome imbalances and cardiovascular disease risk in mice.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00354.2025}, pmid = {41632533}, issn = {1522-1547}, support = {//University of Utah (U)/ ; 20PRE35110066//American Heart Association (AHA)/ ; T32 HL144449/HL/NHLBI NIH HHS/United States ; 17POST33670663//American Heart Association (AHA)/ ; R01AT010247//HHS | NIH | National Center for Complementary and Integrative Health (OAM)/ ; 2019-67017-29253//USDA | National Institute of Food and Agriculture (NIFA)/ ; 16GRNT31050004//American Heart Association (AHA)/ ; RO3AGO52848//HHS | National Institutes of Health (NIH)/ ; RO1HL141540//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; }, abstract = {Primary aging associates with an imbalanced gut microbiome and cardiovascular disease (CVD) risk in mice and humans. Strong evidence from clinical and pre-clinical studies supports that habitual physical exercise improves cardiovascular function and intestinal health in adults. Here we tested the hypothesis that exercise training, even when initiated late-in-life, re-establishes a beneficial and cooperative intestinal microbiome to an extent that associates with reduced risk for CVD. At 21-months of age, male C57BL/6 mice started a progressive resistance treadmill-training program 6-days per week (Old+ETR) for 12-weeks. Twenty-one month old (Old) and 4-month old (Adult) male mice remained sedentary. First, reductions in exercise capacity and soleus muscle citrate synthase activity displayed by Old vs. Adult mice were restored in Old+ETR animals. Next, systolic function (fractional shortening, FS), diastolic function (E/A ratio), and overall left-ventricular function (myocardial performance index, MPI) otherwise depressed in Old vs. Adult mice were normalized in Old+ETR animals. Third, elevated trimethylamine (TMA) and TMA N-oxide (TMAO), and heightened inflammatory markers [e.g., interferon (IFN)-g and keratinocyte-derived chemokine (KC)], observed in Old vs. Adult mice were lowered in Old+ETR animals. Importantly, the abundance of beneficial microbial features, including Bacteroides, Muribaculaceae, Parabacteroides, and the Rikenellaceae RC9 gut group, otherwise depressed by aging, was normalized in Old+ETR mice. Finally, the Rikenellaceae RC9 gut group positively correlated with FS, and Parabacteroides negatively correlated with IFN-γ. These findings support that late-in-life exercise training beneficially remodels the gut microbiome to an extent that associates with reduced CVD risk in male mice.}, } @article {pmid41632104, year = {2026}, author = {Li, J and Song, L and Liang, X and Zhou, J and Luo, J and Sun, X and Jin, R and Zhang, Z}, title = {Lactobacillus plantarum TY-S8 ameliorates hyperuricemia through the regulation of gut microbiota and tryptophan metabolism in mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo04423e}, pmid = {41632104}, issn = {2042-650X}, abstract = {Hyperuricemia (HUA) has become a worldwide metabolic disease, which can lead to acute gout attacks, renal dysfunction, uric acid (UA) urolithiasis, and cardiovascular damage. Probiotics, known for their cost-effectiveness, minimal toxic side effects, and high safety profile, have shown potential in alleviating HUA. In the present study, the beneficial function of Lactobacillus plantarum TY-S8 on HUA and related mechanisms were comprehensively investigated by constructing a mice model of hyperuricaemia, combined with the use of microbiomics and metabolomics. Our results demonstrated that L. plantarum TY-S8 markedly lowered serum UA (SUA) concentrations by 22.41%, suppressed xanthine oxidase (XOD) activity and modulated the level of key transporters, including GLUT9, ABCG2, and NTP1. Furthermore, the pathological damage in the liver, kidney and colon of hyperuricemic mice was alleviated by the probiotics. Meanwhile, the strain upregulated the levels of occludin, a key tight junction protein, and promoted the synthesis of short-chain fatty acids (SCFAs), with a notable increase in butyric acid. Microbiome sequencing and analysis revealed that L. plantarum TY-S8 significantly increased the proportions of Lactobacillus johnsonii and Limosilactobacillus reuteri. Additionally, metabolomic analysis of fecal and blood samples indicated that the differential metabolites among the three groups were primarily indole derivatives, such as indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indole-3-acetaldehyde (IAAld), which are involved in the tryptophan metabolism pathway. Notably, there is a clear correlation between the key bacterial strains and these differential metabolites. At last, fecal microbiota transplantation (FMT) was performed to confirm that the ameliorative effect of L. plantarum TY-S8 on the hyperuricemic mice is primarily mediated by the regulation of gut microbiota and tryptophan metabolites. In conclusion, L. plantarum TY-S8 exerts probiotic effects on hyperuricemic mice through multiple pathways. In particular, it alleviates intestinal inflammation by regulating tryptophan metabolism, thereby effectively promoting uric acid metabolism, which highlights its potential value in the intervention of HUA.}, } @article {pmid41632073, year = {2026}, author = {Kaštovská, E and Choma, M and Čapek, P and Kaňa, J and Tahovská, K and Čapková, L and Kopáček, J}, title = {Contrasting nutrient retention in alpine soils: the role of soil microbiome in phosphorus and nitrogen mobility in scree and meadow environments.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiag008}, pmid = {41632073}, issn = {1574-6941}, abstract = {Alpine catchments encompass heterogeneous soil habitats with varying roles in nutrient cycling. While undeveloped till soils in scree areas are hotspots for nitrate and phosphate leaching, vegetated alpine meadow soils rather efficiently retain nutrients. This study examines the role of microbial communities in nutrient mobilization and retention, beyond the effects of abiotic soil properties. We compared the chemical, microbial, and functional characteristics of scree and meadow soils in four high-elevation catchments of the Tatra Mountains in Central Europe. Despite their lower organic matter content and microbial biomass, scree soils exhibited high concentrations of mobile nitrate and phosphate, low phosphate sorption ability, and significantly greater phosphorus leaching. Their microbiomes were distinct and enriched with pioneer taxa, including lichenized fungi, oligotrophic bacterial lineages (e.g., AD3 and Eremiobacteria), and saprotrophic fungi that specialize in the recycling of microbial necromass. These microbiomes exhibited high biomass-specific activities related to nutrient mobilization. In contrast, meadow soils supported larger microbial communities dominated by fungi with strong plant associations and functional traits that enhance nutrient retention. Our findings demonstrate that soil microbiota actively control nitrogen and phosphorus mobility by acting as either accelerators (in vegetation-free scree areas) or buffers (in meadows) of nutrient leaching from alpine soils.}, } @article {pmid41632030, year = {2026}, author = {Zhang, H and Li, Z and Xiao, Y and Bian, J and He, C and Liu, C and Gong, L and Han, L and Liu, Z and Wang, M}, title = {Gut Microbiota-Derived Anandamide Mediates the Therapeutic Effects of Urolithin A on Alcohol-Induced Cognitive and Social Dysfunction via CB1R-DRD2-RAP1 Signaling Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e08048}, doi = {10.1002/advs.202508048}, pmid = {41632030}, issn = {2198-3844}, support = {CARS-07-E-2//financial support provided by the China Agriculture Research System/ ; 32001701//Natural Science Foundation of China/ ; }, abstract = {Chronic alcohol consumption disrupts the gut microbiome, exacerbating alcohol-induced cognitive and social dysfunction (AICSD), which constitutes a primary etiology of early-onset dementia. Urolithin A (UA) has been well-reported as an effective intervention for neurodegenerative diseases. However, the protective efficacy of UA against AICSD, and its underlying mechanisms remain largely elusive. First, our study demonstrates that UA significantly enhances work memory (60.43%), short-term memory (12-fold), long-term memory (50.32%), social ability (10-fold), and social novelty (12-fold), while concurrently reducing synaptic impairments and neuroinflammation. Moreover, UA restores AICSD by upregulating the dopamine D2 receptor (DRD2) via RAP1 signaling. Furthermore, antibiotic treatment and fecal microbiota transplantation experiments confirm the causality between the host microbiota and behavioral alterations. Treatment with UA-enriched Bacteroids sartorii and Parabacteroids distasonis, or their derived endocannabinoid-anandamide (AEA), also ameliorates AICSD. Finally, AEA inhibits the Rap1 signaling through cannabinoid receptor 1 (CB1R) and DRD2 interaction, eventually ameliorating AICSD. Collectively, our study elucidates that microbiota-derived AEA mediates the therapeutic effects of UA on AICSD through the CB1R-DRD2-RAP1 signaling axis, providing valuable insights for UA and microbiome-targeted endocannabinoid interventions against AICSD.}, } @article {pmid41513858, year = {2026}, author = {Quiles, KR and Shao, FZ and Johnson, WE and Chen, F}, title = {Epithelial remodeling and microbial dysbiosis in the lower respiratory tract of vitamin A-deficient mouse lungs.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4663}, pmid = {41513858}, issn = {2045-2322}, abstract = {UNLABELLED: The World Health Organization identified vitamin A deficiency (VAD) as a major public health issue in low-income communities and developing countries, while additional studies have shown dietary VAD leads to various lung pathologies. Once believed to be sterile, research now shows that transient microbial communities exist within healthy lungs and are often dysregulated in patients suffering from malnourishment, respiratory infections, and disease. The inability to parse vitamin A-mediated mechanisms from other metabolic mechanisms in humans with pathogenic endotypes, as well as the lack of data investigating how VAD affects the lung microbiome, remains a significant gap in the field. To address this unmet need, we compared molecular, metatranscriptomic, and morphometric data to identify how dietary VAD affects the lung as well as the lung microbiome. Our research shows structural and functional alterations in host-microbe-diet interactions in VAD lungs compared to vitamin A-sufficient (VAS) lungs; these changes are associated with epithelial remodeling, a breakdown in mucociliary clearance, microbial imbalance, and altered microbial colonization patterns after 8 weeks of vitamin A deficient diet. These findings confirm vitamin A is critical for lung homeostasis and provide mechanistic insights that could be valuable for the prevention of respiratory infections and disease.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-34926-z.}, } @article {pmid41507840, year = {2026}, author = {Missa, KF and Diallo, K and Tuo, KJ and Bla, KB and Amoikon, TL and Gboko, KDT and Didia, AM and Kovalenko, G and Gragnon, BG and Ngoi, JM and Goodfellow, I and Wilkinson, R and Awandare, G and Bonfoh, B}, title = {Genomic diversity of SARS-CoV-2 carriage in a cohort of schoolchildren in Côte d'ivoire during COVID-19 pandemics: insights from pre-delta emergence.}, journal = {BMC infectious diseases}, volume = {26}, number = {1}, pages = {261}, pmid = {41507840}, issn = {1471-2334}, abstract = {BACKGROUND: After the first case of COVID-19 was reported in Côte d’Ivoire in March 2020, the virus spread significantly, with several epidemic waves. During a carriage study conducted from November 2020 to April 2021 to examine the oropharyngeal microbiome of school children, the presence of several other pathogens was investigated. This study characterised the diversity of SARS-CoV-2 detected in a cohort of school children in Côte d’Ivoire.

METHODS: Oropharyngeal swabs from participants in Korhogo (n = 37) and Abidjan (n = 39) were analysed. RNA was extracted from the samples, followed by RT-qPCR detection of Coronaviruses. Sequencing was done on an Oxford Nanopore platform and data analysed in GISAID.

RESULTS: Out of 445 samples collected, 15 (3.37%; 5 in Abidjan and 10 in Korhogo) tested positive for SARS-CoV-2 and were sequenced. Genomic coverage of over 70% was obtained for 12 genome sequences (80%). There was a significant difference in SARS-CoV-2 carriage over season per sampling visit (p < 0.05). The variants identified were of type Eta and Beta, including variant of concern (VOC) B.1.351 (6.7%), Variants of Interest (VOI) B.1.525 (60%) and other unclassified lineages B.1.1.318 (6.7%), A.19 (13,3%) and A.27 (13,3%). D614G mutation (n = 11, 73,33%) located on the S gene was the most common, followed by the T205I (n = 8, 53,33%) located on the N gene in this collection of genomes.

CONCLUSIONS: This study highlights the diversity of SARS-CoV-2 that circulated in a cohort of children in Côte d’Ivoire and reports carriage of the A.19 lineage, a variant which circulated more frequently in West Africa during the study period.

CLINICAL TRIAL NUMBER: Not applicable.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12374-4.}, } @article {pmid41486108, year = {2026}, author = {Jiang, M and Qu, J and Cao, W and Zou, X and Liu, J and Li, M}, title = {Beauveria bassiana acts as a beneficial endophyte in tea crops, modulating microbial communities and metabolic pathways to enhance plant growth.}, journal = {BMC plant biology}, volume = {26}, number = {1}, pages = {214}, pmid = {41486108}, issn = {1471-2229}, support = {Nos. 32160026 and 32060038//the National Natural Science Foundation of China/ ; QianKeHe-ZK[2022]034//the Science and Technology Program of Guizhou Province/ ; [2020]9//the Talent Fund of Guizhou University/ ; 20230093904557141120//the Guizhou Dashahe Nature Reserve Management Bureau/ ; ZhongYanQianKe 2024XM16//Science and Technology Project of the China Tobacco Guizhou Industry Limited Liability Company/ ; }, abstract = {UNLABELLED: The entomopathogenic fungus Beauveria bassiana is renowned for its insecticidal characteristics; however, its capacity as a plant endophyte within tea plants remains incompletely elucidated. This study investigated the colonization of tea plant tissues by B. bassiana and its effects on tea plant growth. It was found that colonization via foliar as well as root application, particularly colonization that persisted in stems for more than 90 days, enhanced growth traits such as plant height, biomass accumulation, and root system development. The foliar spray method resulted in significant changes in the endophytic microbiome and plant metabolism. The colonization had a more significant effect on endophytic fungi than on endophytic bacteria, leading to an increase in the relative abundance of arbuscular mycorrhizal fungi (AMF) in root tissues and a decrease in the relative abundance of total plant pathogens in tea plant tissues. The colonization of tea plants by B. bassiana led to a dynamic reprogramming of secondary metabolism, with an early enhancement in brassinolide and flavonoids to promote growth and enhance antioxidant capacity. As colonization continued, higher levels of catechins and epicatechins supported long-term defense and functional quality. Moreover, the elevation in chorismate indicated enhanced metabolic flux toward defense-related compounds and growth-regulating pathways, contributing to improved plant growth and stress resistance. These results confirm B. bassiana’s ability to act as a versatile bioregulator, expanding our understanding of fungal-plant symbiosis and offering a sustainable method to improve tea cultivation through combined microbial-metabolic reprogramming.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-025-08004-5.}, } @article {pmid41631832, year = {2026}, author = {Biancheti, LM and Vilela, N and Gomes, E and Olsson, L}, title = {Whole-genome sequencing and annotation of Micrococcus luteus TG3.30 isolated from sugarcane plantation soil in São Paulo, Brazil.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0107325}, doi = {10.1128/mra.01073-25}, pmid = {41631832}, issn = {2576-098X}, abstract = {We report the complete genome sequence of Micrococcus luteus TG3.30, isolated from sugarcane soil in Brazil. The 2.58 Mb genome (GC 72.92%) was assembled from hybrid Illumina-Nanopore sequencing with 99.96% completeness, providing a high-quality resource for taxonomic and comparative genomic studies of this versatile actinobacterium.}, } @article {pmid41631824, year = {2026}, author = {Gao, L and Qiu, Y and Lin, X and Zhou, Y and Lin, Y and Hong, K and Wang, L and Shen, W and Zhang, Q}, title = {Co-occurrence network analysis reveals novel associations between the neonatal airway microbiome and bronchopulmonary dysplasia risk: an observational, population-based study.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0085725}, doi = {10.1128/msphere.00857-25}, pmid = {41631824}, issn = {2379-5042}, abstract = {UNLABELLED: To evaluate the association between respiratory tract microorganisms at birth and the subsequent development and severity of bronchopulmonary dysplasia (BPD) in preterm infants. This prospective cohort study enrolled 98 preterm infants (gestational age < 32 weeks, birth weight < 2,000 g). Tracheal aspirate samples were collected through endotracheal intubation within 2 h after birth. Using 16S rRNA sequencing, we characterized the airway microbiome and performed co-occurrence network analysis with compositionally robust methods. Among 98 preterm infants analyzed, the incidence of BPD was 68.4%, comprising 31 grade I, 20 grade II, and 16 grade III cases. Airway microbiota in infants with BPD exhibited distinct severity-stage patterns: Escherichia-Shigella and Streptococcus were significantly enriched in grade I, while Chryseobacterium increased markedly in grade III, accompanied by a significant reduction in Streptococcus. Microbial co-occurrence network analysis yielded three key insights. (i) Network complexity declined sharply with BPD severity, being sparsest in grade III. (ii) Distinct keystone taxa were identified across different groups: Acinetobacter and Fusobacterium in the non-BPD group; Brevundimonas and Fusobacterium in grade I; Fusobacterium and Acinetobacter at grade II and grade III. (iii) In a multivariable model adjusted for key clinical confounders, a higher microbial network density at birth was independently associated with a substantially reduced risk (OR = 0.12, P < 0.05). The ecological architecture of the neonatal airway microbiome at birth, defined by network complexity and keystone taxa, is associated with BPD severity. This highlights microbial network stability as a novel factor and ecological interactions as a target for future research.

IMPORTANCE: Bronchopulmonary dysplasia (BPD) remains the most common chronic lung disease in preterm infants. While its pathogenesis is incompletely understood, the role of the early respiratory microbe is increasingly recognized. Previous studies have largely focused on individual pathogenic taxa, overlooking the complex ecological interactions within microbial communities. Our analysis reveals that the architecture of microbial co-occurrence networks in the neonatal airway varies significantly with BPD severity. Notably, network complexity decreased markedly as BPD severity increased. We identified specific keystone taxa uniquely associated with disease outcomes, suggesting that microbial ecosystem stability rather than individual species may be a critical factor in BPD pathogenesis. These findings shift the focus from single microbes to the stability of the microbial ecosystem as a novel risk factor for severe BPD, offering new avenues for risk stratification and early intervention.}, } @article {pmid41631397, year = {2026}, author = {}, title = {Correction to "Polystyrene Microplastics Disrupt Vertical Transmission of the Breast Milk Microbiome, Impairing Early-Life Gut Colonization and Immune Development in Offspring".}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {3}, pages = {e71521}, doi = {10.1096/fj.202600412}, pmid = {41631397}, issn = {1530-6860}, } @article {pmid41631341, year = {2026}, author = {Gordon, N and Segal, LN and Wu, BG}, title = {Rethinking pneumonia in terms of the lung microbiome.}, journal = {Current opinion in pulmonary medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCP.0000000000001247}, pmid = {41631341}, issn = {1531-6971}, abstract = {PURPOSE OF REVIEW: This review aggregates, analyzes, and summarizes the current understanding of the lung microbiome as it relates to pneumonia. We will review the composition and function of a healthy lung microbiome and conceptualize dysbiosis associated with pneumonia. Finally, we discuss how the lung microbiome impacts the diagnosis, prognostication and pathogenesis, and recovery from pneumonia.

RECENT FINDINGS: The most tangible benefit of studying the lung microbiome has been the identification of pathogenic organisms in suspected pneumonia; however, as there is a growing body of evidence that suggest the lung microbiome is critical to pneumonia. Generally, detection of potential pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Escherichia coli can be found even when sampling the lung microbiome of healthy individuals, yet it is unclear what determines the transition from potential pathogens present as bystanders to pathogens driving the development of pneumonia. Analysis of the lung microbiome suggests that the loss of "oral commensals" (bacteria found in the oral microbiome) in the lower airways is associated with the development of pneumonia and may provide diagnostic and prognostic insights.

SUMMARY: The lung microbiome is a rich and dynamic ecosystem comprised of numerous bacterial, fungal, and viral taxa that may contribute to pneumonia pathogenesis. There is increasing evidence that the lung microbiome may provide insight into factors that determine the pathogenicity of respiratory microbes and the susceptibility of individuals to those pathogens.}, } @article {pmid41630848, year = {2026}, author = {Klasek, SA and Crants, JE and Frost, KE and Schroeder, BK and Rosen, CJ and Kinkel, LL}, title = {Organic amendments to potato soils inconsistently enrich yield-associated soil microbiota across growing regions of the continental US.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20595}, pmid = {41630848}, issn = {2167-8359}, mesh = {*Solanum tuberosum/growth & development/microbiology ; *Soil Microbiology ; *Microbiota ; *Soil/chemistry ; United States ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics/classification ; Fumigation ; }, abstract = {Plant health is regulated by complex consortia of soil microbes with growth-promoting and pathogenic functions. In potato production, various soil management practices are undertaken to boost yields and suppress diseases, but connections between these practices, soil microbiomes, and tuber yields have not been characterized across diverse growing regions. To identify growing practices and microbes associated with increased yields, we established four-year field trials across eight US sites from Oregon to Maine that consisted of controls, fumigations, organic amendments, and mustard incorporations. Amplicon sequencing of 16S ribosomal RNA (rRNA) genes and intergenic transcribed spacer (ITS) regions was used to investigate bacterial and eukaryotic soil microbiomes, respectively. Fumigation and organic amendment treatments increased tuber yields in 23% and 29% of treatments relative to controls. While soil treatments influenced both microbiome types differently across all field sites, eukaryotes were more sensitive than bacteria to all treatments. Across field sites, soil treatments impacted relative abundances of amplicon sequence variants (ASVs) to varying degrees, even among ASVs belonging to the same genus. Associations between ASVs and tuber yields similarly varied within genera, highlighting the lack of consistent yield-associated taxa across US growing regions. Nevertheless, forty-five "target ASVs" across nine bacterial and three fungal phyla were identified as both treatment-impacted and yield-associated within any particular field site. Models identified three of thirteen organic amendment scenarios and one of thirteen fumigation scenarios where increased relative abundances of specific target ASVs accounted for up to a 23% increase in tuber yields compared to control treatments. These ASVs were largely site-specific and not influenced by treatment-associated changes in soil nutrients or organic matter, highlighting complex relationships within field sites that require further study to achieve the goal of implementing sustainable, microbiome-informed potato production techniques.}, } @article {pmid41630783, year = {2026}, author = {Sachdeva, C and Prasad, SS and Shenoy, KR and Kudva, A and Badareesh, L and Veerabhadrappa, BS and Krishna, SM and Murali, TS}, title = {A longitudinal profiling of microbiome of diabetic foot ulcers shows functional role of microbial communities in wound worsening and chronicity.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100544}, pmid = {41630783}, issn = {2666-5174}, abstract = {Microbial communities in infected diabetic foot ulcers (DFUs) play a critical role in wound morbidity and healing outcomes. While cross-sectional studies that profile the microbial communities using culture-independent approaches are available, we conducted a longitudinal microbiome analysis of 30 diabetic individuals to elucidate the relationship between microbial composition, host factors, and wound healing trajectories. Using a 16S rRNA-based metagenomic approach, we characterized the core microbial communities associated with DFU. Alpha diversity analysis revealed significant differences between DFU microbiome from same individuals across visits, and between DFU and non-DFU cohorts, while no significant differences in beta diversity was observed. Core microbiome analysis identified Pseudomonas to be consistently present across all cohorts, higher abundance of Escherichia and Prevotella in DFU samples across visits while Acinetobacter and Morganella were predominant in non-DFU wounds. Healed DFUs were enriched in Alcaligenes and Corynebacterium while worsened DFUs showed increased abundance of Enterococcus and Serratia. In amputated individuals, Escherichia was found in high abundance, while Staphylococcus was reduced. DFU subjects with high HbA1c levels (7.3-14.9%) had higher abundance of Pseudomonas and Acinetobacter, while Prevotella and Escherichia were abundant in individuals with lower HbA1c (<7.2%). Functional predictive profiling of microbiome communities using MicrobiomeAnalyst showed significant differences between healed and worsened DFUs, especially related to genes with roles in wound healing, drug resistance, biofilm formation, tissue invasion and pathogenicity. Our findings provide insights into the microbial ecology of DFUs, while the longitudinal screening of microbes associated with DFU revealed microbial dynamics and their probable role on wound outcome.}, } @article {pmid41630692, year = {2026}, author = {Hu, X and Kong, F and Chen, J and Li, Z and Cai, Z and Kong, X}, title = {Microbiota in pancreatic ductal adenocarcinoma progression and therapy: The hidden players.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {41630692}, issn = {2542-5641}, abstract = {Pancreatic ductal adenocarcinoma (PDAC), the deadliest epithelial malignancy, is increasingly prevalent and contributes significantly to cancer-related mortality. Research over the past decade has demonstrated that microbiota may play a pivotal role in both PDAC oncogenesis and its resistance to chemotherapy. Emerging preclinical and clinical data highlight the impact of microbiota on therapeutic outcomes in PDAC patients. This review systematically explores the role and underlying mechanisms of microbiota in PDAC, with a particular focus on their clinical implications and translational potential in disease progression and therapeutic responses. Finally, this review addresses the potential of microbiome-based therapies to enhance the efficacy of PDAC treatments.}, } @article {pmid41630319, year = {2026}, author = {Yang, L and Li, L and Liang, B and Yu, J and Wang, J and Sun, F}, title = {Role of CD25 on resting Treg immune cell in mediating the effect of stearate biosynthesis microbiome pathway on lung adenocarcinoma.}, journal = {Medicine}, volume = {105}, number = {5}, pages = {e47505}, pmid = {41630319}, issn = {1536-5964}, support = {2020ZRQNB059//the fund of Southwest Medical University/ ; 2023ZD003//the fund of Southwest Medical University/ ; 2020LZXNYDJ44//the Luzhou City Science and Technology Bureau/ ; S202310632162//Provincial Innovation and Entrepreneurship Training Program for College Students/ ; }, mesh = {Humans ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Interleukin-2 Receptor alpha Subunit/metabolism/immunology ; *Gastrointestinal Microbiome/immunology ; *Lung Neoplasms/immunology/microbiology/genetics ; *Adenocarcinoma of Lung/immunology/microbiology/genetics ; Mendelian Randomization Analysis ; }, abstract = {Gut microbiota (GM) often influences the development of diseases by regulating the immune system. The causal relationship between GM and lung adenocarcinoma (LUAD) and whether it can be mediated by immune cells remains unclear. We conducted two-step, two-sample Mendelian randomization (MR) analyses. The data of GM, LUAD and immune cells for analysis were derived from publicly available genetic data. The causal relationship between GM and LUAD, as well as the mediation effect of immune cells in the association between GM and LUAD were estimated using inverse variance weighted, MR-Egger and weighted median. Sensitivity analyses were implemented with Cochran Q test, MR-Egger intercept test, MR-PRESSO. MR analyses determined the protective effects of PWY-5989 (stearate biosynthesis II bacteria and plants) on LUAD. In addition, CD25 on resting regulatory T cell (Treg) was negatively correlated with LUAD. Of note, the mediation MR illustrated that in the presence of CD25 on resting Treg, PWY-5989 can promote the risk of LUAD by inhibiting the expression of CD25 on resting Treg. The study suggested a causal relationship between PWY-5989 and LUAD, which may be mediated by CD25 on resting Treg.}, } @article {pmid41630095, year = {2026}, author = {White, P and Maybin, JA and Williams, EJ}, title = {Could the untapped potential of the reproductive tract microbiome hold the key to tackling heavy menstrual bleeding?.}, journal = {Reproduction (Cambridge, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/reprod/xaag018}, pmid = {41630095}, issn = {1741-7899}, abstract = {The well-studied role of the microbiome in gut physiology and pathology has led to revolutionary microbiome-targeted treatments, but the function of the reproductive tract microbiome is yet to be delineated. This underexplored avenue could shed light on historically neglected reproductive health symptoms such as heavy menstrual bleeding.}, } @article {pmid41629888, year = {2026}, author = {Luo, M and Xiao, X and Wu, Y}, title = {Impact of phototherapy on gut microbiota composition and function in neonates with hyperbilirubinemia: a metagenomic analysis.}, journal = {BMC pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12887-026-06531-0}, pmid = {41629888}, issn = {1471-2431}, support = {No. YTWS20210102//Science and Technology Funding Program of Yantian District Bureau of Science and Technology/ ; }, } @article {pmid41629832, year = {2026}, author = {Miyamoto, I and Shimizu, T and Hanamura, M and Tanaka, R and Kusahana, R and Nomoto, M and Sugaya, K and Nakagawa, Y and Gon, Y}, title = {Impact of proton pump inhibitor use on immune-related adverse events in patients with non-small cell lung cancer: a retrospective study.}, journal = {BMC cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12885-026-15646-7}, pmid = {41629832}, issn = {1471-2407}, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy; however, immune-related adverse events (irAEs) remain a critical concern. Proton pump inhibitors (PPIs) are frequently co-administered to patients with advanced lung cancer and PPI-induced alterations in the gut microbiota may impair immune responses, potentially affecting ICI efficacy and prognosis. However, the association between PPI use and irAE development remains unclear.

METHODS: We retrospectively analyzed 228 patients with advanced non-small cell lung cancer who received first-line ICI therapy between April 2017 and December 2024. The impact of baseline PPI use on the incidence of irAEs, classified as checkpoint inhibitor pneumonitis (CIP) or irAEs without CIP (non-CIP irAEs), was evaluated.

RESULTS: Multivariate logistic regression analysis showed a non-significant association between PPI use and the incidence of overall irAEs. (odds ratio [OR] = 0.625; 95% confidence interval [CI], 0.348-1.120; p = 0.117). Notably, PPI exposure was significantly associated with a reduced incidence of non-CIP irAEs (OR = 0.510; 95% CI, 0.274-0.947; p = 0.033), whereas no significant association was observed with the incidence of CIP. Median overall survival (OS) was shorter in the PPI-exposed group than in the PPI-unexposed group, but the difference was not statistically significant (16.7 vs. 24.7 months; p = 0.065). In multivariate Cox regression analysis, PPI exposure was not identified as an independent prognostic factor for OS (hazard ratio [HR] = 1.120; 95% CI, 0.768-1.634; p = 0.556). In contrast, the occurrence of non-CIP irAEs (HR = 0.574; 95% CI, 0.368-0.895; p = 0.014) was significantly associated with improved OS.

CONCLUSIONS: PPI use was potentially associated with a lower incidence of non-CIP irAEs, whereas no significant effect was observed for CIP. In contrast, PPI use was not an independent prognostic factor, suggesting that irAE occurrence is influenced by multiple factors beyond PPI use. This study highlights the importance of investigating the interplay between PPI exposure, irAE occurrence, and gut microbiome alterations.}, } @article {pmid41629813, year = {2026}, author = {Astudillo-Guerrero, C and Garrido, Á and Masferrer, D and Sepúlveda, C and Olavarría, L and Del Campo, R and Bravo-Sagua, R and Cubero, FJ and Salech, F and Thumala-Dockendorff, D and Urrutia, PJ and Quera, R and Bunout, D and Espinoza, R and Jorquera, G}, title = {Randomized, double-blind, placebo-controlled trial of fecal microbiota transplantation from young physically active donors to promote resilient aging: clinical trial protocol (ARMOR study).}, journal = {BMC geriatrics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12877-025-06920-7}, pmid = {41629813}, issn = {1471-2318}, } @article {pmid41629538, year = {2026}, author = {Moore, ER and Rahman, MM and Galella, JG and Sena, M and Joshi, B and Yaculak, A and Peipoch, M and Kan, J and Inamdar, S}, title = {Distinct changes in riparian sediment microbial communities with depth and time since dam removal.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-37708-3}, pmid = {41629538}, issn = {2045-2322}, support = {2023-67019-39835//U.S. Department of Agriculture/ ; }, abstract = {Microbes drive biogeochemical changes in ecosystems, including carbon (C) and nitrogen (N) cycling. Dam construction has altered riparian ecosystems worldwide, yet we know little about microbial community composition in riparian sediments and how it changes following dam removal and sediment/soil drainage. Here, we evaluate how riparian microbial communities change with increasing depth in the sediment profile for existing dams and over time following dam removal/breach and assess how various physico-chemical sediment properties influence microbial community composition. We studied microbial community structure for 12 riparian sites over a chronosequence of 0-234 years since dam breach. Sediment was collected every 0.3 m to a depth of 4 m. Aerobic taxa involved with N cycling (e.g., Nitrospirota) were dominant in surficial sediments, and increased in deeper sediments as time since dam breach increased. Anaerobic taxa implicated in C cycling (e.g., Bathyarchaeia, Anaerolineaceae) and iron reduction (e.g., Sva0485) were dominant in deeper, anoxic sediments, but declined the fastest post dam breach. These microbial trends provide insights into how riparian biogeochemical functions are impacted by dam inundation and the recovery and restoration of these ecosystems following dam removals.}, } @article {pmid41629533, year = {2026}, author = {Kaduwal, S and Stuart, EC and Auradkar, A and Washabaugh, S and Meyer, JR and Bier, E}, title = {A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population.}, journal = {npj antimicrobials and resistance}, volume = {4}, number = {1}, pages = {8}, pmid = {41629533}, issn = {2731-8745}, abstract = {Antibiotic resistance (AR) is an escalating public health threat, necessitating innovative strategies to control resistant bacterial populations. One promising approach involves engineering genetic elements that can spread within microbial communities to eliminate AR genes. Previously, we developed Pro-Active Genetics (Pro-AG), a CRISPR-based gene-drive-like system capable of reducing AR colony-forming units (CFU) by approximately five logs. Here, we advance this technology by integrating Pro-AG into a conjugative transfer system, enabling efficient dissemination of an anti-AR gene cassette between two bacterial strains. Additionally, we characterize a complementary homology-based deletion (HBD) process, a CRISPR-driven mechanism that precisely removes target DNA sequences flanked by short direct repeats. Our findings reveal that Pro-AG and HBD are differentially influenced by the bacterial RecA pathway and that HBD components can be delivered via plasmids or phages to selectively delete Pro-AG cassettes. This built-in safeguard prevents uncontrolled spread of a gene cassette and mitigates unanticipated side effects. These refinements enhance the efficiency and flexibility of Pro-AG, expanding its potential applications in microbiome engineering, environmental remediation, and clinical interventions aimed at combating antibiotic resistance. More broadly, this work establishes a proof-of-principle for microbiome engineering strategies that could be leveraged to improve health and restore ecological balance.}, } @article {pmid41629500, year = {2026}, author = {Levhar, N and Hadar, R and Braun, T and Shacham, H and Algavi, Y and Naamneh, R and Efroni, G and Agranovich, B and Abramovich, I and Talan Asher, A and Picard, O and Yavzori, M and Lahat, A and Yablecovitch, D and Kopylov, U and Denson, L and Borenstein, E and Eliakim, R and Ben-Horin, S and Amir, A and Haberman, Y}, title = {Fecal metabolic signals are associated with changes in microbiota and systemic metabolic pathways in Crohn's disease.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-38558-9}, pmid = {41629500}, issn = {2045-2322}, support = {758313//ERC/ ; 785/22//Israel Science Foundation/ ; 4361//Israel Science, Culture, and Sport/ ; 1165359//LITWIN IBD PIONEERS AWARDS/ ; 41/11//I-CORE program/ ; }, } @article {pmid41629499, year = {2026}, author = {Saddik, JN and Naguib, MM and Labib, LM and El-Gendy, AO and Molham, F}, title = {Nano-chitosan modified restorative materials suppress Streptococcus mutans biofilm and virulence gene expression.}, journal = {AMB Express}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13568-025-02004-2}, pmid = {41629499}, issn = {2191-0855}, } @article {pmid41629498, year = {2026}, author = {O'Leary, K}, title = {Babies share microbiomes at nursery.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41591-026-00006-6}, pmid = {41629498}, issn = {1546-170X}, } @article {pmid41629364, year = {2026}, author = {Spörri, L and Studer, JM and Kreuzer, M and Rotzetter, J and Schärer, D and Largiadèr, CR and Jaggi, D and Zinkernagel, MS and Zysset-Burri, DC}, title = {Linking the microbiome to the complement system in geographic atrophy.}, journal = {NPJ genomic medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41525-026-00550-7}, pmid = {41629364}, issn = {2056-7944}, support = {CF10000044-EPFL SCR0237812//Foundation Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique Fédérale de Lausanne), Lausanne, Switzerland/ ; CF10000044-EPFL SCR0237812//Foundation Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique Fédérale de Lausanne), Lausanne, Switzerland/ ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the aged population with the late stage geographic atrophy (GA). Risk factors for AMD include age, genetic variants in the complement system, nutritional factors, and alterations in the gut microbiome (GM). To identify taxonomic and functional differences in the microbiome associated to disease pathophysiology and genetic risk factors, this study investigated the GM and the ocular surface microbiome (OSM) of GA patients compared to healthy controls by whole-metagenome shotgun sequencing. 16 AMD-associated SNPs were genotyped from blood samples using TaqMan assays and Sanger sequencing. While GA patients showed differences in the GM, and altered metabolic pathways including inosine 5'-phosphate degradation, NAD salvage, and ketogenesis, no alterations in the OSM were found. Genetic analysis associated SNP rs1061170 in the complement factor H gene with GA. These findings suggest that microbial alterations may contribute to GA through inflammation and oxidative stress.Registry: ClinicalTrials.gov, NCT02438111, Registration date: 28 April 2015, and NCT04658238, Registration date: 01 December 2020.}, } @article {pmid41629309, year = {2026}, author = {Jastrząb, R and Małecki, A and Kmiecik-Małecka, E and Gorzkowska, A and Krzystyniak, B and Kubas, K and Widłak-Kargul, J and Wolman, D and Matkiewicz, K and Nowacka-Chmielewska, M and Liśkiewicz, D and Grabowska, K and Grabowski, M and Pondel, N and Początek, G and Kłodowska, G and Mytych, J}, title = {Probiotic Lactiplantibacillus plantarum OL3246 supports healthy aging by enhancing quality of life, reducing inflammation, and modulating gut microbiota: a pilot study.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00338-0}, pmid = {41629309}, issn = {2731-6068}, abstract = {Aging is accompanied by low-grade intestinal inflammation, shifts in gut microbiota, and impaired oxidative balance. Probiotic supplementation has been proposed to mitigate these processes, yet evidence in elderly populations remains limited. In this pilot trial, older adults received oral Lactiplantibacillus plantarum OL3246 or placebo, with assessments including fecal calprotectin and zonulin as markers of intestinal inflammation, systemic oxidative stress parameters, self-reported quality of life and mood, and gut microbiome composition analyzed by sequencing and functional profiling. L. plantarum OL3246 supplementation was well tolerated and associated with consistent improvements across clinical, biochemical, and microbial measures. Participants reported enhanced quality of life and mood, while fecal calprotectin levels declined, indicating reduced intestinal inflammation. Moreover, oxidative stress markers improved with lower AOPP, stabilization of SOD, and restoration of redox balance. Microbiome analyses showed greater diversity and enrichment of health-associated taxa. These findings indicate that Lactiplantibacillus plantarum OL3246 may support healthy aging.}, } @article {pmid41629169, year = {2026}, author = {Liu, T and Lai, CH and Wu, YW and Lee, CH and Chen, PL and Wang, JY and Hsieh, MH and Hu, PH and Jeng, SL and Chuang, YC and Chuang, CH and Wang, JL and Kuo, CW}, title = {Comparative analysis of clinical outcomes and short-term treatment response of sputum microbiome between eosinophilic and non-eosinophilic COPD acute exacerbation.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2026.01.004}, pmid = {41629169}, issn = {1995-9133}, abstract = {BACKGROUND: Eosinophilic AECOPD is a specific phenotype; however, the clinical outcomes and the short-term changes in sputum microbiome remain unclear.

METHODS: We retrospectively included AECOPD patients admitted to National Cheng Kung Universal Hospital from January 2013 to December 2022. The primary outcome was respiratory failure rate. In addition, self-expectorated sputum was prospectively collected on days 1 and 5 of hospitalization between June 2020 and May 2021, and 16S rRNA gene segments (V3-V4) were amplified for sputum microbiome identification. Eosinophilic AECOPD were defined as blood eosinophils (bEOS) exceeding 2 % at admission.

RESULTS: From the analysis of 202 AECOPD hospitalizations, patients with bEOS ≥2 % had shorter hospital stays and respiratory failure days (β-coefficient: 2.98 and -3.86, P < 0.001 and = 0.049, respectively), a lower risk of respiratory failure and intensive care unit admission (odds ratio: 0.29 and 0.35, P = 0.007 and = 0.029, respectively). In a sub-cohort of 30 AECOPD patients undergoing sputum microbiome analysis, 12 had bEOS ≥2 %, a significant decrease in Shannon diversity at the phylum level after 5 days of treatment was observed only in the bEOS <2 % group. Moreover, the relative abundance of Proteobacteria increased after treatment in the patients with bEOS ≥ 2 % while a trend of decrease was observed in those with bEOS<2 %.

CONCLUSIONS: Patients with eosinophilic AECOPD demonstrate better short-term clinical outcomes. The sputum microbiota in the eosinophilic and non-eosinophilic patients also respond differently to the treatment for AECOPD.}, } @article {pmid41629027, year = {2026}, author = {Gao, Q and Wu, Y and Huang, J and Xu, S and Chen, R and Jiang, H and Huang, Y and He, Q and Wang, Y and Xiao, J and Cao, H}, title = {Chronic neonicotinoid exposure disrupts survival, development, digestive enzymes, and gut microbiome in honeybee queen larvae (Apis mellifera L.).}, journal = {Pesticide biochemistry and physiology}, volume = {218}, number = {}, pages = {106959}, doi = {10.1016/j.pestbp.2026.106959}, pmid = {41629027}, issn = {1095-9939}, mesh = {Animals ; Bees/drug effects/growth & development/microbiology ; *Neonicotinoids/toxicity ; *Gastrointestinal Microbiome/drug effects ; Larva/drug effects/growth & development/microbiology ; *Insecticides/toxicity ; Nitro Compounds/toxicity ; Guanidines/toxicity ; RNA, Ribosomal, 16S/genetics ; Thiazoles/toxicity ; }, abstract = {Honeybee queens (Apis mellifera L.) are essential for colony sustainability, most study mainly focused on the acute toxicity of chemical insecticides. This study investigated the chronic effects of three prevalent neonicotinoids on honeybee queen larvae development, digestive physiology, and gut microbiota. It was determined that exposure to elevated concentrations (10-40 mg/L) significantly increased larval mortality (up to 41.70%), which reduced both capping and emergence rates, with imidacloprid causing a 43.80% decline in emergence at 40 mg/L. Chronic exposure (1-25 mg/L) to clothianidin notably decreased birth weight by 11.40% and altered thoracic and abdominal morphometrics. Moreover, imidacloprid and clothianidin suppressed amylase activity by up to 94%, while acetamiprid enhanced it by nearly 60%. Additionally, 16S rRNA gene sequencing revealed significant shifts in gut microbiota composition, characterized by increased abundance of Firmicutes and decreased Bacteroidota, despite minor changes in overall diversity. Functional predictions indicated alterations in carbohydrate metabolism, amino acid metabolism, and membrane transport pathways. These findings demonstrate that chronic neonicotinoid exposure disrupts metabolic and microbial homeostasis in honeybee queen larvae, posing a serious threat to honeybee colony fitness, which is important and provides essential evidence for ecological risk assessment and the development of safer pesticide application strategies in apiculture and crop protection.}, } @article {pmid41629015, year = {2026}, author = {Sun, L and Gao, J and Tan, Y and Xia, Y and Wang, R and Liu, R and Zhang, X and Yan, X and Huang, L}, title = {Biocontrol of Apple Valsa Canker by Bacillus sp. H12 and modulation of the apple seedlings microbiome.}, journal = {Pesticide biochemistry and physiology}, volume = {218}, number = {}, pages = {106946}, doi = {10.1016/j.pestbp.2026.106946}, pmid = {41629015}, issn = {1095-9939}, mesh = {*Malus/microbiology/growth & development ; *Plant Diseases/microbiology/prevention & control ; *Seedlings/microbiology/growth & development ; *Ascomycota ; *Microbiota ; *Bacillus/physiology ; Disease Resistance ; Soil Microbiology ; }, abstract = {Apple Valsa Canker (AVC), caused by the fungal pathogen Cytospora mali, is the most devastating stem disease in East Asia apple production systems. As an eco-friendly alternative to chemical control, biological control strategies have attained prominence for mitigating environmental pollution and preventing pathogen resistance. In this study, a soil-derived bacterial strain significantly inhibited AVC and promoted plant growth. The strain was identified as Bacillus amyloliquefaciens using combined morphological and molecular characterization and designated as H12. The bacterium directly induces abnormal branching of C. mali hyphae, cytoplasmic leakage, and cell wall rupture, ultimately leading to mycelia death. H12 exhibits strong control efficacy against AVC on in vitro branches and the leaves of tissue-cultured seedlings. Notably, H12 upregulates immune-related gene expression in apple, enhances reactive oxygen species (ROS) accumulation, and increases callose deposition. Microbiome sequencing indicates that H12 modulates the structure of the apple phyllosphere bacterial community, enriches beneficial microorganisms, and enhances host resistance. Furthermore, the strain achieves a 55.56% disease control efficacy in field trials, demonstrating its potential for practical application as a promising microbial agent. In summary, H12 has dual functions, directly inhibiting pathogenic fungi and inducing host resistance, providing theoretical and practical support for the green management of AVC.}, } @article {pmid41629012, year = {2026}, author = {Zhou, X and Qing, Y and Wang, Y and Deng, H and Wang, J and Kuang, M and Luo, X and Zhao, C and Sun, Z and Wang, Y and Yang, L and Ding, W}, title = {Identification and validating native biocontrol bacteria Bacillus strain MZ3-12 against bacterial wilt.}, journal = {Pesticide biochemistry and physiology}, volume = {218}, number = {}, pages = {106943}, doi = {10.1016/j.pestbp.2026.106943}, pmid = {41629012}, issn = {1095-9939}, mesh = {*Bacillus/physiology/genetics/isolation & purification ; *Plant Diseases/microbiology/prevention & control ; Rhizosphere ; *Nicotiana/microbiology/growth & development ; Soil Microbiology ; *Ralstonia solanacearum/growth & development ; *Biological Control Agents ; Siderophores/metabolism ; Pest Control, Biological ; RNA, Ribosomal, 16S/genetics ; Microbiota ; }, abstract = {Tobacco bacterial wilt is a major threat to sustainable tobacco agriculture. To identify native biocontrol agents for managing this disease, this study integrated rhizosphere microbiome profiling with functional screening. Comparative 16S rDNA amplicon sequencing showed that disease-affected soils had higher abundances of pathogen-linked genera, while healthy soils were enriched in beneficial microbes such as Bacillus and Streptomyces. Then, we isolated thirty potential bacteria from healthy rhizospheres soil, and investigated the effect of screening potential bacteria on R. solanacearum growth, siderophore secretion, protease activity, and cellulase activity. Among these bacteria, four potential biocontrol bacteria were screened, including three Bacillus MZ3-12, MZ4-13, MZ9-28, and a Glutamicibacter MZ8-15. These strains significantly inhibited R. solanacearum growth and secreted highly active proteases, cellulases, and siderophores. They also promoted tobacco growth, increased plant dry weight and fresh weight, and enhanced the expression levels of genes related to the salicylic acid, jasmonic acid, and ethylene pathways. Furthermore, MZ3-12 displays considerable control effect on tobacco bacterial wilt in greenhouse and field conditions. Our results confirm that combining microbiome analytics with culture-based screening is an effective way to identify environment-friendly biocontrol agents, highlighting the role of Bacillus MZ3-12 in maintaining rhizosphere health and managing tobacco bacterial wilt.}, } @article {pmid41628857, year = {2026}, author = {Theodosiou, A and Bogaert, D and Cleary, D and Fady, PE and Feehily, C and Gilbert, J and Greenhough, B and Guardabassi, L and Hall, L and Harman, T and Kuijper, E and Lebeer, S and Lorimer, J and Spector, T and Jones, C}, title = {Microbiome research in practice: priorities for clinical translation and impact.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2026.01.021}, pmid = {41628857}, issn = {1469-0691}, abstract = {BACKGROUND: Rapid advances in microbiome science have sparked clinical and commercial enthusiasm for interventions, yet translation into practice risks outpacing both mechanistic understanding and the infrastructure required for safe adoption.

OBJECTIVES: To outline a coordinated research, clinical, social, and policy agenda for advancing safe, effective, and equitable microbiome-based interventions.

SOURCES: We convened an interdisciplinary Royal Society-funded expert workshop (Leeds, UK, October 2024) with international leaders in microbiome science, clinical trials, regulation, and social science. Thematic analysis of workshop discussions and written contributions identified priority domains for translation.

CONTENT: Three intersecting priorities emerged: scientific credibility, practical viability, and stakeholder engagement. Scientific credibility demands investment in multiomic and strain-level characterisation of host-microbiome interactions on a large scale, benchmarking of clinical and microbiological endpoints, and harmonisation of trial conduct and reporting. Clinical adoption requires fit-for-purpose regulation, diversified investment to address funding bottlenecks, and coordinated capacity building. Meaningful stakeholder engagement with clinicians, patients, policymakers, and the public is essential to foster confidence, develop clinically relevant research questions, and ensure equitable implementation of any new technology.

IMPLICATIONS: To realise the clinical impact of microbiome interventions, sustained collaboration across disciplines is essential. This Review offers a translational roadmap and actionable priorities to accelerate safe, effective, and equitable microbiome-based interventions - ensuring the field fulfils its clinical potential and delivers real-world impact.}, } @article {pmid41628782, year = {2026}, author = {Majumdar, S and Samaiya, PK and Gupta, SK and Krishnamurthy, S and Prajapati, SK}, title = {Aging and neuropathic pain: Mitochondria-to-glia cascade, system mechanisms, and therapeutic strategies.}, journal = {Ageing research reviews}, volume = {116}, number = {}, pages = {103042}, doi = {10.1016/j.arr.2026.103042}, pmid = {41628782}, issn = {1872-9649}, abstract = {Neuropathic pain (NP) creates a severe pathological condition that primarily affects elderly people because of their accumulated neurobiological changes that make them more susceptible to persistent pain. The aging process leads to multiple mechanisms that combine neurodegeneration with immunosenescence and mitochondrial dysfunction with impaired autophagy and glial priming, and ion channel dysregulation to create a nociceptive environment. This review examines how mitochondrial breakdown and dysfunctional autophagy, and ion channel disturbances with glial cell activation form a interconnected system which makes older people more prone to NP. The review also examines how the neuro-immune-metabolic and gut-brain axis maintain persistent pain across the lifespan while discussing its cellular pathology. Preclinical research shows that aged models develop more severe NP symptoms, yet clinical evidence reveals distinct diagnostic and therapeutic challenges that affect older adults. The review presents current treatment strategies which include mitochondrial protectants and autophagy enhancers together with immunomodulators and microbiome-based interventions, and gene therapies to develop appropriate multimodal therapies for different age group. Further, it combines mechanistic knowledge with translational viewpoints to demonstrate the immediate requirement for treating NP as a geroscience challenge to develop better pain management strategies for older adults.}, } @article {pmid41628747, year = {2026}, author = {Vohra, V and Dhanawat, M and Chalotra, R and Bhushan, B and Garima, and Girdhar, J and Madar, IH and Singh, R and Fareed, M}, title = {Shaping immunotherapy through the tumor microenvironment: Translational perspectives.}, journal = {Critical reviews in oncology/hematology}, volume = {220}, number = {}, pages = {105169}, doi = {10.1016/j.critrevonc.2026.105169}, pmid = {41628747}, issn = {1879-0461}, abstract = {The tumour microenvironment (TME) is a simply orchestrator of cancer progression and a principal mediator of resistance to immunotherapy. This review explains the complex immunosuppressive ecosystem of the TME, highlighting mechanisms of immune evasion including the recruitment of regulatory T cells, myeloid-derived suppressor cells, and tumour-associated macrophages; metabolic competition via the Warburg effect and indoleamine 2,3-dioxygenase activity and hypoxia-driven upregulation of immune checkpoints such as PD-L1. We synthesize translational strategies designed to reprogram this hostile niche, moving beyond immune checkpoint inhibitor monotherapy. These approaches encompass metabolic targeting (e.g., MCT1/4, IDO inhibitors), stromal disruption (e.g., CAF inhibition, vascular normalization), and advanced cellular engineering, such as CAR-T cells resistant to exhaustion and cytokine-secreting constructs. We underline the synergy of combination therapies, integrating checkpoint blockade with chemotherapy, radiotherapy, oncolytic viruses, and adenosine pathway antagonists to augment immunogenic cell death and cytotoxic T lymphocyte infiltration. The predictive value of biomarkers including tumour mutational burden, microsatellite instability, and the spatial architecture of tumour-infiltrating lymphocytes is critically appraised. Furthermore, the review explores emerging frontiers such as neoantigen-based vaccines, microbiome modulation, and bispecific antibodies, underscoring their capacity to convert immunologically "cold" tumours into "hot", responsive lesions. By bridging preclinical insights with clinical trial evidence, this review speculates that the precise modulation of the TME is indispensable for unlocking durable, broad-spectrum antitumor immunity and defining the next generation of cancer immunotherapies.}, } @article {pmid41628729, year = {2026}, author = {Romeiro, K and Siqueira, JF and Rôças, IN and Gominho, LF and Villela, LB and Brisson-Suárez, K and Carmo, FL}, title = {Root Canal Microbiome in Patients Undergoing Antineoplastic Therapy: a Next-Generation Sequencing Study.}, journal = {Journal of endodontics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.joen.2026.01.020}, pmid = {41628729}, issn = {1878-3554}, abstract = {INTRODUCTION: This study compared the intracanal microbiome of teeth with apical periodontitis in oncological and healthy patients using 16S rRNA gene-based next generation sequencing.

METHODS: Root canal samples were taken from 46 teeth with pulp necrosis and primary apical periodontitis (23 from oncological patients and 23 from healthy controls). DNA was extracted and sequenced using the Illumina MiSeq platform targeting the V3-V4 region of the 16S rRNA gene. Bioinformatics processing was conducted using QIIME2 and DADA2. Alpha and beta diversity analyses, genus-level abundance comparisons, and indicator species analyses were performed.

RESULTS: After quality filtering, 3,307,822 sequence reads were retained, averaging 68,912.96 reads/sample, and resulting in 3,241 unique amplicon sequence variants. Oncological patients exhibited significantly higher bacterial richness (p = 0.01), while Shannon diversity showed no significant difference between groups. Beta diversity analysis (Bray-Curtis, MDS stress = 0.14) did not reveal significant differences between groups. Indicator species analysis identified some specific taxa more associated with oncological patients, including the candidate endodontic pathogens Prevotella, Selenomonas, Alloprevotella, Rothia, and Fretibacterium.

CONCLUSIONS: The root canal microbiome of oncologic patients with apical periodontitis was broadly similar to that of healthy controls. The oncologic group showed higher species richness, but no significant differences in the overall bacterial diversity or community structure.}, } @article {pmid41628665, year = {2026}, author = {Hartog, M and Korsten, SGPJ and Popa, CD and Pelle, T and Gavriilidou, A and van den Bemt, BJF and Willemsen, LEM and Koenders, MI and Vermeiden, JPW and Smidt, H and van den Ende, CHM}, title = {Effectiveness of Sustained Release Calcium Butyrate on the microbiome and clinical burden in osteoarthritis of the hand: a proof-of-concept placebo-controlled randomized trial.}, journal = {Osteoarthritis and cartilage}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.joca.2026.01.630}, pmid = {41628665}, issn = {1522-9653}, abstract = {OBJECTIVE: This study primarily assessed effects of Sustained Release Calcium Butyrate (SRCaBu) on gut microbiome composition and function in hand OA patients. Secondary objectives included its impact on hand pain and function, markers of intestinal permeability, systemic inflammation, and safety.

METHOD: A participants, researchers, and pharmacy assistants blinded, randomized, placebo-controlled proof-of-concept trial compared 600mg daily dose SRCaBu with placebo over 4-5 weeks. The primary domain was microbiome composition and function, assessed via fecal 16S rRNA gene- and metagenome sequencing, and short-chain fatty acid analysis. Secondary outcomes included parameters for intestinal barrier function, clinical outcomes and adverse events. Primary analyses followed the per-protocol principle.

RESULTS: 35 participants (mean age 62.5±6.9 years, 82% female) were randomized to SRCaBu (n=18) or placebo (n=17). Two SRCaBu participants discontinued treatment for pre-existing liver impairment and need for pain medication. SRCaBu tended to reduce the relative abundance of Streptococcus (regression coefficient:-0.67, 95%CI:-1.46,0.13) and Faecalibacterium -0.38(-0.83,0.07), increase fecal acetate (median between-group difference: 9.5, [IQR]: [-3.5,22.5]), and was inversely associated with microbial LPS biosynthesis- and virulence genes. SRCaBu increased toxin-related genes, primarily from beneficial Blautia species, without association to pathogenicity. SRCaBu did not significantly affect biomarkers of intestinal permeability, inflammation, or clinical outcomes. Adverse events were mild and comparable between groups.

CONCLUSION: Our study yielded indicative findings that SRCaBu supports microbiome health in patient with hand OA by improving compositional and functional characteristics of the microbiome. Although the treatment was well tolerated, effects on serum markers for intestinal barrier function and systemic inflammation, and clinical symptoms remained unclear.

TRIAL REGISTER: 2020-001071-33 / NL73382.091.21.}, } @article {pmid41627741, year = {2026}, author = {Castañeda, S and Ramírez, JD and Poveda, C}, title = {Microbiome Profiling in Chagas Disease: Sample Collection, Sequencing, and Analysis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3013}, number = {}, pages = {265-297}, pmid = {41627741}, issn = {1940-6029}, mesh = {*Chagas Disease/microbiology/parasitology ; Animals ; Mice ; Trypanosoma cruzi ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Computational Biology/methods ; High-Throughput Nucleotide Sequencing/methods ; *Microbiota ; Sequence Analysis, DNA/methods ; Metagenomics/methods ; }, abstract = {Chagas disease, caused by Trypanosoma cruzi, leads to chronic cardiac and gastrointestinal complications. Emerging evidence shows the gut microbiome plays a key role in modulating disease severity, with shifts in microbial composition influencing immune responses and metabolic pathways. Here, we describe a workflow for microbiome analysis in T. cruzi-infected mice. Methods included sample collection from feces and gastrointestinal tissues, DNA extraction, sequencing, and quality control. Then, we outline bioinformatic analyses covering taxonomic profiling, diversity assessment, and microbial network construction. Finally, protocols for functional prediction tools are also included to explore microbial capabilities and the identification of signatures associated with disease progression.}, } @article {pmid41627479, year = {2026}, author = {Zhou, ZY and Liu, X and Gao, F and Wang, ML and Wang, JH and Cui, JL}, title = {Composition characterization of the culturable endophytic fungi in roots and their antagonistic activity against root rot of Astragalus mongholicus.}, journal = {Archives of microbiology}, volume = {208}, number = {4}, pages = {178}, pmid = {41627479}, issn = {1432-072X}, support = {2025ZYYA021//Research Project on Traditional Chinese Medicine of the Health Commission of Shanxi Province/ ; }, mesh = {*Plant Roots/microbiology ; *Endophytes/isolation & purification/classification/physiology/genetics ; *Astragalus Plant/microbiology ; *Plant Diseases/microbiology/prevention & control ; Fusarium ; *Antibiosis ; *Fungi/classification/isolation & purification/genetics/physiology ; Ascomycota/isolation & purification/classification/genetics/physiology ; Phylogeny ; Alternaria ; }, abstract = {This study investigates the spatiotemporal distribution, diversity, and biocontrol potential of culturable endophytic fungi in the healthy roots of cultivated and wild Astragalus mongholicus (CA and WA), aiming to develop a microbiome-driven strategy for sustainable root rot management. A total of 304 endophytic fungal strains were isolated from roots of CA and WA, with 61 morphologically distinct representative strains identified via ITS sequencing. These strains belonged predominantly to Ascomycota (98.36%) and included 21 genera, with Fusarium (43.28%), Paraphoma (25.25%), and Alternaria (12.46%) as dominant genera. WA exhibited higher fungal diversity and evenness than CA, with community composition varying significantly by host age and cultivation status. Among the isolates, 177 strains (53 genera) showed antagonistic activity (≥ 30% inhibition rate) against root rot pathogens (F. acuminatum, F. solani, and F. oxysporum). Notably, Penicillium chrysogenum CA4-3 exhibited 78.96% inhibition against F. solani, while Paraphoma radicina CA3-15 displayed 70.23% inhibition against F. oxysporum. Bioactive strains were concentrated in 2 to 4-year-old CA roots, with Fusarium, Paraphoma, and Alternaria being the primary contributors. Mechanistic studies revealed that these fungi inhibited pathogens via secreted metabolites (causing mycelial deformation) or niche competition. The composition of endophytic fungi in A. mongholicus roots is dynamic and influenced by host development and cultivation practices. The antifungal active strain P. chrysogenum CA4-3 and P. radicina CA3-15 may possess potential value in controlling pathogenic fungi.}, } @article {pmid41627465, year = {2026}, author = {Kumar, N and Das, J and Vanangamudi, M and Mojgani, N and Islam, A and Sridhar, SB and Sharma, H and Kumar, S and Panigrahy, UP and Mantry, S and Sharma, M and Ramzan, M and Chaudhary, P and Ashique, S}, title = {Modulating drug response through the gut microbiome: pathways to precision therapy.}, journal = {Archives of microbiology}, volume = {208}, number = {4}, pages = {163}, pmid = {41627465}, issn = {1432-072X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Precision Medicine ; Pharmaceutical Preparations/metabolism ; Bacteria/metabolism/drug effects/genetics/classification ; Metabolomics ; Animals ; }, abstract = {The mutual association formed between the gut flora and the biological host is pivotal, mainly for drug action. Various examination has spotlighted the potential consequences of the gut microbiome on drug efficacy, revealing its role in controlling metabolism in the body. Furthermore, reciprocal engagement has been examined to investigate how pharmaceutical agents influence the composition of the gut microbiome. This paper emphasizes the intricate relationship between pharmacology and environmental microbiology, directing the extensive significance of pharmaceutical agents on health by controlling the gut microbial consortium. One main highlight of this review is to determine the differences observed in populace as a result of drugs, which is a crucial component in boosting personalized treatment approaches and intensifying therapeutic findings. Apart from their function in drug metabolization, the gut microbiota is disclosed as a source of metabolic products that can alter drug action. These microbially-derived metabolites could notably effect drug results and changes the body's physical mechanisms. The investigation suggests utilizing metabolomics to disclose the complications of gut microbiota-drug interactions. Several latest analytical strategies provide an effective tool for deciphering the complicated association among microbiome-generated fragments and pharmaceutical products, providing detailed understanding into this interesting connection.}, } @article {pmid41627460, year = {2026}, author = {Do, TH and Dao, TK and Pham, TTN and Nguyen, MH and Nguyen, TQ and To, LA and Nguyen, TVH and Phung, TBT}, title = {Understanding the bacteriome, phageome and phage-associated bacteriome in healthy Vietnamese children under two years of age.}, journal = {Archives of microbiology}, volume = {208}, number = {4}, pages = {167}, pmid = {41627460}, issn = {1432-072X}, support = {DTDLCN.63/22//Ministry of Science and Technology/ ; }, mesh = {Humans ; Infant ; Vietnam ; *Gastrointestinal Microbiome ; Feces/microbiology/virology ; *Bacteria/classification/genetics/isolation & purification/virology ; *Bacteriophages/genetics/isolation & purification/classification ; Child, Preschool ; Male ; Female ; Metagenome ; Diarrhea/microbiology ; Southeast Asian People ; }, abstract = {The establishment of the intestinal microbiota during early life plays an important role in physical and mental development and in shaping disease susceptibility in adult. However, knowledge of the gut microbiota in healthy Vietnamese children remains limited. In this study, real-time PCR was used to detect 24 diarrheal pathogens in stool samples, revealing that 41% of healthy infants aged 6-24 months living in Hanoi, Hung Yen were asymptomatic carriers of Escherichia coli (29.1%), Clostridioides difficile (10.3%) and Sapovirus. Pooled metagenomes of gut bacteria (HMG1, HMG2) and viruses (HV1, HV2) from two groups of pathogen-negative infants aged 6-11 months (n = 17) and 12-24 months (n = 13) were subsequently sequenced. As expected, from the classified reads, HMGs comprised of 99.99% bacterial reads, while HVs comprised of bacteria (78.5% in HV1, 42.3% in HV2), phages (8.3% in HV1, 41.0% in HV2) and viruses. The gut microbiota was formed by core bacteria: Actinobacteria (82.6-84.5%), Firmicutes, Proteobacteria and Bacteroidetes, with abundance of Bifidobacterium (> 80%), phages: Podoviridae (65.5-70.2%), Siphoviridae, Myoviridae with dominant crAssphage. The HMGs and HVs shared core bacterial composition but differed in relative abundance. The gut microbiota of older children was characterized by an increase of probiotic bacteria, Escherichia phage, Lactococcus phage and decrease of bacterial pathogens and phages targeting Lactobacillus, Klebsiella, Acinetobacter. Bacterial genes in the gut phage fraction may reflect bacterial community in recent past. Overall, this study provides a scientific basis for understanding the gut microbiome in relation to health and diseases in children particularly within the Vietnamese population.}, } @article {pmid41627458, year = {2026}, author = {Jiang, F and Gu, H and Song, P and Zhang, J and Cai, Z and Liang, C and Gao, H and Zhang, R and Zhang, T}, title = {Post-defecation exposure alters gut microbiota of forest musk deer with implications for conservation metagenomics.}, journal = {Applied microbiology and biotechnology}, volume = {110}, number = {1}, pages = {53}, pmid = {41627458}, issn = {1432-0614}, support = {32200408//National Natural Science Foundation of China/ ; 2023-ZJ-952Q//Natural Science Foundation of Qinghai Province/ ; 2023M743743//China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; *Deer/microbiology ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; *Metagenomics ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; Forests ; DNA, Bacterial/genetics ; Endangered Species ; Conservation of Natural Resources ; Time Factors ; Sequence Analysis, DNA ; }, abstract = {In endangered species conservation, fecal samples are a vital non-invasive tool for gut microbiota analysis. Yet, the influence of external exposure time on microbial composition and function remains unclear, constraining data accuracy and reliability. To address this, we investigated the time-gradient effect in the globally endangered forest musk deer (Moschus berezovskii). Using non-invasive sampling under standardized captive conditions, fecal samples were collected at six storage times: (0, 1, 2, 4, 6, 8 days). Gut microbiota composition, diversity, enterotypes, and functional differences were assessed through 16S rRNA gene sequencing on the Illumina MiSeq platform. In total, 147,013 valid ASVs (amplicon sequence variants) were obtained showing significant shifts in microbial composition with storage time. Dominant phyla included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Increasing storage time led to declining α-diversity, reduced community stability, and more unique genera. PCoA (principal coordinates analysis) and NMDS (non-metric multidimensional scaling) indicated progressive separation of experimental groups from control groups, with Anosim and Adonis confirming progressive separation with storage time. Structurally, Firmicutes decreased while Proteobacteria, specifically the Acinetobacter genus, increased with storage time. Community assembly shifted from deterministic to stochastic processes, reflecting stronger environmental disturbance effects. These results demonstrate that the gut microbiota composition, diversity, and ecological functions in forest musk deer feces are highly sensitive to storage time. Thus, preservation duration must be strictly controlled as a critical variable in microbiome studies. This work establishes methodological standards for non-invasive fecal metagenomics in endangered species, providing theoretical insights and practical guidance for improving scientific rigor in conservation-related microbiome research. KEY POINTS: Fecal microbiota diversity and stability decline significantly with longer storage. Firmicutes decrease while Proteobacteria, especially Acinetobacter, increase over time. Storage duration strongly impacts microbiome data, requiring strict sampling control.}, } @article {pmid41627442, year = {2026}, author = {Jay, M and Eskander, A and Lipscombe, L and Sutradhar, R}, title = {Clarifying the Interpretation of Subdistribution Hazard Ratios in Competing-Risk Analyses: Comment on Riis et al., Eur Thyroid J. 2024;13: e230181.}, journal = {European thyroid journal}, volume = {}, number = {}, pages = {}, doi = {10.1530/ETJ-25-0359}, pmid = {41627442}, issn = {2235-0802}, } @article {pmid41627406, year = {2026}, author = {Salvi, M}, title = {What has changed in Thyroid Eye Disease in the last five years (2020-2025).}, journal = {European thyroid journal}, volume = {}, number = {}, pages = {}, doi = {10.1530/ETJ-25-0363}, pmid = {41627406}, issn = {2235-0802}, abstract = {BACKGROUND: Significant progress has been made in the management of Thyroid eye disease (TED), based on the elucidation of important pathogenic mechanisms. This has led to novel therapeutics validated in randomized clinical trials. Autoreactive antigens that elicit specific orbital immune reactions have not yet been identified, although it has been shown that fibrocytes, circulating stem cells which differentiate into fibroblasts, are expressing the thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) and may be stimulated in the orbit by a cascade of inflammatory reactions inducing adipogenesis.

TED CLINICAL ASSESSMENT: Moderate-severe forms of TED are the target for immune suppressive therapy. Improvement in the assessment of the active and progressive phase of disease is becoming compelling, as the outcome of a treatment depends on how early during the progressive phase the disease is treated. The clinical activity score may not always help define the right time for treating.

THERAPY: In 2020 teprotumumab, an anti-IGF-1 receptor blocker, has been FDA approved for the treatment of TED. Since then other drugs were studied or are under investigation and will seek regulatory approval.

MICROBIOME AND TED: A series of studies have investigated the role of microbiome in thyroid autoimmunity and TED more in detail, based on the observation that treatment with antibiotics may modify the disease phenotype in a murine model of TED.

ARTIFICIAL INTELLIGENCE: This approach is being studied for the assessment of TED, especially trying to standardize the use of orbital and facial images for improving the diagnosis of the disease in the early, progressive phase. In the future these applications will allow the use of synthetic data, in addition to training on real patient images and data.}, } @article {pmid41627377, year = {2026}, author = {Fan, D and Wu, Y and Bao, Y and Xie, H}, title = {Effects of montelukast combined with inhaled corticosteroids on the airway-gut microbiome and immune regulation in children with asthma.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2026.02777}, pmid = {41627377}, issn = {1588-2640}, abstract = {To evaluate the effect of montelukast combined with inhaled corticosteroids (ICS) on the microbiome-metabolism-immunity axis in children with asthma and to quantify the mediating role of short-chain fatty acids, this single-center, randomized controlled trial enrolled 100 asthmatic children (aged 6-11) who received inhaled corticosteroids with or without montelukast for 12 weeks (n = 50 in the combination group and n = 50 in the ICS-alone group). Microbiome profiles from nasal and fecal samples were assessed via 16S sequencing, and short-chain fatty acids (SCFAs) were quantified by LC-MS/MS. Immune markers (Tregs, cytokines) were measured by flow cytometry and Bio-Plex. Efficacy analyses employed linear mixed-effects models, and SCFA mediation was tested using bootstrap analysis. The combination group demonstrated significantly greater improvements in clinical outcomes including fractional exhaled nitric oxide (FeNO) (β_int = -10.24 ppb, 95% CI -16.37 to -4.11, P = 0.001), Childhood Asthma Control Test (C-ACT) score (β_int = +1.83, P < 0.05) and FEV1% (β_int = +1.87, P < 0.05) compared to ICS alone. Microbiome analysis revealed enhanced α-diversity in both nasal and fecal samples (interaction P < 0.01) with significant community structure changes (PERMANOVA interaction P_perm < 0.01). Specific genus-level alterations included reduced nasal Moraxella and Haemophilus (logFC < 0, q < 0.10) and increased fecal SCFA-producing taxa including Faecalibacterium, Roseburia, Subdoligranulum, Agathobacter, and Eubacterium hallii group (logFC > 0, q < 0.10). The combination therapy also led to elevated fecal and serum SCFA levels (β_int > 0, P < 0.01), enhanced regulatory T cell (Treg) and IL-10 responses, and suppressed Th2 cytokines (IL-4/IL-5/IL-13). Mediation analysis confirmed SCFAs partially mediated FeNO improvement, with proportions of 30.0% for total SCFAs and 37.5% for butyrate (ACME and ADE both negative, P < 0.01). The combination of montelukast and inhaled corticosteroids was superior to inhaled corticosteroids alone, providing clinical benefits that were linked to favorable remodeling of the airway-gut microbiome and enhanced Treg/IL-10 immunity. This improvement was partially mediated by short-chain fatty acids, with a comparable safety profile.}, } @article {pmid41627349, year = {2026}, author = {Cheng, X and Pu, S and Wang, Z and Zhang, X and Zuo, M and Ao, Q and Wu, Z}, title = {Gut microbiota dysbiosis and bone mineral density in hemodialysis patients: The mediating role of immune-metabolic pathways and clinical implications for nursing care.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2026.02826}, pmid = {41627349}, issn = {1588-2640}, abstract = {The relationship between gut microbiota dysbiosis and bone mineral density (BMD) in hemodialysis patients, mediated through immune-metabolic pathways, remains to be fully elucidated. In this single-center prospective cross-sectional study, 165 maintenance hemodialysis patients were included to evaluate the independent association between gut microbiota composition and BMD, quantify the mediating roles of immune markers and gut-derived metabolites, and assess the effect modification by nursing-modifiable factors. Fecal samples underwent 16S rRNA sequencing and functional prediction. Inflammatory cytokines (IL-6, TNF-α), gut-derived metabolites (indoxyl sulfate, butyrate), and BMD via dual-energy X-ray absorptiometry (DXA) were measured. Gut microbiota community structure significantly differed across BMD tertiles (R2 = 0.033, P = 0.003). After full adjustment, principal coordinate 1 (PCoA-PC1, beta-diversity) was negatively associated with femoral neck BMD, while the Shannon diversity index showed a positive association (both P < 0.05). We identified 15 differentially abundant genera between high and low BMD groups. Functional prediction revealed short-chain fatty acid pathways were positively associated with BMD, while indole/p-cresol pathways showed negative associations. Mediation analysis demonstrated that immune markers and gut-derived metabolites collectively explained 45.71% of the microbiota-BMD relationship. Nursing factors significantly modified this association, with the negative relationship strengthened by low fiber intake, severe constipation, proton pump inhibitor use, and inadequate dialysis (Kt/V < 1.4). In conclusion, gut microbiota dysbiosis is independently associated with lower BMD in hemodialysis patients, partially mediated through immune-inflammatory pathways and gut-derived metabolites. Dietary fiber optimization, constipation management, prudent proton pump inhibitor prescribing, and dialysis adequacy represent actionable nursing targets to mitigate gut-mediated bone loss in this vulnerable population.}, } @article {pmid41628518, year = {2026}, author = {Aluisio, GV and Santagati, M and Stilo, G and Lentini, M and Sowerby, LJ and Mayo-Yáñez, M and Sedaghat, AR and Lechien, JR and Stefani, S and La Mantia, I and Maniaci, A}, title = {Can microbial profiles influence type II inflammation in chronic rhinosinusitis with nasal polyps?.}, journal = {American journal of otolaryngology}, volume = {47}, number = {2}, pages = {104786}, doi = {10.1016/j.amjoto.2026.104786}, pmid = {41628518}, issn = {1532-818X}, abstract = {OBJECTIVE: This study aimed to assess how different treatments - dupilumab vs surgery - influence the nasal microbiota, type 2 inflammation, and clinical outcomes in CRSwNP patients.

METHODS: This was a prospective observational study of 44 CRSwNP patients assigned to 6 months of biweekly dupilumab injections or functional endoscopic sinus surgery (FESS). Nasal microbiotas were analyzed at baseline and 6 months using culture techniques. Inflammatory biomarkers (IgE, eosinophils) and clinical endpoints (polyp score, SNOT-22, smell test) were measured. Patients were also stratified into groups based on which bacteria were cultured from their sinuses.

RESULTS: At baseline, the most prevalent bacteria were Staphylococcus aureus (43%), Stapylococcus epidermidis (36%), and Pseudomonas aeruginosa (16%). After 6 months, S. aureus and S. epidermidis significantly increased while P. aeruginosa decreased. Eosinophil counts were stable. IgE levels notably decreased in the S. aureus and S. epidermidis groups but increased with P. aeruginosa. All bacterial groups showed reduced polyp score and SNOT-22, and improved smell, but P. aeruginosa had smaller gains. Higher baseline S. aureus and S. epidermidis correlated with more significant IgE decrease.

CONCLUSIONS: Dupilumab and surgery-induced favourable microbiota changes by reducing pathogenic bacteria. Nasal microbiota composition may be associated inflammatory and clinical treatment responses in CRSwNP. S. aureus and S. epidermidis correlated with a greater improvement of IgE levels, whereas P. aeruginosa correlated with worse IgE outcomes. Analyzing each patient's nasal microbiome could enable more personalized, microbiome-directed treatment approaches for optimal CRSwNP management.}, } @article {pmid41628253, year = {2026}, author = {Abdalla, A and Padhi, P and Bakes, N and Thyer, R and Zenitsky, G and Jin, H and Anantharam, V and Kanthasamy, A and Ellington, AD and Phillips, GJ and Kanthasamy, AG}, title = {Preclinical Evaluation of Synthetic Biology-Driven Engineered Escherichia coli Nissle 1917 as a Living Therapeutic for Sustained L-DOPA Delivery.}, journal = {ACS synthetic biology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acssynbio.5c00786}, pmid = {41628253}, issn = {2161-5063}, abstract = {Dopamine deficiency resulting from nigrostriatal dopaminergic neuronal damage manifests as extrapyramidal motor symptoms of Parkinson's disease (PD). Oral tablet dosing of levodopa, administered 3-4 times a day, remains the standard of care due to its tolerability and effectiveness; however, it is prone to deleterious side effects, including off-periods and levodopa-induced dyskinesia after long-term use. Herein, using synthetic biology approaches, we developed and systematically evaluated the feasibility of a probiotic-based live-biotherapeutic system to continuously deliver L-DOPA stably, thereby relieving motor symptoms. Our data demonstrate that our engineered plasmid-based L-DOPA-expressing Escherichia coli Nissle 1917 probiotic strain (EcN[2]LDOPA-P3) efficiently produced up to 12,000 ng/mL L-DOPA in vitro. In mouse model systems, EcN[2]LDOPA-P3 readily colonized for up to 48 h, achieved steady-state plasma L-DOPA concentrations, and increased brain L-DOPA and dopamine levels by 1- to 2-fold. Lastly, EcN[2]LDOPA-P3 significantly diminished motor and nonmotor behavioral deficits in a mouse model of PD compared to traditional chemical L-DOPA therapy. These findings support the therapeutic feasibility of a noninvasive, orally administered bioengineered bacterial therapy for the chronic delivery of L-DOPA, which may address limitations associated with current treatment alternatives.}, } @article {pmid41627982, year = {2025}, author = {Berryman, MA}, title = {Impact of Cetylpyridinium Chloride and Zinc Mouthwash on Oral Health and the Microbiome.}, journal = {Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995)}, volume = {46}, number = {Suppl 2}, pages = {5-8}, pmid = {41627982}, issn = {2158-1797}, mesh = {*Cetylpyridinium/pharmacology/therapeutic use ; *Mouthwashes/pharmacology/therapeutic use ; Humans ; *Microbiota/drug effects ; *Anti-Infective Agents, Local/pharmacology/therapeutic use ; *Zinc Compounds/pharmacology ; *Oral Health ; *Mouth/microbiology ; Dental Plaque/prevention & control ; *Zinc/pharmacology ; Biofilms/drug effects ; Halitosis/prevention & control/drug therapy ; }, abstract = {The widespread use of antimicrobial mouthwashes highlights the importance of understanding their impact on both clinical outcomes and the oral microbiome. This literature review seeks to critically evaluate the current academic knowledge regarding the clinical efficacy of mouthwash containing cetylpyridinium chloride (CPC) and zinc lactate in reducing plaque, gingivitis, and oral malodor, with a particular focus on its interactions with the oral microbiome. Clinical trials have validated the efficacy of CPC and zinc lactate in enhancing oral health metrics, although the long-term impact of their combined use on the oral microbiome warrants further exploration. CPC and zinc lactate in a mouthwash is particularly effective against oral biofilms. While bacteria has the potential to develop resistance against antiseptics, there is no evidence at this time to suggest that CPC and zinc lactate influences resistance in the oral cavity. However, there is evidence that CPC and zinc lactate in combination may be superior to other antibacterial mouthwashes at controlling periodontal pathogens while promoting a healthy and balanced oral microbiome. Future research should prioritize longitudinal, multi-omics investigations to elucidate the nature and extent of these interactions across diverse bacterial communities. The capacity of CPC and zinc lactate to support a healthy oral microbiome, without promoting antimicrobial resistance, underscores their combined potential as a safe and effective oral hygiene solution.}, } @article {pmid41627051, year = {2026}, author = {Shoemaker, WR and Grilli, J}, title = {The macroecological dynamics of sojourn trajectories in the human gut microbiome.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0122125}, doi = {10.1128/msystems.01221-25}, pmid = {41627051}, issn = {2379-5077}, abstract = {The human gut microbiome is a dynamic ecosystem. Host behaviors (e.g., diet) provide a regular source of environmental variation that induces fluctuations in the abundances of resident microbiota. Despite these displacements, microbial community members remain highly resilient. Population abundances tend to fluctuate around a characteristic steady-state over long timescales in healthy human hosts. These temporary excursions from steady-state abundances, known as sojourn trajectories, have the potential to inform our understanding of the fundamental dynamics of the microbiome. However, to our knowledge, the macroecology of sojourn trajectories has yet to be systematically characterized. In this study, we leverage theoretical tools from the study of random walks to characterize the duration of sojourn trajectories, their shape, and the degree that diverse community members exhibit similar qualitative and quantitative dynamics. We apply the stochastic logistic model as a theoretical lens for interpreting our empirical observations. We find that the typical timescale of a sojourn trajectory does not depend on the mean abundance of a community member (i.e., carrying capacity), although it is strongly related to its coefficient of variation (i.e., environmental noise). This work provides fundamental insight into the dynamics, timescales, and fluctuations exhibited by diverse microbial communities.IMPORTANCEMicroorganisms in the human gut often fluctuate around a characteristic abundance in healthy hosts over extended periods of time. These typical abundances can be viewed as steady states, meaning that fluctuating abundances do not continue towards extinction or dominance but rather return to a specific value over a typical timescale. Here, we empirically characterize the (i) length (i.e., number of days), (ii) relationship between length and height, and (iii) typical deviation of a sojourn trajectory. These three patterns can be explained and unified through an established minimal model of ecological dynamics, the stochastic logistic model of growth.}, } @article {pmid41626790, year = {2026}, author = {Barati, S and Ghoflchi, S and Nakhaei, A and Yazdi, MP and Hosseinzadeh, P and Hosseini, H and Jalili-Nik, M}, title = {Gut Microbiome Strategies for Enhancing ICI Delivery Across the BBB in Glioblastoma.}, journal = {BioFactors (Oxford, England)}, volume = {52}, number = {1}, pages = {e70077}, doi = {10.1002/biof.70077}, pmid = {41626790}, issn = {1872-8081}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Glioblastoma/drug therapy/immunology/microbiology/pathology ; *Blood-Brain Barrier/drug effects/metabolism/immunology ; *Immune Checkpoint Inhibitors/administration & dosage/therapeutic use ; *Brain Neoplasms/drug therapy/immunology/microbiology/pathology ; Animals ; Tumor Microenvironment/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {Glioblastoma (GB) is highly malignant with a median survival of 14 months despite conventional treatments like surgery, radiotherapy, and temozolomide. Resistance to these therapies necessitates innovative approaches, such as immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1) to enhance T-cell-mediated tumor destruction. However, clinical trials have shown limited ICI efficacy in GB due to its immunosuppressive microenvironment and the blood-brain tumor barrier (BBTB), which impairs drug delivery. Emerging evidence highlights the gut microbiota as a pivotal modulator of ICI response, enhancing CD8[+] and CD4[+] T-cell function, antigen presentation, and immune modulation via the gut-brain axis in cancers. In addition, studies showed that gut-derived metabolites, including short-chain fatty acids, modulate immune responses and support blood-brain barrier integrity by regulating inflammatory signaling and tight junction proteins. Future GB research should prioritize clinical trials, mechanistic studies, and interventional strategies like fecal microbiota transplantation and probiotics to enhance ICI efficacy.}, } @article {pmid41626630, year = {2026}, author = {Lin, L and Neves, ALA and Ominski, KH and Guan, LL}, title = {Metatranscriptomics uncovers diet-driven structural, ecological, and functional adaptations in the rumen microbiome linked to feed efficiency.}, journal = {ISME communications}, volume = {6}, number = {1}, pages = {ycaf251}, pmid = {41626630}, issn = {2730-6151}, abstract = {The rumen microbiome plays a pivotal role in modulating feed efficiency in ruminants, yet the ecological mechanisms mediating the active interactions among microbial adaptations, dietary inputs, and host feed efficiency within the rumen remain poorly understood. To address this gap, we analyzed 120 metatranscriptomic datasets obtained from 30 purebred Angus bulls (each sampled four times) classified as high-feed-efficiency or low-feed-efficiency based on feed conversion ratio, and fed either forage-based (n = 15) or grain-based (n = 15) diets. We constructed a comprehensive active gene catalog comprising 1 744 067 non-redundant genes and compiled a reference set of 25 115 ruminant microbial genomes. Using integrated Neutral Community Model analysis and carbohydrate-active enzyme profiling, we examined how ecological processes and functional capacities differed across host phenotypes and diets. Neutral Community Model fits revealed that stochastic processes broadly governed rumen microbial community structures (R[2] = 0.779 for high-feed-efficiency; R[2] = 0.781 for low-feed-efficiency). Within the predominantly stochastic processes, however, high-feed-efficiency bulls exhibited strong positive selection for diet-responsive microbial lineages: Fibrobacter spp. (positively selected species-level genome bins: 61.3%-76.0%; negatively selected: 0%-1.3%), Butyrivibrio spp. (positively selected: 13.3%-46.0%; negatively selected: 1.0%-11.2%) under forage feeding, and UBA1067 spp. (positively selected: 33.3%-48.5%; negatively selected: 0%-8.3%) under grain feeding. These lineages encoded catalytic domains appended with carbohydrate-binding modules, such as tandem carbohydrate-binding modules linked to glycoside hydrolases, thereby enhancing substrate adhesion and degradation. In contrast, low-feed-efficiency bulls showed more random community structures and reduced functional specialization. Therefore, these suggest that cattle hosts with higher feed efficiency promote microbial populations functionally aligned with dietary inputs, a process we define as efficient host-mediated microbial amplification. These findings offer new insight into how ecological assembly and functional adaptation of the microbiome contribute to feed efficiency and lay the foundation for microbiome-informed strategies to enhance ruminant production sustainability.}, } @article {pmid41626616, year = {2026}, author = {Zhang, X and Lv, X and Zhang, L and Jia, T and Zhao, S}, title = {Association between a novel Dietary Index for Gut Microbiota and periodontitis: a cross-sectional study.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1714913}, pmid = {41626616}, issn = {2296-861X}, abstract = {BACKGROUND: The gut microbiota and periodontitis have attracted increasing research interest. The Dietary Index for Gut Microbiota (DI-GM), a novel metric for assessing gut microbiome diversity, has not yet been investigated in relation to periodontitis.

METHODS: This cross-sectional study analyzed data from the 2009-2014 National Health and Nutrition Examination Survey including 9,978 participants aged 30-80 years who had periodontal examination records. Participants were categorized into two groups: no periodontitis (n = 4,879) and periodontitis (mild, moderate, or severe; n = 5,099). The DI-GM was calculated using dietary recall data, incorporating both beneficial and unfavorable components for gut microbiota. Multivariable logistic regression was applied to examine the association between DI-GM and periodontitis, with body mass index (BMI) evaluated as a potential mediator. Secondary analyses included subgroup evaluations, restricted cubic spline (RCS) modeling, and multivariable imputation.

RESULTS: A higher DI-GM score was inversely associated with periodontitis (odd ratio [OR] = 0.94, 95% confidence interval [CI]: 0.91-0.97). Similarly, a higher beneficial microbiota score was linked to a lower prevalence of periodontitis (OR = 0.90, 95% CI: 0.87-0.94). After adjustment, DI-GM remained inversely associated with moderate (OR = 0.94, 95% CI: 0.91-0.97) and severe periodontitis (OR = 0.89, 95% CI: 0.85-0.94; both p < 0.001). Likewise, higher beneficial microbiota scores correlated with reduced odds of moderate (OR = 0.91, 95% CI: 0.87-0.95) and severe periodontitis (OR = 0.84, 95% CI: 0.79-0.90; all p < 0.001). The RCS model indicated a linear association between DI-GM and periodontitis. BMI showed a significant mediating effect (4.9, 95% CI: 0.96-11.05%; p = 0.014).

CONCLUSION: The newly proposed DI-GM demonstrated an inverse association with the prevalence of periodontitis, with BMI acting as a significant mediator in this relationship.}, } @article {pmid41626567, year = {2026}, author = {Wang, J and Qu, J and Ye, M and Feng, R and Hui, X and Yang, X and Jin, J and Tong, Q and Zhang, X and Wang, Y}, title = {Beyond conventional therapies: Gut microbiota modulation and macromolecular drugs in the battle against cardiometabolic diseases.}, journal = {Journal of pharmaceutical analysis}, volume = {16}, number = {1}, pages = {101416}, pmid = {41626567}, issn = {2214-0883}, abstract = {Cardiometabolic diseases (CMDs) represent an ongoing major global health challenge, driven by complex interactions among genetic, environmental, microbiome-related, and other factors. While small-molecule drugs and lifestyle interventions can provide clinical benefits, they are possible to be constrained by the limited druggability of key target proteins, the potential risks of off-target effects, and difficulties in maintaining long-term adherence. In recent years, gut microbiota modulation and macromolecular drugs have emerged as promising therapeutic strategies. Gut microbiota modulation (e.g., probiotics, synbiotics, or natural products) exerts systemic metabolic and immune effects, supporting a therapeutic approach targeting multiple diseases. Meanwhile, macromolecular drugs (e.g., peptides, antibodies, and small nucleic acids) offer precise, pathway-targeted interventions. Despite advancements, limitations remain in addressing ethical considerations in microbiota modulation and optimizing targeted delivery systems, all of which may hinder clinical translation. Here, we provide a comprehensive overview of therapeutic approaches for CMDs, with a focus on obesity, type 2 diabetes mellitus (T2DM), and atherosclerosis (AS). The review is structured around three key aspects: i) conventional therapies, including small-molecule drugs and lifestyle interventions; ii) emerging therapies encompassing gut microbiota modulation, macromolecular drugs, and their interactions; and iii) challenges and opportunities for comorbidity management, microbiota ethics, and artificial intelligence (AI)-driven therapeutic optimization. We hope this review enhances the understanding of small-molecule drugs, lifestyle interventions, gut microbiota modulation, and macromolecular drugs in the management of CMDs, thereby fostering medical innovation and contributing to the development of system-based comprehensive therapeutic paradigms.}, } @article {pmid41626521, year = {2026}, author = {Al-Khatib, A and Naous, A and Sokhn, ES}, title = {Prevalence and characterization of bacterial rectal colonization patterns in pediatric patients: A cross-sectional study.}, journal = {New microbes and new infections}, volume = {70}, number = {}, pages = {101707}, pmid = {41626521}, issn = {2052-2975}, abstract = {BACKGROUND: Antimicrobial resistance is a major public health concern requiring ongoing surveillance to determine its extent and associated factors. This study evaluates bacterial isolates from pediatric patients in terms of distribution, resistance mechanisms, and demographic/clinical correlations.

METHODS: In this cross-sectional study, after obtaining parental assent, rectal swabs were aseptically collected from children by pediatric doctors at Healthcare Centers in Beirut. Necessary data were collected through validated questionnaires provided to parents. Bacterial identification was performed using standard culture, isolation, and biochemical techniques. Susceptibility of bacterial strains was studied using antimicrobial susceptibility testing. Finally, Polymerase Chain Reaction (PCR) was used to characterize resistance genes. Associations between resistance phenotypes and sample characteristics were assessed using chi-square or Fisher's exact test, as appropriate.

RESULTS: Among 118 rectal isolates, Escherichia coli predominated (75.4 %), followed by other Enterobacterales and Staphylococci. Overall, 31.36 % of isolates harbored a major resistance mechanism (ESBL, AmpC, CRE, or MRSA), with ESBL-producing E. coli being the most frequent (22 %) and blaCTX-M detected in the majority of ESBL isolates. Previous antacid intake was the only characteristic significantly associated with resistance phenotypes (p = 0.03). AmpC, CRE, and MRSA remained relatively infrequent but represented clinically important resistance mechanisms.

CONCLUSION: Rectal colonization with multidrug-resistant organisms was frequent, driven mainly by ESBL-producing, blaCTX-M-positive E. coli, while AmpC, CRE, and MRSA were less common but remained important resistance mechanisms. The association between resistance phenotypes and prior antacid use highlights the need for larger pediatric surveillance studies and careful evaluation of antacid and antibiotic use in this population.}, } @article {pmid41626182, year = {2025}, author = {Yao, B and Hou, C and Zhang, W and Bao, Z and Li, Y and Zhang, Z}, title = {Research progress on the impact and mechanisms of helicobacter pylori infection on the efficacy of immunotherapy for gastric cancer.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1674814}, pmid = {41626182}, issn = {2234-943X}, abstract = {BACKGROUND: Helicobacter pylori (H. pylori), recognized as a Group I carcinogen by the World Health Organization, is a key etiological agent in gastric cancer (GC). The majority of GC patients, particularly in China, present at advanced stages with constrained therapeutic options. Tumor immunotherapy, especially immune checkpoint inhibitors targeting the PD-1/PD-L1 axis, has emerged as a promising strategy. However, immunotherapy benefits only a subset of patients. Notably, H. pylori infection plays a significant role in GC and may also influence the efficacy of immunotherapy.

MAIN CONTENT: This review systematically summarizes the role and mechanisms of H. pylori in GC development, progression, and immunotherapy, focusing on the following aspects. Pathogenic mechanisms: H. pylori drives GC development through virulence factors (e.g., CagA, VacA, urease), which induce chronic inflammation, epithelial damage, immune evasion, and remodeling of the tumor microenvironment. Impact on immunotherapy and underlying mechanisms: The clinical efficacy is conflicting, some studies associate H. pylori infection with poor prognosis following immunotherapy, while others to better responses. Proposed mechanisms include PD-L1 upregulation via multiple signaling pathways, modulation of immune cells within the tumor microenvironment, and gut microbiota alterations affecting PD-1/PD-L1 inhibitor efficacy.

CONCLUSION: H. pylori has a complex influence on GC immunotherapy. Further research is needed to clarify the underlying mechanisms and assess the predictive value of H. pylori testing in clinical practice. Combining microbiome-based strategies with immunotherapy may enable more personalized and effective treatment.}, } @article {pmid41625959, year = {2026}, author = {de Melo Pereira, GV and da Silva Vale, A and Ribeiro-Barros, AI and Rodrigues, LRS and de França Bettencourt Mirção, GM and Camilo, B and da Piedade Ernesto Tapaça, I and de Mello Sampaio, V and Brar, SK and Soccol, CR}, title = {Integrated microbial-metabolomic analysis reveals how fermentation contributes to the unique flavor of African Arabica coffee.}, journal = {Food chemistry. Molecular sciences}, volume = {12}, number = {}, pages = {100344}, pmid = {41625959}, issn = {2666-5662}, abstract = {Post-harvest fermentation is a decisive stage in shaping the flavor complexity of Arabica coffee. In this study, we mapped for the first time the microbial-driven flavor metabolic network underlying the fermentation of high-quality African coffee, using a combined metabolomic, meta-barcoding, and metagenomic approach applied to samples from Chimanimani National Park, Mozambique. Over 72 h of spontaneous fermentation, chemical analyses revealed rapid sucrose hydrolysis, lactic acid accumulation, and the formation of 74 volatile compounds. These transformations were driven by a previously unreported core microbiome (Leuconostoc-Hanseniaspora-Galactomyces axis), whose functional repertoire (1791 genes) highlighted the Ehrlich pathway and ester biosynthesis as central flavor routes. Among the volatiles formed, linalool, phenylethyl alcohol, and ethyl acetate were most abundant, emerging as predictive drivers of the floral and fruity notes identified in the resulting high-quality coffee beverage (score 87.25 ± 0.25). This study underscores microbial terroir as a key factor adding value to emerging African origins.}, } @article {pmid41625945, year = {2026}, author = {Larionova, E and Moran, GP}, title = {The role of Fusobacterium nucleatum in the tumour microenvironment and carcinogenesis of oral and colonic malignancies.}, journal = {FEMS microbes}, volume = {7}, number = {}, pages = {xtag002}, pmid = {41625945}, issn = {2633-6685}, abstract = {The intra-tumoural microbiome is an increasing area of research with potential benefits in cancer diagnostics and treatment development. Numerous studies have implicated Fusobacterium nucleatum, a member of the oral microbiota, in the development, immune evasion, and dissemination of oral and colorectal tumours. Although F. nucleatum is yet to be classified as a cause or consequence of cancer, reports indicate the microorganism's involvement in DNA damage, pathologic glucose uptake, and cellular proliferation. This accumulation of genetic instability is consistent with the multistep nature of malignant neoplasm progression. Virulence factors of F. nucleatum were shown to maintain an unresolved inflammatory state and impair the normal function of immune cells. The accompanying pro-inflammatory conditions facilitate vasculature remodelling, expediting tumour expansion, through a range of mechanisms. Pro-metastatic epithelial-to-mesenchymal transition and changes in gene expression have been observed in cancer cells upon F. nucleatum infection, suggesting an association with poorer prognosis. As a frequently encountered microorganism in the oral and colorectal intra-tumoural microbiome, F. nucleatum represents an intriguing, yet cautious research prospect with opportunities for novel prevention and therapeutic strategies. The objective of this work is to review the relevant evidence, taking into account the complexity of the tumour microenvironment.}, } @article {pmid41625836, year = {2025}, author = {Matsukawa, M and Sakai, Y and Aoki, K and Ishii, Y}, title = {Urinary Microbiome Profiling by Shotgun Metagenomic Sequencing in Women Having Acute Cystitis-Like Symptoms With Negative Urine Cultures.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e100451}, pmid = {41625836}, issn = {2168-8184}, abstract = {BACKGROUND: Women presenting with typical symptoms of acute cystitis but with negative urine cultures, termed acute cystitis-like symptoms with negative urine cultures (ACNCs) in this study, are not uncommon. Despite previous attempts to detect bacterial DNA in urine, the etiology remains unclear. Although alterations in the urinary microbiome have been linked to other urological disorders, its involvement in ACNC has not been thoroughly investigated.

METHODS: Between September 2016 and December 2017, midstream urine samples were collected from women aged ≥16 years who had at least one typical symptom of acute cystitis and a negative urine culture. Samples were obtained at the initial (V1) and follow-up (V2) visits. Shotgun metagenomic sequencing (SMG) was performed via an Illumina MiSeq system. Taxonomic analysis at the genus level included taxa with ≥10 assigned reads in samples with ≥10,000 human-subtracted reads (HSRs).

RESULTS: Of 206 eligible women, 15 (7.3%; median age, 65 years) met the ACNC criteria and were enrolled. SMG was conducted for 15 samples at V1 and nine samples at V2. At V1, the HSR varied widely, and only five samples met the criteria for reliable interpretation. Seven samples, particularly those with high-grade pyuria, contained fewer than 1,000 HSRs, indicating potentially very low microbial loads or technical limitations. ACNC microbiomes demonstrated marked interindividual variation in taxonomic composition. The predominant taxa most frequently observed were Lactobacillus spp., Gardnerella spp., and JC polyomavirus. Conventional uropathogens, such as Escherichia spp., were not identified at interpretable levels. At V2, microbial diversity remained heterogeneous, but eight samples yielded sufficient read counts for interpretation.

CONCLUSIONS: While conventional uropathogens below interpretable criteria are unlikely to be responsible for most ACNCs, it is not necessarily recommended to regard the leading taxon in each case as the cause or to exclude microbiological involvement simply due to a low HSR because no validated metagenomic signature distinguishes pathogens from commensals. However, the observed diversity in ACNC microbiome profiles may reflect a heterogenous group of microbial conditions, including potentially viral, and nonmicrobial etiologies.}, } @article {pmid41625766, year = {2025}, author = {Zhao, H and Liu, Y and Su, L and Cui, P and Sai, J and Li, S and Wang, N and He, P}, title = {Gut-liver-muscle axis: linking gut microbiota dysbiosis to malnutrition and sarcopenia in liver disease.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1727270}, pmid = {41625766}, issn = {2296-858X}, abstract = {Nutritional disorders and muscle wasting associated with liver disease are key determinants of poor prognosis in patients with chronic liver disease. The formation of these conditions involves multiple factors, including impaired energy metabolism, enhanced protein degradation, and gut microbiota imbalance. In recent years, with the deepening of microbiome research, the concept of the "gut-liver-muscle axis" has gradually emerged to explain the more systematic interaction between gut microbiota, liver metabolism, and skeletal muscle homeostasis. Gut dysbiosis can promote liver inflammation and metabolic disorders through various pathways, further weakening muscle energy utilization and protein synthesis, ultimately leading to malnutrition and sarcopenia. This review systematically explores the crucial role of gut microbiota in liver disease-related malnutrition and muscle wasting, elucidates its potential mechanisms in influencing host metabolism and nutritional status through the "gut-liver-muscle axis," and discusses the prospects of microbiome interventions in improving nutritional outcomes in liver disease.}, } @article {pmid41519896, year = {2026}, author = {Domańska, M and Kuśnierz, M and Charazińska, S and Gawor, J and Kamińska, J}, title = {Similarity of activated sludge and treated wastewater with special reference to nitrifiers and their seasonal variability.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4375}, pmid = {41519896}, issn = {2045-2322}, support = {2022/06/X/ST10/01775//National Science Centre/ ; }, abstract = {UNLABELLED: While the research into the activated sludge (AS) microbiome using next-generation sequencing (NGS) are increasingly being published, they still apply to a few wastewater treatment plants (WWTPs). Little information can be found in the scientific literature on the microbial composition of treated wastewater (TW) and bacterial activity in real WWTPs facilities. In this study, AS and TW are compared in terms of their physico-chemical parameters and bacterial community composition, with particular emphasis on nitrifying bacteria, based on the results from 16S rRNA amplicon sequencing using DNA and complementary DNA (cDNA) data and fluorescence in situ hybridization (FISH). Using a 24-h composite sample of TW rather than a grab sample yields highly representative microbial community profiles. The research revealed a decrease in biodiversity in months with lower sludge temperatures both in AS and TW. Differences among groups of nitrifying bacteria were observed during the monitoring of WWTP, suggesting that their presence in TW may not be a random occurrence but could serve as an indicator of physicochemical and operational changes within biological reactors.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-34503-4.}, } @article {pmid41485070, year = {2026}, author = {Chen, JM and Zhang, C and Yu, LL and Sun, JX and Zhang, JH and Chen, L and Zhu, F and Shi, G and Yang, L and Guo, AC and Wu, JP and Tang, TS and Wang, Q}, title = {Microbiota-derived IPA mitigates post-stroke neuroinflammation by inhibiting TREM2-dependent pyroptosis.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {47}, pmid = {41485070}, issn = {1742-2094}, support = {82501758//National Natural Science Foundation of China/ ; U24A20695 and 82371449//National Natural Science Foundation of China/ ; 20221060//Hebei Province Medical Science Research Project/ ; 13000023P002DB4102678//the Introduction of Foreign Intelligence Program of Hebei Province/ ; K1297701, J.W//Faculty Development grants from Hubei University of Medicine/ ; 2023YFA1801904 and 2025YFA1805102//National Key Research and Development Program of China/ ; 2022YFC2503800//National Key Research and Development Program of China/ ; 7232045 and Z200024//Natural Science Foundation of Beijing Municipality/ ; 2024-1-2041//Capital Health Research and Development of Special grants/ ; }, abstract = {UNLABELLED: Ischemic stroke remains the leading cause of long-term disability globally, underscoring the urgent need for novel therapeutic strategies. Here, we explore a microbiota-gut-brain axis that provides valuable insights for achieving this objective. Utilizing a distal middle cerebral artery occlusion (dMCAO) mouse model, we observed a marked reduction in Duncaniella muris (D. muris) post-stroke, alongside dysregulated tryptophan metabolism, characterized by elevated levels of indole-3-lactic acid (ILA) and decreased indole-3-propionic acid (IPA). D. muris supplementation restored metabolic balance by converting ILA to IPA, leading to significant improvements in neurological recovery. Mechanistically, IPA exerted neuroprotective effects by attenuating neuroinflammation through TREM2-dependent modulation of microglial activation, promoting an anti-inflammatory phenotype and inhibiting NLRP3 inflammasome-mediated pyroptosis. These findings highlight the therapeutic potential of the D. muris-IPA-TREM2-pyroptosis axis as a novel target for ischemic stroke treatment, providing a basis for future microbiome-based interventions aimed at improving stroke outcomes.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-025-03660-8.}, } @article {pmid41625367, year = {2025}, author = {He, S and Li, Z and Huang, W and Peng, Y and Niu, L and Wen, H and Xv, Y and Li, S and Li, Z}, title = {Functional phyto-nanozymes for dual regulation of microbial metabolism and overinflammation microenvironment in diabetic wound.}, journal = {Materials today. Bio}, volume = {35}, number = {}, pages = {102293}, pmid = {41625367}, issn = {2590-0064}, abstract = {Chronic wound management demands multifunctional therapeutic strategies that simultaneously address excessive inflammation and oxidative stress. To meet this challenge, we engineered a three-dimensional biomimetic scaffold (CSSTF) by integrating collagen-based thermosensitive hydrogel, a SiO2-supported copper single-atom catalyst (Cu-SAC-SE), and tea tree oil-encapsulated liposomes (TTO@Lpo). This composite design enables sustained release of bioactive components, achieving synergistic ROS scavenging, mitochondrial protection, and suppression of NLRP3 inflammasome-mediated pyroptosis. Notably, CSSTF exhibits dual immunomodulatory effects by attenuating neutrophil extracellular trap (NET) formation and shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, thereby mitigating inflammation-associated tissue damage. Parallelly, TTO@Lpo orchestrates microbial remodeling by selectively inhibiting pathogenic bacteria while enriching beneficial commensals, coupled with elevated production of anti-inflammatory metabolites (e.g., short-chain fatty acids), establishing a self-reinforcing "microbiota-metabolism-inflammation" regulatory loop. In diabetic murine models, CSSTF significantly accelerated wound closure through coordinated mechanisms: (1) enhanced angiogenesis via VEGF upregulation, (2) NETosis suppression that dampens cytokine storms, and (3) ECM reconstruction facilitated by fibroblast activation. Beyond material innovation, this work pioneers a phyto-bionic therapeutic platform leveraging enzymatic catalysis and microbiome reprogramming, offering a paradigm shift in chronic wound treatment through simultaneous physical barrier restoration and dynamic biological modulation.}, } @article {pmid41625355, year = {2026}, author = {Ling, X and Peng, Y and Zhang, Y and Yim, CC and Chan, HN and Yang, Y and Sun, Q and Zhang, XJ and Kam, KW and Chu, WK and Ip, P and Young, AL and Hammond, CJ and Tsui, SKW and Tham, CC and Pang, CP and Chen, LJ and Yam, JC}, title = {Associations between Ocular Surface Microbiome and Refractive Status in Children and Adolescents.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101042}, pmid = {41625355}, issn = {2666-9145}, abstract = {PURPOSE: To identify the compositional and functional alterations in the ocular surface microbiome (OSM) which are associated with myopia in children and adolescents.

DESIGN: A population-based, cross-sectional study.

PARTICIPANTS: Eight hundred forty-seven children and adolescents aged 3 to 17 years were included.

METHODS: Conjunctival swab samples were collected from the participants and processed via 16S ribosomal RNA gene sequencing.

MAIN OUTCOME MEASURES: Microbial profiles of participants were processed with QIIME2. Alpha (species diversity) and beta diversity (community structure) metrics were calculated. Microbial functional profile was predicted using PICRUSt2.

RESULTS: Shannon (P < 0.001) and observed (P = 0.010) indexes were different among samples from myopic eyes (n = 432), as compared with those from emmetropic (n = 214) and hyperopic (n = 201) eyes. They were correlated with spherical equivalent (Shannon P = 0.0036, observed P = 0.0129) and axial length (Shannon P = 0.0057, observed P = 0.012). Beta diversity with distinct microbial signatures was unique (P < 0.05) among the eyes with myopia (Haemophilus, Aquabacterium, Anaerococcus), emmetropia (Sphingobium, Clostridium sensu stricto 1, and Fusobacterium) and hyperopia (Streptococcus, Kocuria, and Gemella). Functional profiling found enrichment of several Kyoto Encyclopedia of Genes and Genomes pathways, including oxidative phosphorylation, in the myopic ocular surface, suggesting a distinct energy utilization pattern in the myopic microbiome.

CONCLUSIONS: This study reveals distinct compositional and functional profiles in the OSM of myopic children and adolescents. These findings demonstrate an association between refractive status and the OSM; however, causality has not been established, highlighting the need for further research.

FINANCIAL DISCLOSURES: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.}, } @article {pmid41625281, year = {2026}, author = {Nieto Fernandez, FE and Roccanova, P and Fantal-Pinckombe, B and Catapano, R}, title = {Soil microbiome analysis of a northeastern deciduous forest in SUNY Old Westbury, Long Island, New York.}, journal = {microPublication biology}, volume = {2026}, number = {}, pages = {}, pmid = {41625281}, issn = {2578-9430}, abstract = {We studied spatial changes in soil bacterial microbiome composition and diversity in a 111 acres old growth mixed hardwood forest plot in Long Island, NY. Forty soil samples were collected from four forest transects across the forest plot representing various soil features, and dominant vegetation. Three phyla account for 91% of the bacteria in the samples, Acidobacteriota (43%), Proteobacteriota (30%), and Actinobacteriota (18%). We also found 16 different classes and 33 orders. Sites dominated by black birch, Betula lenta were significant more diverse than all other sites. We also found significant differences in microbiome composition based on pH and vegetation.}, } @article {pmid41624431, year = {2026}, author = {Shahzad, M and Ismail, M and Islam, MJU and Yumna, S and Irum, T and Malalai, K and Sara, I and Al Nabhani, Z and Andrews, SC}, title = {The oral microbiome profile of Pakistani infants characterized by 16S rRNA amplicon sequencing.}, journal = {Data in brief}, volume = {64}, number = {}, pages = {112449}, pmid = {41624431}, issn = {2352-3409}, abstract = {The oral microbiome is the second most complex and diverse ecosystem in the human body. A number of longitudinal studies assessing oral microbiome development in diverse populations has been reported recently. However, oral microbiome development in vulnerable populations such as infants who are at risk of malnutrition is rarely explored. The current study aims to assess oral bacterial community development and associated factors in Pakistani infants residing in malnutrition endemic areas of Pakistan. Data and oral swab samples were collected from infants (n = 71) at baseline (age <28 days) and 3-months follow-up (n = 65) followed by DNA extraction, PCR amplification and 16S rRNA amplicon sequencing on a DNBSEQ-G400 platform. Of the total 136 samples, 119 samples were successfully sequenced and analyzed further. Bioinformatics and statistical analyses were performed using Cutadapt, FLASH and R. Overall, the Bacillota (formerly known as Firmicutes) was the predominant bacterial phylum, accounting for 87.6 % relative abundance at baseline and 84.3 % at 3-months. The Streptococci and Veillonella were the predominant bacterial genera with 66.9 % and 13.4 % relative abundance at baseline and 55.4 % and 26.1 % at 3-months, respectively. This study provides the first comprehensive insights into oral bacterial community development of vulnerable infants at risk of malnutrition. The data can be used to longitudinally assess oral microbiome develop during early infancy and associated maternal, infant and environmental factors. Sequencing data are deposited in the NCBI Sequence Read Archive as BioProject PRJNA1303979.}, } @article {pmid41624250, year = {2026}, author = {Si, M and Yan, S and Ding, S and Liu, R and Xiong, X and Qiao, J and Qi, X}, title = {Changes in Metabolites and Microbial Communities in Follicular Fluid Associated With Ovarian Function in Patients With Polycystic Ovary Syndrome.}, journal = {MedComm}, volume = {7}, number = {2}, pages = {e70622}, pmid = {41624250}, issn = {2688-2663}, abstract = {Polycystic ovary syndrome (PCOS) is a well-documented endocrine disorder associated with metabolic abnormalities. Research has indicated potential links between PCOS and the gut microbiome, and the presence of microbial communities in follicular fluid (FF) has been demonstrated; however, their functional interplay with metabolites has not been elucidated. This case-control study involved 40 patients with PCOS and 40 controls matched for age. A comprehensive analysis of FF metabolites and microbial communities by means of metabolomics analysis and 16S rDNA sequencing was performed. Twelve metabolites and 15 microbial communities were significantly different between the PCOS and control groups. AMH and AFC were significantly associated with the majority of the differentially abundant metabolites and bacteria, suggesting a potential association between FF components and ovarian function. In this study, we found that D-glucose and Alicyclobacillus were the most important variables in the metabolite model and microbial model, respectively. Mechanistically, Alicyclobacillus acidoterrestris, Terrimonas ferruginea, or Terrimonas pekingense can efficiently utilize glucose thereby reducing FF glucose levels, which provides insights into the microbiome-metabolite connection. These findings suggest a potential link among bacteria-metabolite-ovarian function, which could have implications for understanding the pathophysiology of PCOS and developing novel diagnostic and therapeutic strategies targeting metabolic and microbial aspects.}, } @article {pmid41624197, year = {2025}, author = {Govaert, M and Duysburgh, C and Kesler, B and Marzorati, M}, title = {Effects of NatureKnit™ organic, a blend of organic fruit and vegetable fibers rich in naturally occurring bound polyphenols, on the metabolic activity and community composition of the human gut microbiome using the M-SHIME[®] gastrointestinal model.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1740906}, pmid = {41624197}, issn = {2296-861X}, abstract = {OBJECTIVES: The effects of a proprietary blend of organic fruit and vegetable fibers rich in naturally occurring bound polyphenols (commercially known as NatureKnit™ Organic) on the human gut microbiome were assessed.

METHODS: Short-term (48 h) in vitro colonic simulations using the validated Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME[®]) platform, with fecal inoculum from nine individual healthy human donors, were performed. Purified organic fibers (inulin and psyllium) were evaluated as comparators and a negative control was included. Primary measures included pH, gas pressure, short-chain fatty acid (SCFA) production, and microbial community composition.

RESULTS: All test products were well fermented with NatureKnit™ Organic showing slower fermentation kinetics than the purified fibers. SCFAs were significantly increased with all test products versus the negative control (p < 0.0001 for all) and NatureKnit™ Organic reached significance versus both purified fibers (p < 0.0001 for both). While relative abundances in the mucosal compartment were similar among all test conditions, luminal bacterial abundance increased with NatureKnit™ Organic and psyllium versus the negative control. The latter was mainly associated with statistically increased abundance (p < 0.05) of the genera Eisenbergiella and Monoglobus, with an additional strong enrichment of Bacteroidaceae. Furthermore, bacterial species richness was significantly increased with NatureKnit™ Organic versus the negative control (p = 0.0495), which was not observed for the purified organic fibers (p = 0.0567 and p = 0.4285 for inulin and psyllium, respectively).

CONCLUSION: Overall, the obtained results indicate that NatureKnit™ Organic may have a greater and gentler prebiotic effect compared with established purified prebiotic fibers.}, } @article {pmid41624190, year = {2025}, author = {Betancur, D and Jara, EL and Lima, CA and Victoriano, M}, title = {Diet type and the oral microbiome.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1691952}, pmid = {41624190}, issn = {2296-861X}, abstract = {BACKGROUND: The oral microbiome changes across the lifespan and is modulated by behavioral and metabolic exposures. Tobacco consumption, suboptimal hygiene, and frequent sugar intake disrupt microbial homeostasis, thereby increasing vulnerability to chronic oral diseases. While diet influences systemic metabolic and inflammatory health, evidence describing persistent, direct ecological effects on oral microbial communities remains limited.

OBJECTIVE: The objective of this study is to synthesize mechanistic insights on how dietary patterns shape the oral microbiome and influence systemic inflammatory or metabolic risk.

METHODOLOGY: A narrative, non-systematic review was conducted through expansive literature exploration. Peer-reviewed original and clinical studies reporting defined dietary exposures caloric restriction, plant-based diets, inorganic nitrate and fiber intake, and high-fat or high-sugar processed diets, were qualitatively evaluated for mechanistic relevance.

KEY FINDINGS: Plant-enriched, high-fiber diets, nitrate intake, and caloric restriction were associated with reduced oxidative stress, lower pro-inflammatory cytokines, and greater diversity of commensal taxa, suggesting improved ecological stability. In contrast, processed diets promote metabolic conditions that indirectly remodel the oral habitat, favoring dysbiosis and a niche permissive to periodontitis.

CONCLUSION: The diet-oral microbiome-systemic inflammation axis is bidirectional and clinically relevant. Understanding both direct ecological regulation and indirect metabolic effects is essential to support precision nutrition strategies aimed at maintaining oral microbial balance and systemic inflammatory risk mitigation.}, } @article {pmid41624188, year = {2025}, author = {Ohmi-Shimizu, N and Takano, C and Tsuji, NM and Iwama, M and Okamura, N and Komine-Aizawa, S and Hayakawa, S and Ogawa, E and Morioka, I and Ishige, M}, title = {Sibling-controlled study of the impact of dietary therapy on the gut microbiota in children with phenylketonuria.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1662634}, pmid = {41624188}, issn = {2296-861X}, abstract = {BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase activity. Due to intolerance to the dietary intake of phenylalanine (Phe), the patients need to take a low-protein diet alongside immediate utilization of Phe-free medical formula upon diagnosis to maintain optimal plasma Phe concentrations. While dietary influences on gut microbiome composition are well-established, the potential alterations in microbiota and their impact on the immune function of children with PKU remain underexplored. We therefore conducted a pilot, sibling-controlled study to assess how dietary therapy for PKU affects gut microbiota and whether these changes are associated with food allergy incidence.

MATERIALS AND METHODS: A questionnaire-based survey was conducted across multiple institutions to determine the prevalence of food allergies in children with PKU. Four children with PKU who have unaffected siblings were recruited to investigate their dietary intake and immunological profiles. Stool samples from both groups were collected and analyzed for gut microbiota composition and short-chain fatty acid (SCFA) profiles.

RESULTS: The survey indicated a notably low prevalence of food allergies in children with PKU (approximately 1%). The four children with PKU strictly adhered to a low-protein diet and maintained their blood phenylalanine levels within the target therapeutic range. Among the PKU group, only one child had an egg allergy, while the remaining children showed no allergic tendencies. Although no adverse immunological effects were observed, the gut microbiota composition of the PKU group significantly differed from that of the unaffected siblings, as indicated by the weighted UniFrac distance (p = 0.027). In the PKU group, the abundance of Faecalibacterium prausnitzii was significantly reduced (p = 0.002), that of Bifidobacterium was increased, and Akkermansia muciniphila was detected. No overall decrease in total SCFA levels was observed in the PKU group, although the acetate/butyrate ratio significantly increased.

DISCUSSION: This study is the first to characterize the gut microbiota of children with PKU using their unaffected siblings as genetically and environmentally matched controls. Our findings suggest that the distinctive dietary management in PKU results in a characteristic gut microbial profile. We further propose a novel hypothesis that these compositional shifts may establish a unique intestinal microenvironment in diet-adherent PKU, which could be negatively associated with the development of food allergy. Larger cohort studies incorporating host metabolomic profiling are needed to determine causal links between dietary therapy and immunological background, ultimately contributing to improved nutritional management.}, } @article {pmid41624179, year = {2026}, author = {Rana, MS and Shamsuzzaman, M and Shin, JH and Lee, YJ and Kim, B and Seo, MG and Seo, SM and Kim, SH and Lee, JC and Kim, J and Kim, S}, title = {Bentonite-Based Functional Nanoclay Enhances Bacteriophage Therapy against Enteric Infections via Toxin Adsorption and Microbiome Recovery.}, journal = {Biomaterials research}, volume = {30}, number = {}, pages = {0310}, pmid = {41624179}, issn = {1226-4601}, abstract = {Diarrheal infections caused by antibiotic-resistant Escherichia coli pose a serious threat to human and animal health, driving the need for innovative therapeutic strategies. This study introduces a dual-action strategy that integrates bacteriophage EC.W2-6 with bentonite to enhance bacterial clearance and macromolecular toxin removal. Phage EC.W2-6 demonstrated high specificity against enterotoxigenic E. coli (ETEC) H10407, achieving nearly 100% adsorption to host cells within 15 min and a moderate burst size of approximately 80 plaque-forming units per infected cell. Bentonite exhibited substantial dose-dependent binding of ETEC-secreted proteins and outer membrane vesicles (OMVs), with the 30-g treatment showing the highest efficiency. Nanoparticle tracking analysis confirmed a 3.56-fold reduction in OMVs at 5 g bentonite and near-complete removal at 30 g. Physicochemical analysis indicated a stabilizing effect of bentonite, showing that bentonite-phage association partially neutralized the phage surface charge (from -34.2 to -13.4 mV), forming a more stable colloidal complex with an approximately 2-fold decrease in colloidal size. In a murine diarrheal model, single therapy with either EC.W2-6 (multiplicity of infection = 0.1) or 8% bentonite conferred 60% survival, whereas combination treatment provided 100% protection with a synergistic effect. Microbiome analysis revealed that dual therapy restored gut microbial diversity and suppressed Proteobacteria expansion, closely resembling healthy controls. These findings highlight the therapeutic potential of combining bentonite with phage therapy as an integrated macromolecular intervention against ETEC-induced diarrhea and intestinal dysbiosis.}, } @article {pmid41623987, year = {2026}, author = {Ren, H and Fan, J and Guo, X and Zhang, B and Zhao, H and Ma, D and Liu, S and Mao, J and Zhang, B and Qiao, J and Jia, C and Ding, X}, title = {Deciphering the characteristics of strong-flavor Daqu at different grades through integrated microbiome and metabolome analysis.}, journal = {Food chemistry: X}, volume = {33}, number = {}, pages = {103526}, pmid = {41623987}, issn = {2590-1575}, abstract = {In strong-flavor Baijiu production, Daqu quality is crucial, yet grading often relies on subjective evaluation. This study compares physical and chemical properties, metal content, microbial composition, and metabolic profiles of three Daqu grades (P90, F90, S90) using a multi-omics approach. P90 exhibits superior esterification power and is dominated by Bacillus, Thermoactinomyce, and Thermomyces, with enhanced ester formation and aromatic precursor accumulation. Although S90 has higher microbial diversity, its lower abundance of key functional strains may limit fermentation efficiency and flavor compound production. PICRUSt analysis reveals grade-specific differences in carbohydrate, amino acid, and nucleotide metabolism pathways. Metabolomic profiling identifies 23 amino acids and derivatives enriched in Daqu, primarily mapping to tryptophan, phenylalanine, and arginine-proline pathways. These likely contribute to aroma precursor synthesis and microbial stability. Overall, these findings elucidate the microbiome-metabolome interactions underlying Daqu quality grading and inform strategies for Daqu quality evaluation and improvement in Baijiu fermentation.}, } @article {pmid41623644, year = {2025}, author = {Chang, Y and Wang, J and Xu, C and Qu, F and Sun, X and Quan, Z and Yin, L and Fang, Y and Wang, C}, title = {Niche-specific maize microbiomes enhance productivity and nitrogen uptake under intercropping.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1711988}, pmid = {41623644}, issn = {1664-302X}, abstract = {Intercropping is widely used to improve crop yield, but the microbial mechanisms driving biomass and nitrogen (N) gains remain unclear. In a maize-soybean intercropping system, we compared intercropped and monocultured maize to investigate niche-specific microbial processes. At the tasseling stage, bacterial and fungal communities were profiled across above- and belowground maize compartments and linked to organ-level biomass and N content. We found that intercropping significantly enhanced maize total biomass and nitrogen uptake, due to the greater increase in roots and leaves. The intercropping also restructured bacterial and fungal communities in a niche-specific manner: bacterial diversity declined in the phylloplane and root, leaf endospheres, whereas fungal diversity increased in the leaf endosphere and stem episphere. Moreover, higher bacterial diversity was associated with lower biomass and N content, while higher fungal diversity showed the opposite trend. Shifts in microbial composition, particularly enrichment of Proteobacteria, Bacteroidota, and Ascomycota, better predicted plant performance than diversity metrics alone. Overall, our findings suggest that intercropping enhances maize growth and N acquisition by steering niche-specific microbial assemblies, highlighting cross-compartment microbiome organization as a promising target for microbiome-informed crop management.}, } @article {pmid41623642, year = {2025}, author = {Kuang, HF and Jiang, XY and Tie, SY and Lian, K and Hao, MY and Xu, H and Huang, X and Yang, Y and Guo, Q and Li, J and Chen, LL}, title = {Global research trends in bacteriophage and gut microbiota: a bibliometric and visual analysis from 2012 to 2025.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1738456}, pmid = {41623642}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiota constitutes a complex microbial ecosystem that plays a fundamental role in host metabolism and immune homeostasis. As the most abundant viral entities in the gut, bacteriophages are increasingly recognized as key modulators of microbial community structure and function. Nevertheless, the global research landscape and thematic evolution of bacteriophage-gut microbiota studies have not been systematically evaluated.

METHODS: Publications related to bacteriophages and the gut microbiota published between 2012 and 2025 were retrieved from the Web of Science Core Collection and Scopus databases. Bibliometric and visual analyses were conducted using CiteSpace, VOSviewer, and Scimago to examine publication trends, countries/regions, institutions, authors, journals, references, and research hotspots.

RESULTS: A total of 687 articles and reviews were included. The annual number of publications increased steadily, with accelerated growth after 2018 and a peak in 2023. China ranked first in publication output, while the United States demonstrated strong centrality in global collaboration networks. The University of California, San Diego and the University of Copenhagen were identified as leading institutions. Highly productive authors included Colin Hill, Bernd Schnabl, Zhang Yue, Li Shenghui, and Ross R. Pau. Frontiers in Microbiology and Nature are the most influential journals in this field. Keyword analyses revealed major research hotspots, including viral metagenomics, antimicrobial resistance, phage-microbiota-immune interactions, and the transition from phage therapy toward microecological and immunomodulatory interventions.

CONCLUSION: Research on bacteriophage-gut microbiota interactions has shifted from descriptive profiling to mechanistic and translational studies, driven by advances in viral metagenomics and phage culturomics. Increasing attention has been directed toward disease-associated phage-microbiota interactions, particularly in inflammatory bowel disease, as well as the development of precision interventions such as phage therapy and engineered phages. This bibliometric analysis provides a comprehensive overview of global research trends and highlights emerging directions for future microbiome research.}, } @article {pmid41623622, year = {2025}, author = {Li, Y and Cheng, Y and Liu, W and Li, J and Li, S and Suriguga, and Ma, T and Kwok, LY and Cai, Z and Sun, Z}, title = {Gut microbial and functional signatures in breast cancer: an integrated metagenomic and machine learning approach to non-invasive detection.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1722632}, pmid = {41623622}, issn = {1664-302X}, abstract = {INTRODUCTION: Breast cancer is associated with significant restructuring of the gut ecosystem. Gut microbial composition and function may influence cancer development and progression through immune modulation, metabolic regulation, and inflammation-related pathways.

METHODS: Using shotgun metagenomic sequencing of fecal samples from 38 stage I-III breast cancer patients and 36 age- and body mass index-matched healthy controls. Machine learning models were constructed to evaluate the diagnostic potential of integrated microbial and metabolic features.

RESULTS: Significant alterations were observed in gut microbiota composition, including depletion of beneficial taxa (Limosilactobacillus fermentum, Blautia sp.) and enrichment of Prevotella copri. Pathways involved in short-chain fatty acid and purine metabolism were reduced. The gut phageome exhibited structural changes and altered correlations with bacterial hosts. Predictive analysis revealed depletion of short-chain fatty acids (butyrate, propionate), purine intermediates (hypoxanthine, xanthine), and nicotinate in patients. A machine learning model integrating microbial and predicted metabolic features achieved an area under the curve values of 0.78 in the discovery cohort and 0.73 (recall = 0.74) in an independent validation cohort.

DISCUSSION: Coordinated gut microbiome, phageome, and metabolome alterations characterize breast cancer, offering potential non-invasive biomarkers and mechanistic insights for disease detection and intervention.}, } @article {pmid41623619, year = {2025}, author = {Wei, T and Qian, N and Wang, H and Song, Y and Wang, W and Li, Y and Zhao, Z and Xu, F and Yang, W}, title = {Wilson's disease-associated gut dysbiosis: novel insights into microbial functional alterations, virulence changes, and resistance markers.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1714276}, pmid = {41623619}, issn = {1664-302X}, abstract = {BACKGROUND: Although the gut microbiota is associated with a variety of metabolic, inflammatory, and neurological disorders through microbial dysbiosis, current studies on the gut microbiota in Wilson's disease (WD) remain limited. Critical gaps exist in understanding the roles of key functional microbial factors in WD pathogenesis, which hinders the acquisition of mechanistic insights into this disease.

OBJECTIVE: This study aims to characterize alterations in the gut microbiome associated with WD, with a particular emphasis on virulence factors (VFs) and antibiotic resistance genes (ARGs), as well as functional mobile genetic elements (MGEs), in order to elucidate their potential roles in disease progression and clinical manifestations.

METHODS: We analyzed fecal samples from 37 patients with WD and 33 healthy controls (HCs) using metagenomic sequencing, with a specific focus on examining virulence gene profiles and antibiotic resistance patterns and MGE composition in relation to liver function markers.

RESULTS: Beta diversity analysis revealed significant differences in the gut microbial community structure between patients with WD and HCs, and a distinct set of microbial taxa was identified that showed significant associations with clinical indicators. A gut microbial co-occurrence network identified key species playing central roles in the microbial community structure, including Prevotella stercorea, Firmicutes bacterium CAG 110, Bacteroides salyersiae, Lactococcus petauri, Streptococcus cristatus, Actinomyces sp. HMSC035G02, and Streptococcus viridans. Widespread functional dysbiosis was detected across multiple biological levels in patients with WD, with significant correlations identified between these microbial alterations and clinical indicators. Significant disruptions were identified in key metabolic pathways, including the Pentose Phosphate Pathway, Pyruvate Metabolism, and Starch and Sucrose Metabolism, which were associated with the dysregulation of carbohydrate-active enzymes (CAZymes). These alterations showed significant correlations with clinical markers of liver dysfunction (e.g., procollagen III N-terminal peptide PIIINP, aspartate transaminase/alanine transaminase AST/ALT). A total of 54 virulence factor (VF) genes exhibited differential abundance in WD, with 36 genes depleted and 18 enriched. Notably, these included colibactin genes (clbB, clbH) from Escherichia coli and type IV secretion system genes (aec19, pilB). These VFs were significantly associated with indicators of liver function (e.g., bilirubin levels) and coagulation abnormalities. Among the detected antibiotic resistance genes (ARGs), 21 exhibited disease-specific patterns in WD, notably tetQ (encoding tetracycline resistance), ErmB (conferring macrolide resistance), and cfxA6 (mediating cephamycin resistance). Furthermore, ARG profiles were associated with Bifidobacterium enrichment and showed significant correlations with lipid metabolism markers [e.g., triglycerides (TG), high-density lipoprotein cholesterol (HDL-C)]. Critically, we identified significant enrichment of 60 functional mobile genetic elements (MGEs) in WD, spanning categories involved in DNA replication/repair, phage activity, and conjugative transfer, indicating heightened genomic plasticity and horizontal gene transfer potential. Strikingly, correlation network analysis revealed strong and specific co-occurrence between key ARGs (e.g., ErmX) and defined suites of MGEs, suggesting MGE-facilitated dissemination of resistance determinants.

CONCLUSION: Wilson's disease (WD) patients exhibit significant alterations in gut microbial community structure and functional dysbiosis, wherein the enrichment of virulence genes (such as colibactin genes clbB/clbH) and the specific antibiotic resistance genes (such as tetQ and ErmB), and the activation of mobile genetic elements are closely associated with clinical indicators including liver function impairment, coagulation abnormalities, and lipid metabolism disorders.}, } @article {pmid41623616, year = {2025}, author = {Zheng, Y and Zhao, W and Hu, X and Li, Z and Gao, K and Jiao, N}, title = {Phosphorus fertilization and maize intercropping with peanut synergistically reshape rhizosphere microbiome and enhance crop yield.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1732662}, pmid = {41623616}, issn = {1664-302X}, abstract = {INTRODUCTION: Optimizing nutrient cycling in diversified cropping systems is essential for sustainable agriculture. While intercropping legumes with cereals can enhance complementary resource use, the interaction between phosphorus (P) fertilization and such systems in restructuring rhizosphere microbiomes and driving synergistic productivity gains in alkaline soils remains unclear.

METHODS: We conducted a long-term field experiment, integrating amplicon sequencing with comprehensive agronomic and soil analyses to investigate this interaction in a maize-peanut intercropping system under P fertilization.

RESULTS: Phosphorus fertilization significantly increased the yields of intercropped maize (by 52.12%) and peanut (by 43.60%), while simultaneously enhancing the intercropping yield advantage (IYA; +60.77%) and land equivalent ratio (LER; +2.54%). Soil P availability was the dominant environmental driver, explaining 73.46% and 84.39% of the variance in bacterial and fungal community structure, respectively. Phosphorus addition and intercropping selectively enriched keystone functional taxa, including the nitrifying bacterium Nitrospirae and the saprophytic fungus Mortierellomycota, whose abundances correlated strongly with improved soil nutrient availability and crop performance. Concurrently, intercropping suppressed the pathogen-rich phylum Ascomycota.

DISCUSSION: Our findings demonstrate that the synergy between P fertilization and intercropping enhances crop productivity through a microbiome-mediated mechanism. This synergy restructures the rhizosphere community into a functionally beneficial state, fostering a self-reinforcing plant-microbe-soil feedback loop. This study provides a mechanistic framework for developing integrated, microbiome-informed management strategies to support sustainable agricultural intensification.}, } @article {pmid41623615, year = {2025}, author = {Lai, X and Hou, S and Liu, S and Zhang, W and Peng, Z and Yang, J and Yan, L and Wang, X}, title = {Mixed application of microbial fertilizers reshapes the tobacco rhizosphere microbiome and enhances metabolic coordination to improve crop quality.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1726681}, pmid = {41623615}, issn = {1664-302X}, abstract = {Sustainable management of flue-cured tobacco requires a careful balance among productivity, chemical composition, and soil ecological function, which are often disrupted by excessive chemical fertilization. This study aimed to elucidate how microbial fertilization regulates plant performance, chemical coordination, and rhizosphere microbial structure under field conditions. A two-year factorial field experiment was conducted in Sichuan, China, using a Bacillus-based plant growth-promoting microorganism (PGPM) and a commercial microbial consortium (Xi⋅Weifeng), applied individually or in combination at gradient doses. Agronomic traits, cured-leaf chemical composition, secondary metabolites, and rhizosphere bacterial communities were comprehensively analyzed using multivariate statistics, network correlation analysis, and structural equation modeling (SEM). Moderate PGPM application (27 kg⋅ha[-1]) significantly increased plant height (8.6%), internode length (15.3%), and leaf width (7.8%) at the vigorous growth stage. Co-application further enhanced leaf expansion (9.7%) and improved chemical coordination, maintaining optimal sugar/nicotine (8-12) and N/nicotine (0.7-1.0) ratios. Chlorogenic acid (18.8 mg⋅g[-1]) and neochlorogenic acid (2.7 mg⋅g[-1]) were markedly elevated under the A27B54 treatment. Rhizosphere bacterial diversity peaked under co-application, with Bacillus, Rhizobiales, and Sphingomonas emerging as key taxa positively associated with both metabolic and agronomic improvements. SEM demonstrated that fertilization effects on leaf quality were mediated indirectly through microbial community restructuring and metabolite modulation. Microbial fertilizer co-application enhances tobacco performance by promoting rhizosphere microbial diversity and functional coordination, which in turn improves metabolic balance and nutrient-use efficiency. These findings highlight a soil microbiome-mediated pathway linking fertilization strategy to crop physiological and chemical responses, providing mechanistic insights for sustainable fertilization management.}, } @article {pmid41623467, year = {2026}, author = {Bisht, A and Ahn-Jarvis, J and Corbin, K and Harris, S and Troncoso-Rey, P and Olupot-Olupot, P and Calder, N and Walsh, K and Maitland, K and Frost, G and Warren, FJ}, title = {Gut microbial diversity impacts carbohydrate fermentation by children with severe acute malnutrition.}, journal = {iScience}, volume = {29}, number = {2}, pages = {114640}, pmid = {41623467}, issn = {2589-0042}, abstract = {African children suffering from severe acute malnutrition (SAM) have a disrupted gut microbiome and low short-chain fatty acids (SCFAs). These are linked to persistently high mortality and morbidity rates. Supplementing recovery feeding regimes with suitable fermentable carbohydrate may improve outcomes in SAM. We adapted in vitro colon models to investigate the ability of children with SAM to utilize four carbohydrate substrates: milk powders (with and without human milk-like oligosaccharides), chickpea-enriched feed, and inulin. All substrates, except inulin, were fermented to produce SCFAs. The inability to utilize inulin ex vivo, a widely used prebiotic, is attributed to low microbial diversity, enriched with Proteobacteria. Stool samples obtained after partial anthropometric recovery showed increased microbial diversity and higher levels of GH32 enzyme family, responsible for inulin metabolism. These findings can inform the design of future therapeutic feeds for the treatment of SAM, where inulin has been found ineffective during initial hospitalization. Alternative carbohydrates appear to be more effective in supporting gut recovery during both the initial and later treatment phases.}, } @article {pmid41455033, year = {2025}, author = {Liu, Y and Eirin, A and Lerman, LO}, title = {Novel Therapeutic Strategies for Obesity-Related Glomerulopathy.}, journal = {Current hypertension reports}, volume = {28}, number = {1}, pages = {3}, pmid = {41455033}, issn = {1534-3111}, support = {DK122734/DK/NIDDK NIH HHS/United States ; HL158691/HL/NHLBI NIH HHS/United States ; AG062104/AG/NIA NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW:: Conventional management primarily focuses on weight reduction and renin-angiotensin-aldosterone blockade; however, these approaches are often insufficient to halt disease progression.

RECENT FINDINGS:: Recent advances have identified novel therapeutic targets and strategies aimed at addressing the metabolic, inflammatory, and hemodynamic abnormalities, as well as gut microbiome dysbiosis, driving obesity-related glomerulopathy (ORG). Pharmacological agents like sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, finerenone, mitochondrial transfer, and fecal microbiota transplantation have demonstrated renoprotective effects through improving weight, insulin sensitivity, blood pressure, inflammation, and gut microbiome. The potential direct renoprotective effects of these medications in ORG, independent of weight loss, warrant further investigation. Additionally, artificial intelligence and emerging biomarkers represent promising strategies for personalized and precise management, early non-invasive diagnosis, and prognostic evaluation of ORG.}, } @article {pmid41623087, year = {2026}, author = {Perucca, P and Perucca, E}, title = {Novel pharmacological therapies in development.}, journal = {Current opinion in neurology}, volume = {}, number = {}, pages = {}, pmid = {41623087}, issn = {1473-6551}, abstract = {PURPOSE OF REVIEW: To review progress in developing new pharmacological treatments for epilepsy, focusing on agents in clinical development.

RECENT FINDINGS: Over 30 different treatments are currently in clinical development, including novel small molecules, nucleic acid-based therapies, stem cells, microbiome-targeting bacteria, and repurposed drugs originally approved for other indications. Most of these treatments target rare epilepsies, particularly the developmental and epileptic encephalopathies, reflecting a development shift from common epilepsies to rare drug-resistant syndromes where unmet therapeutic needs are greatest. Most compounds are still in early development, and publicly accessible data consist mainly of conference reports and congress abstracts. For only two compounds (the Kv7 activator azetukalner and the inhaled emergency treatment Staccato alprazolam) has evidence of efficacy been obtained from relatively large, well designed randomized placebo-controlled trials.

SUMMARY: New paradigms in drug discovery have brought to development innovative treatments with diverse targets and mechanisms of action. Many of these treatments are etiology-targeting and have the potential for disease-modifying effects. Although high-quality evidence is awaited, there is hope that over the next few years, much needed life-changing therapies will be widely available for millions of people with disabling, drug-resistant epilepsies.}, } @article {pmid41622839, year = {2026}, author = {Wei, G and Zhang, H and Zhao, S and Jiang, J and Liu, C and Li, P and Ni, Y and Dai, H and Fan, L and Wei, H and Xi, J}, title = {Polysaccharide Engineered Nanozymes Target Inflammation for Alleviating Colitis-Associated Mental Disorders via Microbiome-Gut-Brain Axis.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e22010}, doi = {10.1002/adma.202522010}, pmid = {41622839}, issn = {1521-4095}, support = {22472146//National Natural Science Foundation of China/ ; BK20231329//Natural Science Foundation of Jiangsu Province/ ; YZLYJFJH2024YXBS164//Yangzhou "Lvyang Jinfeng" Talent Program/ ; YZ2024084//Yangzhou Key Research, Development Program (Social Development)/ ; 2025M782949//China Postdoctoral Science Foundation/ ; 25KJD416004//Natural Science Foundation of Jiangsu Higher Education Institution/ ; YZ2025125//Natural Science Foundation of Yangzhou Municipality/ ; }, abstract = {Molecular therapies for colitis-associated mental disorders show limited efficacy because they usually focus on a single pathway and exhibit substantial off-target toxicity toward healthy tissues. To tackle this limitation, bioinformatic approaches are employed to predict that inflammation and metabolism may be potential targets for Fucoidan. Guided by this prediction, we develop oral polysaccharide engineered nanozymes, Fucoidan-cerium nanocomplexes (FucCeNCs), which are capable of targeting the inflamed colon through electrostatic interactions, exerting anti-inflammatory effects, and concurrently regulating gut microbiota-derived metabolism. In a murine model of ulcerative colitis-associated mental disorders, FucCeNCs show anti-inflammatory and gut barrier-protective effects, thereby suppressing microglial/astrocytic overactivation and preserving neuronal integrity through the transmission of anti-inflammatory cytokines via gut-brain axis. Importantly, FucCeNCs restore gut microbial homeostasis through increasing the relative abundance of probiotics and reducing proportions of pathogens. This shift results in a marked attenuation of abnormal amino acid biosynthesis and metabolism in fecal metabolites, which in turn leads to elevated levels of bioactive metabolites such as homovanillic acid and γ-aminobutyric acid. These metabolites ultimately attenuate neuroinflammation via the microbiome-gut-brain axis, ameliorating depression- and anxiety-like behaviors. These results identify microbiome-gut-brain axis as pivotal therapeutic target for colitis-associated mental disorders therapy, which can be addressed by polysaccharide engineered nanozymes.}, } @article {pmid41622714, year = {2026}, author = {Weinberg, F and Achreja, A and Roy, A and Animasahun, O and Meghdadi, B and Mittal, A and Yang, F and Davis, M and De La Torre, KM and Mohamed, O and Barnett, SL and Mohan, A and Choppara, S and Kaur, G and Hulbert, A and Weinberg, SE and Dickson, RP and Tripathi, A and Reddy, RM and Ramnath, N and Nagrath, D}, title = {Integrative Analysis of Multi-omic Pathways Predict Cancer-Affected Lobes in Lung Cancer.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1158/1940-6207.CAPR-25-0141}, pmid = {41622714}, issn = {1940-6215}, abstract = {Lung cancer is the leading cause of cancer-related deaths. The human microbiome plays an important role in regulating response to cancer therapeutics, outcomes, and biological processes. However, little is known regarding the interplay between the lung microbiome and other biological processes in cancer. In an exploratory pilot study, we collected bronchoalveolar lavage fluid and brushings from 20 patients with early-stage lung cancer and performed microbial sequencing, untargeted metabolomics, and cytokine analysis. In addition, we employed computational and machine-learning approaches to identify integrated microbial-immunometabolic pathways. Finally, we performed preliminary mechanistic studies to confirm our findings. Previously, we published that upper airway microbiota were selectively enriched in tumor-affected lobes. In the present study we demonstrate that enrichment of pro-tumorigenic cytokines and specific fatty acids are associated with tumor-affected lobes. Finally, we find that long-chain fatty acid stimulation of macrophages leads to neoplastic transformation of lung epithelial cells. Therefore, the findings of this study identify a perturbed fatty acid-macrophage axis that is a potential biomarker of early-stage lung cancer and will lead to development of novel therapeutic agents.}, } @article {pmid41622628, year = {2026}, author = {Yamada, T and Tateishi, R and Fujishiro, M}, title = {Post-Transplant Hepatocellular Carcinoma: Balancing Immunosuppression and Immune Checkpoint Inhibitors.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2025.1179}, pmid = {41622628}, issn = {2287-285X}, abstract = {Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and hepatocellular carcinoma (HCC). Advances in surgical techniques and immunosuppressive regimens have markedly improved early post-transplant survival. However, long-term outcomes remain compromised by HCC recurrence, chronic rejection, metabolic complications, and de novo malignancies. Recurrence of HCC after LT remains a major clinical challenge, with available prognostic models providing limited accuracy in risk stratification. Simultaneously, systemic therapies for unresectable HCC have rapidly advanced, particularly with immune checkpoint inhibitors (ICIs), providing new opportunities and unique challenges in transplant settings. With ICIs carrying a risk of acute and potentially fatal rejection and lacking controlled data on efficacy or safety in the post-transplant setting, tyrosine kinase inhibitors currently represent a standard option for post-transplant recurrence. Novel biomarkers, such as donor-derived cell-free DNA and the gut microbiome, are emerging as potential tools to refine risk stratification and guide immunosuppression. Furthermore, innovative immunotherapies, including oncolytic viruses and mRNA vaccines, are being explored as tumor-specific approaches. Collectively, these advances may reshape future management of LT recipients.}, } @article {pmid41622615, year = {2026}, author = {Wang, J and Cheng, L and Zhang, J and Qin, Y and Fu, Q and Bai, X and Qi, F and Wu, F and Yang, J and Pan, Y}, title = {Comprehensive Evaluation of Body Lotion in Alleviating Xerosis: A Multi-Omics Approach to Lipid Metabolism and Microbial Community Modulation.}, journal = {Journal of cosmetic dermatology}, volume = {25}, number = {2}, pages = {e70711}, doi = {10.1111/jocd.70711}, pmid = {41622615}, issn = {1473-2165}, mesh = {Humans ; *Lipid Metabolism/drug effects ; *Microbiota/drug effects ; Female ; Ceramides/administration & dosage ; *Skin Cream/administration & dosage/pharmacology ; Lipidomics ; Adult ; Skin/microbiology/drug effects/metabolism ; Middle Aged ; Male ; *Skin Diseases/drug therapy/microbiology ; Water Loss, Insensible/drug effects ; Treatment Outcome ; Multiomics ; }, abstract = {BACKGROUND: Xerosis, marked by a compromised skin barrier and disrupted lipid metabolism, leads to dryness, scaling, and itching. Ceramide and natural oil-based moisturizers can improve skin hydration and barrier repair, but their effects on lipid networks and microbiome interactions have not been well understood.

METHODS: A multicenter, randomized, self-controlled study was conducted to assess the efficacy of a body lotion formulated with ceramides and natural oils in the management of xerosis. The lotion was applied daily to one leg for 4 weeks, with the other leg as a control. Skin radiance, skin scaliness, skin smoothness, stratum corneum hydration, transepidermal water loss, and pH were measured at various intervals. Lipidomics and microbiomics analyses evaluated changes in lipid metabolism and microbial structure.

RESULTS: The body lotion enhanced skin hydration, radiance, and smoothness, while decreasing TEWL and scaling. Lipidomics showed higher levels of essential lipids in the treatment group. Microbiome analysis revealed increased diversity, with more Firmicutes and Cutibacterium and less Proteobacteria, indicating improved skin barrier and microbial balance.

CONCLUSION: This body lotion effectively alleviates dryness, significantly improving skin hydration, barrier function, and texture. It achieves these benefits by restoring the skin's lipid balance and optimizing the microbial community, with lipid-microbiome crosstalk identified as a key mechanism. This multi-omics insight provides a foundation for the targeted management of dry skin.}, } @article {pmid41622331, year = {2026}, author = {Geraldi, MV and Brättemark, E and Lorentzon, M}, title = {Longitudinal associations of dietary intake, physical activity, and short-chain fatty acids with bone development in early postmenopausal women.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {}, number = {}, pages = {}, pmid = {41622331}, issn = {1433-2965}, abstract = {UNLABELLED: Bone loss accelerates in early menopause, increasing fracture risk. In 223 women followed for 2 years, higher fiber and energy intake were linked to better bone structure, while higher fat intake and some physical activity domains were inversely associated. Specific short-chain fatty acids showed positive associations, highlighting diet-microbiome interactions in bone health.

BACKGROUND: The early postmenopausal period is characterized by accelerated loss of bone mineral density (BMD), underscoring the importance of modifiable lifestyle factors as potential targets for prevention.

METHODS: This study is a secondary analysis of the ELBOW trial, a 2-year longitudinal study of early postmenopausal Swedish women. We investigated the association between dietary intake, physical activity, and short-chain fatty acids (SCFAs) with bone outcomes in 223 early postmenopausal Swedish women aged 50-60 years. Assessments were conducted at baseline, 1 year, and 2 years. Diet and physical activity were assessed using validated questionnaires, and SCFAs were measured in plasma. Bone parameters, including total hip BMD, tibial volumetric BMD (vBMD), and bone microarchitecture, were evaluated using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Associations were analyzed using linear mixed models for repeated measures.

RESULTS: Higher baseline fiber intake was positively associated with trabecular bone volume fraction, while total fat was inversely associated with total hip BMD, total vBMD, and cortical area. Greater energy intake during follow-up was positively associated with cortical area. No associations were observed between bone characteristics and calcium or vitamin D intake. Baseline transport-related and changes in domestic/gardening activity were inversely associated with bone measurements. Among SCFAs, baseline levels of acetic acid, formic acid, and isovaleric acid were positively associated with bone outcomes, while changes in caproic acid levels were negatively associated.

CONCLUSION: These findings suggest that specific dietary components and gut microbiota-derived metabolites may play a role in maintaining bone health during early postmenopause and highlight the need for further investigation into their preventive and therapeutic potential.}, } @article {pmid41622302, year = {2026}, author = {Li, S and Zhang, J and Han, L and Yu, Y and Mousa, AA and Zhu, W and Leng, J and Xie, F and Mao, S}, title = {Comparative metagenomic and metatranscriptomic analyses reveal the role of the gayal rumen and hindgut microbiome in high-efficiency lignocellulose degradation.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {18}, pmid = {41622302}, issn = {1674-9782}, support = {U2202203//Joint Funds of the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The gayal (Bos frontalis), a semi-domesticated bovine species, demonstrates exceptional adaptability to lignocellulose-rich diets dominated by bamboo, suggesting the presence of a specialized gastrointestinal microbiome. However, the functional mechanisms underlying this host-microbiome interaction remain poorly understood. Here, we conducted integrated metagenomic and metatranscriptomic analyses of rumen, cecum, and colon digesta from yellow cattle and gayal raised on the same bamboo-based high-fiber diet.

RESULTS: The results showed that gayal exhibited superior fiber-degrading capacity relative to yellow cattle, evidenced by significantly higher (P < 0.05) fiber digestibility, cellulase and xylanase activities, and increased volatile fatty acids production despite identical feed intake. Microbial community analysis revealed distinct composition in both the rumen and hindgut of gayal compared to yellow cattle, with notable enrichment of taxa specialized in lignocellulose degradation. Metatranscriptomic profiling further identified upregulation of key lignin-modification enzymes, particularly AA6, AA2, and AA3, primarily encoded by Prevotella, Cryptobacteroides, Limimorpha, and Ventricola. These enzymes are known to modify lignin structure to increase polysaccharide accessibility. These results demonstrate that gayal hosts a unique and metabolically active gastrointestinal microbiome capable of efficient lignocellulose deconstruction through a coordinated enzymatic cascade, especially effective in dismantling lignin barriers.

CONCLUSIONS: This study provides novel insights into host-microbiome co-adaptation to fibrous feeds and highlights the potential of gayal-derived microbial consortia and enzymes for improving roughage utilization in ruminant agriculture.}, } @article {pmid41621781, year = {2026}, author = {Wang, E}, title = {Deciphering Plant-Microbe Symbioses: A Molecular Blueprint for Precision Agriculture.}, journal = {Journal of molecular biology}, volume = {}, number = {}, pages = {169668}, doi = {10.1016/j.jmb.2026.169668}, pmid = {41621781}, issn = {1089-8638}, abstract = {Symbioses between plants and microbes such as mycorrhizal fungi and rhizobia, provide critical advantages in plant nutrient acquisition and stress resilience, and thereby underpin agricultural sustainability. However, plants coexist with a myriad of soil microbes, including mutualists, pathogens and commensals, and so must accurately differentiate between beneficial, detrimental, and neutral partners to optimize tradeoffs between growth and defense. Since 2013, our research group has been dedicated to addressing fundamental questions in plant-microbe symbioses. Our work encompasses the exchange of nutrients and signals between symbionts, and the differentiation between mutualistic and pathogenic microbes within the rhizosphere microbiome. We first discovered fatty acids as the main carbon source supplied by plants to arbuscular mycorrhizal (AM) fungi and later revealed the phosphate starvation response-centered regulatory network that controls the root and AM fungi phosphorus uptake pathways. In addition, we identified the receptors that recognize Myc factors and have made inroads on revealing the mechanisms underlying how plants distinguish symbiotic and immune signals. The legume-rhizobium symbiosis is understood to have evolved from arbuscular mycorrhizal symbiosis. Related to this, our group identified the Nod factor co-receptor, MtLICK1/2, and revealed that a SHR-SCR module specifies legume cortical cell fate to enable root nodulation. Collectively, our work has provided fundamental insights into the two most agriculturally important plant-microbe symbioses, thereby paving the way for innovative strategies that harness these interactions to advance sustainable agriculture.}, } @article {pmid41621544, year = {2026}, author = {Aragón-Barroso, AJ and González-Martínez, A and González-López, J and Osorio, F}, title = {Impact of operational conditions and microbial dynamics on expanded granular sludge bed reactor performance: A comprehensive review.}, journal = {Bioresource technology}, volume = {}, number = {}, pages = {134118}, doi = {10.1016/j.biortech.2026.134118}, pmid = {41621544}, issn = {1873-2976}, abstract = {Expanded granular sludge bed (EGSB) reactors have emerged as promising high-rate anaerobic treatment systems for industrial wastewater (WW) with increasing organic loads and complex compositions. This review provides a systematic overview of the main operational parameters, including organic loading rate (OLR), volatile fatty acids (VFA), pH, temperature, influent solids, upflow velocity (Vup), extracellular polymeric substances (EPS) production and solids retention time (SRT), focusing on their effects on granule formation and process performance. EGSB stability is governed by defined operational limits, with optimal performance at OLRs of 10-30 kg COD m[-3] d[-1], VFAs below 500-1000 mg L[-1], and moderate Vup (3-6 m h[-1]). Exceeding critical thresholds in VFA, Vup, or influent solids (>5000 mg L[-1]) induces washout and granulation failure, while protein-rich EPS enhance the cohesion and shear resistance of granular biomass under high hydraulic and organic loads. Special attention is paid to microbial community dynamics, emphasizing how substrate characteristics, operational conditions, height-to-diameter ratio, and microbial kinetics jointly shape community shifts, syntrophic interactions, and overall process stability in EGSB reactors. Furthermore, the insights derived from these analyses are used to provide a more robust explanation of anaerobic granulation mechanisms, integrating conceptual models, key physicochemical drivers, and the role of quorum sensing (QS). Based on this integrated framework, this review identifies existing knowledge gaps and proposes future directions to support the development of robust and efficient EGSB systems for the sustainable treatment of complex industrial wastewaters.}, } @article {pmid41621408, year = {2026}, author = {Mesto, G and Al Atrash, E and Rawat, D and Elzayat, H and Miqdady, M and Al-Marzooq, F}, title = {Multispecies Signatures and Driving Factors of Oral Microbiome Dysbiosis in Pediatric Crohn's Disease in the United Arab Emirates.}, journal = {Archives of medical research}, volume = {57}, number = {4}, pages = {103389}, doi = {10.1016/j.arcmed.2026.103389}, pmid = {41621408}, issn = {1873-5487}, abstract = {PURPOSE: Despite the recognized impact of the gut microbiome, research on the oral microbiome is limited, particularly in pediatric patients with Crohn's disease (CD). This study aims to explore salivary microbiome signatures in pediatric patients with CD from the United Arab Emirates (UAE), compared to healthy controls (HC), by analyzing early-life, lifestyle, and disease-specific factors driving dysbiosis.

METHODS: Salivary samples from 52 pediatric patients with CD and HC (n = 26/group) were subjected to 16S rRNA sequencing using Oxford Nanopore technology. Bioinformatics and biostatistical analyses were employed to compare groups and identify microbiota signatures correlated with clinical data.

RESULTS: Enrichment of several species, including Veillonella parvula, Veillonella dispar, and Prevotella denticola, with depletion of beneficial bacteria was observed in CD. Machine learning-based composite biomarker analysis identified 36 species distinguishing CD from HC, most of which are opportunistic pathogens, raising concerns about their potential impact on vulnerable pediatric patients with CD. Multifactorial analysis revealed significant oral microbiome dysbiosis in patients with CD across all 15 analyzed factors, with unique CD-specific biomarkers. The strongest associations with microbial alterations were demonstrated by disease duration, diet, exercise habits, early antibiotic exposure, and delivery method. Among the 19 species analyzed, Capnocytophaga gingivalis demonstrated multifactorial associations, emerging as an integrative biomarker of disease burden. The α-diversity was significantly lower in patients with CD, with distinctive β-diversity patterns.

CONCLUSION: This is the first comprehensive multifactorial analysis of the oral microbiome in pediatric patients with CD from the Middle East, employing novel machine learning approaches for composite biomarker discovery. Core dysbiotic species in CD may serve as potential diagnostic and prognostic biomarkers requiring validation in larger-scale studies.}, } @article {pmid41621364, year = {2026}, author = {Valenzisi, B and Gaston, TF and Parsons, M and Huggett, MJ}, title = {Effect of noise on the behaviour and microbiome of a common temperate estuarine fish.}, journal = {Marine pollution bulletin}, volume = {226}, number = {}, pages = {119347}, doi = {10.1016/j.marpolbul.2026.119347}, pmid = {41621364}, issn = {1879-3363}, abstract = {Underwater noise pollution is an increasing stressor in marine and estuarine environments, with anthropogenic activity altering natural soundscapes and adversely affecting animal behaviour, which is often an early indicator of environmental stress with broader physiological implications. Host-associated microbiomes, particularly the gut, are central to organism health, influencing digestion, immunity, metabolism, and stress regulation. The gut microbiome also plays a key role in linking environmental disturbances with physiological condition and behavioural changes, yet the impacts of noise on these microbial communities remain poorly understood. We examined the behavioural and gut microbial response of Pelates sexlineatus exposed to three acoustic treatments: continuous white noise (i.e. urban hum), short-pulsed white noise (i.e. intermittent boat noise), and ambient control (no added noise), under controlled aquarium conditions. Fish in ambient tanks spent the most time swimming, while fish exposed to noise exhibited increased resting and erratic movements. Microbial communities in fish and water samples, characterised using 16S rRNA gene amplicon sequencing, identified 44 phyla in the fish microbiome and 11 comprised the core microbiome. Strong differentiation was observed between fish and water communities with fish dominated by Firmicutes, Proteobacteria and Actinobacteriota, and water dominated by Bacteroidota and Proteobacteria. Although short-term acoustic exposure did not significantly alter overall microbial diversity, subtle compositional shifts and strong host-environment distinctions highlight the complexity of microbiome responses to environmental stress. This study provides novel insights into the short-term stability of the gut microbiome in estuarine fish and highlights the need for integrated research assessing behavioural and microbial responses to noise pollution.}, } @article {pmid41621269, year = {2026}, author = {Li, J and Dong, W and Kong, A and Wang, G and Yang, J and Zhou, Y and Song, K and Kong, L and Tong, L}, title = {Floating macrophyte growth and decomposition greatly affects the exogenous antimony mobility and microbial community functions in water-sediment system.}, journal = {Water research}, volume = {293}, number = {}, pages = {125448}, doi = {10.1016/j.watres.2026.125448}, pmid = {41621269}, issn = {1879-2448}, abstract = {Anthropogenic antimony (Sb) contamination in aquatic systems poses persistent ecological risks, yet the role of floating macrophyte life-cycle processes in regulating Sb migration and speciation remains poorly understood. In this study, a mesocosm experiment was conducted to investigate how the growth and decomposition of Alternanthera philoxeroides (AP) influence Sb mobility and transformation following exogenous Sb(V) input. Results show that Sb was ultimately sequestered in sediments, which acted as a dynamic regulator rather than a passive sink, controlling Sb retention and long-term reactivity. Rapid surface adsorption was followed by progressive downward migration driven by redox-sensitive remobilization and re-adsorption onto deeper mineral phases, with Sb predominantly associated with amorphous and poorly crystalline Fe/Al (hydr)oxides (67.3-84.1%). Growth of AP accelerated Sb removal from the water column mainly through indirect, DOM-mediated sequestration rather than direct plant uptake, while simultaneously enhancing the vertical redistribution of bioavailable Sb within sediments. In contrast, AP removal followed by decomposition caused pronounced physical and biogeochemical disturbances. These disturbances induced transient reducing conditions, organic matter release, and a marked increase in pH (up to 9.14), collectively promoting Sb remobilization and Sb(III) release into the overlying water. As a result, Sb(III) concentrations were up to 67-fold higher than those in the unvegetated control. Exogenous Sb strongly reshaped sediment microbial communities, selectively enriching metal-tolerant taxa such as Actinomycetota (genus Streptomyces) and favoring functional traits related to Sb detoxification and elemental cycling. Metagenomic evidence indicates that Sb resistance, coupled with coordinated C, N, P, and S cycling functions, enables the indigenous microbiome to actively regulate Sb speciation and mobility, particularly under organic matter inputs derived from macrophyte growth and decomposition. These findings demonstrate that floating macrophytes exert process-level control over Sb cycling, with life-cycle-mediated biogeochemical feedbacks governing its mobility, speciation, and persistence in water-sediment systems.}, } @article {pmid41621204, year = {2026}, author = {Leong, C and Scanlon, R and Kyne, A and Sharpton, TJ and Kent, ML}, title = {Pseudocapillaria tomentosa infections in laboratory larval and Adult Zebrafish (Danio rerio): Development and advances in an in vivo anthelmintic drug discovery model.}, journal = {Veterinary parasitology}, volume = {343}, number = {}, pages = {110704}, doi = {10.1016/j.vetpar.2026.110704}, pmid = {41621204}, issn = {1873-2550}, abstract = {Zebrafish (Danio rerio) are a widely used biomedical model and offers powerful high-throughput screening capabilities for assessing chemical bioactivity. We have previously employed adult zebrafish infected with the intestinal nematode Pseudocapillaria tomentosa to investigate nematode-microbiome interactions, nematode-promoted intestinal neoplasia, and anthelmintic drug discovery. Here we transition this model to a larval zebrafish infection infection to enable larger-scale experimentation and ultimately accelerate anthelmintic discovery. Infection conditions were optimized across 5-30 days post fertilization (dpf). The 30 dpf larvae exhibited the most robust and reproducible infections in multi-well formats, as well as the highest survival relative to younger stages. We described worm development from hatching through larval progression and maturation, addressing a major gap in foundational data with fish capillarids. Using in vitro-hatched larvae and infected larval and adult zebrafish, we documented developmental trajectories from 1 to 37 days post-exposure. Change-point analysis identified putative ecdysis transitions at the following worm lengths (mm): L1/L2 = 0.220, L2/L3 = 0.571, L3/L4 = 1.174, and L4/L5 = 1.584. Finally, we demonstrated proof-of-concept for anthelmintic screening by exposing fish to larvated eggs in the presence of emamectin benzoate (macrocyclic lactone) or fenbendazole (benzimidazole). Both compounds reduced worm burdens after 3 days, with the strongest effects at higher concentrations (0.7 µM emamectin benzoate; 0.3 µM fenbendazole). Together, these findings establishes a proof of concept for larval zebrafish infection platform which bridges the gap between in vitro and mammalian in vivo assays, enabling scalable, efficient, and biologically relevant screening for anthelmintic drug discovery.}, } @article {pmid41620752, year = {2026}, author = {Sharma, A and Küsel, K and Wegner, CE and Pérez-Carrascal, OM and Taubert, M}, title = {Two worlds beneath: Distinct microbial strategies of the rock-attached and planktonic subsurface biosphere.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02325-1}, pmid = {41620752}, issn = {2049-2618}, support = {218627073//Deutsche Forschungsgemeinschaft/ ; B 715-09075//Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft/ ; }, abstract = {BACKGROUND: Microorganisms in groundwater ecosystems exist either as planktonic cells or as attached communities on aquifer rock surfaces. Attached cells outnumber planktonic ones by at least three orders of magnitude, suggesting a critical role in aquifer ecosystem function. However, particularly in consolidated carbonate aquifers, where research has predominantly focused on planktonic microbes, the metabolic potential and ecological roles of attached communities remain poorly understood.

RESULTS: To investigate the differences between attached and planktonic communities, we sampled the attached microbiome from passive samplers filled with crushed carbonate rock exposed to oxic and anoxic groundwater in the Hainich Critical Zone Exploratory and compared it to a previously published, extensive dataset of planktonic communities from the same aquifer ecosystem. Microbial lifestyle (attached vs. planktonic) explained more variance in community composition than redox conditions, prompting us to further investigate its role in shaping functional and activity profiles. Metagenomic analysis revealed a striking taxonomic and functional segregation: the 605 metagenome-assembled genomes (MAGs) from attached communities were dominated by Proteobacteria (358 MAGs) and were enriched in genes for biofilm formation, chemolithoautotrophy, and redox cycling (e.g., iron and sulfur metabolism). In contrast, the 891 MAGs from planktonic communities were dominated by Cand. Patescibacteria (464 MAGs) and Nitrospirota (60 MAGs) and showed lower functional versatility. Only a few genera were shared, and even closely related MAGs (> 90% average nucleotide identity) differed in assembly size and metabolic traits, demonstrating lifestyle-specific functional adaptation. Analysis of active replication indicated that the active fraction of the attached community was primarily represented by the most abundant MAGs. Planktonic communities featured a higher fraction of active MAGs compared to attached communities, but overall with lower relative abundances.

CONCLUSIONS: The high abundance, metabolic specialization, and carbon fixation potential of attached microbes suggest that they are key drivers of subsurface biogeochemical processes. Carbonate aquifers may act as much larger inorganic carbon sinks than previously estimated based on CO2 fixation rates of the planktonic communities alone. Our findings underscore the need to incorporate attached microbial communities into models of subsurface ecosystem function. Video Abstract.}, } @article {pmid41620643, year = {2026}, author = {Ratcliff, JS and Kumari, M and Varga-Weisz, P and O'Gorman, R}, title = {Socioeconomic position and the gut microbiota: a narrative synthesis of the association and recommendations.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2623356}, doi = {10.1080/19490976.2026.2623356}, pmid = {41620643}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Socioeconomic Factors ; Bacteria/classification/genetics/isolation & purification ; *Social Class ; }, abstract = {Evidence suggests that socioeconomic position (SEP) may shape the gut microbiota (GM), representing a mechanism through which social and environmental factors may drive health inequalities, yet no systematic review has examined this association. In this narrative systematic review, we searched PubMed, Web of Science, and Scopus up to 30 November 2024 for observational studies examining associations between measures of SEP and GM diversity, composition, or function in participants of any age, ethnicity, or location. We identified 1,479 unique studies, of which 26 met the inclusion criteria for this review. Associations were observed between SEP indicators and GM features, including alpha (α) and beta (β) diversity, taxonomic composition, and functional pathways. Notably, socioeconomic patterns in α-diversity differed by context, with greater diversity observed in advantaged groups in high-income countries (HICs) but in disadvantaged groups in low- and middle-income countries (LMICs). Differences in β-diversity suggest that advantaged and disadvantaged groups have distinct GM profiles. Furthermore, considerable heterogeneity was evident across studies, particularly in sampling, sequencing, and analytical methods. Overall, socioeconomic-related differences in the GM are evident globally, highlighting the microbiota as a potential target for interventions aimed at reducing health disparities. Further research employing larger and more diverse cohorts, longitudinal designs, metagenomic sequencing approaches, and comprehensive measurement and adjustment of key covariates is needed to deepen understanding of this relationship.}, } @article {pmid41620634, year = {2026}, author = {Du, H and Lin, Q and He, X and Yang, B and Huang, Y and Li, Q and Wang, Y and Wen, R and Lin, W and Li, S and Zheng, L and Ou, Z}, title = {Dynamic involvement of the core gut microbiome XNP_Guild1 in the evolution of gestational diabetes mellitus.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2623353}, doi = {10.1080/19490976.2026.2623353}, pmid = {41620634}, issn = {1949-0984}, mesh = {Humans ; *Diabetes, Gestational/microbiology ; Female ; Pregnancy ; *Gastrointestinal Microbiome ; Adult ; *Bacteria/classification/genetics/isolation & purification ; Prospective Studies ; China ; Infant, Newborn ; Infant ; }, abstract = {Integrated large-scale maternal microbiome cohort analyses are critical for understanding the development of gestational diabetes mellitus (GDM) and its impact on maternal and offspring health. Here, we analyzed the microbiomes of 2,717 mothers and infants from 9 global cohorts, including both public datasets and a prospective cohort in China, using high-throughput sequencing and multilayer network modeling. We systematically identified and characterized a group of "predicted grey zone" individuals whose gut microbial network features fell between those of healthy and GDM subjects, which represent dynamic ecological transition states in disease development. Notably, we identified and validated across cohorts a core gut microbial guild (XNP_Guild1) that remained highly stable and functionally cohesive across healthy, grey zone, and GDM states, and was significantly associated with both disease progression and early pregnancy risk. In an exploratory intergenerational network analysis, we estimated the vertical transmission effect of the core guild and its potential influence on neonatal growth outcomes. These findings highlight the tight interconnection among core functional gut microbes, transitional ecological states, disease evolution, and maternal-infant health, providing a foundation for future targeted interventions and mechanistic studies of the maternal-offspring microecosystem in GDM.}, } @article {pmid41620582, year = {2026}, author = {Mei, LN and Shen, JS and Duan, Y and Shi, ZQ and Peng, HZ and Luo, XD}, title = {Dietary ellagic acid inhibiting gastrointestinal pathogens by modulation of microbiome-metabolite-immune axis.}, journal = {Natural products and bioprospecting}, volume = {16}, number = {1}, pages = {21}, pmid = {41620582}, issn = {2192-2195}, support = {2022SCP003//the High-level Talent Promotion and Training Project of Kunming/ ; No. U2202212//the National Natural Science Foundation of China/ ; 2022YKZY001//Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform/ ; }, abstract = {Antibiotic-induced depletion of the gut microbiota facilitated the colonization of vancomycin-resistant Enterococci (VRE) in the gastrointestinal tract, and then increased patients' susceptibility to secondary infections. Ellagic acid, a major constituent of fruits and nuts, showed various bioactivities except for antibacterial. Interestingly, it promoted the recovery of gut microbiota, enhanced microbial diversity and stimulated the proliferation of probiotic gut microbes, and then ameliorated the overgrowth of pathogens in vivo in our experiment. Moreover, ellagic acid activated Gpr41 and Gpr43 mainly by promoting the production of short chain fatty acids (SCFAs) such as acetic acid and propionic acid to inhibit the NF-ĸB signaling pathway. Then the dietary supplement with ellagic acid might treat infected gut to avoid antibiotic-associated intestinal diseases, and the finding also provided a novel strategy for exploring antibacterial agent besides screening in vitro.}, } @article {pmid41620525, year = {2026}, author = {Yang, Y and Qiu, K and Zhang, Y and Cui, Q and Liu, W and Guo, Y and Liu, H and Xie, Y}, title = {Rhizosphere microbial functions drive ecological stoichiometry in soils across an elevational gradient of a temperate mountain ecosystem.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-026-09553-7}, pmid = {41620525}, issn = {2399-3642}, support = {42001095//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The soil microbiome plays a vital role in maintaining soil nutrient levels and ecological stoichiometry balance. However, the relationships between rhizosphere microbiomes and soil ecological stoichiometric characteristics, including organic carbon (SC), total nitrogen (SN), total phosphorus (SP), and their ratios, remain poorly understood. Here, we used a temperate mountain ecosystem as a natural laboratory along a ~ 2190 m elevational gradient spanning a desert steppe-alpine meadow transition. We investigated rhizosphere microbiomes from 20 dominant plant populations across 17 sites by integrating environmental factors, microbial community structure, functional genes, microbial biomass, and ectorhizosphere soil stoichiometric characteristics. Ectorhizosphere soil stoichiometric characteristics were significantly associated with microbial biomass stoichiometric characteristics, rhizosphere community composition, and C-, N-, and P-cycling genes, with functional genes emerging as the strongest predictors. Structural equation modeling further identified the composition and diversity of functional genes as key drivers of soil stoichiometric characteristics. Geographic and edaphic factors exerted primarily direct effects, whereas climatic influences were indirect and mediated through the rhizosphere microbiome. These findings highlight the rhizosphere microbiome as a critical biological filter linking climate to soil nutrient stoichiometry at the root-soil interface.}, } @article {pmid41620213, year = {2026}, author = {Pope, CE and Jones, RM and Rashied, AA and Nagy, T and Hanson, WH}, title = {Evaluating the Impact of Prophylactic Administration of Ivermectin on the Fecal Microbiome of Healthy C57BL/6J Mice (Mus musculus).}, journal = {Journal of the American Association for Laboratory Animal Science : JAALAS}, volume = {}, number = {}, pages = {1-8}, doi = {10.30802/AALAS-JAALAS-25-139}, pmid = {41620213}, issn = {2769-6677}, abstract = {Upon importation, laboratory mice may undergo prophylactic antiparasitic treatment during quarantine to prevent the introduction of parasites into established colonies. While quarantine protocols vary across institutions, ivermectin is commonly used, administered either orally or topically. However, the impact of these practices on the fecal microbiome remains poorly understood, raising concerns about unintended consequences for experimental outcomes. This study investigated the effects of ivermectin on fecal microbiome composition in naïve, healthy male and female C57BL/6J mice. Animals received either ivermectin-impregnated feed (12 ppm, ad libitum for 4 weeks), weekly topical ivermectin solution (2.0 mg/kg for 4 weeks), or no treatment (controls). Fecal samples were collected for 16S rRNA-based microbiome analysis before ivermectin treatment, immediately posttreatment, and 4 weeks after treatment cessation. Weekly body weights were recorded, and histopathologic evaluation of the small intestine and colon was performed at study completion. Both oral and topical ivermectin treatments resulted in significant alterations in microbiome α and β diversity at the end of treatment, with more pronounced effects observed in female mice. Some of these changes persisted for up to 4 weeks after treatment cessation. Furthermore, the findings indicate a sex-specific effect of ivermectin on specific bacterial orders, with Bacillales predominantly affected in male mice, whereas Coriobacteriales and Bacteriodales were primarily impacted in female mice. During treatment, males receiving topical ivermectin weighed significantly less than controls, while females receiving dietary ivermectin weighed significantly more. Histopathological analysis revealed no abnormalities in intestinal tissues across all groups at 4 weeks posttreatment. These findings demonstrate that ivermectin administration induces measurable and persistent changes in the fecal microbiome of healthy mice. Researchers should consider these effects when designing experiments, and institutions must weigh the benefits of colony protection against potential microbiome-related confounding variables.}, } @article {pmid41619875, year = {2026}, author = {Mathias, K and Petronilho, F and Danielski, LG}, title = {Nose-to-brain axis: mechanistic links between nasal microbiome dysbiosis, neuroinflammation, and brain disorders.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2026.01.039}, pmid = {41619875}, issn = {1873-7544}, abstract = {The nasal microbiome has emerged as a previously underrecognized modulator of neuroinflammation and central nervous system (CNS) homeostasis. Beyond its role in respiratory host defense, this microbial niche is anatomically positioned to directly influence brain physiology through olfactory neuronal pathways, systemic immune signaling, and inter-organ communication within the gut-lung-brain axis. Accumulating evidence indicates that nasal microbiome dysbiosis contributes to blood-brain barrier (BBB) dysfunction, microglial activation, and propagation of neurotoxic protein aggregates, processes implicated in neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and major depressive disorder. This review synthesizes experimental and clinical studies elucidating key mechanisms by which nasal microbial imbalance may impact CNS pathology, including microbial translocation along olfactory neurons, release of pathogen-associated molecular patterns and inflammatory mediators, extracellular vesicle-mediated signaling, and peripheral immune crosstalk. We further highlight clinical observations linking nasal microbiome signatures with olfactory dysfunction, cognitive decline, and altered inflammatory profiles, particularly in systemic conditions such as sepsis. Despite rapid advances in this field, significant knowledge gaps persist, including the limited availability of longitudinal human cohorts capable of establishing causality, incomplete mechanistic validation in translational models, and insufficient characterization of how environmental exposures and aging reshape the nasal microbiome-brain interface. By integrating current evidence and defining these unmet needs, this review positions the nasal microbiome as a promising source of diagnostic biomarkers and a therapeutic target for modulating neuroinflammation and mitigating neurodegenerative progression.}, } @article {pmid41619780, year = {2026}, author = {Saiz-Gonzalo, G and O'Connell, O and Joy, S and McSweeney, S and Kia, NV and Brodkorb, A and Bleiel, SB}, title = {New Insights into Probiotic Enumeration in a Complex Food Matrix: Flow Cytometry and Plate Count Correlation.}, journal = {Journal of AOAC International}, volume = {}, number = {}, pages = {}, doi = {10.1093/jaoacint/qsag009}, pmid = {41619780}, issn = {1944-7922}, abstract = {BACKGROUND: Accurate probiotic enumeration ensures the dose delivered to the mammalian host. Plate counting (PC) detects only culturable cells and can underestimate the total number of viable cells, particularly when some cells are injured or dormant and do not form colonies.

OBJECTIVE: To qualify a flow cytometry assay reporting active fluorescent units (AFU) and to compare counts with the plate-count (PC) method for micro-encapsulated Lacticaseibacillus rhamnosus GG in a snack product.

METHODS: Following AOAC/ICH/USP principles, precision, accuracy, ruggedness, specificity, and robustness of plate count and flow cytometry methods were evaluated for the first time in a commercial yogurt-bite snack product.

RESULTS: Both methods fulfilled the pre-specified performance targets (%RSD ≤ 15; AFU recovery 100-104%; live/dead R2 ≥ 0.95). Analyst to analyst differences were not significant. Flow cytometry spike recoveries were 100-104% across targets. Live/dead mixtures tracked linearly (R2 ≥ 0.95). Across matched samples, AFU and CFU values were equivalent within a pre-specified ± 0.5 log band; batch means typically differed by ≤ 0.2 log with no systematic bias.

CONCLUSIONS: The qualified flow cytometry method provides same-day counts and enumerates all membrane-intact cells, complementing plate counts while meeting analytical performance criteria. Findings endorse the use of AFU in tandem to CFU assessment for probiotic quantification, label accuracy and estimation of microbiome-relevant dose in snack and finished-product matrixes.

HIGHLIGHTS: Flow-cytometry provided same-day results and enumerated all membrane-intact cells for label verification in snack matrixes.s.}, } @article {pmid41619561, year = {2026}, author = {Inoki, L and Toyoda, S and Fukuokaya, W and Yanagisawa, T and Inamoto, T and Nukaya, T and Takahara, K and Tsujino, T and Maenosono, R and Komura, K and Bekku, K and Araki, M and Iwata, T and Fujita, K and , }, title = {Impact of Proton Pump Inhibitor Use on the Efficacy of IO-IO Versus IO-TKI Therapy in Metastatic Renal Cell Carcinoma.}, journal = {Clinical genitourinary cancer}, volume = {24}, number = {2}, pages = {102500}, doi = {10.1016/j.clgc.2025.102500}, pmid = {41619561}, issn = {1938-0682}, abstract = {BASCKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC). Proton-pump inhibitors (PPIs), frequently used to treat gastrointestinal conditions, have been implicated in modulating ICI efficacy, potentially through gut microbiome dysbiosis. However, the impact of PPIs on ICI-based therapies for mRCC remains unclear.

METHODS: This multicenter retrospective cohort study analyzed 427 patients with mRCC classified as intermediate or poor risk according to the IMDC criteria treated with first-line IO-IO (ipilimumab plus nivolumab) or IO-TKI (ICI plus tyrosine kinase inhibitor) therapies. Patients were stratified by PPI use during the 30 days before and including the day of ICI initiation. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between PPI users and nonusers.

RESULTS: PPI use was significantly associated with shorter OS in patients receiving IO-IO therapy (median OS, 23.34 months vs. not reached; P = .002), but not in those receiving IO-TKI therapy (P = .909). Multivariate analysis confirmed PPIs as an independent prognostic factor for OS in the IO-IO group (HR, 1.647; 95% CI, 1.007-2.693; P = .046). No significant differences in PFS or ORR were observed between PPI users and nonusers in either group, although the complete response rate was notably lower in PPI users treated with IO-IO (1.6% vs. 10.3%; P = .025).

CONCLUSIONS: PPI use was associated with inferior survival in mRCC patients receiving IO-IO therapy, potentially through microbiome modulation and other immunologic or clinical mechanisms; however, these findings are based on retrospective data and should be regarded as hypothesis-generating. Caution is advised when prescribing PPIs to patients undergoing ICI-based therapy, particularly IO-IO regimens, and prospective studies are needed to confirm whether avoiding unnecessary PPI use can improve clinical outcomes.}, } @article {pmid41619552, year = {2026}, author = {Lian, Y and Chen, X and Shen, X and Gan, Z and Sun, J and Li, Q and Li, M and Li, J and Luo, J and Liu, X and Feng, W and Jiang, G}, title = {Spatial metabolomics combined with MALDI-MSI unveils gut-brain axis mechanisms of angelica dahurica radix in migraine rats.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {152}, number = {}, pages = {157815}, doi = {10.1016/j.phymed.2026.157815}, pmid = {41619552}, issn = {1618-095X}, abstract = {BACKGROUND: Migraine is a highly disabling neurological disorder characterized by recurrent headaches and complex metabolic disturbances, affecting approximately 15% of the global population. Angelica dahurica Radix (Baizhi), a classic traditional Chinese medicine documented in Shennong Bencao Jing, has been used for millennia to treat migraine, but its underlying mechanism remains unclear.

PURPOSE: This study aimed to explore the gut-brain axis mechanisms underlying Baizhi's anti-migraine effects by integrating multi-omics approaches to clarify its regulatory effects on intestinal barrier function, gut microbiota, and cerebral metabolism.

STUDY DESIGN: A nitroglycerin (NTG)-induced migraine rat model was used, with 48 male Sprague-Dawley rats randomized into four groups (n=12 each): Control (CON, 10 mL/kg water p.o.), Migraine model (NTG, water + NTG 10 mg/kg s.c.), Positive control (SS+NTG, sumatriptan succinate 260 mg/kg p.o. + NTG), and Baizhi aqueous extract (CBZ) group (7.2 g/kg crude drug + NTG). Migraine-like behaviors and biological samples were assessed after 22 days of intervention.

METHODS: The study combined MALDI mass spectrometry imaging (MALDI-MSI)-based spatial metabolomics (to analyze brain metabolic changes), fecal metabolomics (to identify systemic metabolic perturbations), and 16S rRNA sequencing (to profile gut microbiota composition). Additionally, histopathological staining (H&E) and immunohistochemistry (for Occludin and ZO-1) was used to evaluate intestinal barrier function, and ELISA(Enzyme-linked immunosorbent assay) was applied to detect pain-related biomarkers (5-HT, CGRP, TNF-α) in plasma and brain.

RESULTS: CBZ alleviated migraine-like behaviors (reduced head-scratching frequency) and normalized levels of pain-related biomarkers (5-HT, CGRP, TNF-α) in plasma and brain. It repaired intestinal barrier dysfunction by upregulating tight junction proteins (Occludin, ZO-1). 16S rRNA sequencing showed that CBZ reversed NTG-induced gut microbiota dysbiosis, specifically enriching Lactobacillus and reducing pro-inflammatory taxa (e.g., Blautia). Fecal metabolomics indicated restoration of key pathways, including lipid metabolism, glutathione metabolism, and short-chain fatty acid synthesis. MALDI-MSI visualized spatial metabolic normalization in the brain, with CBZ correcting abnormal glucose accumulation, restoring energy metabolism (e.g., ATP/GTP ratios), and regulating lipid signaling (e.g., phosphatidylinositol 4,5-bisphosphate) in specific brain regions.

CONCLUSION: Baizhi alleviates migraine through multi-target regulation of the gut-brain axis, including intestinal barrier repair, gut microbiota remodeling, and cerebral metabolic restoration. Notably, this study on Baizhi represents the first integration of spatial metabolomics (MALDI-MSI) with gut microbiome and systemic metabolomics to elucidate migraine mechanisms, providing a novel multi-omics strategy for understanding the holistic therapeutic effects of traditional Chinese medicine. These findings provide a mechanistic basis for its clinical application in migraine treatment.}, } @article {pmid41619271, year = {2026}, author = {Dissanayaka, DMS and Jayasinghe, TN and Sohrabi, HR and Rainey-Smith, SR and Taddei, K and Masters, CL and Martins, RN and Fernando, WMADB}, title = {Functional Pathways of the Gut Microbiome Associated with SCFA Profiles in Preclinical Alzheimer's Disease.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.1539}, pmid = {41619271}, issn = {2152-5250}, abstract = {Functional activities of the gut microbiome, particularly those contributing to short-chain fatty acid (SCFA) metabolism, play a central role in host-microbe interactions and are linked to neuroinflammatory mechanisms underlying Alzheimer's disease (AD). How microbial metabolic functions relate to SCFA concentrations and cerebral amyloid-β (Aβ) burden during the preclinical stage of AD remains poorly understood. In this study, faecal metagenomes from 87 cognitively unimpaired adults were profiled using HUMAnN3 to generate MetaCyc pathway abundance data, normalised and filtered to retain pathways present in at least 30% of participants. A keyword-based search identified 362 SCFA-related pathways spanning acetate, propionate, butyrate, isobutyrate, valerate and isovalerate metabolism. Associations between microbial functions, SCFA concentrations and Aβ status were evaluated using Spearman correlations, Kruskal-Wallis tests across SCFA quartiles, and multivariable linear regression with false discovery rate correction, supported by canonical correspondence analysis and network modelling. A total of 38 significant SCFA pathway correlations were identified. Acetate, butyrate and total SCFA levels showed positive associations with biosynthetic pathways, including L-arginine biosynthesis II, peptidoglycan biosynthesis and flavin biosynthesis, whereas fermentative pathways such as pyruvate fermentation to acetone and lysine fermentation to butanoate were negatively correlated. Butyrate quartiles demonstrated dose-dependent increases in biosynthetic functions and declines in fermentative routes. Canonical Correspondence Analysis (CCA) confirmed a significant multivariate association, and network analysis revealed enhanced fermentative and methanogenic connectivity among Aβ High participants. These findings indicate that amyloid burden is associated with a shift from anabolic to fermentative microbial metabolism and may inform future studies examining potential mechanistic links in preclinical AD.}, } @article {pmid41619244, year = {2025}, author = {Zahanuddin, A and Rahim, FF and Lau, YL and Mokhtar, AS}, title = {Genetic diversity, microbiome composition and socio-sanitary predictors of head lice (Pediculus humanus capitis) among disadvantaged children in Klang Valley, Malaysia.}, journal = {Tropical biomedicine}, volume = {42}, number = {4}, pages = {435-445}, doi = {10.47665/tb.42.4.010}, pmid = {41619244}, issn = {2521-9855}, mesh = {Humans ; Malaysia/epidemiology ; *Pediculus/genetics/classification ; Animals ; *Microbiota ; Male ; *Lice Infestations/epidemiology/parasitology ; Female ; Child ; Child, Preschool ; *Genetic Variation ; RNA, Ribosomal, 16S/genetics ; Vulnerable Populations ; Infant ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {Pediculosis capitis remains a neglected public health issue in Malaysia, particularly among disadvantaged children. While the genetic diversity of head lice is well studied, their associated microbiome and links to socio-sanitary conditions remain unclear. This study examined 266 children from ten children's establishments in Klang Valley and Greater Kuala Lumpur, of whom 89 (33.46%) were positive for pediculosis capitis. Cytochrome c oxidase subunit I (COI) barcoding identified two clades: A (36%) and C (64%). 16S rRNA metagenomic profiling of pooled samples revealed higher microbial diversity in Clade C compared to Clade A, with opportunistic bacteria, including Propionibacterium acnes, Streptococcus spp., Bacteroides fragilis, and Staphylococcus aureus being detected. Logistic regression identified age, head lice awareness, and eating with hands as significant predictors of infection. These findings demonstrate that head lice not only cluster genetically but also may harbour clade-dependent microbiomes, with potential health implications. The integration of genetic diversity, microbial variation, and socio-sanitary data highlights the multifactorial risks of pediculosis capitis in vulnerable populations, underscoring the importance of combined ectoparasite control and hygiene interventions.}, } @article {pmid41619222, year = {2026}, author = {Hilger, E and Chan, K and Yip, A and Wang, XM and Broderick, C and Arents, B and van Bart, K and Eyerich, K and Rastrick, J and Weidinger, S and Flohr, C and , }, title = {Biomarkers for therapeutic response and adverse outcomes in atopic dermatitis: A systematic review.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {}, number = {}, pages = {}, doi = {10.1111/jdv.70330}, pmid = {41619222}, issn = {1468-3083}, support = {821511//Innovative Medicines Initiative 2 Joint Undertaking (JU)/ ; }, abstract = {INTRODUCTION AND OBJECTIVES: Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease characterized by intense itch that affects approximately 20% of children and up to 10% of adults. Our systematic review aims to identify biomarkers with clinical significance for predicting response to systemic therapies and treatment-related adverse events (AEs) for AD patients.

MATERIALS AND METHODS: A systematic search was conducted across the electronic databases Embase and MEDLINE from database inception to September 2024. All records were independently screened at both the title/abstract and full-text stages. Included articles were randomized controlled trials, cohort studies or case-control studies that reported relevant data for investigating associations between biomarkers and disease progression and/or change in disease activity over time. All discrepancies at any stage were resolved through adjudication by a senior reviewer.

RESULTS: We identified 28 papers evaluating biomarkers for treatment response and 11 for AEs. Across treatment response studies, biomarkers investigated included IgE, eosinophils, LDH, TARC, cytokines, genetic variants and the skin microbiome. Most studies investigated the association between biomarkers and dupilumab, while studies reporting associations between biomarkers and AEs were limited to dupilumab-related conjunctivitis and ocular surface disease (DAOSD). The primary findings on treatment response were inconsistent, demonstrating that while elevated LDH was associated with poorer response to dupilumab, neither IgE nor eosinophil count showed consistent predictive value. Regarding the association between biomarkers and AEs, IgE was identified as the most promising predictor of DAOSD.

CONCLUSION: Predicting therapeutic responses and identifying patients at risk of developing AEs will be increasingly important with an expanding range of treatment options for AD. Finding robust predictive biomarkers for AD, however, is complicated by its clinical heterogeneity and multifactorial aetiology. Collaborative projects, such as BIOMAP, hold great potential to advance precision medicine and enhance individualized care.}, } @article {pmid41619209, year = {2026}, author = {Tang, R and Wang, J and Wang, X and Zeng, M and Gao, W and Yang, K and Xu, L and Li, Y and Zhou, C and Yue, B and Fan, Z and Song, Z}, title = {Large-scale metagenomic analysis reveals host genetics shapes microbiomes in wild freshwater fish gut and skin.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116930}, doi = {10.1016/j.celrep.2026.116930}, pmid = {41619209}, issn = {2211-1247}, abstract = {Wild freshwater fish microbiomes remain underexplored despite their ecological and economic importance. Through metagenomic sequencing of 903 gut/skin samples from 121 species in southwest China, we constructed the Wild Freshwater Fish Microbiome Catalog, comprising 705 metagenome-assembled genomes and 3,271 viral operational taxonomic units). Host phylogeny dominates microbial community variation, explaining 48.2% (skin) and 22.28% (gut) of the variation. Significant phylosymbiosis occurs in wild freshwater fish, particularly Cyprinidae, with a stronger skin than gut signal. Deterministic selection underpins phylosymbiosis via host-specific ecological filtering. Lifestyle factors (diet, living water layer) and geographical location also impact microbial communities. Notably, wild freshwater fish microbiota harbor a complete set of vitamin B12de novo biosynthesis genes, with Cetobacterium as a keystone genus with probiotic potential. Our work expands gut and skin microbial genome resources, reveals host-microbe coevolution in freshwater fishes, and provides probiotic resources for aquaculture.}, } @article {pmid41618640, year = {2026}, author = {Salehimoghaddam, Z and Hynes, AP and Doyle, RT}, title = {From bacterial predators to partners: phages in agriculture.}, journal = {The New phytologist}, volume = {}, number = {}, pages = {}, doi = {10.1111/nph.70959}, pmid = {41618640}, issn = {1469-8137}, support = {2018-05996//Natural Sciences and Engineering Council of Canada (NSERC)/ ; //Farncombe Family Chair in Phage Biology/ ; //McMaster University - Department of Biology/ ; 2023-05144//Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, abstract = {Bacteriophages, viruses that infect bacteria, are critical players for shaping the taxonomic and functional composition of plant-associated microbiomes. Yet, their roles in plant health remain overlooked, along with their implications for sustainable agriculture. While phages are recognized as bacterial predators, they can also promote bacterial survival and competitiveness. Here, we highlight the roles phage play in shaping soil microbiomes and promising phage-based applications for sustainable agriculture. Ongoing research highlights the diverse roles of phages in regulating bacterial populations, enhancing nutrient cycling, improving stress tolerance, and suppressing soil-borne pathogens - microbial traits that directly link to plant health. Additionally, emerging applications such as bioremediation, phage-based biosensors, and microbiome engineering underscore phages' potential to revolutionize sustainable farming and optimize agricultural productivity.}, } @article {pmid41618562, year = {2026}, author = {Shelake, RM and Waghunde, RR and Kim, JY}, title = {Coevolution of plant-microbe interactions, friend-foe continuum, and microbiome engineering for a sustainable future.}, journal = {Molecular plant}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molp.2026.01.010}, pmid = {41618562}, issn = {1752-9867}, abstract = {The coevolution of plant-microbe (PM) associations over approximately 450 million years has been a fundamental driver of terrestrial life, giving rise to mutualistic, commensal, and pathogenic relationships along a dynamic friend-foe continuum. The need to adapt to the host environment has driven the convergent evolution of common strategies among mutualists and pathogens, enabling them to evade or modulate the plant immune system. This review synthesizes PM coevolution within a deep-time, three-pillar framework: organellogenesis, root evolution, and immune gatekeeping, linking ancient endosymbiotic events (mitochondria, chloroplast, and nitroplast) to contemporary holobiont-level phenotypes and biotechnological applications. We organize the friend-foe continuum around a coevolution-guided cost-benefit and tipping-point framework, using identified molecular switches and evolutionary constraints to derive actionable design rules for engineering PM associations. Moving beyond a descriptive toolbox of technologies, we integrate recent breakthroughs to analyze how four principal axes: host and microbial genetics, evolutionary dynamics, environmental and ecological conditions, and metabolic switches define the thresholds that govern microbial lifestyle transitions. Finally, we propose specific, testable strategies for PM coevolution-informed crop improvement, distinguishing near-term feasible targets from long-term speculative goals in nitrogen utilization, synthetic microbial communities, immune receptor engineering, modulation of plant memory, and microbiome-integrated breeding through genome editing, synthetic biology, AI, and microbiome engineering. Together, these approaches extend existing syntheses into a predictive, evolution-informed framework that transforms coevolutionary principles into a functional blueprint for sustainable and resilient agriculture.}, } @article {pmid41618437, year = {2026}, author = {Chong-Nguyen, C and Artiles, RF and Pilgrim, T and Yilmaz, B and Döring, Y}, title = {The gut-heart axis in coronary artery disease: a scoping and narrative review of sex-based microbial and metabolic disparities.}, journal = {Biology of sex differences}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13293-026-00824-w}, pmid = {41618437}, issn = {2042-6410}, abstract = {BACKGROUND: The gut microbiota significantly influences cardiovascular health by regulating host metabolism and generating bioactive compounds like trimethylamine-N-oxide (TMAO) and indoxyl sulfate (IS), both linked to coronary artery disease (CAD). Emerging research indicates sex-based differences in microbial composition and metabolite production, yet their impact on CAD pathophysiology remains unclear. This scoping review summarizes current findings on sex-specific microbial and metabolic differences in individuals with CAD.

METHODS: A systematic search of PubMed and EMBASE was conducted through March 2025 for peer-reviewed studies comparing gut microbiota or metabolite profiles between male and female patients with CAD. Eligible studies used 16S rRNA sequencing, shotgun metagenomics, or metabolite profiling to analyze microbial communities and atherosclerosis-associated metabolites. Mechanistic links from genetics, epigenetics, and hormone-microbiota interactions were integrated to provide a more comprehensive understanding of how gut microbiota may contribute to sex differences in CAD.

RESULTS: Eleven studies met the inclusion criteria for this review. Men with CAD exhibited increased relative abundances of taxa such as Prevotella, Clostridia_UCG_014, UCG_010, and other pro-inflammatory genera, whereas women microbiota was comparatively enriched in Barnesiella, Bifidobacteriales, and other potentially beneficial taxa. Parallel differences emerged in microbial metabolite profiles: men demonstrated elevated plasma levels of TMAO and IS, both associated with heightened cardiovascular risk and disease burden. Conversely, women with CAD had higher circulating levels of secondary bile acids and lower TMAO concentrations.

CONCLUSION: Preliminary studies suggest sex-related differences in gut microbiota composition and metabolite profiles in CAD patients. Integrating mechanistic links from microbial metabolism, genetics, epigenetics, and hormones supports a potential role of the microbiota in sex-dependent disease pathways. Current evidence is limited and mostly observational; well-designed studies are needed to clarify mechanisms, clinical relevance of sex-specific microbiome signatures and specifically assess whether these sex-specific microbial and metabolic differences influence CAD progression and outcomes.}, } @article {pmid41618422, year = {2026}, author = {Wang, T and Gyori, B and Weiss, ST and Menichetti, G and Liu, YY}, title = {Revealing interactions between microbes, metabolites, and dietary compounds using genome-scale analysis.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02312-6}, pmid = {41618422}, issn = {2049-2618}, support = {K25HL173665/HL/NHLBI NIH HHS/United States ; 24MERIT 1185447//American Heart Association/ ; R01AI141529, R01HD093761, RF1AG067744, UH3OD023268, U19AI095219, and U01HL089856/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: The role of gut microbiome in predicting diet response and developing personalized dietary recommendations has been increasingly recognized. Yet, we still lack comprehensive, genome-based insights into which gut microbes metabolize specific dietary compounds.

RESULTS: Here, we leveraged the metabolic networks constructed from well-annotated microbial genomes to characterize the potential interactions between microbes and metabolites, specifically emphasizing the interactions between microbes and dietary compounds. We revealed a substantial, approximately fourfold variation in both the number of metabolites and dietary compounds in the microbial genome-scale metabolic networks across different genera, whereas species within the same genus showed a high metabolic similarity (mean coefficient of variation in microbial network degree CV¯ = 0.023 for metabolites and 0.015 for dietary compounds). We found that the number of species that can utilize a metabolite drastically varies, ranging from 1 to 818 species, with some metabolites being used by a wide range of species (211 out of 1390 metabolites used by more than 95% of species) and others only by a few species (435 metabolites used by less than 5% of species). Leveraging a longitudinal microbiome study, we observed that microbial taxa with similar metabolic capacity tend to have positively correlated abundances, and the gut microbiome's capacity to process dietary compounds is functionally stable. Finally, we propose a network-based method to identify the dietary compounds that are specific to no more than 10 microbial species, offering a new strategy for combining a dietary compound and its linked microbial species to design synbiotics.

CONCLUSIONS: Our results quantitatively reveal large-scale variation and redundancy in gut microbial metabolism and identify dietary compounds linked to only a few microbial species. These findings improve understanding of microbe-metabolite interactions and provide a foundation for the rational design of microbiome-based interventions for healthy benefits. Video Abstract.}, } @article {pmid41618396, year = {2026}, author = {Capparotto, A and Chesneau, G and Tondello, A and Orellana, E and Stevanato, P and Bonato, T and Squartini, A and Hacquard, S and Giovannetti, M}, title = {Plant phenotypic differentiation outweighs genetic variation in shaping the lettuce leaf microbiota.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00850-6}, pmid = {41618396}, issn = {2524-6372}, support = {DOT1471523//PON Ricerca e Innovazione 2014-2020 PhD fellowship/ ; NextGenerationEU 2021 STARS Grants@Unipd program P-NICHE//European Commission/ ; Progetti di Ricerca Dipartimentali - PRID, grant number BIRD214519 to MG//Dipartimento di Biologia, Università degli Studi di Padova/ ; }, abstract = {Lettuce, a widely consumed raw vegetable, harbors leaf-associated microbial communities whose understanding and prediction are crucial for plant and human health. While environmental factors are known to strongly influence plant leaf microbiomes, the role of plant-specific determinants in shaping microbial diversity remains unclear. In this study, we investigated how three key plant factors -genetic distance, plant variety and leaf micro- and macronutrient content- influence the composition and diversity of lettuce leaf bacterial communities, by analyzing 131 fully-sequenced Lactuca sativa genotypes via 16S rRNA amplicon sequencing. Our findings revealed that variety, as defined by breeders, exerts a greater influence on bacterial community diversity than genetic distance or variations in leaf nutrient levels. Together with available and detailed shoot traits they explained 13.4% of the observed bacterial diversity. Inspection of 9 specific leaf morphological traits, with further validation by MAGs analysis, showed that heart formation, head height, and venation types significantly shaped bacterial richness and evenness, mainly acting on non-hub members. These results highlight the strong relationship between leaf morphology and bacterial community structure, suggesting that phenotypic traits play an outsized but understudied role in shaping the leaf microbiota, a crucial aspect of the edible microbiome.}, } @article {pmid41618136, year = {2026}, author = {Liu, J and Elsheikha, HM and Lei, CC and Qin, SY and Liu, Y and Ni, HB and Qin, Y and Yu, HL and Su, JW and Chen, BN and Jiang, J and Sun, HT and Zhang, XX}, title = {Genome-resolved analysis of bile acid-metabolizing microbiota in Tibetan antelope (Pantholops hodgsonii).}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04750-0}, pmid = {41618136}, issn = {1471-2180}, support = {2025ZD01900110//National Science and Technology Major Project for Prevention and Control of Emerging and Re-emerging Infectious Diseases/ ; 2022KJ169//Shandong Province Higher Education Institutions "Youth Innovation Team Plan"/ ; }, } @article {pmid41618101, year = {2026}, author = {Park, SJ and Özdinç, BE and Coker, KG and Walsh, DM and Fox, DJ and Evans, S and Farahnik, J and Moffat, K and Boomgaarden, M and Mischley, LK}, title = {Metagenomics indicates an interplay of the microbiome and functional pathways in Parkinson's disease.}, journal = {NPJ Parkinson's disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41531-026-01271-5}, pmid = {41618101}, issn = {2373-8057}, abstract = {Previous studies suggest there are distinct gut microbial and functional variations in patients with Parkinson's disease (PwPD) that may reveal potential microbiome signatures or biomarkers to aid in early detection of the disease. In this case-control study, we used whole genome sequencing to compare the stool samples of 55 PwPD to 42 healthy controls (HC) from a public database (BioProject Accession PRJEB39223). For bacterial phyla, we observed a greater relative abundance in Firmicutes and Actinobacteria among PwPD, while that of Bacteroidetes was lower. For phages, PwPD had a greater relative abundance of Siphoviridae, Tectiviridae, and Podoviridae, while Microviridae was lower. Moreover, we described 10 functional pathways that most significantly differed between PwPD and HC (all P < 0.0001). In conclusion, significant differences were observed in gut bacteria, phages, and functional pathways between PwPD and HC that both support and conflict with previous case-control studies and warrant further validation.}, } @article {pmid41617858, year = {2026}, author = {Ma, A and Xun, W and Zhang, S and Liang, S and Wei, W and Huang, H and Shen, Q and Xu, G and Zhang, R}, title = {Amino-acid-transporter-mediated assembly of rhizosphere microbiota enhances soil organic nitrogen acquisition in rice.}, journal = {Nature plants}, volume = {}, number = {}, pages = {}, pmid = {41617858}, issn = {2055-0278}, abstract = {Amino acids are plant-available organic nitrogen (N) that can be directly absorbed, but their availability relies on microbial decomposition of organic matter in the soil. Natural variation in Lysine-Histidine-Type Transporter-1 (OsLHT1) (NCBI Gene ID: 3974662) is associated with higher amino acid uptake in japonica rice than in indica. However, how this genetic variation influences rhizosphere microbiome assembly and its subsequent impact on amino acid acquisition remains unclear. In this study, we demonstrate that the OsLHT1a allele in japonica is prevalent in rice grown in high-organic-N soils, where it recruits a distinct rhizosphere microbiome to enhance amino acid acquisition. A synthetic microbiota composed of bacteria enriched by the OsLHT1a allele in japonica enhanced amino acid production in soil through organic matter decomposition and increased root amino acid uptake by upregulating OsLHT1 gene expression. The rhizosphere colonization of the synthetic microbiota was specifically driven by the function of OsLHT1. Notably, organic fertilization facilitated this colonization, thereby improving organic N use efficiency and rice yield. This root-rhizosphere microbiome functional synergy under organic fertilization presents a promising strategy to increase organic fertilizer use efficiency and demonstrates the potential for harnessing plant-gene-associated rhizosphere microbiomes for sustainable agriculture.}, } @article {pmid41617724, year = {2026}, author = {Dong, Z and Sun, MS and He, YD and Zhou, L and Xiang, W and Li, X and Huang, P and Zeng, JG}, title = {Fungal photobiont and microbiome genome composition in the Cladonia uncialis tripartite symbiosis.}, journal = {Scientific data}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41597-026-06624-6}, pmid = {41617724}, issn = {2052-4463}, abstract = {As symbiotic complexes formed through the association of bacteria or algae with fungi, lichens exhibit exceptional adaptability to extreme environments and function as pioneer species in rocky habitat ecological succession. The absence of high quality chromosome-level genome has constrained investigations into lichen adaptive evolution, while functional contributions of symbiotic bacterial communities remain inadequately explored. This study presents the chromosome-level genome assembly of the mycobiont Cladonia uncialis, comprising 28 chromosomes with a total size of 43.49 Mb, generated through integrated PacBio HiFi and Hi-C methodologies. We characterized the symbiotic microbiota using integrated short and long-read sequencing and constructed 31 metagenome-assembled genomes. The community was dominated by Ascomycota (41.16%), Proteobacteria (17.61%), and Bacteroidota (14.20%). Long-read sequencing significantly enhanced detection sensitivity for low-abundance taxa. This study provides essential genomic resources and comprehensive profiles of the symbiotic microbiota, enabling mechanistic exploration of adaptive evolution within lichen symbiotic systems under extreme environmental conditions.}, } @article {pmid41617669, year = {2026}, author = {Jiang, Y and Jiang, S and Wang, Z and Zhu, P and Zhang, J and Teng, F and Huang, S}, title = {Precise probiotic therapy: Advances, bottlenecks, and the road to microbiome-informed nutrition.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2623359}, doi = {10.1080/19490976.2026.2623359}, pmid = {41617669}, issn = {1949-0984}, mesh = {*Probiotics/therapeutic use/administration & dosage ; Humans ; *Gastrointestinal Microbiome ; Precision Medicine/methods ; Host Microbial Interactions ; }, abstract = {The human gut microbiome is a cornerstone of health, yet conventional probiotic therapies often exhibit limited efficacy owing to heterogeneity in host-microbe-environment dynamics. This review dissects the biological and environmental drivers of such variability and highlights emerging frameworks that integrate cross-sectional and longitudinal multi-omics data to predict probiotic treatment outcomes and host metabolic responses. We further spotlight breakthroughs in methodological development in efficient mining and engineering of probiotic strains, which enable the rational design of functionally enhanced, personalized probiotics. By synthesizing these advances, the review underscores the transformative potential of combining data-driven models with precision-engineered microbial therapeutics to address current limitations and usher in a new era of future microbiome-informed nutrition and personalized interventions.}, } @article {pmid41617485, year = {2026}, author = {Chang, YH and Hong, TC and Lin, KT and Hsiao, YJ and Hsu, HE and Waniwan, JT and Silva, RE and Lai, IR and Lee, PC and Lin, MT and Shun, CT and Hsieh, MS and Chen, YJ and Wang, SW and Hsu, WH and Wu, IC and Wang, YK and Li, CC and Wang, JY and Hsu, YC and Fang, H and Lin, ZS and Chang, WH and Lin, JH and Chen, YS and Ko, YC and Shen, CY and Chen, YM and Wang, CY and Jheng, YT and Liu, WY and Wang, YT and Yeh, CW and Huang, PR and Liou, JM and Chen, LT and Han, CL and Wu, DC and Chen, HY and Yu, SL and Wu, MS and Chen, YJ and , }, title = {Integrative proteogenomics maps multifactorial aetiology, progression and therapeutic vulnerabilities in gastric cancer.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-337247}, pmid = {41617485}, issn = {1468-3288}, abstract = {BACKGROUND: Gastric cancer, with disproportionately higher incidence in East Asia, arises from complex host-microbiome-environment interactions beyond Helicobacter pylori (HP) infection. However, the molecular architecture linking environmental carcinogens, microbial succession and host response remains unclear.

OBJECTIVE: To delineate multifactorial aetiologies and clinically actionable subtypes/biomarkers of gastric cancer through integrative proteogenomic, microbial and environmental exposure profiling.

DESIGN: We established a multiomics atlas of paired tumour, adjacent mucosa tissues and blood from 154 treatment-naïve Taiwanese patients, integrating whole-exome sequencing, RNA-seq, proteome and phosphoproteome profiling with carcinogen signatures, HP status, microbiome composition and refined anatomical mapping. Cell-based functional assays tested carcinogen effects. Microbial subtype was assessed in an independent cohort.

RESULTS: A polycyclic-aromatic-hydrocarbon signature, dibenz[a,h]acridine, emerged as a high-risk exposure promoting invasion, immune suppression and poor survival, significantly exceeding nitrosamine-linked risk in this cohort. Multilayer integration defined three initiation ecologies: HP-driven inflammatory, non-HP microbiome-enriched immune-silent and HP-free microbially depleted states. Among HP-negative tumours, a Streptococcus-enriched subtype associated with tight-junction (CLDN18.2/ZO-1/OCLN) disruption and epithelial-mesenchymal transition, whereas a subset of clinically aggressive cases retained CLDN18.2-high epithelial-stable subtype for therapeutic accessibility. An independent cohort revealed gastric juice-derived Streptococcus anginosus abundance inversely correlated with tight-junction proteins. Anatomical mapping reveals location-specific, sex-specific, subtype-specific oncogenic networks and kinase activity, including CDK4 activation in clinical biomarker-negative tumours. Decision-tree models combining exposure and proteome-immune states refined recurrence and survival prediction beyond stage.

CONCLUSION: This proteogenomic framework defines exposure-informed and microbiome-informed gastric cancer subtypes, providing a molecular schema for patient stratification, prevention and actionable therapeutic vulnerabilities.}, } @article {pmid41617205, year = {2026}, author = {Størdal, K and Andersen, S and Mårild, K and Larsson, V and Imberg, H}, title = {Systematic review and meta-analysis of childhood exposure to antibiotics and the subsequent risk of IBD.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf324}, pmid = {41617205}, issn = {1536-4844}, abstract = {BACKGROUND: Antibiotic use in early childhood may alter the developing microbiome and has been proposed as a risk factor for inflammatory bowel disease (IBD). We conducted a systematic review to examine the association between childhood antibiotic use and subsequent risk of IBD.

METHODS: In a systematic literature search, we identified cohort and case-control studies reporting the association between antibiotic use (exposure age <1 to 17 years) and development of IBD. MEDLINE and EMBASE databases were searched from inception through December 31, 2024. Studies reporting a hazard ratio, odds ratio, or risk ratio (RR) were included. To account for heterogeneity, pooled estimates were calculated using the DerSimonian-Laird random-effects model. Estimates were adjusted for potential confounding as reported in the original studies.

RESULTS: We identified 10 studies, of which 8 (n = 2783 cases) reported associations between childhood antibiotics and IBD risk. Additionally, 2 studies on Crohn's disease (CD) and 1 on ulcerative colitis were included in disease-specific analyses. In pooled analyses, antibiotic exposure compared with no exposure was associated with increased risk of IBD (RR, 1.42; 95% confidence interval [CI], 1.23-1.66), CD (RR, 1.59; 95% CI, 1.39-1.81), and ulcerative colitis (RR, 1.23; 95% CI, 1.08-1.40). Heterogeneity was low to moderate (I2 = 0%-35%), and funnel plots did not indicate publication bias (Egger's test, P = .12-.43). Adjustment for infections did not attenuate the association between childhood antibiotic exposure and IBD development.

CONCLUSIONS: While causal interpretation should be cautious, childhood exposure to antibiotics was associated with an increased risk of later IBD, particularly for CD.}, } @article {pmid41617030, year = {2026}, author = {Picking, J and Li, Y and Ticak, T and Ferguson, DJ and Hao, B and Krzycki, JA}, title = {Delineation of the Active Site of MtgB, a Cobalamin-dependent Glycine Betaine Methyltransferase.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {111216}, doi = {10.1016/j.jbc.2026.111216}, pmid = {41617030}, issn = {1083-351X}, abstract = {The MttB superfamily member MtgB catalyzes the methylation of a cognate corrinoid protein with glycine betaine and representatives have been described from both bacteria and archaea. Here we focused on MtgB from Desulfitobacterium hafniense, a protein for which a crystal structure had been previously obtained. We employed different programs to predict the binding of glycine betaine and identified a consensus binding site. The modelled binding site consisted of two aromatic residues, Y97 and a F356, which are both proposed to interact with the quaternary amine portion of glycine betaine via pi:cation interactions. Additionally, two basic residues, H348 and R312, were proposed to interact with the carboxylate group. We carried out site directed substitutions and subsequently tested the necessity of these residues for glycine betaine:cob(I)alamin methyltransferase activity. These experiments supported a role in catalysis for each residue, presumably in placement of glycine betaine at proper position for nucleophilic attack by the Co(I) ion of cobalamin. Subsequently, the structure of the glycine betaine bound enzyme was obtained and confirmed the interaction of these residues with glycine betaine. Other MttB superfamily members with specificity for different quaternary amines were modeled and compared with the glycine betaine bound structure of MtgB. The nitrogen of each quaternary amine was brought within an average value of 1.8 Å to each other, suggesting that members of the superfamily bring their methyl groups into nearly the same space within the TIM barrel prior to methyl group transfer to cob(I)alamin.}, } @article {pmid41616776, year = {2026}, author = {Liu, C and Sun, S and Ren, X and Geisen, S and Wang, S and Jiang, G and Xu, Y and Shen, Q and Jousset, A and Wei, Z and Xiong, W}, title = {Predation by soil protists shifts bacterial metabolism from competitive to cooperative interactions.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2026.01.006}, pmid = {41616776}, issn = {1934-6069}, abstract = {Many soil protists are bacterivores, yet how protist predation reshapes bacterial metabolic interactions and functions remains poorly understood. Here, we combine global soil samples with microbial metabolic simulations, along with soil microcosm-pot validations, to investigate the influence of protists on bacterial metabolic interactions. Across 3,785 metabolic simulations spanning 757 soils, increased protists predicted higher bacterial metabolic interaction potential and cross-feeding but lower metabolic resource overlap and competition. These patterns were confirmed using an independent rhizosphere dataset and metagenomic analysis. Protist predation selected bacterial communities containing GC-rich genomes, acid-carbon-preferring taxa, and enhanced metabolite exchange. Additionally, exposing a synthetic community (SynCom) to protist predation elevated the expression of bacterial genes associated with plant growth-promoting functions. Consistently, microcosm- and pot-based experiments showed that protist addition increased bacterial cross-feeding over time and improved plant performance. Together, we establish a scalable framework to evaluate protist-driven bacterial cooperation and function to guide rational rhizosphere microbiome engineering.}, } @article {pmid41616767, year = {2026}, author = {Dhariwala, MO and Carale, RO and DeRogatis, AM and Rodriguez-Valbuena, H and Okoro, JN and Ekstrand, CA and Weckel, A and Tran, VM and Habrylo, I and Barrere-Cain, R and Ojewumi, OT and Tammen, AE and Tsui, J and Shaikh, S and Yellamilli, S and Aladhami, AK and Schwartz, R and Leech, JM and Merana, GR and Hiam-Galvez, KJ and Mack, M and Halkias, J and Gardner, JM and Rutishauser, RL and Fragiadakis, GK and Spitzer, MH and Combes, AJ and Scharschmidt, TC}, title = {Commensal-myeloid crosstalk in neonatal skin regulates interleukin-1 signaling and cutaneous type 17 inflammation.}, journal = {Immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.immuni.2026.01.005}, pmid = {41616767}, issn = {1097-4180}, abstract = {Early-life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory toward health versus disease. Monocytes, macrophages, and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin. Transient post-natal depletion of these monocytes resulted in heightened interleukin (IL)-17A production by skin T cells, which was particularly sustained among CD4[+] T cells and was sufficient to exacerbate inflammatory skin pathologies. Neonatal skin monocytes were enriched in expression of negative regulators of the IL-1 pathway. Functional in vivo experiments confirmed a key role of excessive IL-1R1 signaling in T cells as contributing to the dysregulated type 17 response in neonatal monocyte-depleted mice. Thus, a commensal-driven wave of monocytes into neonatal skin critically facilitates immune homeostasis in this prominent barrier tissue.}, } @article {pmid41616716, year = {2026}, author = {Breyer, GM and Torres, MC and Rebelatto, R and Wuaden, CR and Pastore, J and Lazzarotti, M and Nicoloso, RDS and Dorn, M and Kich, JD and Siqueira, FM}, title = {From farm to environment: the microbiome and the silent spread of antimicrobial resistance genes in soil despite manure management in swine farms.}, journal = {Journal of environmental management}, volume = {400}, number = {}, pages = {128747}, doi = {10.1016/j.jenvman.2026.128747}, pmid = {41616716}, issn = {1095-8630}, abstract = {The swine industry generates large amounts of organic waste containing antimicrobial residues, requiring efficient manure management to reduce environmental risks. Covered lagoon biodigesters (CLBs) and waste stabilization ponds (WSPs) are commonly used digestion systems, with digestates subsequently applied as organic fertilizers. Although these systems successfully reduce pathogenic bacteria, their effectiveness in removing antimicrobial resistance genes (ARGs) remains unclear. In this study, we compared microbiome and resistome profiles from CLB- (n = 23) and WSP-farms (n = 20) using shotgun metagenomic sequencing of raw and digested manure, as well as fertilized and non-fertilized soils. Our findings indicate that digestate application slightly shifted soil microbial communities and significantly increased bacterial diversity, suggesting the introduction of diverse manure-derived bacteria. Reads from taxonomic markers associated with clinically important pathogens, including Enterobacterales, streptococci (groups A and B), Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Salmonella enterica were still detected in digestates and fertilized soils, regardless of the digestion system. Moreover, DNA sequences associated with ARGs against critical antimicrobials, such as carbapenems, cephalosporins, and glycopeptides persisted. Notably, WSPs exhibited greater accumulation of some ARGs, including OXA-347 and vanG. Overall, although CLBs exerted a lower impact on soil microbial communities and resistomes compared to WSPs, neither system effectively eliminated ARGs. These findings highlight the potential for environmental dissemination of ARGs through manure fertilization and underscore the urgent transition toward more sustainable production practices, including eliminating non-therapeutic antimicrobial use in the swine industry, as well as the need for improved digestion technologies and continuous monitoring under the One Health framework.}, } @article {pmid41616707, year = {2026}, author = {Wasim, I and Mondal, NS and Dey, J and Saikia, L and Law, D and Sen, S and Gautam, MK and Dutta, PP}, title = {Seborrheic dermatitis and dandruff: An overview of pathogenesis, role of Malassezia spp., and natural treatment approaches.}, journal = {Journal de mycologie medicale}, volume = {36}, number = {1}, pages = {101604}, doi = {10.1016/j.mycmed.2026.101604}, pmid = {41616707}, issn = {1773-0449}, abstract = {Seborrheic Dermatitis (SD) and dandruff are prevalent dermatological disorders that primarily affect the sebaceous glands and have significant implications for adults and children. While chronic skin lesions characterise SD, dandruff is characterised by excessive scalp flaking, pruritus, and erythema. Despite their overlapping clinical manifestations, these conditions differ in their underlying pathophysiology, with overgrowth of Malassezia species (spp.) emerging as a central pathogenic factor in both. Malassezia, a commensal yeast naturally residing on the skin, has been implicated in exacerbating inflammation and triggering immune responses, thereby contributing to the initiation and progression of SD and dandruff. In this comprehensive review, we systematically evaluated the role of natural and plant-derived ingredients in managing SD and dandruff, with a particular focus on their effects on Malassezia spp. The literature search was conducted using Google Scholar, Google Patents, PubMed, and SciFinder until December 2025. The extracted data were qualitatively synthesised to identify key findings and highlight existing research gaps. The results indicate that Malassezia spp., particularly Malassezia furfur, play a pivotal role in SD and dandruff by overgrowing, leading to excessive sebum production, yeast colonisation, and subsequent inflammation. M. furfur has been shown to stimulate the release of proinflammatory cytokines and activate the NLRP3 inflammasome, further promoting the inflammatory cascade associated with these conditions. Plant-derived ingredients, such as antimicrobial and anti-fungal compounds, have garnered attention for their potential therapeutic effects. Several studies suggest that substances like tea tree oil, aloe vera and various herbal extracts may reduce Malassezia load and mitigate the inflammation associated with these disorders. However, there remains a lack of clarity regarding the precise mechanisms by which these natural agents influence the skin's microbiome and immune system. Further clinical investigations are essential to assess the efficacy, safety, and optimal formulations of these plant-based treatments. Despite promising evidence supporting their use, additional well-designed studies are needed to clarify their roles and to establish standardised treatment protocols for SD and dandruff management.}, } @article {pmid41616686, year = {2026}, author = {Sattari Khavas, D and Schwartz, SK and Bird, P and Truong, A and Silberg, JJ}, title = {Microbial spies and bloggers: programming cells to convert environmental information into discernible signals.}, journal = {Current opinion in biotechnology}, volume = {98}, number = {}, pages = {103436}, doi = {10.1016/j.copbio.2026.103436}, pmid = {41616686}, issn = {1879-0429}, abstract = {Microbes regulate their dynamic behaviors using the chemical and physical characteristics of their environment. The ability of microbes to continuously convert this physicochemical information into biochemical information and to use organic matter in the environment as a power source makes these organisms attractive as chassis for building sensors. However, most biosensors have severe limitations when considering applications in hard-to-image settings like soils, sediments, and wastewater. Emerging technologies at the interface of biomolecular design, microbiome engineering, and synthetic biology offer new tools to program cells and communities as biosensors for these settings. In this review, we describe innovations in biosensor outputs that are enabling new applications in complex environments, including reporters that are read out using electrochemical, gas chromatography, hyperspectral imaging, and next-generation sequencing methods. We also discuss computational advances that are accelerating the diversification of sensing components by mining metagenomics data for new transcriptional regulators and by designing allosteric protein switches that directly regulate reporter outputs using analytes. We highlight emerging opportunities for programming undomesticated microbes in communities to function as distributed sensors in the environment. Finally, we discuss the need for responsible biosensor development and to modernize regulatory frameworks to support evidence-based assessment of environmental biosensors.}, } @article {pmid41615983, year = {2026}, author = {Gin, TE and Moore, CO and Tomlinson, T and Wilson, G and Gray, A and Sutherland, C and Miller, K and Li, K and Canfield, M and Herrin, B and Lashnits, E and Callahan, B}, title = {Pathogenic bacterial species and the microbiome of cat fleas (Ctenocephalides felis) inhabiting flea-infested homes.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0341824}, pmid = {41615983}, issn = {1932-6203}, mesh = {Animals ; Cats ; *Ctenocephalides/microbiology ; *Microbiota/genetics ; Dogs ; RNA, Ribosomal, 16S/genetics ; *Flea Infestations/veterinary/parasitology/microbiology ; *Bacteria/genetics/classification/isolation & purification ; Phylogeny ; Cat Diseases/parasitology ; Bartonella/genetics/isolation & purification ; }, abstract = {BACKGROUND: Ctenocephalides felis is a common ectoparasite of dogs and cats and can transmit a variety of pathogens including Bartonella and Rickettsia species. These bacteria, along with the known endosymbiont Wolbachia, are well-documented members of the C. felis microbiome, but species-level information is limited. Additionally, little is known about the variation in the C. felis microbiome in fleas from different sources and when different sequencing methods are applied to the same samples.

OBJECTIVE: This study aimed to characterize the flea microbiome using both short-read (V3/V4) and long-read (full-length) 16S rRNA gene sequencing, determine whether long-read sequencing improves species-level identification especially in known pathogenic genera, and evaluate differences in microbial composition between fleas collected from cats, dogs, and environmental traps.

METHODS: Fleas were collected from cats, dogs, and traps in flea-infested homes in Florida, pooled by source, and sequenced using short- (V3/V4) and long-read (full-length) 16S rRNA gene sequencing. Microbial prevalence and abundance were compared across sequencing approaches. Community composition was evaluated for differences between sources and houses. Candidate members of the flea microbiome were identified based on a combination of prevalence, abundance, and statistical signatures of potential contaminant origin. For Rickettsia and Bartonella, species-level taxonomic assignments were refined using a phylogenetic approach.

RESULTS: Wolbachia, Rickettsia, and Bartonella were the most prevalent and abundant taxa. Spiroplasma was identified as a fourth core member of the flea microbiome. Long-read sequencing enabled better, but not perfect, species-level classification of Bartonella and Rickettsia compared to short-read sequencing. Important relationships between specific ASVs and flea sources were identified, for example fleas from cats harbored higher abundances of B. clarridgeiae and B. henselae than fleas from traps.}, } @article {pmid41615917, year = {2026}, author = {Shokoohi, E and Masoko, P}, title = {Morphological traits and microbiome diversity in the free-living nematodes Acrobeles complexus and Zeldia punctata.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0341018}, pmid = {41615917}, issn = {1932-6203}, mesh = {Animals ; *Microbiota ; *Nematoda/microbiology/anatomy & histology ; Bacteria/classification/genetics ; Biodiversity ; }, abstract = {Morphological adaptations play a key role in shaping the feeding behavior and microbiome associations of Cephalobidae nematodes. To investigate how morphology influences nematode-associated microbiomes, we selected two widely distributed species: Acrobeles complexus, exhibiting elaborated oral structures, and Zeldia punctata, with simpler oral morphology. Unlike earlier studies that reported the microbiomes of A. complexus and Z. punctata independently, this study is the first to directly compare the two species. By integrating in silico re-analysis of our previously published microbiome datasets with new light microscopy and scanning electron microscopy (SEM) observations, we demonstrate how morphological adaptations, such as labial probolae and cuticle structures, shape associated bacterial communities. Our results revealed that A. complexus harbored a more diverse bacterial community than Z. punctata. Morphology showed that the complex oral structures of A. complexus facilitated selective bacterial capture, supporting greater microbial diversity compared to the simpler morphology of Z. punctata. Although statistical significance was not observed, the two species showed distinct patterns of microbial richness and diversity. Principal Coordinate Analysis (PCoA) revealed clearly separated bacterial community structures between the species. Linear discriminant analysis effect size identified potential microbial biomarkers at the genus level, including Firmicutes and Clostridium in A. complexus and Actinobacteria and Pseudomonas in Z. punctata. Predicted functional pathway analysis revealed notable differences in microbial metabolism, such as enrichment of bacterial secretion systems in A. complexus and amoebiasis and lipid metabolism pathways in Z. punctata. This study highlights the role of morphological adaptations in shaping microbiome composition in Cephalobidae nematodes and provides insights into the contribution of free-living bacterivorous nematodes to soil microbial balance. These findings lay the groundwork for further studies on nematode-mediated microbial interactions in soil ecosystems.}, } @article {pmid41615721, year = {2026}, author = {Vásquez-Dean, J and Canales, A and Orellana, CA and Garrido, D}, title = {Bifidobacterium as Keystone Species Driving Microbial Interactions in the Infant Digestive Tract.}, journal = {Annual review of food science and technology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-food-052924-065321}, pmid = {41615721}, issn = {1941-1421}, abstract = {Bifidobacterium plays a keystone role in the ecological assembly of the infant-gut microbiome and in shaping host immune and metabolic development. These anaerobic bacteria possess specialized transporters and glycosyl hydrolases that enable the degradation of human milk oligosaccharides (HMOs), driving early microbial succession through coexistence, competition, and priority effects. Their fermentation products, mainly acetate and lactate, acidify the gut environment, inhibit pathogens, and sustain cross-feeding with butyrate-producing microbes, whereas aromatic lactic acids contribute to immune modulation. Ecological and clinical evidence indicates that loss of Bifidobacterium perturbs community structure and increases disease risk. Understanding these interactions has guided the design of HMO-based and synbiotic strategies that aim to restore healthy colonization patterns. Ongoing efforts now integrate ecological, metabolic, and computational approaches to better predict and replicate the health-promoting functions of Bifidobacterium throughout life.}, } @article {pmid41615587, year = {2026}, author = {Zhu, B and Chen, YE and Guo, Y}, title = {Emerging Mechanisms of Abdominal Aortic Aneurysm.}, journal = {Current atherosclerosis reports}, volume = {28}, number = {1}, pages = {17}, pmid = {41615587}, issn = {1534-6242}, support = {HL109946, HL134569/GF/NIH HHS/United States ; HL166203, HL165688/GF/NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Abdominal aortic aneurysm (AAA) is a progressive and often fatal vascular disease for which effective pharmacological therapies are lacking. This review synthesizes recent mechanistic advances in AAA pathogenesis and evaluates their translational significance for therapeutic development.

RECENT FINDINGS: Single-cell and spatial transcriptomic findings have delineated marked cellular heterogeneity within aneurysmal tissue, revealing dynamic interactions among vascular and immune cell populations. Vascular smooth muscle cell phenotypic modulation and programmed cell death compromise aortic wall integrity, while endothelial dysfunction promotes leukocyte recruitment and mediates early vascular responses. Infiltrating macrophages, neutrophils, and adaptive immune cells orchestrate chronic inflammation and extracellular matrix degeneration, whereas eosinophils and regulatory T cells exert context-dependent protective effects. Local factors, including intraluminal thrombus and perivascular adipose tissue, as well as systemic modulators such as dyslipidemia, gut microbiota, and sex hormones, further shape disease initiation and progression. These mechanistic insights have identified novel therapeutic targets, including inhibitors of regulated cell death, immunomodulatory agents, lipid-lowering interventions, and microbiome-directed strategies, and potential biomarkers for earlier diagnosis and improved risk stratification.

SUMMARY: Emerging mechanistic insights have highlighted the complex interplay among vascular cells, immune cells, the local microenvironment, and systemic modulators in the pathogenesis of AAA. Integrating mechanistic insights with translational research will be crucial in developing targeted interventions that pave the way for effective AAA therapies.

GRAPHICAL ABSTRACT: [Image: see text]}, } @article {pmid41615200, year = {2026}, author = {Yang, J and Qin, X and Zhang, D and Dong, C}, title = {Microbial landscape: composition and health associations of environmental microbiome in key functional spaces of premium elderly care facilities.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0183725}, doi = {10.1128/spectrum.01837-25}, pmid = {41615200}, issn = {2165-0497}, abstract = {The environmental microbiome in elderly care facilities plays a crucial role in the health of aging populations with immunosenescence; however, its composition and health associations remain underexplored. This study characterizes the microbial ecology of premium elderly care facilities, focusing on key functional spaces, environmental drivers, and implications for resident health. We conducted 16S rRNA gene sequencing (V3-V4 regions) on 320 surface and air samples from six functional spaces (dining areas, medical facilities, bedrooms, bathrooms, recreational rooms, and corridors) across four premium elderly care facilities. Environmental parameters (temperature, humidity, CO2, and occupancy) were measured concurrently. Bioinformatics analysis (QIIME 2, DADA2, and Silva database) and statistical modeling (permutational multivariate analysis of variance, distance-based redundancy analysis, and PICRUSt2) were employed to assess microbial diversity, taxonomic composition, functional potential, and environmental correlations. Using 16S rRNA gene sequencing across four facilities in different geographic regions, we identified significant spatial heterogeneity in microbial diversity and composition, with dining areas and recreational rooms exhibiting higher richness (Shannon index: 6.07 ± 0.37) and human-associated taxa (e.g., Firmicutes), while medical facilities and bathrooms harbored lower diversity but elevated opportunistic pathogens (Pseudomonas and Klebsiella). Environmental parameters-particularly relative humidity (explaining 13.8% of community variation) and occupancy-strongly influenced the microbial structure. A core microbiome dominated by Proteobacteria, Firmicutes, and Actinobacteria was conserved across facilities, while functional predictions revealed space-specific traits, including predicted enrichment of antibiotic resistance genes in medical facilities (ARG Shannon diversity: 4.87 ± 0.42) and carbohydrate metabolism pathways in dining areas. Negative correlations between beneficial (Lactobacillus) and pathogenic taxa (Staphylococcus aureus) were consistent with potential ecological strategies for microbial balance, although validation with absolute quantification is needed. This study highlights the need for space-specific microbial management in elderly care environments, emphasizing humidity control, ventilation, and targeted hygiene to mitigate pathogen risks while preserving beneficial communities. Our findings suggest the potential value of ecologically informed stewardship over pathogen-centric approaches. Future research should integrate multi-omics and longitudinal health data to optimize microbiome-resident health interactions.IMPORTANCEAs people age, their immune systems weaken, making the elderly especially vulnerable to germs in their surroundings. This study reveals that the types and amounts of bacteria living on surfaces and in the air within premium elderly care facilities differ significantly depending on the room's purpose-such as dining areas, medical rooms, or bathrooms. We found that humidity and how many people use a space strongly influence these bacterial communities. Crucially, areas like medical rooms had more bacteria linked to infections and antibiotic resistance, while social spaces hosted more diverse and potentially beneficial bacteria. This shows that a "one-size-fits-all" cleaning approach is not ideal. Instead, tailoring hygiene practices and environmental controls (like managing humidity) to specific spaces could better protect residents' health by reducing harmful germs while supporting helpful ones, offering a smarter way to manage these critical living environments for our aging population.}, } @article {pmid41615149, year = {2026}, author = {Mora-Martínez, C and Molina-Mendoza, G and Cenit, MC and Medina-Rodríguez, EM and Larroya-García, A and Sanchez-Carro, Y and Gonzalez-Blanco, L and Bobes, J and Lopez-Garcia, P and Zandio-Zorrilla, M and Lahortiga-Ramos, F and Gili, M and Garcia-Toro, M and Barcelo, B and Ibarra, O and Sanz, Y}, title = {Gut microbiome signatures associated with depression and obesity.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0126325}, doi = {10.1128/msystems.01263-25}, pmid = {41615149}, issn = {2379-5077}, abstract = {UNLABELLED: Depression and obesity are highly comorbid and likely involve common risk factors and pathophysiological mechanisms, which could crosslink to gut microbiome dysfunction. Here, we performed a case-control study with a total of 105 subjects, 43 with major depressive disorder (MDD) and 62 non-depressed controls free from psychiatric comorbidities, to identify gut microbiome signatures associated with MDD and dissect its relation to body mass index (BMI) and lifestyle (diet and exercise). We performed shotgun metagenomics, followed by taxonomic and functional annotations. Using different machine learning methods, we were able to classify subjects into depressed and non-depressed controls with a balanced accuracy of 0.90 and into depressed or non-depressed and normal weight or overweight with a balanced accuracy of 0.78 based solely on taxonomic profiles. We identify novel bacterial taxa associated with depression, including reductions in Butyrivibrio hungatei and Anaerocolumna sedimenticola, and also replicate previously reported associations, such as decreased Faecalibacterium prausnitzii in patients with MDD. Functional annotation of metagenomes shows differences in pathways linked to the synthesis of fundamental nutrients, which have been associated with diet, as well as inflammation. Strikingly, we found an increase in tryptophan degradation and a decrease in queuosine synthesis pathways, both of which are directly related to a decrease in monoaminergic neurotransmitter availability. Additionally, our functional analysis shows that most of the functions that are more abundant in controls than in depressed subjects are encoded by F. prausnitzii. These findings reveal distinct microbial and functional signatures associated with depression, including taxa and pathways linked to neurotransmitter metabolism and independent of other covariates. This suggests that gut microbiome profiling could support diagnosis and the development of gut-directed depression treatments.

IMPORTANCE: This study identifies gut microbiome signatures that are predictive of major depressive disorder (MDD) and explores their links to body mass index (BMI). We uncover bacterial species and metabolic pathways that are associated with MDD, some of them related to neurotransmitter metabolism and inflammation. Among the differences identified, depletion of Faecalibacterium prausnitzii stands out as an important feature in the MDD microbiome, which suggests the possible use of this species to improve depression symptoms. Importantly, we demonstrate shared microbiome features between MDD and BMI, suggesting common underlying mechanisms. This research not only provides a framework for developing microbiome-based diagnostics but also informs future stratified interventions targeting gut microbial functions to improve mental health outcomes.}, } @article {pmid41615148, year = {2026}, author = {Khan, MQN and Xiang, W-Q and Wei, Y-l and Ren, M-X}, title = {Microbial assembly among plant parts of a tropical tree in different habitats and seasons.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0183525}, doi = {10.1128/spectrum.01835-25}, pmid = {41615148}, issn = {2165-0497}, abstract = {Microorganisms are exhibited in every environment, but their role in the ecosystem and host association remains to be understood. Microbiome research highlights environmental filtering as a factor shaping microbial communities in terrestrial ecosystems. We analyzed bacterial and fungal communities in flowers, leaves, branches, trunks, roots, and soil of wild and rice field-grown Bombax ceiba under different seasons using the recent advanced techniques of 16S rRNA and ITS rRNA amplicon pyrosequencing, respectively. Our findings revealed variation in microbial communities across different plant parts and heights (flower, leaf, branch, trunk, roots, and soil). NMDS and hierarchical clustering (Bray-Curtis dis) analysis revealed that bacterial and fungal communities related to endophytic (within plant tissue) and epiphytic (external plant surfaces) niches of above and below-ground parts significantly differed due to seasonal variation in rice and wild habitats. Moreover, seasonal variation significantly affected the number of shared OTUs and bacterial and fungal taxa across all plant parts in both habitats. The spring season significantly influenced microbial diversity, assembly, and correlation networks in plant parts, with the most potent effects in the rice field compared to the wild habitat of Bombax ceiba, influencing flowering and boosting Firmicutes abundance. Wild habitats possessed higher functional diversity than rice-grown fields in spring and autumn across all plant parts, indicating their strong relation with different environments. The outcomes of the present study revealed that seasonal changes across various habitats dynamically shape the plant microbiome, suggesting distinct ecological roles (e.g., nutrient cycling, pathogen suppression, and stress tolerance) for bacterial and fungal communities in various niches.IMPORTANCEThis study shows that seasonal variation and habitat type (wild vs rice field) significantly influence the diversity, composition, and assembly of bacterial and fungal communities in different plant parts of Bombax ceiba. By analyzing both endophytic and epiphytic niches across above- and below-ground compartments, it reveals the spatial complexity of plant microbiomes. Wild habitats support greater stability to microbiome and their functions as compared with rice fields, particularly in spring, indicating that land-use practices affect microbiome structure and function. The study gives the details on how the compositions of microbiomes associated with plants change with season, which can impart insight into sustainable crop-management strategies, as well as conservation measures.}, } @article {pmid41615027, year = {2026}, author = {Jiménez, DJ and Marasco, R and Schultz, J and Rodríguez, CAD and Nogales, J and Rodriguez-R, LM and Overmann, J and Rosado, AS}, title = {Discovery and cultivation of prokaryotic taxa in the age of metagenomics and artificial intelligence.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrag012}, pmid = {41615027}, issn = {1751-7370}, abstract = {Despite advances in sequencing, microbial genomics, and cultivation techniques, the vast majority of prokaryotic species remain uncultured, which is a persistent bottleneck in microbiology and microbial ecology. This perspective outlines a conceptual framework to improve the transition from genome-resolved metagenomics to the targeted isolation of yet-uncultured prokaryotic taxa. The proposed framework integrates the induced reshaping of microbiomes, genome-based inferences of physiological and phenotypic traits, culture media design, and targeted culturomics, enabling hypothesis-driven cultivation. In addition, this manuscript addresses the critical limitations in the field, including the sequence-to-function gap, and emphasizes the synergistic potential of experimental microbiology, microbial ecology, metagenomics, and artificial intelligence (AI)-based predictions to enhance rational and actionable roadmaps for discovering and cultivating novel prokaryotic lineages.}, } @article {pmid41615012, year = {2026}, author = {Bazzar, B and Reshadfar, E and Namdar, P and Pourbagher, D and Lafmejani, RB and Soleimanzadeh, A}, title = {The Relationship Between Seminal Microbiome and Male Reproductive Wellness: A Systematic Review†.}, journal = {Biology of reproduction}, volume = {}, number = {}, pages = {}, doi = {10.1093/biolre/ioag003}, pmid = {41615012}, issn = {1529-7268}, abstract = {The seminal microbiome, which is composed of different types of bacteria in semen and seminal plasma, has a significant impact on male reproductive health by changing the quality of semen and fertility. Previously regarded as sterile, the male reproductive tract contains microbes originating from the gastrointestinal tract, reproductive organs, and external sources such as sexual partners. Dysbiosis alters sperm parameters, triggers inflammation and oxidative stress, and is associated with conditions such as infertility, HPV infection, prostatitis, prostate cancer, and azoospermia. This systematic review adhered to the PRISMA 2020 guidelines (with 2025 extensions for reproducibility) and examined studies from PubMed, Scopus, and Science Direct (2015-2025, with prior context), concentrating on human, in vitro, and rodent models. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes are among the most important phyla. Beneficial genera, such as Lactobacillus, improve sperm motility, concentration, and DNA integrity, whereas dysbiotic taxa, such as Prevotella, Pseudomonas, and Ureaplasma, are associated with declines. Sexual activity facilitates bidirectional microbial transfer, modifying diversity and fostering the dysbiosis. Inflammatory cytokines, reactive oxygen species, and metabolic disruptions are all involved in this process. Changes that are specific to a disease, such as higher levels of Fusobacterium in HPV-positive samples, worsen the situation. This review highlights how the microbiome alters sperm function and causes infertility. Standardized methods and long-term studies are needed to prove causality. Probiotics and other therapeutic interventions show promise in restoring balance and boosting fertility.}, } @article {pmid41614969, year = {2026}, author = {Williamson, E and Hill, K and Eisenhofer, R and Hogendoorn, K}, title = {Experimental evidence for the absence of a functional gut microbiome in the solitary bee Megachile tosticauda.}, journal = {FEMS microbiology letters}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsle/fnag012}, pmid = {41614969}, issn = {1574-6968}, abstract = {The eusocial honey bee is a model for insect microbiome research, with socially transmitted gut communities that play key roles in health and development. In contrast, solitary bees lack social transmission pathways and often have an environmentally acquired microbiome, which may or may not be functionally important. Using 16S rRNA gene metabarcoding, previous work has described the bacterial communities in the solitary resin bee Megachile tosticauda larval pollen provisions, brood, and adult bees, but their functional significance has yet to be studied. Here, we investigate the importance of live bacteria for larval development and survival with an antibiotic-feeding experiment, and test whether bacteria are present in adult guts using scanning electron microscopy. Removing live bacteria in the food and gut of feeding larvae had no significant effect on survival or growth. Microscopy revealed no bacterial colonisation of the adult gut, and the dominant taxon detected in larval pollen could not be cultured under targeted conditions. These results suggest an absence of a beneficial gut microbiome in M. tosticauda. Based on our findings, we propose that some bacteria detected by DNA-based methods in M. tosticauda may represent relic DNA, surface-associated or transient bacteria. Our findings highlight fundamental differences in the bacterial associations between social and solitary bees.}, } @article {pmid41614864, year = {2025}, author = {Li, J and Wang, F and Liu, D and Yang, W and Sun, H and Gao, M and Chen, D and Xu, H}, title = {Transcriptomic Profiling of Cutibacterium acnes IA1-Infected Keratinocytes Reveal Hub Genes and CLR Pathway in Acne Pathogenesis.}, journal = {Current issues in molecular biology}, volume = {48}, number = {1}, pages = {}, pmid = {41614864}, issn = {1467-3045}, abstract = {Acne vulgaris is a prevalent chronic inflammatory skin disorder affecting over 85% of adolescents. Emerging evidence indicates that Cutibacterium acnes phylotype IA1 contributes to acne initiation and progression, yet its precise mechanisms in epidermal keratinocytes remain unclear. This study investigated C. acnes IA1's effects on keratinocyte behavior using an in vitro HaCaT cell model. Cells were co-cultured with live C. acnes IA1 (CICC 10864) for 24 h. Transcriptomic profiling identified 769 differentially expressed genes (DEGs; adjusted p < 0.05, |log2FC| > 1), including 392 upregulated and 377 downregulated. The protein-protein interaction network analysis via Cytoscape revealed key hub genes (HNRNPA2B1, HNRNPM, RBM39). Enrichment analyses (GO, KEGG, Reactome, DO) highlighted significant involvement of the C-type lectin receptor (CLR) signaling pathway. Validation experiments showed cellular morphological changes, altered structure, and markedly elevated interleukin-6 (IL-6; p < 0.01), underscoring its role in inflammation. These findings suggest C. acnes IA1 drives acne pathogenesis by regulating hub genes that influence sebaceous gland inflammation, immune activity, and keratinocyte proliferation, positioning them as potential biomarkers for microbiome-targeted therapies. Limitations include the in vitro model's lack of in vivo skin microenvironment complexity and use of only one representative IA1 strain.}, } @article {pmid41614786, year = {2025}, author = {Baek, J and Cho, S and Lee, G and Ki, H and Kim, SY and Choi, GM and Kim, JH and Kim, JW and Park, CM and Kim, SY and Choi, BM and Choi, YG}, title = {Modulation of Moisturizing and Barrier Related Molecular Markers by Extracellular Vesicles Derived from Leuconostoc mesenteroides DB-21 Isolated from Camellia japonica Flower.}, journal = {Current issues in molecular biology}, volume = {47}, number = {12}, pages = {}, pmid = {41614786}, issn = {1467-3045}, support = {RS-2023-KH140908//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Among the microorganisms present in the microbiome of Camellia japonica flowers, extracellular vesicles (EVs) derived from Leuconostoc mesenteroides were isolated to investigate their modulatory effects on moisturizing and barrier-related molecular markers. To identify the function of major proteins in L. mesenteroides DB-21-derived extracellular vesicles (LEVs), Gene Ontology (GO) analysis was performed, revealing ATP binding, ribosomal structural proteins, and metal ion binding as predominant molecular-function categories. These proteomic characteristics provide a molecular context that supports the interpretation of the moisturizing and barrier-related responses observed in this study. To further verify new findings, we performed functional evaluations using in vitro and 3D skin models. LEVs increased the mRNA expression level of HAS3, which encodes hyaluronic acid synthase. In addition, the expression levels of filaggrin and involucrin, key proteins involved in skin barrier formation, increased, and these markers were determined a concentration-dependent increase in a 3D artificial skin model. Also, we confirmed that the expression levels of filaggrin and involucrin, which were reduced by UVB damage, were restored when LEVs were applied. In conclusion, LEVs are effective in enhancing various molecular markers related to the skin barrier function, and these results reveal that they hold promise as next-generation microbiome-based functional ingredients.}, } @article {pmid41614733, year = {2025}, author = {Kim, D and Kim, WJ and Woo, HM and Jeong, H}, title = {PixelCut: A Unified Solution for Zero-Configuration 16S rRNA Trimming via Computer Vision.}, journal = {Current issues in molecular biology}, volume = {47}, number = {12}, pages = {}, pmid = {41614733}, issn = {1467-3045}, support = {ncheon National University Research Grant in 2023. 284//Incheon National University/ ; }, abstract = {16S rRNA amplicon sequencing has been an effective method for profiling microbial taxonomy in microbiome research, as it offers lower per-sample costs and higher sample throughput than shotgun metagenomics. Although 16S rRNA sequencing offers clear advantages over shotgun sequencing, it depends on precise trimming of low-quality bases at the 3' ends of reads. Given the widespread use of 16S rRNA amplicon sequencing, there is an increasing demand for analysis tools that can identify errors in the 3' region of reads and remove erroneous bases. While various algorithms for predicting trim locations are widely employed, most are command-line standalone tools, which pose challenges for users with limited computational background or resources. Furthermore, in the absence of biological or experimental priors such as amplicon size, trim position predictions may be unreliable. Here, we introduce PixelCut, a fully automated trim-position prediction framework that requires no hyperparameters or prior biological information for accurate prediction. Unlike most available algorithms that operate on raw FASTQ data, PixelCut analyzes the per-base quality report generated by FastQC to infer trimming positions. Based on the recommended quality score threshold from the quality report, PixelCut inspects the quality scores across bases and automatically determines the recommended trim position using character recognition techniques based on computer vision. We have also developed a user-friendly web application to make the method accessible to those without programming expertise, while offering a command-line version for advanced users. Through comprehensive computer simulations, we show that PixelCut produces taxonomic profiling results that are consistent with those from popular trim-location prediction algorithms.}, } @article {pmid41614677, year = {2026}, author = {Pettersson, M and La Sala, G and Gunnarsson, A and Vildhede, A and Sparklin, B and Holm, B and Petrović, D and Lasky, G and Turick, S and Szydlowska, M and Gopalakrishnan, V and Bake, T and Petersen, J and Brånalt, J and Westerlund, K and Taillefer, M and Henricsson, M and Ek, M and Warrener, P and Roth, R and Cohen, T and Sjögren, T and Fahlander, U and Jurva, U and Morias, Y and Liddle, J}, title = {Discovery of a Highly Potent and Selective Small-Molecule Inhibitor of In Vivo Anaerobic Choline Metabolism by Human Gut Bacteria.}, journal = {Journal of medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jmedchem.5c01451}, pmid = {41614677}, issn = {1520-4804}, abstract = {Trimethylamine (TMA) Lyase is an enzyme expressed in human gut bacteria that plays a pivotal role in the formation of trimethylamine oxide (TMAO), a metabolite implicated in the development of heart failure. Here, we describe a strategy to design covalent inhibitors targeting the active site thiyl radical involved in the catalytic cycle of the enzyme under anaerobic conditions. This strategy led to the discovery of 7, a previously unreported highly potent and selective inhibitor of TMA Lyase. When dosed orally to rats, 7 shows a significant reduction of circulating TMAO levels and, importantly, demonstrates inhibition of TMAO generated from a human microbiome when profiled in a human fecal mouse transplant model.}, } @article {pmid41614625, year = {2026}, author = {Vilela Rodrigues, T and Lima de Jesus, L and Langella, P and de Castro Soares, S and Jan, G and Ariston de Carvalho Azevedo, V and Chatel, JM}, title = {Bacterial cell envelope components of gut commensals: effects in host-microbe interaction.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2618429}, doi = {10.1080/07853890.2026.2618429}, pmid = {41614625}, issn = {1365-2060}, mesh = {*Gastrointestinal Microbiome/physiology/immunology ; Humans ; *Host Microbial Interactions/immunology/physiology ; *Bacteria/immunology/metabolism ; Symbiosis ; *Cell Wall/immunology ; Animals ; Homeostasis ; }, abstract = {The bacterial cell envelope is a complex structure composed of proteins, lipids, and other molecules that form the physical boundary between bacteria and the environment. In the gut microbiome, commensal bacteria play a fundamental role in maintaining intestinal homeostasis and modulating host physiology. Due to their strategic location, bacterial cell envelope components interact directly with the host immune system, intestinal cells, mucus, and other gut structures, leading to diverse biological effects. Even though beneficial bacteria produce effector molecules, the functional diversity of these molecules, especially among gut bacteria, remains largely unknown. This review compiles current knowledge on the structure and function of bacterial cell envelope components, with a specific focus on gut microbiome commensals and their role in host interactions. It highlights key effector molecules, their immunological recognizers, and the downstream mechanisms involved in such microbial-host interactions, in addition to stating important knowledge gaps. Identifying and characterizing these molecular interactions is a crucial step toward developing novel biotherapeutic targets, particularly for inflammatory bowel diseases and other gut-related disorders. By reviewing current findings and outlining key research deficits, this review deepens our understanding of how bacterial cell envelope components shape host-microbe interactions.}, } @article {pmid41614418, year = {2026}, author = {Liang, L and Liu, X and Li, B and Lei, H and Tang, Z and Mai, S and Yang, C and Zhou, Y and Zhang, S and Liu, L}, title = {MicroRNA‑microbiome cross‑kingdom networks drive inflammatory bowel disease through dynamic regulatory ecosystems (Review).}, journal = {International journal of molecular medicine}, volume = {57}, number = {3}, pages = {}, pmid = {41614418}, issn = {1791-244X}, mesh = {Humans ; *MicroRNAs/genetics ; *Inflammatory Bowel Diseases/microbiology/genetics ; *Gastrointestinal Microbiome/genetics ; Animals ; *Gene Regulatory Networks ; }, abstract = {Inflammatory bowel disease (IBD) pathogenesis reflects complex interactions between host immunity and gut microbiome dynamics, with microRNAs (miRNAs) functioning as key mediators of cross‑kingdom communication. Host‑derived miRNAs modulate bacterial gene expression and reshape microbial communities, while gut microbiota influences host miRNA expression through microbial metabolites and multiple immune signaling. In IBD, dysregulated miRNAs disrupt immune homeostasis by affecting inflammatory responses, lymphocyte differentiation and epithelial barrier integrity. Yet many miRNAs exhibit context‑dependent dual functions, complicating therapeutic targeting. Despite their biomarker potential for distinguishing IBD subtypes and tracking disease activity, clinical validation faces substantial obstacles including methodological inconsistencies, patient heterogeneity and temporal expression variability. Single-target miRNA therapeutics have yielded modest clinical outcomes, exposing the resilience of regulatory networks and compensatory mechanisms that limit intervention efficacy. The bidirectional architecture of miRNA‑microbiome communication argues against reductionist approaches. Effective IBD management requires integrated strategies that address multiple regulatory nodes rather than isolated pathways. Advancing this field demands deeper investigation of temporal dynamics, spatial organization and network‑level interactions. Such understanding will inform precision medicine strategies that restore regulatory equilibrium without compromising the adaptive capacity of host‑microbiome systems. Progress depends on recognizing the integrated nature of these regulatory networks rather than treating components in isolation.}, } @article {pmid41614224, year = {2026}, author = {Lyndon, S}, title = {Pathophysiology of Chronic Pain.}, journal = {The Clinical journal of pain}, volume = {}, number = {}, pages = {}, doi = {10.1097/AJP.0000000000001362}, pmid = {41614224}, issn = {1536-5409}, abstract = {OBJECTIVES: Chronic pain affects one in five people and persists because protective nociception is converted into maladaptive neural, immune and psychological states. This review aimed to consolidate mechanistic and clinical evidence to clarify that transformation and identify leverage points for durable relief.

METHODS: Following the Scale for the Assessment of Narrative Review Articles (SANRA) guidance, we conducted a narrative review of articles published 1 January 2000-30 June 2025 across PubMed, Embase, Web of Science, Scopus, CINAHL, PsycINFO and the Cochrane Library, supplemented by grey literature. Eligible studies explored biological, immunological, genetic, epigenetic or psychosocial mechanisms or tested mechanism-targeted interventions. Data were thematically synthesised and appraised for methodological quality.

RESULTS: Convergent findings reveal a multistage cascade: peripheral sensitisation driven by aberrant ion channels and inflammatory mediators; spinal and supraspinal sensitisation sustained by glial activation and loss of inhibition; large-scale cortical and limbic reorganisation that embeds pain within memory and emotion circuits. Neuro-immune dialogue, microbiome dysbiosis, sex-specific responses and environment-induced epigenetic changes amplify these processes, while psychological stress and social adversity modulate their expression. Mapping these mechanisms to neuropathic, nociceptive and nociplastic syndromes highlights therapeutic windows exploited by emerging agents such as calcitonin-gene-related-peptide antibodies, chemogenetic nociceptor silencing, closed-loop neuromodulation, targeted cytokine blockade and microbiota modulation. Biomarker-informed precision approaches promise to replace empirical prescribing.

DISCUSSION: Synthesising cross-disciplinary evidence positions chronic pain as a systems disease requiring integrated, mechanism-based and person-centred care. Defining the shared biological scaffold clarifies why traditional symptom-focused treatments fail and outlines research priorities for disease-modifying analgesics and equitable delivery models.}, } @article {pmid41614138, year = {2025}, author = {Ma, CD and Liao, XB and Yue, JC and Gao, Z and Zhao, SQ and Huang, EW and Zhao, H}, title = {Postmortem submersion interval prediction model based on the rat muscle microbiome.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1685097}, pmid = {41614138}, issn = {1664-302X}, abstract = {OBJECTIVE: Accurate estimation of post-mortem submersion interval (PMSI) is a critical challenge in forensic science. The current research has largely focused on the microbial communities in the skin and gut, which are susceptible to environmental contamination, while the potential of internal tissues remains underexplored. This study aimed to investigate whether the microbiome of skeletal muscle, a relatively closed ecosystem, undergoes a predictable succession following submersion in water PMSI and to evaluate its potential for building a high-precision PMSI prediction model, which is independent of the cause of death (drowning vs. post-mortem submersion).

METHODS: Using 72 male Sprague-Dawley rats, we established drowning (D group) and post-mortem submersion (PS group) models. After submersion in natural aquatic environment for 14 days, skeletal muscle samples were collected at six time. The microbial communities were profiled by high-throughput sequencing of the V3-V4 region of the 16S rRNA gene, followed by analyses of alpha and beta diversity. Based on the observed successional patterns, a two-stage prediction model combining classification and regression algorithms (e.g., random forest, RF) was developed.

RESULTS: The skeletal muscle microbiome exhibited a significant and predictable successional pattern, clearly partitioning into an early-phase (0-3 days) and a late-phase (5-14 days) (PERMANOVA, p < 0.001). This succession was characterized by a shift from the dominant community of Proteobacteria to the dominant community of Firmicutes. Importantly, the cause of death did not significantly impact either the alpha or beta diversity of the microbial communities (PERMANOVA, p = 0.251). The resulting two-stage prediction model demonstrated excellent performance: the classification model distinguished the early and late phases with an accuracy of 90.9% (AUC = 0.9504), and the mean absolute errors (MAE) of regression models was 0.303 days in the early phase and 1.293 days in the late phase.

CONCLUSION: The rat skeletal muscle microbiome undergoes a regular and predictable post-mortem succession unrelated to the cause of death. The stable "microbial clock" within the internal tissue allows the construction of a high-precision two-stage machine learning model for PMSI estimation. Our results establish skeletal muscle as a highly promising new target for forensic microbiology, offering a robust theoretical basis and technical approach to resolving challenges in long-term PMSI estimation.}, } @article {pmid41614136, year = {2025}, author = {Zhao, S and Wang, X and Zhu, H and Guo, G and Mustafa, GR and Mustafa, A and Chen, Y and Li, X and Wang, Y and Zhao, B}, title = {Metagenomic analysis revealed the distribution of antibiotic resistance genes of Awang sheep (Ovis aries) gut microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1740198}, pmid = {41614136}, issn = {1664-302X}, abstract = {Antimicrobial resistance (AMR) in livestock is a major contributor to the global AMR crisis, yet little is known about its dynamics in high-altitude pastoral systems. We performed deep metagenomic sequencing of 100 fecal samples from Tibetan Awang sheep reared under grazing (aw_fm) and captive (aw_qs) conditions. Microbiome profiling revealed striking community shifts: grazing sheep were enriched in Bacteroidetes and Firmicutes, whereas captive sheep showed expansion of Proteobacteria, particularly Acinetobacter, suggesting dysbiosis. The resistome comprised 302 unique ARGs, dominated by rpoB2 (43.3%), Bifidobacterium_adolescentis_rpoB (11.2%), and ugd (10.2%). Grazing sheep carried ARGs mainly against rifamycins and peptide antibiotics, reflecting natural selective pressures, while captive sheep exhibited significantly broader resistance, including tetracyclines, macrolides, and fluoroquinolones (p < 0.05). Enrichment of efflux pump genes (MexK, adeJ) in captive sheep highlighted a shift toward multidrug resistance. These findings demonstrate that rearing practices profoundly restructure the gut resistome, underscoring the need for targeted antibiotic stewardship in high-altitude livestock systems.}, } @article {pmid41614132, year = {2025}, author = {Giese, M and Stefani, E and Larger, S and Pindo, M and Farneti, B and Ajelli, M and Cattani, M and Delgado-Baquerizo, M and Coleine, C and Donati, C}, title = {Highly compartmentalized microbiomes in blueberry microhabitats.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1732372}, pmid = {41614132}, issn = {1664-302X}, abstract = {INTRODUCTION: Blueberries are considered a superfood because of their rich content of vitamins, antioxidants, and fiber, supporting multiple health benefits. Plants host complex microbiomes that play crucial roles in resistance to pathogens, productivity, and stress tolerance. Despite its importance, a comprehensive characterization of the microbiota across all major compartments of cultivated blueberry (Vaccinium corymbosum) is still lacking.

METHODS: Using high-throughput sequencing of marker genes, we provide the first integrative survey of fungal and bacterial communities associated with three distinct plant compartments: rhizosphere, leaf surface, and fruit surface, as well as the bulk soil, across 100 samples, generating datasets of over 4,000 unique fungal and 38,000 unique bacterial amplicon sequence variants (ASVs).

RESULTS: We found clear compartment differentiation, with pronounced shifts in richness, diversity, and taxonomic composition between belowground and aboveground compartments. Alpha diversity peaked in bulk soils and declined progressively toward aboveground tissues. We further detected minimal overlap across compartments, with only 9 fungal and 12 bacterial ASVs shared across all compartments. These findings challenge the soil-origin hypothesis for aboveground microbiota.

CONCLUSION: Blueberry plants harbor highly compartmentalized microbial communities shaped by selective environmental and physiological filtering. Our findings provide a baseline for future development of targeted, compartment-specific bioinoculants aimed at enhancing beneficial microorganisms for blueberry cultivation.}, } @article {pmid41614131, year = {2025}, author = {Xu, Z and Zhang, J and Zhou, H and Zhang, L and Zhang, X}, title = {Gut microbiota composition correlates with insomnia severity: insights from high-throughput sequencing analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1733772}, pmid = {41614131}, issn = {1664-302X}, abstract = {OBJECTIVE: This study investigates differential alterations in gut microbiota characteristics across varying degrees of insomnia severity, aiming to provide empirical evidence elucidating the relationship between sleep disorders and the gut microbiome.

METHODS: A total of 120 insomnia patients, treated at the Clinical Psychology Department of Hangzhou Hospital of Traditional Chinese Medicine between October 2023 and May 2024, were enrolled and categorized into mild (Group B, n = 16), moderate (Group C, n = 42), and severe (Group D, n = 42) cohorts based on Pittsburgh Sleep Quality Index (PSQI) scores. A control group of 20 healthy volunteers (Group A) was recruited for comparison. Fecal samples were collected from all participants for gut microbiota DNA extraction. High-throughput sequencing of the 16S rDNA was performed on the Illumina NovaSeq platform to analyze the alpha diversity, beta diversity, and species composition of the gut microbiota across the groups.

RESULTS: Alpha diversity analysis revealed significantly elevated Chao1 and ACE indices in the insomnia cohorts compared to controls (p < 0.01). Notably, the Shannon index was significantly elevated only in the mild group (Group B, p < 0.05). Beta diversity analysis indicated significant differences in the microbial community structure among groups, with a gradient shift corresponding to increasing PSQI scores. Compositional analysis revealed a progressive decline in the Firmicutes/Bacteroidetes (F/B) ratio that paralleled increasing insomnia severity. The abundance of Clostridia demonstrated a graded decline with increasing insomnia severity, with a significant reduction of approximately 15% observed even in the mild sleep disorder group. LEfSe analysis identified distinct differential microbiota for each group: the healthy group was characterized by Firmicutes and Akkermansia, while the sleep disorder groups were, respectively, enriched in Fusobacteriota, Cyanobacteria, and Desulfobacterota.

CONCLUSION: Gut microbiota structure is intrinsically linked to insomnia severity, characterized by a diminished F/B ratio, reduced Clostridia abundance, and enrichment of pro-inflammatory taxa. The reduction in SCFA-producing Clostridia may impair neuro-immune regulation via the gut-brain axis, potentially exacerbating sleep dysregulation.}, } @article {pmid41614129, year = {2025}, author = {Khang, J and Martinez, R and Brag, K and McGee, JS}, title = {Pharmacomicrobiomics in inflammatory skin diseases: past, present, and the future.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1745985}, pmid = {41614129}, issn = {1664-302X}, abstract = {This mini review article focuses on pharmacomicrobiomics, or the study of how the composition and activity of microorganisms in the body, in particular in the gut, impact drug pharmacokinetics and pharmacodynamics. This evolving field has profound implications for personalized medicine in the management of chronic inflammatory diseases. Particularly in dermatology, patient response to an expanding collection of biologic and small molecule inhibitor therapies coming out on the market remains unpredictable. The decision to start which therapy depends on physician preference, rather than based on what is expected to be the treatment response of each individual. This therapeutic uncertainty leads to sequential treatment failures, increased patient morbidity, and substantial healthcare expenditure. This mini-review synthesizes the evidence surrounding the gut microbiome as a predictive biomarker for therapeutic response in inflammatory skin diseases. We will examine the past use of pharmacomicrobiomics in oncology, where gut microbial signatures were found to predict response to immunotherapy in melanoma. We then analyze the present, focusing on the robust translational models from inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), and the established gut dysbiosis in dermatologic conditions such as psoriasis and hidradenitis suppurativa (HS). Finally, we consider the future, discussing the potential for microbiome-based diagnostics to guide therapy selection for chronic inflammatory skin diseases.}, } @article {pmid41614128, year = {2025}, author = {Wang, J and Bai, C and Tian, Y and Bao, J and Liu, J}, title = {Intercropping reshapes soil stress resistance and growth promotion capabilities through rhizosphere exudates in conjunction with the microbiome.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1708938}, pmid = {41614128}, issn = {1664-302X}, abstract = {Terrestrial plants can affect the growth and health of neighboring plants through interspecific interactions. Long-term monoculture in agricultural and pastoral production can lead to the occurrence of soil-borne diseases, depletion of nutrients, and a decline in soil microbial diversity, thereby affecting the sustainable development of cultivated ecosystems. In this study, we employed three cultivation patterns: monoculture of Melilotus officinalis (L.) Pall. (M. officinalis), monoculture of Avena sativa L. (A. sativa), and intercropping of M. officinalis and A. sativa. To introduce ecologically protective plants into cultivated ecosystems and investigate the effects of plant root exudates on the recruitment of rhizosphere microbiota of neighboring plants, as well as the disease resistance and growth promotion capabilities of intercropping, we conducted non-targeted metabolomics and metagenomics analyses on root exudates and soil microbiota. The sequencing data obtained provided strong evidence for the interaction mechanisms between root exudates and microorganisms in intercropping ecosystems. We observed that in intercropping ecosystems, the abundance and variety of root exudates were more similar to those of the crop plants. The differential metabolites between intercropping and A. sativa were inclined to be chemically defensive, while those between intercropping and M. officinalis were more inclined to promote material synthesis. Compared with A. sativa, intercropping enhances the alpha and beta diversity of soil microbial communities, particularly increasing the enrichment abundance in pathways such as the bacterial secretion system, sulfur metabolism, and phenylpropanoid biosynthesis, which is closely associated with the suppression of soil-borne pathogens. Compared with M. officinalis, intercropping further enhanced the synthesis of plant-available substances in the soil, driving microorganisms to optimize the levels of carbon, nitrogen, and trace elements in the soil. In comparison, intercropping had a significant impact on the aggregation of soil-specific microorganisms, which can optimize nitrogen utilization to promote plant growth and enhance plant defense and stress tolerance. The results of this study will provide a theoretical basis for cultivated ecosystems and sustainable land management.}, } @article {pmid41614125, year = {2025}, author = {Aoki, Y and Tate, M and Ochiai, K and Tsuchimochi, K and Mizuguchi, U and Okazaki, K and Moritake, H}, title = {Brief early antibiotic exposure (≤2 days) is not associated with disruption of gut microbiome in very low birth weight infants.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1742512}, pmid = {41614125}, issn = {1664-302X}, abstract = {Early empirical antibiotic therapy is common in preterm and very low birth weight (VLBW) infants but may disrupt the developing gut microbiome. However, the effects of brief antibiotic courses remain unclear, particularly in the most immature infants. In this prospective multicenter cohort study, we examined gut microbiome trajectories in VLBW infants (many of whom were extremely preterm) receiving no antibiotics, a short course (≤2 days), or prolonged exposure (≥3 days). Serial stool samples were analyzed using 16S rRNA gene sequencing. Microbiome composition and diversity in the short-course group were similar to those in unexposed infants at all timepoints, indicating that brief antibiotic exposure did not disrupt microbial development. In contrast, prolonged exposure was associated with transient dysbiosis characterized by reduced Bifidobacterium abundance and lower alpha diversity, with partial recovery by discharge. These findings suggest that limiting empirical antibiotic therapy to ≤2 days (48 h) when infection is unconfirmed may not disrupt microbiome development even in highly immature preterm VLBW infants, supporting evidence-based antibiotic stewardship in neonatal intensive care.}, } @article {pmid41442422, year = {2026}, author = {Mahdavi, A and Greffard, K and Trottier, J and Barbier, O and Bilodeau, JF and Lebel, M and Rudkowska, I}, title = {Dairy Product Intake Alters the Correlations between Circulating Bile Acids and Short-Chain Fatty Acids with the Bacterial Taxa <italic>Roseburia</italic>, <italic>Faecalibacterium</italic>, <italic>Flavonifractor</italic>, and Verrucomicrobia.}, journal = {Lifestyle genomics}, volume = {19}, number = {1}, pages = {46-62}, doi = {10.1159/000550224}, pmid = {41442422}, issn = {2504-3188}, mesh = {Humans ; *Fatty Acids, Volatile/blood ; *Bile Acids and Salts/blood ; *Gastrointestinal Microbiome ; Male ; *Dairy Products ; Female ; Middle Aged ; Adult ; Cross-Over Studies ; Diabetes Mellitus, Type 2/microbiology/blood ; RNA, Ribosomal, 16S/genetics ; Faecalibacterium/genetics ; }, abstract = {INTRODUCTION: Type 2 diabetes (T2D) risk factors are associated with gut microbiota dysregulation that can alter circulating metabolite levels such as bile acids (BAs) and short-chain fatty acids (SCFAs). The objective was to investigate how the high dairy (HD) (≥4 servings/day) product intake compared to adequate dairy (AD) (≤2 servings/day) intake influences the correlations between Roseburia, Faecalibacterium, Flavonifractor, as well as Verrucomicrobia and circulating BAs and SCFAs in subjects at risk of T2D.

METHODS: In a randomized crossover trial, 10 hyperinsulinemic adults were randomized to HD or AD for 6 weeks separated by a 6-week washout period. Gut microbiota were measured with 16S rRNA-based high-throughput sequencing. BA profiling in plasma was performed by high-performance liquid chromatography-tandem mass spectrometry. Serum SCFAs were determined using headspace gas chromatography.

RESULTS: No significant differences were observed in mean circulating BA or SCFA levels between AD and HD consumption. Verrucomicrobia and Flavonifractor showed positive correlations with secondary BAs following HD and AD intake, respectively. Additionally, Flavonifractor correlated positively with acetic and propionic acids after HD intake. Roseburia correlated positively with primary BAs, propionate, and butyrate after HD intake. Faecalibacterium was positively correlated with cholic acid after AD intake and with hexanoic acid after HD intake.

CONCLUSION: These findings suggest that HD intake may modulate microbiota-metabolite interactions without altering circulating metabolite concentrations, highlighting a potential role for dietary patterns in shaping gut-derived metabolic signals in individuals at risk of T2D.}, } @article {pmid41614121, year = {2025}, author = {Shi, M and Guo, A and Qin, S and Kang, Y and Zhang, W and Yang, X}, title = {Metagenomic insights into short-term legume rotation: modulating potato rhizosphere microbiota to enhance tuber yield and quality.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1680056}, pmid = {41614121}, issn = {1664-302X}, abstract = {OBJECTIVE: This study aims to investigate the effects of legume crop rotation on the rhizosphere microbiota and its potential to improve potato (Solanum tuberosum L.) productivity and tuber quality. We specifically focus on the microbial functional potential revealed through metagenomic sequencing under different legume rotation systems in the intensive agricultural region of the Chinese Loess Plateau.

METHODS: A five-year field experiment (2018-2022) was conducted to establish three cropping systems: (1) continuous potato monocropping for 5 years (CK), (2) continuous potato cropping for 3 years followed by one-year pea rotation and one-year potato cropping (T1), and (3) continuous potato cropping for 3 years followed by one-year faba bean rotation and one-year potato cropping (T2). The impacts of these rotation regimes on potato yield formation, tuber quality, and rhizosphere microbial communities were systematically evaluated, with a focus on microbial diversity and functional potential, using metagenomic sequencing and network analysis.

RESULTS: Metagenomic analysis demonstrated that legume rotation, particularly the T2 system, significantly enriched the relative abundances of Actinobacteria (38.31%) and Proteobacteria (28.40%) in the potato rhizosphere while reducing Acidobacteria (10.03%). Functional annotation further revealed that T2 promoted the expression of microbial genes involved in carbon fixation (K00626, K01895, etc.), nitrogen assimilation (narB, narA, etc.), and sulfur metabolism (cysNC, cysN, etc.), enhanced potential for nutrient cycling. Co-occurrence networks revealed Actinobacteria and Acidobacteria as keystone taxa forming robust interaction modules potentially linked to soil ecological stability. Compared to CK, T2 increased the commercial tuber rate by 85.82%, overall tuber yield by 28.38%, starch content by 34.85%, and vitamin C content by 30.79%, while reducing sugar levels decreased by 9.35%.

CONCLUSION: Faba bean-potato rotation (T2) effectively mitigated the adverse impacts caused by continuous potato cropping by altering the rhizosphere microbial structure and enhancing microbial functional pathways related to nutrient cycling. This study provides a detailed metagenomic perspective on the microbial mechanisms underlying the benefits of crop rotation and offers a theoretical basis for developing microbiome-informed ecological management strategies to mitigate continuous cropping obstacles in potato production on the Loess Plateau.}, } @article {pmid41613796, year = {2026}, author = {Pawłowska, M and Jarek, D and Milanowski, J and Szewczyk-Golec, K}, title = {Parasitic Infections and Carcinogenesis: Molecular Mechanisms, Immune Modulation, and Emerging Therapeutic Strategies.}, journal = {Oncology research}, volume = {34}, number = {2}, pages = {8}, pmid = {41613796}, issn = {1555-3906}, mesh = {Humans ; Animals ; *Parasitic Diseases/immunology/complications/parasitology ; *Neoplasms/immunology/parasitology/therapy/etiology ; *Carcinogenesis/immunology ; Tumor Microenvironment/immunology ; Host-Parasite Interactions/immunology ; Immunomodulation ; }, abstract = {Parasitic infections are increasingly recognized as contributors to cancer development, yet the underlying oncogenic mechanisms remain insufficiently understood. Growing evidence from molecular oncology, immunology, and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation, deregulated signaling pathways, genomic instability, and the release of parasite-derived exosomes that reshape the tumor microenvironment. These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better. The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities. We examine pathogens such as Schistosoma haematobium, Opisthorchis viverrini, Toxoplasma gondii, Plasmodium falciparum, and Leishmania spp., detailing their roles in chronic inflammation, immune modulation, and interactions with tumor-associated immune cells. The review further discusses parasite-induced immunosuppression, coinfections, and their cumulative impact on cancer risk. Additionally, we explore novel therapeutic approaches, including pathway inhibitors, epigenetic drugs, microbiome modulation, and engineered parasites. Future perspectives emphasize parasite-based immunotherapies, long-term epigenetic consequences of infection, and AI-driven multi-omics strategies for identifying oncogenic signatures. This review integrates advances from parasitology and oncology to provide new insights into biomarkers, targeted therapies, and mechanisms of infection-induced tumorigenesis. The literature search covered studies indexed in PubMed, Scopus, and Web of Science up to July 2025.}, } @article {pmid41613795, year = {2026}, author = {Liu, K and Xue, X and Qin, H and Zhu, J and Jin, M and Dai, D and Tang, Y and Bukhari, I and Liu, H and Qiu, C and Ren, F and Zheng, P and Mi, Y and Chen, W}, title = {Gut Associated Metabolites Enhance PD-L1 Blockade Efficacy in Prostate Cancer.}, journal = {Oncology research}, volume = {34}, number = {2}, pages = {23}, pmid = {41613795}, issn = {1555-3906}, mesh = {Male ; Humans ; Animals ; *Prostatic Neoplasms/metabolism/drug therapy/pathology/immunology ; *B7-H1 Antigen/antagonists & inhibitors/metabolism/genetics ; Mice ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; *Gastrointestinal Microbiome ; Cell Line, Tumor ; Exosomes/metabolism ; Mice, Transgenic ; Disease Models, Animal ; }, abstract = {BACKGROUND: The gut microbiome has emerged as a critical modulator of cancer immunotherapy response. However, the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer (PC) remain not fully explored. The study aimed to explore how gut metabolites regulate death-ligand 1 (PD-L1) blockade via exosomes and boost immune checkpoint inhibitors (ICIs) in PC.

METHODS: We recruited 70 PC patients to set up into five subgroups. The integrated multi-omics analysis was performed. In parallel, we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate (TRAMP) models.

RESULTS: We identified two metabolites, 16(R)-Hydroxyeicosatetraenoic acid (16(R)-HETE) and 6-Keto-Prostaglandin E1 (6-Keto-PGE1), that positively correlated with the plasma exosomal PD-L1 levels. The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA, protein, and exosome levels in both human and mouse PC cell lines, which were also validated in vivo based on subcutaneous mouse models. Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.

CONCLUSIONS: Targeting the "gut-tumor metabolic axis" is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.}, } @article {pmid41613600, year = {2025}, author = {Li, L and Zhang, Q and Zhang, L and Wei, R and Qin, Y and Zhao, J and Wu, H}, title = {A cross-sectional study of salivary and gut microbiomes in hemodialysis patients with heart failure with preserved ejection fraction.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1683657}, pmid = {41613600}, issn = {2235-2988}, mesh = {Humans ; *Heart Failure/microbiology/physiopathology ; Cross-Sectional Studies ; *Saliva/microbiology ; *Gastrointestinal Microbiome ; Male ; Female ; Aged ; *Renal Dialysis/adverse effects ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Dysbiosis/microbiology ; Bacteria/classification/genetics/isolation & purification ; Stroke Volume ; DNA, Bacterial/genetics/chemistry ; }, abstract = {BACKGROUND: Heart failure (HF) is a primary cause of death in patients on maintenance hemodialysis (MHD), yet the role of microbial dysbiosis is poorly defined. This study characterized the salivary and gut microbiomes of MHD patients with heart failure with preserved ejection fraction (HFpEF), those without HF (NHF), and healthy controls (CON).

METHODS: In this cross-sectional study (n=88), we compared the salivary and fecal microbiomes of HFpEF (n=30), NHF (n=30), and CON (n=28) groups using 16S rRNA gene sequencing. Microbial community structure and composition were analyzed.

RESULTS: Alpha diversity and Beta diversity analysis revealed a distinct salivary microbial structure, which effectively distinguished the MHD group from the Con group (P < 0.05). Conversely, the overall gut community structure showed no significant separation. At the genus level, both MHD groups showed depletion of salivary Veillonella and gut Faecalibacterium compared to controls. Notably, LEfSe analysis highlighted salivary Anaerocolumna as a promising candidate feature associated with the HFpEF group.

CONCLUSION: Our analyses suggest that HFpEF in MHD patients may be associated with structural alterations in the oral microbiome, which appear more pronounced than those in the gut. Specific oral microbial signatures, particularly the enrichment of Anaerocolumna, showed associations with the HFpEF cohort in our study. This preliminary evidence positions the oral microbiome as an area worthy of further investigation for its potential role in this high-risk population.}, } @article {pmid41613599, year = {2025}, author = {Lu, S and Wu, Z and Zhao, Y and Tang, T and Dong, Y and Wu, M and Zhang, P and Ma, Z}, title = {Comprehensive microbiome and metabolome analysis revealed the changes of semen microbial characteristics and metabolic phenotypes in patients with idiopathic oligoasthenozoospermia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1741184}, pmid = {41613599}, issn = {2235-2988}, mesh = {Humans ; Male ; *Semen/microbiology/metabolism ; *Metabolome ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Adult ; Metabolomics/methods ; *Oligospermia/microbiology/metabolism ; Phenotype ; Biomarkers ; Bacteria/classification/genetics/isolation & purification/metabolism ; *Asthenozoospermia/microbiology/metabolism ; Case-Control Studies ; }, abstract = {BACKGROUND: The etiology and pathogenesis of idiopathic oligoasthenospermia (IOA) remain unclear, and current treatment options yield suboptimal outcomes. Consequently, there is an urgent need to identify novel biomarkers and develop diagnostic tools to improve patient identification and clinical management. Multi-omics technologies offer a promising pathway toward achieving this goal in the future.

METHODS: This study included 40 untreated patients with idiopathic oligoasthenospermia (IOA) and 30 healthy fertile males (HP) as controls. Semen samples were analyzed using 16S rRNA gene sequencing (microbiome) and non-targeted metabolomics (GC-MS/LC-MS coupled). A microbe-metabolite association network was integrated at the genus level based on Spearman correlation algorithms.

RESULTS: Semen microbiome analysis revealed that both microbial composition and species richness differed between IOA patients and HP controls. Non-targeted metabolomics further demonstrated characteristic metabolic dysregulation in seminal plasma of IOA patients, with a metabolic signature effectively distinguishing cases from controls (VIP > 1, FDR < 0.05). KEGG pathway enrichment analysis indicated that differentially expressed metabolites primarily involved amino acid metabolism, carbohydrate metabolism, and related signaling pathways (corrected p-value < 0.05). Construction of a Spearman correlation network between microbiota and metabolites (|r| > 0.6) identified significant interactions between core bacterial genera such as Dialister, Prevotellaceae_NK3B31_group, Lawsonella, and Blautia with seminal plasma metabolites, suggesting potential involvement of the microbiota-metabolite axis in the pathological process of IOA.

CONCLUSION: The microbial community structure and metabolic profiles in the semen of IOA patients exhibit significant disruption. Diagnostic models constructed based on combined microbial-metabolite features demonstrate potential for effectively distinguishing disease phenotypes. The core dysregulated bacterial genera, associated metabolites, and related pathways may serve as early diagnostic biomarkers and therapeutic intervention targets.}, } @article {pmid41613399, year = {2025}, author = {Gao, Y and Wei, Y and Zeng, D and Zhang, J and Dong, J and Gao, X and Yuan, H and Li, X and Qiu, D and Burford, M}, title = {Restructuring of the epiphytic microbiome and recruitment of algicidal bacteria by Vallisneria natans for the suppression of Microcystis.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1731742}, pmid = {41613399}, issn = {1664-462X}, abstract = {The effective suppression of cyanobacteria by submerged macrophytes is a key mechanism underlying the successful restoration of aquatic vegetation in some eutrophic water bodies. However, the responses and functional roles of epiphytic microorganisms in this process remained largely unclear, limiting a clear understanding of how macrophytes inhibit cyanobacterial growth. In this study we investigated the temporal dynamics of the epiphytic microbiome on Vallisneria natans before, during and after exposure to toxic cyanobacterium Microcystis, corresponding to three distinct physiological stages of the plant: pre-stress, stress, and recovery. It was observed that the diversity of epiphytic bacteria and eukaryotic algae increased during the stress stage, while that of other eukaryotes, particularly fungi and protozoa, decreased. The complexity and stability of the epiphytic microbiome were enhanced, with bacteria emerging as central hubs in the co-occurrence network in response to Microcystis stress. More importantly, a selective enrichment and recruitment of potential algicidal bacteria, particularly Streptomyces, Pseudomonas and Chryseobacterium, occurred on macrophyte surfaces during the stress phase. Their abundance peaked under Microcystis stress and returned to baseline levels during the plant recovery phase. Our findings demonstrate that V. natans did not function alone, but rather actively recruited and sustained a beneficial microbiome to enhance its suppressive effects on Microcystis. This study revealed a previously neglected macrophyte-epiphytic microbiome synergy, providing novel mechanistic insights into how submerged vegetation effectively suppresses harmful cyanobacteria.}, } @article {pmid41613388, year = {2025}, author = {Fasipe, B and Laher, I}, title = {Obesity and metabolic disease in migrants: a role for the gut microbiome?.}, journal = {Frontiers in clinical diabetes and healthcare}, volume = {6}, number = {}, pages = {1745885}, pmid = {41613388}, issn = {2673-6616}, abstract = {Migration, while often motivated by safety, education, or economic opportunity, often heightens the risk of obesity and metabolic syndrome. Resettlement in industrialized nations is associated with sedentary lifestyles, irregular sleep schedules, and Westernized dietary patterns rich in ultra-processed, high-fat, and high-sugar foods. These changes disrupt metabolic homeostasis through endocrine and circadian dysregulation, promoting insulin resistance, visceral adiposity, and systemic inflammation. Migration alters the composition and diversity of the gut microbiome, suggesting that the characteristics of the microbiome could be important in linking migration to changes in health outcomes after resettlement. However, the precise mechanisms underlying these microbiome-mediated effects remain poorly understood. We propose that a dynamic metabolic interface is reshaped via a rapid "microbiome acculturation", which is a process by which the gut microbiome rapidly adapts to a new cultural and environmental milieu, such as caused by migration, shifting from traditional, fiber-rich microbial profiles to Westernized, Bacteroides-dominant communities associated with metabolic dysfunction. This is characterized by the depletion of fiber-fermenting Prevotella and enrichment of Bacteroides species, leading to reduced short-chain fatty acid production, impaired gut barrier function, and increased endotoxemia. Dietary transitions, chronic psychosocial stress, circadian disruption to night-shift work, and reduced physical activity experienced by immigrants reshapes gut microbial composition and function to a pro-inflammatory milieu and enhancing insulin resistance. Thus, gut dysbiosis serves as both a biomarker and mechanistic driver of post-migration metabolic deterioration, integrating dietary, behavioral, and environmental stressors into a unified pathogenic pathway. Effective prevention should target the gut-brain-metabolic axis using multidimensional strategies: restoring microbial diversity using high-fiber, prebiotic, and probiotic nutrition; promoting physical activity and circadian alignment; and addressing social determinants of health such as work patterns, food access, and acculturation stress.}, } @article {pmid41613338, year = {2025}, author = {Qian, T and He, Y and Yan, R and Yu, S and Chen, Y and He, W}, title = {Recurrent urinary tract infections and psychological burden: mechanisms and integrative perspectives.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1721343}, pmid = {41613338}, issn = {2296-858X}, abstract = {Recurrent urinary tract infections (rUTIs) remain a global health concern with significant physical and psychological impacts, particularly in women. Recent evidence indicates a strong bidirectional association between rUTIs and psychological burden, yet the underlying mechanisms remain incompletely understood.This review integrates findings from biomedical and traditional Chinese medicine (TCM) perspectives to elucidate potential pathways linking rUTIs with anxiety and depression. Four major mechanisms-immune dysregulation, endocrine imbalance, microbiome alteration, and neuroendocrine dysfunction-are proposed to explain this complex interaction. In addition, TCM conceptualizes this relationship through the theory of the "coexistence of disease and depression syndromes" emphasizing that emotional regulation is a key determinant of both urinary and systemic health. By synthesizing these insights, this narrative review underscores the importance of integrative approaches in preventing and managing rUTIs while addressing concurrent psychological distress.}, } @article {pmid41613307, year = {2025}, author = {Lee, J and Song, H and Kim, KY}, title = {Association of lifestyle, physiological factors, and body composition with the facial skin microbiota in acne vulgaris.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1679925}, pmid = {41613307}, issn = {2296-858X}, abstract = {INTRODUCTION: The skin microbiota plays a crucial role in maintaining skin health and overall well-being. The composition of this microbial community is influenced by various host factors, including lifestyle habits, physiological parameters, and body composition.

METHODS: 1,053 participants were included in this study. The composition of the skin microbiota was determined by analysing facial skin microbiome collection, obtained after the consent of participants. Also, physical characteristics of each participant were evaluated using answers from questionnaire. Potential microorganisms that contribute to acne vulgaris development were investigated. Statistical analysis was then performed based on the characteristics of the patient and normal groups, and the differences in the bacterial ratio grade assigned to each individual.

RESULTS: C. acnes, S. aureus, and S. epidermidis were significantly correlated with acne vulgaris. Several characteristics of the participants were closely correlated with the composition of the skin microbiota. There was significant differences among the participants' characteristics.

DISCUSSION: By analyzing the body composition and daily life of the study subjects, we identify associations of acne vulgaris and suggest specific lifestyle modifications that may be beneficial for acne sufferers.}, } @article {pmid41613170, year = {2026}, author = {Siziya, IN and Seo, MJ and Park, CS and Jung, DH}, title = {Bacterial fructan-metabolizing enzymes: modular architecture and biotechnological potential.}, journal = {3 Biotech}, volume = {16}, number = {2}, pages = {85}, pmid = {41613170}, issn = {2190-572X}, abstract = {Bacterial fructan-metabolizing enzymes exhibit substantial structural and mechanistic diversity to support their biotechnological uses. Recent findings on glycoside hydrolase (GH) families 32 and 68 emphasize the conserved catalytic triads, calcium-binding motifs, and domain architectures that define their reaction frameworks. Differences in carbohydrate-binding modules (CBMs), extended loops, and accessory domains contribute to variations in substrate affinity, polymer length, and the balance between polymerization and hydrolysis. Aggregated data shows that GH68 enzymes generally exhibit higher catalytic efficiencies on sucrose, while GH32 hydrolases display stronger preferences for inulin and short-chain fructooligosaccharides (ScFOS). In gut commensals, distinct fructan utilization operons provide the basis for substrate-driven cross-feeding interactions, with ScFOS typically exhibiting shorter fermentation times compared to high molecular-weight levans. Rapid progress in artificial intelligence for structural predictions, molecular dynamics simulations, and CRISPR-enabled pathway engineering now supports the rational redesign of fructan-active enzymes, enabling the generation of catalysts with customized product profiles, enhanced stability, or altered chain-length distributions. This review provides a comprehensive overview of bacterial fructan-metabolizing enzymes, integrating structural, biochemical, and ecological perspectives to establish a foundation for applying fructan-modifying enzymes to prebiotic production, food texturization, microbiome modulation, and emerging oral enzyme therapeutics.}, } @article {pmid41613163, year = {2026}, author = {Ganamurali, N and Sabarathinam, S}, title = {Bidirectional interplay between the gut microbiota and GLP-1 receptor agonists: towards Microbiome-Mediated therapeutics in type 2 diabetes mellitus.}, journal = {Journal of diabetes and metabolic disorders}, volume = {25}, number = {1}, pages = {44}, pmid = {41613163}, issn = {2251-6581}, abstract = {Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in T2DM management due to their ability to lower HbA1c, promote weight loss, and offer cardiovascular and renal protection. However, inter-individual variation in therapeutic response has been observed, potentially influenced by gut microbiota composition. A brief review was conducted to explore current evidence on the interaction between GLP-1RAs and gut microbiotatermed the "pharmaco-gut axis." Literature was examined to understand how specific microbial populations affect drug efficacy and insulin sensitivity. Studies suggest that certain gut microbes, including Bacteroides species, Akkermansia muciniphila, and those producing short-chain fatty acids (SCFAs), enhance GLP-1RA efficacy by improving insulin sensitivity and stimulating endogenous GLP-1 secretion. Conversely, dysbiosis characterized by reduced microbial diversity and increased lipopolysaccharide (LPS)-producing pro-inflammatory bacteria correlates with poor therapeutic response. Furthermore, GLP-1RAs may exert beneficial modulatory effects on the gut microbiota itself, indicating a bidirectional relationship. The interaction between GLP-1RAs and gut microbiota introduces a novel pharmaco-gut interface, emphasizing the role of microbial composition in drug response. This emerging concept has the potential to enhance precision medicine in diabetes care by utilizing microbiome profiling to guide GLP-1RA therapy and improve clinical outcomes.}, } @article {pmid41613132, year = {2025}, author = {Sîrbu, AE and Gradisteanu Pircalabioru, G and Deaconu, DM and Andronic, O and Gheorghe, DC}, title = {The pediatric nasal microbiome and its role in chronic ENT disorders: a narrative review.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1699707}, pmid = {41613132}, issn = {1664-3224}, mesh = {Humans ; *Microbiota/immunology ; Chronic Disease ; Child ; *Otorhinolaryngologic Diseases/microbiology/immunology ; }, abstract = {The human microbiome is increasingly recognized as a key factor in immune development and disease susceptibility, especially in early life. Nasal microbiome has emerged as a critical element in upper airway health, yet its role in pediatric otorhinolaryngological conditions remains underexplored. This narrative review synthesizes current evidence on the microbial nasopharyngeal patterns in healthy children compared with children suffering from chronic ENT conditions such as otitis media, allergic rhinitis, chronic rhinosinusitis, adenoid and tonsillar hypertrophy associated with obstructive sleep apnea. A structured search of Web of Science, PubMed, Google Scholar and CrossRef databases was conducted for peer-reviewed articles published in the past ten years. Nasal microbiota of healthy children was proved to be dominated by commensal protective taxa such as Dolosigranulum and Corynebacterium which contribute to mucosal immune stability. In contrast, patients with chronic ENT pathologies exhibited reduced diversity and increased prevalence of potential pathogens microbial species such as Haemophilus, Streptococcus and Staphylococcus. Several extrinsic factors appear to play an important role in modulating the nasal microbiota such as environmental exposure, delivery mode, feeding practices and antibiotic treatment. Growing evidence supports the predictive and modulatory potential of the nasal microbiome, however methodological variability, limited pediatric-specific studies and unclear causal relationships remain challenging components. This review highlights key microbial patterns, outlines the limitations of current research and suggests future directions for clinical integration of nasal microbiome analysis in pediatric ENT standard of care as it may hold promising utilisation of biomarkers for disease risk stratification and targeted therapeutic or preventative interventions in early life.}, } @article {pmid41613128, year = {2025}, author = {Koh, JH and Park, S and Kang, M and Park, JI and Lee, J and Cho, H and Kim, JE and Nam, H and Kim, D and Li, M and Park, S and Moon, KC and Kim, HJ and Kim, YS and Kim, DK and Lee, H}, title = {Altered acetate metabolism and signaling in IgA nephropathy: an integrated gut microbiome and glomerular spatial transcriptome analysis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1665585}, pmid = {41613128}, issn = {1664-3224}, mesh = {Humans ; *Glomerulonephritis, IGA/metabolism/microbiology/genetics ; *Gastrointestinal Microbiome ; Male ; Adult ; Gene Expression Profiling ; Female ; *Transcriptome ; Middle Aged ; *Acetates/metabolism ; Signal Transduction ; *Kidney Glomerulus/metabolism/pathology ; Feces/microbiology/chemistry ; RNA, Ribosomal, 16S/genetics ; }, abstract = {INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulonephritis, and emerging evidence implicates the gut microbiome in its pathogenesis. Additional studies focusing on the molecular mechanisms linking gut microbial signals to intraglomerular changes are warranted.

METHODS: We performed 16S rRNA-based microbial profiling of fecal samples of 172 IgAN patients, 51 healthy controls, and other glomerular disease controls including 15 diabetic nephropathy, 35 minimal change disease, and 63 membranous nephropathy cases. Serum and fecal acetate levels were measured by liquid chromatography-mass spectrometry. Glomerular spatial transcriptomic profiling was performed with the GeoMx Digital Spatial Profiler. DESeq2 analysis was performed to identify differentially expressed genes, followed by gene ontology annotations.

RESULTS: Beta diversity differed significantly between IgAN and healthy controls (p = 0.001). While no single taxon showed consistent differences in abundance, the methanogenesis from acetate pathway was significantly enriched in IgAN, accompanied by an increased proportion of major acetate-producing gut microbial genera. Serum acetate levels were elevated in IgAN (p = 0.03), while fecal acetate levels were comparable to those in healthy controls. In glomerular transcriptomes, functional annotations of 1,227 upregulated and 1,078 downregulated genes in IgAN indicated decreased activities of G protein-coupled receptors, short-chain fatty acid transporters, and beta-1,3-galactosyltransferases.

DISCUSSION: IgAN is characterized by gut microbial enrichment in acetate metabolism and increased systemic acetate levels, along with altered intraglomerular expression of metabolic and signaling genes. These findings suggest a gut microbiome-glomerular signaling axis contributing to disease pathogenesis.}, } @article {pmid41613126, year = {2025}, author = {Zhang, R and Li, Z and Liu, X and Qiu, Z and Li, Y and Gao, C and Guo, C}, title = {Intratumoral microbiota: synergistic reshaping of lung cancer microenvironment via inflammation and immunity.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1653727}, pmid = {41613126}, issn = {1664-3224}, mesh = {Humans ; *Tumor Microenvironment/immunology ; *Lung Neoplasms/immunology/microbiology/therapy/pathology/metabolism ; *Microbiota/immunology ; Animals ; *Inflammation/immunology/microbiology ; Immunotherapy/methods ; }, abstract = {As high-throughput sequencing tools have advanced in recent years, scientists have discovered that lung cancer tissues are not sterile. The intratumoral microbiota exists in the tumor parenchyma and stroma in a low-biomass form. This finding has overturned the traditional concept of "sterile tumors" and brought the intratumoral microbiota to the forefront of tumor research. In this review, we focus on elucidating the mechanisms by which intratumoral microbiota influence lung cancer cells and the tumor microenvironment (TME), with the aim of clarifying their role in lung cancer progression. The intratumoral microbiota does not exist as a passive resident. Instead, it may actively induce and maintain a chronic inflammatory state through the secretion of metabolites, activation of signaling pathways, immune suppressor cell recruitment, and upregulation of immune checkpoint molecule expression, thereby promoting tumor cell proliferation, invasion, and immune evasion. From a clinical translation perspective, we explore the potential of using intratumoral microbiota characteristics to predict immunotherapy efficacy. Additionally, we assess the application prospects of engineered bacteria and targeted nanobiotics, which are based on synthetic biology, in reshaping the immune microenvironment. However, the field still faces significant challenges, particularly as the low biomass nature of lung tissues makes sequencing data highly susceptible to reagent contamination and batch effects. Additionally, the synergistic role of non-bacterial components such as fungi and viruses in the tumor ecosystem is often overlooked. Future research needs to establish rigorous quality control standards and integrate multi-omics technologies to comprehensively analyze the dynamic interaction network between the microbiota and host immunity, which will drive the clinical implementation of microbiome-based precision diagnostic and therapeutic strategies for lung cancer.}, } @article {pmid41613079, year = {2025}, author = {Martínez-Ortiz, IC and Garcia-Atutxa, I and Sanchez-Villamil, JI and Machain-Williams, C and Reyes-López, MA and Villanueva-Flores, F}, title = {Predictive multi-omic biomarkers for urban zoonotic spillover detection: an integrative review.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1720300}, pmid = {41613079}, issn = {2296-2565}, mesh = {*Zoonoses/diagnosis/epidemiology ; Humans ; Animals ; *Biomarkers/analysis ; Animals, Wild/microbiology ; Multiomics ; }, abstract = {Urban wildlife is an overlooked yet critical component of zoonotic disease surveillance, especially in biodiversity hotspots where human-animal interfaces accelerate spillover risk. This review synthesizes five complementary omics layers: Host microRNAs, host-pathogen genetic markers, bacterial microbiome profiling, viromics, and host transcriptomics into a single predictive framework for early spillover detection. Across taxa and pathogen classes, we highlight convergent molecular signatures of infection, from receptor polymorphisms and shifts in MHC diversity to pathogen-responsive miRNAs, high-risk bacterial genera, novel viral sequences, and transcriptomic profiles associated with pathogen tolerance. By integrating these biomarkers into a cross-validated, multi-omics architecture, we outline a workflow from non-invasive sampling to predictive modeling that enhances sensitivity for detecting both known and cryptic pathogens. We also identify key barriers, including Field preservation, cross-species assay standardization, and bioinformatics capacity, and propose practical solutions, such as interoperable pipelines and open-access databases. This integrative approach shifts surveillance from reactive detection to anticipatory risk profiling, providing a transformative tool for One Health strategies aimed at forecasting and preventing zoonotic epidemics.}, } @article {pmid41612732, year = {2026}, author = {Ma, ZS}, title = {How Host Phylogeny and Diet Shape the Specificity and Specificity Diversity of Animal Gut Microbiomes.}, journal = {Environmental microbiology reports}, volume = {18}, number = {1}, pages = {e70253}, pmid = {41612732}, issn = {1758-2229}, support = {//Bullard Fellowship/ ; 72274192//National Natural Science Foundation of China/ ; //Prosperous Yunnan Talent Support Program/ ; }, mesh = {Animals ; *Phylogeny ; *Gastrointestinal Microbiome ; *Host Specificity ; *Diet ; *Bacteria/classification/genetics/isolation & purification ; Species Specificity ; Biodiversity ; }, abstract = {The forces shaping host specificity in the animal gastrointestinal microbiome (AGM) are often studied through separate lenses: community-level patterns (phylosymbiosis) or lineage-level histories (cophylogeny). Furthermore, traditional diversity metrics fail to capture compositional heterogeneity from host-specific distributions. We bridge these gaps using our SSD (Species Specificity and Specificity Diversity) framework, a recent conceptual and computational advance that quantifies host specificity across scales via: (i) Species Specificity (SS), locating species on the specialist-generalist continuum; (ii) Specificity Diversity (SD), quantifying community compositional heterogeneity; and (iii) statistical tests for identifying unique/enriched species. Applying SSD to 4903 AGM samples from 318 species, we identified unique and enriched microbial species in specific host taxa and diets, demonstrating that host phylogeny and diet jointly shape these patterns. A PTSD (Phylogenetic Timeline-Specificity Diversity) power-law model reveals the evolution of more complex microbiome structures in modern species. One surprising finding is the high similarity amongst animal AGMs, with only 252 microbial species being exclusively unique at the animal class level-somewhat analogous to the high genomic similarity between humans and primates. Our findings demonstrate a unified quantitative approach to dissecting the eco-evolutionary forces that shape microbial specificity and specificity heterogeneity, with potential synthesis with established phylosymbiosis and cophylogeny frameworks.}, } @article {pmid41612514, year = {2026}, author = {Enagbonma, BJ and Pierneef, RE and Modise, DM and Babalola, OO}, title = {Effects of legume-based rotation on subsequent sorghum rhizosphere microbial communities and their drought tolerance-related genes.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-025-00829-9}, pmid = {41612514}, issn = {2524-6372}, support = {CRP/ZAF22-03//ICGEB/ ; }, abstract = {INTRODUCTION: The impacts of incorporating legumes into cereal crops on soil microbial structure, composition, functional genes involved in nitrogen, carbon and phosphorus cycling, signaling pathways and hydraulic conductivity adaptations have been well studied. However, the same cannot be said for functional genes that increase drought tolerance.

OBJECTIVES: Here, we examined the changes in microbial community structure and functional genes involved in drought tolerance in response to legume‒cereal rotation and cereal‒cereal rotation. This study provides a preliminary, exploratory characterization of microbial community and functional gene shifts, without direct evidence of functional impact on plant physiology or productivity.

METHODS: DNA extracted from soil samples collected across cowpea-sorghum treatment (CS) or maize-sorghum treatment (MS) was sequenced via shotgun sequencing.

RESULTS: Nonmetric multidimensional scaling analysis revealed that the microbial communities in the CS treatment significantly differed from those in the MS treatment. Compared with the MS rotation, the CS rotation increased the relative abundances of Pseudomonadota, Acidobacteriota, Chloroflexota, Gemmatimonadota, Euryarchaeota, and Candidatus Bathyarchaeota and reduced the abundances of Actinomycetota, Ascomycota, and Nitrososphaerota at the phylum level. Furthermore, the CS rotation increased the abundance of microbial genera such as Solirubrobacter, Sphingomonas, Nitrosocosmicus, Nitrosotenuis Aspergillus, and Metschnikowia when related to the MS rotation. STAMP analysis revealed that in the CS rotation, genes involved in trehalose biosynthesis, biofilm formation, oxidative stress mitigation (e.g., sodA, katG), stress signaling (e.g., rpoS, ipdC), nutrient provisioning (e.g., nifH, pqqC), membrane fluidity (desA, desB), dormancy (spo0A, spoVF), and ion homeostasis (nhaB, kup) predominated. In the MS rotation, proline biosynthesis (proA, proB, and proC), glycine betaine synthesis (betA and betB), aquaporin (aqpZ), and structural integrity genes (murA and murC) were predominant. The RDA results revealed that crop rotation influenced the soil physicochemical parameters, which in turn impacted both the microbial communities and drought tolerance genes in both treatments, probably creating a favorable environment for resilience under drought.

CONCLUSION: These research findings provide insight into the relationships between cowpea cropping sequences and the soil microbiome and drought-tolerant functional genes fundamental for the productivity of successive crops and this understanding guides sustainable crop selection.}, } @article {pmid41612472, year = {2026}, author = {Wang, Y and Shen, Y and Shen, J and Bi, J and Xu, J and Wei, T and Wang, R and Wu, X and Li, F and Bai, J and Jie, Z and Hou, D and Song, Y}, title = {Airway microbiome dysbiosis in severe pneumonia: metagenomic evidence of pathogen expansion and commensal depletion.}, journal = {European journal of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40001-026-03892-1}, pmid = {41612472}, issn = {2047-783X}, support = {ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; GWVI-11.1-18//Shanghai Three-year Action Plan to Strengthen the Construction of Public Health System/ ; 82130001//National Natural Science Foundation of China/ ; 2024YFC3044400//National Key Research and Development Program of China/ ; GZNL2024A02003//R&D Program of Guangzhou National Laboratory/ ; W2020-013//The Construction of Multi-Disciplinary Treatment System for Severe Pneumonia/ ; 22Y11900800//Science and Technology Commission of Shanghai Municipality/ ; shslczdzk02201//Shanghai Municipal Key Clinical Specialty/ ; }, abstract = {BACKGROUND: The pulmonary microbiome is increasingly recognized as a key determinant of pneumonia severity, yet its clinical implications remain incompletely understood. Disruption of microbial ecology, or dysbiosis, may impair host immune responses and exacerbate disease progression. This study aimed to characterize microbiome alterations associated with severe pneumonia and their correlation with host inflammatory and coagulative parameters.

METHODS: In this multicenter, prospective observational cohort study conducted across nine hospitals in Shanghai (2021-2025), bronchoalveolar lavage fluid (BALF) samples from 306 patients with clinically diagnosed pulmonary infections were analyzed using metagenomic next-generation sequencing (mNGS). Patients were stratified into severe (n = 196) and non-severe (n = 110) groups using WHO-derived severe pneumonia criteria at the time of bronchoalveolar lavage (BAL). Microbial taxonomic profiles, diversity indices, co-occurrence networks, and correlations with clinical markers were comprehensively assessed using standard bioinformatic and statistical approaches.

RESULTS: Severe pneumonia was associated with marked microbial dysbiosis, including reorganization of co-occurrence network topology with centrality shifting away from commensals toward opportunistic taxa in severe disease, characterized by reduced α-diversity, altered β-diversity, and enrichment of opportunistic Gram-negative pathogens including Acinetobacter and Klebsiella. In contrast, commensals such as Rothia and Prevotella were depleted. Co-occurrence network analysis revealed fragmentation of microbial interactions in severe cases, with centrality shifting from commensals to opportunists like Corynebacterium striatum. Shannon diversity negatively correlated with SOFA scores, and specific taxa positively associated with systemic inflammation (CRP, PCT) and coagulation abnormalities. Nearly all samples demonstrated polymicrobial infection, with distinct microbial patterns observed across monomicrobial and polymicrobial subgroups.

CONCLUSION: Our multicenter observational analysis suggests that severe pneumonia is associated with marked ecological disruption of the lower-airway microbiome, characterized by commensal loss, opportunist expansion, and fragmented interspecies networks, and with concurrent inflammatory and coagulative abnormalities. These hypothesis-generating findings warrant external validation in independent, multi-region cohorts and longitudinal sampling to test directionality and causality before informing clinical decision-making.}, } @article {pmid41612446, year = {2026}, author = {Kwon, HJ and Ahn, JH and Won, MH and Kim, DW}, title = {Chronic periodontitis and systemic inflammation in the elderly: implications for neurodegeneration.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {43}, pmid = {41612446}, issn = {1742-2094}, support = {NRF-2021R1A6A3A01086738//Ministry of Education/ ; NRF-2021R1F1A1048079//Ministry of Science and ICT, South Korea/ ; }, mesh = {Humans ; *Inflammation ; *Chronic Periodontitis/complications/microbiology ; *Neurodegenerative Diseases ; Aged ; Animals ; *Aging/pathology ; Dysbiosis ; }, abstract = {Chronic periodontitis is increasingly recognized as a potential upstream contributor to neurodegenerative processes through sustained systemic inflammation, microbial dysbiosis, and blood-brain barrier (BBB) alterations. This review synthesizes human and experimental evidence linking periodontal pathogens-including but not limited to Porphyromonas gingivalis as well as broader dysbiotic consortia such as Tannerella forsythia, Treponema denticola, and other keystone oral taxa-to neuroinflammatory cascades associated with cognitive decline. Mechanistic insights highlight the roles of glial activation, proinflammatory cytokines, and polymicrobial virulence-mediated neuronal stress in bridging oral and brain pathology, while age-related factors such as immunosenescence and microbiome imbalance amplify systemic vulnerability. Human biomarker and imaging studies support an association between chronic periodontal inflammation and neurovascular dysfunction, suggesting that oral disease may act as a persistent peripheral amplifier of central immune activation. Recent research has expanded into biomarker discovery and translational implementation, yet progress remains limited by population heterogeneity, methodological variability, and regulatory complexity. Promising interventions-including anti-inflammatory therapies, oral hygiene optimization, probiotic or dietary modulation, and molecular strategies such as polymicrobial-targeted approaches, gingipain inhibition, and microRNA-based modulation-are discussed within emerging multi-omics and precision-medicine frameworks. Although standardization and longitudinal validation are still required, integrative approaches combining inflammatory, microbial, and genetic profiling may enable individualized risk assessment and targeted prevention. As global populations age, addressing the oral-brain axis offers a practical and modifiable pathway to lessen the burden of neurodegenerative diseases and support healthier cognitive aging.}, } @article {pmid41612376, year = {2026}, author = {Sánchez-Morán, M and Valverde-Benítez, I and Corcuera Tejada, J and Velasco, O and Aurrekoetxea-Oribe, J and Saso-Jiménez, L and Martinez de Lapiscina, I and Castaño, L and , }, title = {Oral microbiota assessment at different time points during the first year of life: delivery mode and breastfeeding shape the bacterial community.}, journal = {International breastfeeding journal}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13006-026-00813-0}, pmid = {41612376}, issn = {1746-4358}, abstract = {BACKGROUND: The assembly of the oral microbiota during the first year of life is a critical process that may influence long-term health and immunological development. While the gut microbiome has been extensively studied, early oral colonization patterns remain less understood. This study aimed to characterize the oral microbial succession in infants and to evaluate the impact of two primary clinical factors-delivery mode and breastfeeding practices-on microbial composition from birth through the first 12 months of life.

METHODS: Forty-eight newborns were prospectively recruited between January and June 2022 through the Basque Health Service (Osakidetza, Spain). Oral samples were collected at five time points (4-10 days, 1 month, 4 months, 6 months, and 12 months). Feeding status was categorized as exclusive breastfeeding (EBF) or mixed feeding (MF) for the first 4 months, after which the EBF group transitioned to a "Breast milk -No Formula" (BM-NF) group to account for the complementary feeding. Microbial communities were assessed via 16S rRNA amplicon sequencing. To compare alpha diversity (Shannon, Chao1, ACE, Simpson, Observed, and Fisher indices) between groups, Mann-Whitney or Kruskal-Wallis tests were employed. Beta diversity was evaluated via non-metric multidimensional scaling (NMDS) based on Bray-Curtis distances. PERMANOVA was employed to assess community shifts over time, and relative abundance differences across delivery and lactation type´s groups were analyzed using Mann-Whitney tests.

RESULTS: Oral bacterial diversity increased significantly over time as the oral cavity transitioned towards a more complex community. Streptococcus, Ralstonia, Gemella, and Rothia were the primary early colonizers. Significant taxonomic shifts were associated with birth and feeding modes. C-section infants exhibited a higher abundance of Veillonella and Neisseria during the first days of life. Regarding nutrition, mixed feeding (MF) infants showed higher proportions of Rothia, Prevotella, and Veillonella during the initial months. Conversely, Streptococcus remained significantly predominant in infants receiving breast milk (EBF/BM-NF) at the 6-month mark.

CONCLUSIONS: These findings demonstrate that delivery mode and lactation significantly shape the neonatal oral ecosystem. Specific microbial signatures up to 12 months suggest that early-life factors and feeding choices are key in establishing the mature oral microbiota.}, } @article {pmid41470031, year = {2025}, author = {Ge, T and Fang, D and Zhong, L and Pang, S and Hua, LB and Chen, J and Zhao, J and Huang, H}, title = {The dysbiosis of intestinal microbiota associated with isolated tricuspid valve regurgitation.}, journal = {Journal of cardiothoracic surgery}, volume = {21}, number = {1}, pages = {56}, pmid = {41470031}, issn = {1749-8090}, support = {No.2022YFC2407406//National Key Research and Development Program of China/ ; No. 2023B03J0596//the Guangzhou Science and Technology Planning Project/ ; No. 2023A031004//the Science and Technology Foundation of Guangzhou Health/ ; No. KD022023019//the 2023 Stability Support for Innovative Capacity Building of Guangdong Provincial Scientific Research Institutions/ ; No.2023FTJCZ0011//the Health Commission of Guangdong Province/ ; No.82270373//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Isolated tricuspid regurgitation (TR) is an increasingly recognized yet frequently underappreciated valvular disorder that adversely affects both survival and quality of life, with progressively worse outcomes as severity increases. Advances in high-throughput sequencing technologies have considerably expanded our understanding of the human microbiome, uncovering its close associations with a range of cardiovascular diseases, including atherosclerosis, heart failure, and hypertension. However, the potential role of intestinal dysfunction and the gut–heart axis in TR pathophysiology remains largely unexplored.

METHODS: A total of 20 patients diagnosed with TR and 10 healthy age- and gender-matched patients were enrolled in this study. Fecal samples were collected before the operation and subjected to 16 S rDNA gene sequencing.

RESULTS: The gut microbiomes of TR and healthy patients were significantly different in terms of alpha-diversity and beta-diversity analysis. Indicator analysis further showed 9 indicative bacterial genera and 2 bacterial species. Genera known to produce short-chain fatty acids (SCFAs), including Faecalibacterium, Blautia, and Ruminococcus were depleted, whereas Lactobacillus and Veillonella were enriched. Their correlations with clinical features using Pearson analysis showed that Ruminococcus, Lactobacillus, and Veillonella were potentially involved in the pathophysiology of TR. Functional predictions indicated enrichment of pathways related to carbohydrate, lipid, and nucleotide metabolism, as well as immune and cardiovascular diseases, whereas pathways linked to amino acid and vitamin metabolism were reduced. Notably, pathways involving D-arginine and D-ornithine metabolism and Staphylococcus_ aureus infection were upregulated.

CONCLUSIONS: Patients with tricuspid regurgitation (TR) exhibit gut dysbiosis, characterized by significant alterations in taxonomic composition. These findings suggest a dysregulation of the gut-host interaction in TR.}, } @article {pmid41466244, year = {2025}, author = {Blomqvist, M and Mørch, MB and Ghafouri, B and Wåhlén, K and Shannon, O and Davies, JR}, title = {Immunomodulatory effects of eubiotic and dysbiotic multi-species biofilms on oral keratinocytes.}, journal = {BMC oral health}, volume = {26}, number = {1}, pages = {203}, pmid = {41466244}, issn = {1472-6831}, abstract = {BACKGROUND: Elucidating host‒microbe interactions is essential for understanding oral health and disease. In periodontitis, the host inflammatory response to accumulated plaque shifts eubiotic biofilm communities toward dysbiosis, with enrichment of proteolytic bacterial species. The first line of host defence in the subgingival niche involves oral keratinocytes, which communicate with immune cells in the mucosa. Host responses to individual bacterial species have been widely characterized, but in this study, we used a co-culture model to better understand how changes in the multispecies biofilm phenotype affect keratinocyte effector function as well as the effects on inflammatory cells.

METHODS: Biofilms representative of eubiotic (HA) or dysbiotic (DA) bacterial communities were developed on nitro-cellulose membranes over 7 days and then co-cultured with oral keratinocytes for 6 h. Biofilm proteolytic activity was measured with a fluorescent substrate. Multiplex cytokine analysis of the co-culture medium was used to study keratinocyte responses and the activation of inflammatory cells was investigated via flow cytometry.

RESULTS: Proteolytic activity was greater in the DA biofilms than in the HA biofilms, most likely due to gingipains from Porphyromonas gingivalis. Keratinocytes released a range of cytokines, chemokines and growth factors, and the response to DA was more pro-inflammatory than that to HA biofilms, with relatively high levels of factors such as MIP-3a, IL-8, GM-CSF and IL-17 C. Co-culture medium from both the HA and DA biofilms elicited strong monocyte and neutrophil activation responses, although the effect of the DA biofilms was greater for monocytes than for neutrophils.

CONCLUSIONS: In this study, we show that keratinocytes have distinct response profiles to HA as compared to DA periodontal biofilm communities. The combination of products from the biofilm and the activated keratinocytes generated significant activation of inflammatory cells. This in vitro model thus provides insight on the complex host-microbiome interactions during development of periodontal disease.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12903-025-07576-w.}, } @article {pmid41457283, year = {2025}, author = {Sadeghi, N and Shams, S and Mirlohian, RS and Haerifar, F and Bakhshi-Kashi, M and Ghaderi, A}, title = {The effect of probiotics on anxiety, depression, nicotine dependence, and metabolic biomarkers in smokers: a randomized clinical trial.}, journal = {BMC complementary medicine and therapies}, volume = {26}, number = {1}, pages = {36}, pmid = {41457283}, issn = {2662-7671}, support = {401110//Kashan University of Medical Sciences/ ; }, abstract = {BACKGROUND: Cigarette smoking (CS) has long been associated with both metabolic disturbances and psychological dysfunction. Recent evidence suggests that the gut microbiome may play a role in these processes. This study examined whether probiotic supplementation could influence metabolic markers, nicotine dependence, and symptoms of anxiety and depression in smokers.

METHODS: In this randomized, double-blind, placebo-controlled clinical trial, seventy-four adult smokers were recruited (Kashan, Iran) and randomly assigned to receive either probiotic capsules containing Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium lactis (1.8 × 10⁹ CFU/day; n = 36) or a matching placebo (n = 38) for 12 weeks. Primary endpoints included changes in depressive symptoms (Beck Depression Inventory-II; BDI-II), anxiety (Beck Anxiety Inventory; BAI), and nicotine dependence (Nicotine Dependence Syndrome Scale; NDSS). Secondary endpoints included changes in metabolic, inflammatory, and oxidative stress biomarkers.

RESULTS: After 12 weeks, participants receiving probiotics showed significant reductions in fasting plasma glucose, triglycerides, very-low-density lipoprotein (VLDL) cholesterol, and C-reactive protein (CRP) compared with the placebo group (p = 0.025, p = 0.022, p = 0.026, and p = 0.004, respectively). High-density lipoprotein (HDL) cholesterol levels also increased significantly in the probiotic group (p = 0.007). No significant changes were observed in insulin, HOMA-IR, total cholesterol, LDL cholesterol, total antioxidant capacity, plasma nitric oxide, malondialdehyde, glutathione, or in scores for anxiety, depression, and nicotine dependence.

CONCLUSIONS: Twelve weeks of probiotic supplementation produced favorable effects on fasting glucose, some lipid profile, and CRP levels in smokers, though no measurable benefits were observed for anxiety and depression symptoms or nicotine dependence. These findings highlight a potential metabolic benefit of probiotics in populations exposed to cigarette smoking.

TRIAL REGISTRATION: This trial was registered at the Iranian Registry of Clinical Trials (IRCT20170420033551N13; registration date: December 6, 2022).}, } @article {pmid41612192, year = {2026}, author = {Li, L and Wang, H and Gao, Y and Zhang, B and Chen, Y}, title = {Integrative profiling of gut microbiome, bacteriophagenome, and predicted metabolome in obese adults: novel insights into intervention targets.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04682-1}, pmid = {41612192}, issn = {1471-2180}, support = {2023QN03043//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; 2025ZD034//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; 2025TYL08//First-Tier Team of the Yingcai Xingmeng Project/ ; }, } @article {pmid41612181, year = {2026}, author = {Zhang, J and Deng, J and He, B and Wang, H and Lin, D and Li, J and Zhong, Q and Chen, Y and Liao, S and Wang, J and Wang, Y and Su, M and Guo, X}, title = {The study on the identification of cross-boundary microbiome enterotypes between high-altitude and coastal populations and their predictive value.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04578-0}, pmid = {41612181}, issn = {1471-2180}, support = {2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; 2024B03J0562//the Science and Technology Program of Guangzhou/ ; }, } @article {pmid41612134, year = {2026}, author = {Bracken, AK and Malarney, KP and Chang, PV}, title = {Chemical Proteomics Reveals Regulation of Bile Salt Hydrolases via Oxidative Post-translational Modifications.}, journal = {Journal of the American Chemical Society}, volume = {}, number = {}, pages = {}, doi = {10.1021/jacs.5c18912}, pmid = {41612134}, issn = {1520-5126}, abstract = {The gut microbiome is the vast, diverse ecosystem of microorganisms that inhabits the human intestines and provides numerous essential functions for the host. One such key role is the metabolism of primary bile acids that are biosynthesized in the host liver into a plethora of secondary bile acids produced by gut bacteria. These metabolites serve as both antimicrobial and chemical signaling agents within the host. The critical microbial enzyme that plays a gatekeeping role in secondary bile acid metabolism is bile salt hydrolase (BSH), a cysteine hydrolase that is primarily known for its deconjugating and reconjugating activities on bile acid substrates. Despite the crucial nature of these biotransformations, regulation of BSH activity is not well understood. Here, we found that the catalytic cysteine 2 (Cys2) within the BSH active site exists in multiple sulfur oxidation states including sulfenic acid (Cys-SOH). Importantly, we show this reversible oxidative post-translational modification (oxPTM) ablates BSH catalytic activity. We have leveraged this discovery to develop a chemoproteomic platform featuring a sulfenic acid-reactive bile acid probe to profile BSH Cys2 oxPTMs throughout the gut microbiome. Our results reveal that though most gut microbiota-associated BSHs exist in the active Cys2-SH state, some are preferentially and reversibly inactivated in the Cys2-SOH state. This reversible oxidation of Cys2 may serve as a general mechanism to regulate BSH activity in vivo in response to a changing physiological environment.}, } @article {pmid41612130, year = {2026}, author = {Dimmers, F and Reichert, D and Wigmann, C and Trullàs, C and Piquero-Casals, J and Brown, A and Foyaca, M and Esser, C and Krutmann, J}, title = {Effects of solar-simulated (UVB plus UVA) radiation on the skin microbiome: An exploratory study.}, journal = {Photochemistry and photobiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/php.70078}, pmid = {41612130}, issn = {1751-1097}, support = {//ISDIN, Barcelona, Spain/ ; }, abstract = {This exploratory in vivo study investigated the impact of solar-simulated ultraviolet (UV) radiation (UVB plus UVA) on the composition of the human skin microbiome in healthy male volunteers. Thirty Caucasian men were exposed to suberythemal and erythemal doses of UV radiation (0.5, 0.7, and 1.0 minimal erythema dose, MED) on defined areas of the lower back. Skin swabs were collected from both irradiated (n = 243) and nonirradiated control sites (n = 81) 30 min, 24 h, and 96 h postexposure. The microbial profiles were generated using flow cytometry, and the data were analyzed via the open-access bioinformatic platform FlowSoFine™. The results revealed pronounced alterations in the microbial composition, with changes already detectable 30 min after exposure. Although partial recovery was observed over time, certain microbial shifts persisted. Further analysis indicated dose-dependent trends in microbiome changes, suggesting a potential relationship between the extent of microbial alteration and the applied UV dose. These results suggest that even low, nonerythematous exposure to solar-simulated UV radiation can rapidly alter the microbial balance of the skin and emphasize the role of UV radiation as a potent modulator of the skin microbial homeostasis.}, } @article {pmid41612069, year = {2026}, author = {Sun, G and Cheng, H and Yin, M}, title = {Oral hygiene and cancer risk: emerging evidence and public health perspectives.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-026-04527-x}, pmid = {41612069}, issn = {2730-6011}, support = {22JR5RA916//the Gansu Province Natural Science Foundation Project/ ; ldyyyn2020-46//the In-House Fund of Lanzhou University First Hospital/ ; 2020-ZD-92//the Science and Technology Development Plan Project of Lanzhou City/ ; CYXZ2023-06//the Scientific Research Cultivation Program for Cuiying Scholars, Second Hospital of Lanzhou University/ ; }, } @article {pmid41611923, year = {2026}, author = {Costa-Santos, M and Sario, S and Mendes, RJ and Santos, C}, title = {Seasonal dynamics and core stability of the bacterial microbiome of a Drosophila suzukii wild population.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-37656-y}, pmid = {41611923}, issn = {2045-2322}, support = {2021.06319.BD//Fundação para a Ciência e a Tecnologia/ ; PTDC/ASP-PLA/4477/2020//Fundação para a Ciência e a Tecnologia/ ; PTDC/ASP-PLA/4477/2020//Fundação para a Ciência e a Tecnologia/ ; PTDC/ASP-PLA/4477/2020//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {Drosophila suzukii (spotted-wing drosophila, SWD) is an invasive pest with pronounced sexual dimorphism and seasonal polyphenism. While seasonal morphotypes are well documented, how these phenotypic traits shape the SWD microbiome remains poorly understood. Here, we investigate how sex and seasonal phenotypes shape microbiome composition in SWD. We hypothesize that these factors drive microbial shifts, with some taxa varying between phenotypes and others forming a stable core. Understanding these patterns may reveal microbiome-associated adaptations relevant to SWD ecology and management. To investigate this, we monitored SWD microbiome dynamics over one year by collecting individuals during spring, summer, and autumn of 2022 and winter of 2023 from an organic farm in northern Portugal. Bacterial communities were compared using 16 S rRNA amplicon sequencing. This SWD population retained a core bacterial community, highly represented by Gluconobacter, Pseudomonas, Commensalibacter and Pantoea, consistent with other SWD Portuguese populations. Moreover, microbiome composition varied significantly across seasons but not between sexes, although females exhibited higher microbial alpha diversity. Linear discriminant analysis of relative abundance (LEfSe) revealed enrichment of Morganella, Methanosaeta, Serratia, Duganella, Frateuria, Suttonella, and Janthinobacterium in winter groups. However, functional prediction analyses revealed no significant differences in microbiome functional potential across seasons, suggesting functional redundancy despite taxonomic variation. This study offers baseline insights into the seasonal stability and plasticity of the D. suzukii microbiome, contributing to a deeper ecological understanding of this invasive pest.}, } @article {pmid41611306, year = {2026}, author = {Shen, Y and Solís-Lemus, C}, title = {Bayesian chain graph models to characterize microbe-environment dynamics.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {23}, number = {2}, pages = {499-546}, doi = {10.3934/mbe.2026020}, pmid = {41611306}, issn = {1551-0018}, mesh = {Bayes Theorem ; Algorithms ; Computer Simulation ; *Microbiota ; Linear Models ; Humans ; Computational Biology ; Gastrointestinal Microbiome ; Models, Biological ; Models, Statistical ; }, abstract = {Microbiome data require statistical models that can simultaneously decode microbes' reaction to the environment and interactions among microbes. While a multiresponse linear regression model seems like a straight-forward solution, we argue that treating it as a graphical model is problematic given that the regression coefficient matrix does not encode the conditional dependence structure between response and predictor nodes. This observation is especially important in biological settings when we have prior knowledge on the edges from specific experimental interventions that can only be properly encoded under a conditional dependence model. Here, we propose a chain graph model with two sets of nodes (predictors and responses) whose solution yields a graph with edges that indeed represent conditional dependence, thus agreeing with the experimenter's intuition on the average behavior of nodes under treatment. The solution to our model is sparse via the Bayesian linear regression (LASSO). In addition, we propose an adaptive extension so that different shrinkages can be applied to different edges to incorporate edge-specific prior knowledge. Our model is computationally inexpensive through an efficient Gibbs sampling algorithm and can account for binary, counting, and compositional responses via an appropriate hierarchical structure. We test the performance of our model in a variety of simulated datasets, thereby showing superior performance to state-of-the-art approaches. We further apply our model to human gut and soil microbial compositional datasets, and we highlight that CG-LASSO can estimate biologically meaningful network structures in the data. Our software is available as an R package at https://github.com/YunyiShen/CAR-LASSO.}, } @article {pmid41611115, year = {2026}, author = {Kuribayashi, S and Naik, N and Miller, AW and Lundy, SD}, title = {Micro-Management: How the Male Reproductive Microbiome Shapes Male Fertility.}, journal = {Fertility and sterility}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.fertnstert.2026.01.019}, pmid = {41611115}, issn = {1556-5653}, abstract = {IMPORTANCE: One in six couples worldwide experience infertility, and male factors contribute to at least half of these cases. The pathophysiology of male infertility is complex and often multifactorial, and the male reproductive microbiome has now been implicated as a potentially critical component in male reproductive health and disease.

OBJECTIVE: To summarize the emerging evidence describing the male reproductive microbiome with a focus on clinically relevant aspects within spermatogenesis and reproductive outcomes.

EVIDENCE REVIEW: We performed a librarian-led search of MEDLINE, Embase, and Web of Science and a targeted PubMed search for antibiotic and probiotic trials, focusing on human studies that reported male reproductive microbiome data together with semen parameters, oxidative, DNA-damage, or inflammatory indices, or assisted reproduction outcomes. Given heterogeneity in design and laboratory methods, we conducted a narrative synthesis and integrated relevant mechanistic animal work.

FINDINGS: Across heterogeneous cohorts, anaerobe-leaning seminal profiles (often with Prevotella or Atopobium) are more often linked to higher oxidative stress, greater sperm DNA fragmentation, and lower motility or total motile count. In contrast, Lactobacillus-rich profiles more often align with better redox status and DNA integrity. Couple-level data show rapid and robust partner microbiome exchange that can shift semen over short periods. Work on the gut-testis axis has identified a link between gut dysbiosis and systemic inflammation with semen quality via the gut-testis axis. Proposed mechanisms underlying the effect of the microbiome on fertility include local inflammation, oxidative injury, altered seminal rheology (e.g., viscosity/viscoelastic properties of seminal plasma), adherence/biofilms, and immune-metabolic crosstalk. Small trials to date using antibiotics and/or probiotics show variable benefits; durability and reproductive endpoints remain limited.

CONCLUSION AND RELEVANCE: Emerging evidence supports a role for the male reproductive microbiome in sperm function and fertility and highlights it as a potential target for clinical intervention. However, predominantly small, cross-sectional studies and methodological heterogeneity limit causal inference and immediate translation, underscoring the need for longitudinal, couple-integrated cohorts and adequately powered randomized trials of targeted microbiome modulation.}, } @article {pmid41611114, year = {2026}, author = {Young, RB and Correia, GDS and MacIntyre, DA}, title = {Host, microbial and environmental drivers of vaginal microbiota composition.}, journal = {Fertility and sterility}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.fertnstert.2026.01.020}, pmid = {41611114}, issn = {1556-5653}, abstract = {The human vagina harbours a microbial community that differs markedly in compositional structure from all mammals, including closely related primates. Lactobacilli are the most abundant vaginal species, and their dominance in this niche are associated with protection against adverse health outcomes including preterm birth, sexually transmitted infections and bacterial vaginosis. However, the vaginal environment can also support compositions of diverse anaerobic bacteria, which have been linked to poor reproductive health outcomes. Here, we review current knowledge on host and microbial determinants that influence microbial community structure within the vaginal niche, emphasising the interplay between host physiology, immune and metabolic interactions as well as lifestyle factors. This integrated understanding provides a foundation for linking vaginal microbiome compositions to clinically relevant phenotypes and highlights mechanisms that could be exploited to promote improved reproductive health.}, } @article {pmid41611056, year = {2026}, author = {Saeed, Q and Lu, X and Farooqi, ZUR and Ghafoor, A and Naveed, M and Maqsood, N and Kareem, HA and Mustafa, A}, title = {Root Traits and Rhizosphere Responses as Emerging Bioindicators of Microplastic Pollution in Agricultural Soils: A review.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123866}, doi = {10.1016/j.envres.2026.123866}, pmid = {41611056}, issn = {1096-0953}, abstract = {In agricultural soils, crop roots are central to regulating soil health, nutrient cycling, and long-term carbon sequestration through rhizosphere-driven processes such as root exudation, microbial modulation, and litter decomposition. However, the increasing prevalence of microplastics (MPs) in farmlands arising from mulching films, sewage sludge, composts, and atmospheric deposition is increasingly recognized as a pervasive threat to root-soil-microbe interactions. This review focused on how crop root traits (architecture, chemistry, turnover) are influenced by MPs and explores their cascading impacts on rhizosphere functionality, with a specific focus on their potential as emerging bioindicators of MPs pollution in agricultural soils. MPs disrupt root morphology, alter microbial communities, reduce carbon inputs as exudates, and interfere with organo-mineral associations, and reshape rhizosphere responses that govern soil aggregation, nutrient availability, and microbial carbon stabilization. These responses vary across crop functional types, including grasses, legumes, vegetables, and fodder crops, reflecting differences in root architecture, turnover, and rhizosphere regulation. Collectively, these trait-based responses provide integrative and sensitive indicators of MPs stress in agroecosystems. We highlight future research strategies emphasizing rhizosphere engineering such as microbiome manipulation, exudation modulation, breeding for resilient root traits, and multi-indicator integration, to mitigate MPs stress and enhance overall ecosystem resilience. Collectively, this review underscores the potential of root-based bioindicators and rhizosphere responses as robust tools for monitoring MPs pollution and supporting sustainable soil management in plastic-impacted agroecosystems.}, } @article {pmid41610908, year = {2026}, author = {Barash, JR and Sambol, SP and Skinner, AM and Johnson, S and Gerding, DN}, title = {Clostridioides difficile colonization of Twin Patients Recovering From Infant Botulism.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {103022}, doi = {10.1016/j.anaerobe.2026.103022}, pmid = {41610908}, issn = {1095-8274}, abstract = {OBJECTIVES: The prevalence of Clostridioides difficile co-colonization of 107 California patients with suspect infant botulism (IB) was studied over a two-year period. One set of twins with lab-confirmed IB and C. difficile co-colonization was followed longitudinally and their isolated C. difficile was typed by restriction endonuclease analysis (REA).

METHODS: Stool specimens sent to California Department of Public Health for routine IB diagnostic testing were cultured for C. botulinum and C. difficile. After diagnostic testing identified twin IB patients, their stools collected at weekly and monthly intervals were cultured to determine duration of C. botulinum and C. difficile co-colonization until three consecutive specimens were culture negative for each organism.

RESULTS: Twins X and Y were colonized by C. botulinum for a duration of nearly three and four months, followed by C. difficile for eight and seven months, respectively. Continuous colonization by C. difficile was identified in each twin as C. botulinum colonization was waning. They sequentially shared four identical REA types, three toxigenic and one non-toxigenic, including epidemic strain type J9. Neither twin developed C. difficile illness and colonization ceased spontaneously in each.

CONCLUSIONS: C. difficile co-colonization of laboratory-confirmed IB patients is infrequently encountered. IB in both twins was followed by asymptomatic C. difficile colonization. Risk factors for their respective co-colonization remain unknown, including if previous illness with IB was a potential contributing factor. Although the environmental source of the colonizing strains was not determined, this study highlights the ability of C. difficile to spread to close contacts and persist in the infant intestinal microbiome.}, } @article {pmid41610853, year = {2026}, author = {Weiler, BA and Kron, N and Bonacolta, AM and Vermeij, MJA and Baker, AC and Del Campo, J}, title = {Temporal transcriptional rhythms govern coral-symbiont function and microbiome dynamics.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2026.01.004}, pmid = {41610853}, issn = {1934-6069}, abstract = {Diel rhythms align physiological processes with light/dark cycles, driving predictable oscillations in gene expression and protein activity through tightly controlled transcriptional-translational feedback loops. This study presents in situ transcriptomic analyses of the stony coral Pseudodiploria strigosa and its photosymbionts, Breviolum sp., at key daily time points. P. strigosa shows precise transcriptional control: dawn triggers a molecular reset marked by RNA metabolism and protein turnover; midday emphasizes anabolic and phosphate-regulated pathways; dusk reflects transitional lipid and amino acid metabolism; and midnight reveals stress responses, mRNA catabolism, and mitochondrial organization. Photosymbionts display subtler diel patterns, with photoprotection at dawn, metabolite transport and nitrogen cycling through midday/dusk, and cell cycle and ion homeostasis at night. Microbial communities show time-dependent restructuring of co-occurrence networks, driving diel-related functional consequences like changes in microbial metabolism. These findings present a system-level molecular framework of diel regulation across the coral-photosymbiont-microbe holobiont, revealing time-specific transcriptional control of coordinated function and homeostasis.}, } @article {pmid41610813, year = {2026}, author = {Ramos-Madrigal, J}, title = {The potential of plant palaeogenomic research.}, journal = {Current opinion in plant biology}, volume = {90}, number = {}, pages = {102856}, doi = {10.1016/j.pbi.2025.102856}, pmid = {41610813}, issn = {1879-0356}, abstract = {Plant palaeogenomics has transformed the way we study plant evolution. After a slow start, the last decade has seen a shift from the study of a few genomic markers to genome-wide data and complete genomes across multiple species. These studies have changed fundamental ideas about plant domestication and evolution. The field still has great potential to unlock. Emerging approaches promise to recover genomic information from both plants and their associated microbes from macrobotanical remains, providing a new perspective to study deep-time plant-microbiome coevolution. Environmental DNA preserved in ancient sediments may soon yield complete plant genomes, expanding our ability to study population dynamics well before the rise of agriculture. Ancient genomes also provide a reservoir of lost genetic diversity that we could exploit to improve crop resilience and adaptation.}, } @article {pmid41610734, year = {2026}, author = {Widyarman, AS and Bur, R and Udawatte, NS and Agaristi, PM and Razari, I and Bahri, S and Richi, M and Astoeti, TE and Seneviratne, CJ}, title = {Mouthrinses differentially rewire salivary virus-microbiome interaction dynamics in COVID-19 patients: A randomized controlled trial.}, journal = {Archives of oral biology}, volume = {184}, number = {}, pages = {106524}, doi = {10.1016/j.archoralbio.2026.106524}, pmid = {41610734}, issn = {1879-1506}, abstract = {OBJECTIVE: In this randomized clinical trial (RCT) we evaluated the efficacy of mouthrinses containing sodium chlorite (NaClO2), povidone iodine (PVP-I), cetylpyridinium chloride (CPC) compared to sterile water control in modulating salivary SARS-CoV-2 viral load and the oral microbiome in COVID-19 patients.

METHODS: Forty PCR-confirmed COVID-19 patients were randomly allocated to four groups (n = 10 each) and rinsed with 10 ml of their assigned solution for 30 s. Saliva was collected pre-rinse and at 5-min, 3-hour, and 6-hour post-rinse. Viral load was quantified via RT-qPCR targeting N and ORF1ab genes, and oral microbiome was analyzed using 16S rRNA sequencing.

RESULTS: CPC reduced viral load by 1.5-fold (P = 0.12), PVP-I by 1.2-fold (P = 0.18), and NaClO2 by 1.1-fold (P = 0.34) at 6-hour, though not statistically significant. Overall oral microbiome diversity and composition remained stable (P = 0.67), although CPC and PVP-I significantly altered specific taxa such as Leptotrichia sp. and Lautropia mirabilis. Moreover, CPC and PVP-I disrupted the salivary microbiome network with SARS-CoV-2 genes, namely N and ORF1ab genes.

CONCLUSION: This study to provide new insight into the modulation dynamics of mouthrinses on salivary SARS CoV-2 and oral microbiome, suggesting that CPC and PVP-I may provide potential health benefits by reducing viral load and modulating microbiome-virus networks.}, } @article {pmid41610732, year = {2026}, author = {Chen, S and Li, H and Ning, M and Yu, BYM and Wu, S and Cheng, WY and Li, Y and Yeung, WF}, title = {The association between gut microbiota and insomnia: A systematic review and meta-analysis.}, journal = {Sleep medicine reviews}, volume = {86}, number = {}, pages = {102236}, doi = {10.1016/j.smrv.2026.102236}, pmid = {41610732}, issn = {1532-2955}, abstract = {Emerging evidence suggests interactions between gut microbiota and sleep regulation, but specific associations with insomnia remain unclear. This systematic review evaluated alterations in gut microbiota in patients with insomnia compared with healthy controls. A systematic literature search was performed on eight databases from inception to June 2025. Case-control, cohort, and cross-sectional studies examining gut microbiota in adults with insomnia versus healthy controls were included. Fourteen studies encompassing 9036 participants (58.4 % female) were included. Alpha diversity was reduced in patients with insomnia in most of the included studies, among which observed species significantly decreased (SMD: 0.90, 95 % CI: 1.39, -0.40, k = 5). Beta diversity analysis revealed a consistently distinct microbial community structure between individuals with insomnia and healthy controls. Taxonomically, insomnia correlated with shifted Firmicutes-to-Bacteroidetes ratios. Meta-analyses revealed alterations in key genera, including significantly decreased Faecalibacterium and Lachnospira, and significantly increased Blautia and Eubacterium hallii. Changes in gut microbiota were also correlated with inflammatory markers and metabolic disturbances. In summary, gut microbiota dysbiosis was associated with insomnia and characterized by reduced microbial diversity and altered bacterial composition. These findings suggest potential applications for microbial biomarkers in insomnia diagnosis and subtyping, and the development of personalized microbiota-targeted interventions.}, } @article {pmid41610646, year = {2026}, author = {Kumar, S and Srivastava, S and Tan, CS and Abohashrh, M and Malviya, R}, title = {Correlation between oral disease and neurodegenerative disorders: Role of biological proteins for the modulation of oral-brain axis and gut-brain axis.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {262}, number = {}, pages = {115480}, doi = {10.1016/j.colsurfb.2026.115480}, pmid = {41610646}, issn = {1873-4367}, abstract = {Biological proteins play a crucial role at the intersection of oral health and neuroscience, offering promising opportunities for improved diagnosis, prevention, and treatment. This review highlights the molecular, inflammatory, and biochemical pathways linking oral diseases, particularly periodontal disease and microbial dysbiosis, with neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Key inflammatory, neuroprotective, and tissue-repair proteins play a crucial role in maintaining both oral integrity and neural function. Advances in proteomics and molecular imaging have clarified how protein misfolding, aggregation, and immune responses drive neuroinflammation and cognitive decline. Emerging therapies include protein-based biomaterials, such as hydrogels, nanocarriers, and protein-polymer hybrids, for delivering neuroprotective and regenerative agents through oral and nasal routes. Early diagnosis is being transformed by salivary proteomics and transcriptomics, enabling non-invasive detection of neurodegenerative biomarkers. Host-defense peptides and antimicrobial proteins also show promise in controlling oral infections that may exacerbate brain inflammation. Integrating oral biology, biomaterials science, and neuroscience is accelerating clinical translation through the development of innovative scaffolds and smart delivery systems. Despite challenges in biomarker validation and clinical application, advances in artificial intelligence, bioinformatics, and protein engineering are driving the future of personalized regenerative and preventive medicine. Overall, biological proteins provide a critical molecular link between oral and neural health, paving the way for novel non-invasive diagnostic and therapeutic strategies.}, } @article {pmid41610568, year = {2026}, author = {Yousaf, MW and Nadeem, AH and Nadeem, MF and Qaisar, R}, title = {The role of artificial intelligence in sarcopenia: Advances, applications, and future directions.}, journal = {Computational biology and chemistry}, volume = {122}, number = {}, pages = {108930}, doi = {10.1016/j.compbiolchem.2026.108930}, pmid = {41610568}, issn = {1476-928X}, abstract = {Sarcopenia, the gradual loss of skeletal muscle mass, strength, and function, is a growing concern in aging populations. Early detection is vital to reduce the risk of frailty, disability, and mortality, yet traditional diagnostic methods such as imaging and physical performance tests are often costly, inconsistent, or difficult to implement in routine care. Artificial intelligence (AI), including machine learning (ML) and deep learning (DL), is emerging as a powerful tool in sarcopenia research and clinical practice. This review explores how AI is being applied to early detection, imaging-based diagnosis, prediction of functional outcomes, and personalized monitoring. Models trained on large datasets, such as NHANES, have demonstrated strong predictive performance using standard clinical variables. DL has enabled automated analysis of CT scans for muscle segmentation, reducing the need for manual interpretation. At the same time, ML systems integrated with wearable devices allow real-time tracking of physical function. Emerging approaches such as explainable AI, federated learning, and the integration of diverse data sources, including omics and microbiome profiles, are expanding opportunities for individualized care. Despite these advances, significant challenges remain, including variability in data quality, limited model transparency, algorithmic bias, and ethical concerns. Regulatory oversight and clinician engagement will be key to successful implementation. AI offers a promising path toward proactive, scalable, and personalized management of sarcopenia.}, } @article {pmid41610179, year = {2026}, author = {Singh, D and Liu, J and Luo, J and Huang, L and Huang, QS and Yang, L and Zhou, Z}, title = {Sugar-sweetened orange beverages: A silent risk factor for colorectal cancer?.}, journal = {Nutrition and health}, volume = {}, number = {}, pages = {2601060251383198}, doi = {10.1177/02601060251383198}, pmid = {41610179}, issn = {2047-945X}, abstract = {BackgroundEriodictyol is a flavonoid primarily found in citrus fruits for dietary consumption. Laboratory studies have shown that it has antioxidant and anti-inflammatory properties, which help prevent colorectal cancer (CRC). However, consuming eriodictyol through citrus drinks and added sugars may increase the risk of CRC. These beverages can raise blood sugar levels and disrupt the gut microbiome, potentially increasing the risk of CRC.AimThis study aims to evaluate the relationship between dietary intake of eriodictyol flavonoid, commonly consumed through citrus drinks or sugar-sweetened orange beverages, and the increased risk of CRC, as well as its connection with diabetic patients.MethodsData from 53,914 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were analyzed using Dietary Questionnaire (DQX) and Dietary History Questionnaire (DHQ). LASSO regression identified significant associations, while restricted cubic spline analysis examined nonlinear relationships between eriodictyol intake and CRC risk.ResultsDiabetes was confirmed as a significant risk factor for CRC in both the DHQ and DQX cohorts. Additionally, higher eriodictyol intake was associated with increased CRC risk in the DQX group, suggesting a possible link between diabetes, elevated eriodictyol consumption, and CRC development. The primary source of dietary eriodictyol in the USA is sugar-sweetened beverages.ConclusionsThe findings show that hyperglycemic patients have a notably higher risk of CRC, and this increased risk remains even with dietary intake of eriodictyol, a flavonoid commonly found in citrus fruits and increasingly consumed through citrus beverages in industrialized countries.}, } @article {pmid41609982, year = {2026}, author = {Rustamova, N and Wali, A and Litao, N and Movlanov, J and Davranov, K and Yili, A}, title = {Characterization and biological activities of endophytic bacteria from Vernonia anthelmintica flowers.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41609982}, issn = {1874-9356}, support = {2019-FPGGRC-004 and 2019-FPGGRC-005//West Light Foundation of the Chinese Academy of Sciences Grant/ ; }, abstract = {Endophytic bacteria associated with medicinal plants are a vital component of the plant microbiome and represent a valuable biological resource. This study investigates the diversity and biological activities of endophytic bacteria isolated from the flowers of Vernonia anthelmintica, a medicinal plant native to China. The research focuses on evaluating the cytotoxic, antimicrobial, antioxidant, and antidiabetic properties of natural products derived from these bacteria, as well as their effects on melanin synthesis and tyrosinase activity in B16 cells. A total of 32 bacterial strains were isolated and cultured, of which eight crude extracts exhibiting antimicrobial activity were selected for further analysis. These isolates. belong to four genera: Bacillus, Streptococcus, Priestia and Paenibacillus. Among them, Priestia megaterium XJB-41 demonstrated the most substantial pharmacological potential, warranting further investigation to optimize its culture conditions for enhanced bioactive compound production. The optimal growth conditions for P. megaterium XJB-41 were determined to be LB and Nutrient Broth (NB) media, with peptone as the carbon source and yeast extract as the nitrogen source, under 24 h of incubation. These conditions significantly enhanced both bacterial growth and metabolite yield. Moreover, two secondary metabolites: cyclo(D-leu-L-pro) [1] and 2-benzoxazolone [2] were isolated for the first time from the ethyl acetate fraction of P. megaterium XJB-41. This strain shows promise for further investigation as a potential source of therapeutic agents.}, } @article {pmid41609895, year = {2026}, author = {Moreiras-Arias, N and Nieto-Fontarigo, JJ and Salgado, FJ and González-Vilas, D and Paredes-Suárez, C and Combo-García, E and Rodríguez-Otero, C and Flórez, Á}, title = {Novel Therapeutic Strategies for Atopic Dermatitis: Biomarker Modulation and Clinical Implications. A Systematic Review.}, journal = {Clinical reviews in allergy & immunology}, volume = {69}, number = {1}, pages = {4}, pmid = {41609895}, issn = {1559-0267}, mesh = {Animals ; Humans ; *Biomarkers/metabolism ; Chemokine CCL17/metabolism ; *Dermatitis, Atopic/diagnosis/drug therapy/therapy/metabolism/etiology/immunology ; Janus Kinase Inhibitors/therapeutic use ; }, abstract = {Advances in the understanding of atopic dermatitis (AD) pathogenesis have driven the development of innovative systemic therapies targeting key immunologic pathways. This systematic review summarizes current evidence on the impact of biologic agents, Janus kinase (JAK) inhibitors, and other emerging treatments on AD-related biomarkers and their correlation with clinical outcomes. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published between 2014 and 2024. Eighty studies met the inclusion criteria. Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab. Across drug classes, consistent reductions in CCL17/TARC, LDH, and total IgE levels were observed, generally paralleling clinical improvement in EASI and SCORAD scores. Transcriptomic and proteomic analyses revealed normalization of Th2/Th22 inflammatory signatures and restoration of barrier-related gene expression, while microbiome studies showed a reduction in Staphylococcus aureus colonization. Despite these advances, the heterogeneity of study designs and analytical techniques limits the comparability of results. CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management.}, } @article {pmid41609714, year = {2026}, author = {Koch, BL and Singla-Rastogi, M and Innes, RW}, title = {Extracellular Vesicles and Extracellular RNAs in Plant-Microbe Interactions.}, journal = {Annual review of plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-arplant-063025-110704}, pmid = {41609714}, issn = {1545-2123}, abstract = {Plants and microbes exchange macromolecules such as RNA and proteins. How this exchange is accomplished is poorly understood, but extracellular vesicles (EVs) have been proposed as likely vehicles. Here, we review recent work on the biogenesis and functions of plant EVs and the current evidence in support of and against their role in cross-kingdom RNA interference. Plant EVs, like EVs from other kingdoms of life, are released in part by the fusion of multivesicular bodies with the plasma membrane, a complex and conserved mechanism involving lipid-modifying proteins, the exocyst complex, and Rab GTPases. Though some plant EV subpopulations are involved in immunity, it appears unlikely that plant EVs contribute to cross-kingdom RNA interference. Recent work has shown that plants secrete extravesicular RNA, including small RNAs and long noncoding RNAs, into the leaf apoplast and onto leaf surfaces, while very little RNA is found inside of EVs. We propose that these free extracellular RNAs play a central role in maintaining a healthy leaf microbiome.}, } @article {pmid41609616, year = {2026}, author = {Han, SH and He, MT and Baek, KW and Kim, HY and Lee, S and Lee, AY}, title = {Protective Effect of Luteolin Isolated from Taraxacum coreanum Against Neuroinflammatory Responses Induced by Lipopolysaccharide: Involvement of Gut-Brain Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c12437}, pmid = {41609616}, issn = {1520-5118}, abstract = {Neuroinflammation can be brought on by intestinal inflammatory agents and metabolites generated by the gut microbiota that can pass across the blood-brain barrier. Taraxacum coreanum is rich in the bioactive compound luteolin (LT), a molecule known for its potent antioxidant and anti-inflammatory activities. The current research investigated whether LT prevents inflammatory responses and barrier dysfunction in the brain and gut of lipopolysaccharide (LPS)-injected mice. LT (10 and 20 mg/kg/day) effectively lowered the brain levels of pro-inflammatory mediators and cytokines triggered by LPS stimulation. Moreover, occludin and ZO-1 are two tight junction proteins whose expression was markedly elevated by LT. In the intestine, LT not only attenuated the levels of inflammatory mediators but also markedly upregulated tight junction protein expression relative to the LPS-treated group. LT markedly reversed LPS-induced dysbiosis by increasing beneficial taxa such as Bacteroidota, Actinobacteriota, Murivaculaceae, and Lactobacillus. In addition, LT reduced the relative abundance of Firmicutes and Desulfovibrio. Collectively, LT from Taraxacum coreanum may attenuate neuroinflammation and maintain blood-brain barrier integrity by suppressing inflammatory responses, protecting the gut barrier, and modulating the gut microbiome.}, } @article {pmid41609448, year = {2026}, author = {Koçak, Ö and Sharafi, P and Gökdemir, Ş and Görkem, Ü and Al-Kaleel, A and Taylan Özkan, A}, title = {[Changes in Gut Microbiome Profile in Pregnant Women with Hyperemesis Gravidarum: A Comparative Study Based on 16S rRNA Sequencing].}, journal = {Mikrobiyoloji bulteni}, volume = {60}, number = {1}, pages = {53-71}, doi = {10.5578/mb.2026018}, pmid = {41609448}, issn = {0374-9096}, mesh = {Humans ; Female ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome/genetics ; *Hyperemesis Gravidarum/microbiology ; Adult ; Feces/microbiology ; Case-Control Studies ; *Bacteria/classification/genetics/isolation & purification ; DNA, Bacterial/chemistry/genetics ; }, abstract = {Hyperemesis gravidarum (HEG) is a pregnancy complication characterized by severe nausea, vomiting more than four times a day and dehydration, especially occurring in the first trimester of pregnancy. In recent years it has been shown that the intestinal bacterial microbiome profile may be associated with a wide range of diseases. The aim of this study was to determine whether the intestinal bacterial microbiome profiles differ between pregnant women diagnosed with hyperemesis gravidarum (HEG) and those with healthy pregnancies. Fresh stool samples were collected from 15 pregnant women diagnosed with HEG and 14 healthy pregnant women who did not have any complaints in the first trimester. After DNA isolation from the samples, 16S rRNA gene-based microbial profiling was performed with next-generation sequencing. The 16S rRNA V3-V4 region was sequenced with paired-end reads (2×250 base pair) on the Illumina MiSeq platform. The average sequence number for each sample was similar (HEG= ~2.54 million, control= ~1.48 million; p> 0.05). After quality filtering, reads obtained from all samples were analyzed by rarefaction at equal depth. Alpha diversity measures were found to be significantly higher in the HEG group compared to the control group (Shannon, ACE, and Chao1 indices; p< 0.05 for all). In the beta diversity analysis, it was observed that the gut microbiome compositions of the two groups were separated; In the Principal Coordinates Analysis plot, the groups were clearly clustered and the group difference was found to be statistically significant by PERMANOVA test (p< 0.01). Significant differences were also found in the comparisons at the taxonomic level. At the class level, the relative abundance of Clostridia was significantly higher in the HEG group (p< 0.05), while the class Bacilli was dominant in the control group (p< 0.05). At the family level, the abundances of Lachnospiraceae and Prevotellaceae were found to be significantly higher in the HEG group than in the control group (p< 0.05). In contrast, at the family level, the rates of Enterobacteriaceae and at the genus level, the rates of Escherichia-Shigella were found to be significantly higher in the control group (p< 0.05). Some bacterial taxa detected only in the HEG group samples were also noteworthy: Collinsella, Blautia, and Dialister genera, which are only found in the intestines of patients with HEG, were not detected in the control group. In conclusion, these findings reveal that there are significant differences between the intestinal microbiome profiles of pregnant women with HEG and healthy pregnant women. The high microbial diversity observed in the HEG group and changes in certain bacterial groups suggest that processes related to lipid and carbohydrate metabolism may play a role in the pathogenesis of HEG. In the future, the clinical significance and possible therapeutic targets of these differences can be evaluated with more comprehensive studies aiming at clarifying causality.}, } @article {pmid41609372, year = {2026}, author = {Motta, EVS and Seong, J and Dickey, M and Ellis, JT and Rangel, J}, title = {Divergent microbiome signatures between managed and wild honey bee (Apis mellifera) populations in South Texas.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0339425}, doi = {10.1128/spectrum.03394-25}, pmid = {41609372}, issn = {2165-0497}, abstract = {UNLABELLED: Animal microbiomes are shaped by a complex interplay of host genetics, environment, and lifestyle. Transitions of animals from wild to managed or domesticated conditions can impact the structure and function of their microbiomes. Among insects, the Western honey bee (Apis mellifera) is a promising model for studying these dynamics, given its long history of domestication and importance in agriculture. Despite extensive research on managed honey bee microbiomes, direct comparisons with wild populations remain scarce. Here, we compared the gut microbiomes of wild honey bee colonies from the Welder Wildlife Refuge in South Texas, which have remained unmanaged for over 30 years, with those from the closest managed apiary, located approximately 40 miles away. Using quantitative PCR and 16S ribosomal RNA gene sequencing, we found that managed bees harbored significantly higher bacterial loads but lower microbial diversity than wild bees. Although both groups shared a conserved microbiome dominated by core bacterial genera, distinct amplicon sequence variants and predicted metabolic pathway profiles differentiated them. Managed bee microbiomes were enriched in amino acid interconversion and antibiotic resistance-associated pathways, whereas wild bee microbiomes exhibited broader metabolic versatility, including amino acid biosynthesis and aromatic compound degradation. PCR screening further revealed a higher prevalence of tetracycline resistance markers in managed bees. Together, these findings indicate that long-term absence of human management and distinct ecological pressures shape honey bee gut microbiomes, influencing community composition and potentially functional capacity, underscoring the importance of natural environments to maintain microbial diversity and resilience.

IMPORTANCE: Understanding how human management shapes the microbiomes of domesticated species is essential for predicting their resilience to environmental stressors. Honey bees (Apis mellifera) are critical pollinators whose health and productivity are closely tied to their gut microbiota, but nearly all microbiome studies have focused on managed colonies. This study leverages the Welder Wildlife Refuge in South Texas, one of the few documented and well-studied sites in the United States where honey bee colonies have persisted unmanaged for decades, to directly compare managed and wild populations. We show that managed bees harbor higher bacterial loads but reduced microbial diversity and greater antibiotic resistance potential. These findings demonstrate that long-term absence of human intervention can preserve microbial diversity, offering insights into how domestication, antibiotic exposure, and environmental simplification influence the evolution and ecology of host-associated microbiomes.}, } @article {pmid41609371, year = {2026}, author = {Panattoni, A and De Boeck, I and Wittouck, S and Deffner, P and Lillie-Jaschniski, K and Stadler, J and Lebeer, S and Theuns, S}, title = {Exploring the functional microbiome of pigs within the porcine respiratory disease complex: viral-bacterial co-infections and virulence factor profiling.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0191025}, doi = {10.1128/spectrum.01910-25}, pmid = {41609371}, issn = {2165-0497}, abstract = {Respiratory infections are among the most impacting on pigs' health and economic productivity. Despite this, detailed insights into the microbial community of the lower respiratory tract (LRT) are currently lacking, mainly because of difficulties in the processing of respiratory samples. In this study, we characterized the microbiota of the LRT of finisher pigs aged 3-5 months with respiratory symptoms for both the viral and bacterial components, using a previously validated metagenomic diagnostic assay and a full-length 16S rRNA gene sequencing approach, respectively. Functional characterization was carried out using metagenomic shotgun sequencing, revealing the presence of specific virulence factors (VFs). Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and swine Influenza A Virus (swIAV) were the most prevalent viruses, being detected in 30% and 23% of the tested samples, respectively. Mesomycoplasma hyopneumoniae, Glaesserella parasuis, and Pasteurella multocida were the three most abundant bacterial taxa based on both sequencing approaches, while other detected bacterial taxa consisted mainly of Streptococcus, Clostridium, and Rothia species. Detected virulence factors belonged mainly to Mesomycoplasma and Pasteurella and consisted of adhesion factors such as p102, p97, p146, mhp108, mhp107 and the hemolysin-encoding gene hlyA for Mesomycoplasma, and adhesin-encoding ptfA and endoxtoxin-related gene lpxC for Pasteurella. Our data show how the microbial community of the lower respiratory tract in pigs with respiratory symptoms includes key viral (PRRSV, swIAV) and bacterial pathogens (M. hyopneumoniae, G. parasuis, and P. multocida), along with specific virulence factors likely contributing to disease.IMPORTANCEThe obtained results offer insights into the composition of the swine respiratory tract microflora, opening new perspectives on its correlation with viral infections, functional characteristics, and overall health conditions. Moreover, the present study provides technical advancement on the possibility of extracting and amplifying bacterial DNA from low-biomass respiratory samples, with the resulting possibility of identifying virulence factors and better understanding their contribution to the disease state. These discoveries pave the way for future studies aimed at improving diagnostic accuracy and treatment strategies for respiratory disease in both veterinary and human medicine.}, } @article {pmid41609355, year = {2026}, author = {Li, Y and Li, Q and Quan, K and Xie, Y and Yang, N and Ma, T and Zheng, L and Zhou, W and Li, Y and Jin, H and Sun, Z and Chen, Y and Kwok, L-Y and Lu, N and Zhu, W and Liu, W and Zhang, H}, title = {Adjunctive probiotic therapy sustains symptom relief in gastroesophageal reflux disease through gut microbiome-metabolome remodeling.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0156825}, doi = {10.1128/msystems.01568-25}, pmid = {41609355}, issn = {2379-5077}, abstract = {Proton pump inhibitors (PPIs) are standard therapy for gastroesophageal reflux disease (GERD), but long-term use causes dysbiosis, gastrointestinal side effects, and symptom relapse after discontinuation. Probiotics may offer adjunctive benefits by modulating the gut ecosystem. The study aimed to evaluate the efficacy of a multi-strain probiotic (Lihuo) with rabeprazole in GERD and its impact on gut microbiota and metabolome. A randomized, double-blind, placebo-controlled trial was conducted in 120 GERD patients assigned to receive rabeprazole with either Lihuo (n = 64) or placebo (n = 56) for 8 weeks, followed by 4 weeks of probiotic or placebo alone. The primary outcome was change in the Reflux Disease Questionnaire (RDQ) score. Secondary outcomes included Gastrointestinal Symptom Rating Scale, endoscopic healing, and multi-omics profiling (shotgun metagenomics, phageome, and untargeted/targeted metabolomics). Compared with the placebo group, the probiotic group exhibited a pronounced 36.51% reduction in RDQ scores after 12 weeks of intervention (P = 0.017), alongside a higher numerical endoscopic healing rate (36.84% vs 12.50%; P = 0.365). Metagenomics revealed enrichment of Bifidobacterium animalis, Lactiplantibacillus plantarum, and Clostridium sp900540255, with reductions in Bacteroides uniformis and Clostridium Q fessum. Metabolomics showed increased γ-aminobutyric acid, succinate, citrulline, and short-chain fatty acids levels, with interesting microbe-metabolite correlations such as Bifidobacterium animalis-γ-aminobutyric acid and Bacteroides fragilis-succinate (r ≥ 0.30, P < 0.01). Our findings support that adjunctive probiotic therapy sustains post-PPI symptom relief, associated with targeted modulation of gut microbiota and bioactive metabolites.IMPORTANCELong-term proton pump inhibitor use in gastroesophageal reflux disease (GERD) may disrupt gut microbiota and cause symptom relapse after discontinuation. We found that adjunctive probiotic therapy sustained reflux reduction post-proton pump inhibitor. Probiotic use enriched beneficial taxa (Bifidobacterium and Lactiplantibacillus plantarum) and increased γ-aminobutyric acid, succinate, citrulline, and short-chain fatty acids. Strong correlations linked microbial shifts to metabolic and clinical improvements. This study demonstrates that adjunctive probiotic therapy enhances symptom control and supports microbial-metabolic homeostasis in GERD.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2000038409.}, } @article {pmid41609167, year = {2026}, author = {Koo, WLY and Thng, KX and Tiew, PY and Chotirmall, SH}, title = {The Airway Microbiome in Chronic Obstructive Pulmonary Disease (COPD): A Guide for Clinicians.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {87}, number = {1}, pages = {50163}, doi = {10.31083/BJHM50163}, pmid = {41609167}, issn = {1750-8460}, support = {MOH-001636//National Research Foundation Singapore/ ; MOH-001356//Singapore Ministry of Health's National Medical Research Council/ ; MOH-000710//Singapore Ministry of Health's National Medical Research Council/ ; MOH-001275-00//Singapore Ministry of Health's National Medical Research Council/ ; MOH-000955//Singapore Ministry of Health's National Medical Research Council/ ; RT1/22//Singapore Ministry of Education/ ; }, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/microbiology/therapy ; *Microbiota ; Dysbiosis/microbiology ; *Lung/microbiology ; Disease Progression ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating respiratory condition marked by chronic symptoms and frequent exacerbations, contributing to significant morbidity and mortality. The advent of molecular microbiology and next-generation sequencing (NGS) has expanded our understanding of the lung microbiome, and integration of microbiome datasets with other omics reveals important microbial-metabolic-immuno-inflammatory interactions that influence COPD pathogenesis. Recent studies have highlighted dysbiosis of the airway microbiome, with shifts in bacterial, viral, and fungal communities playing a crucial role in disease progression, exacerbations and clinical outcomes. Moreover, microbiome changes are observed in COPD associated overlap syndromes, complicating diagnosis and treatment. This review synthesizes current microbiome research in COPD, focusing on its clinical relevance, including its potential as a diagnostic and prognostic tool. We additionally discuss the challenges of integrating microbiome data into clinical practice, emphasizing the need for personalized, precision medicine approaches to optimize COPD management and improve patient outcomes.}, } @article {pmid41609081, year = {2026}, author = {Yang, J and Wang, B and Yu, Y and Zhang, H and Zhou, X and Wu, G and Liu, Y and Shi, X}, title = {Gut Microbiota and Metabolome Dynamics Along Gastric Cancer Progression: An Exploratory Multi-Omics Analysis.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {1}, pages = {46553}, doi = {10.31083/FBL46553}, pmid = {41609081}, issn = {2768-6698}, support = {//2023 Chizhou City major science and technology special project/ ; }, mesh = {Humans ; *Stomach Neoplasms/microbiology/metabolism/pathology ; *Gastrointestinal Microbiome ; *Metabolome ; Disease Progression ; Metabolomics/methods ; Male ; Middle Aged ; Female ; Feces/microbiology ; Aged ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; Multiomics ; }, abstract = {BACKGROUND: Gastric cancer (GC) remains a major global health burden, particularly in East Asia, with complex etiologies involving Helicobacter pylori infection, diet, host genetics, and environmental exposures. GC development follows the Correa sequence (CS), a multistep cascade from gastritis to atrophy, erosion, and carcinoma. Although gut microbiota (GM) dysbiosis and metabolic reprogramming have each been implicated in GC, their integrated dynamics across CS remain incompletely defined.

METHODS: We recruited participants across five groups: normal controls (G1), gastritis (G2), atrophy (G3), erosion (G4), and GC (G5). Fecal and gastric tissue samples were analyzed using 16S rRNA sequencing and untargeted metabolomics under both ion modes. Microbial diversity was assessed by α- and β-diversity indices, linear discriminant analysis effect size (LEfSe), and functional prediction. Metabolic features were profiled by UHPLC-Q Exactive Orbitrap MS, and differential metabolites were identified using t-tests and partial least squares discriminant analysis (PLS-DA). Diagnostic potential was evaluated using receiver operating characteristic (ROC) curves.

RESULTS: Microbial α-diversity decreased significantly with progression, particularly in G3, while compositional shifts included depletion of Bacteroides and Faecalibacterium alongside enrichment of Actinobacteria, Peptostreptococcaceae, and Lachnoclostridium. LEfSe identified Bifidobacterium and Oscillospiraceae as potential biomarkers of advanced stages. ROC analyses demonstrated strong discriminatory power, with the class Actinobacteria achieving an area under the ROC curve (AUC) of 0.935 in distinguishing controls from GC. Fecal metabolomics revealed reductions in anti-inflammatory short-chain fatty acids (SCFAs) and increases in pro-inflammatory metabolites emerging at G3, while tissue metabolomics showed broader reprogramming in GC involving amino acid, nucleotide, lipid, and energy metabolism. Notably, erosion (G4) exhibited transitional features, whereas atrophy (G3) marked a distinct metabolic "breakpoint".

CONCLUSIONS: By integrating GM and metabolomic data, this study delineates stage-specific microbial and metabolic alterations along the CS. Atrophy represents a pivotal inflection point in the transition from homeostasis to carcinogenesis, while erosion serves as a transitional state. Combined microbiota-metabolite signatures hold promise for non-invasive early detection, disease stratification, and mechanistic insights into metabolic dependencies in GC.}, } @article {pmid41609075, year = {2026}, author = {Wang, Z and Ma, Y and Li, M and Jiang, X and Pan, Q and Deng, M and Guo, L}, title = {Akkermansia muciniphila Ameliorates Chronic Sleep Deprivation-Induced Glucose Intolerance and Inflammatory Cytokine Activation.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {1}, pages = {45680}, doi = {10.31083/FBL45680}, pmid = {41609075}, issn = {2768-6698}, support = {BJ-2022-145//National High Level Hospital Clinical Research Funding/ ; 82200928//National Natural Science Foundation of China/ ; 2021-N-03//China Endocrinology and Metabolism Young Scientific Talent Research Project/ ; }, mesh = {Animals ; *Sleep Deprivation/complications/microbiology ; *Cytokines/metabolism/blood ; Mice ; Male ; *Akkermansia/physiology ; *Glucose Intolerance/etiology/microbiology/therapy ; Gastrointestinal Microbiome ; Zonula Occludens-1 Protein/metabolism/genetics ; Mice, Inbred C57BL ; Mucin-2/metabolism/genetics ; *Verrucomicrobia ; Disease Models, Animal ; Lipopolysaccharides/blood ; }, abstract = {OBJECTIVE: Emerging evidence indicates that Akkermansia muciniphila (A. muciniphila or AKK) regulates host glucose metabolism through multiple pathways. In this study, we examined the therapeutic effects of A. muciniphila on chronic sleep deprivation (CSD)-induced glucose dysregulation and the underlying mechanisms.

METHODS: A modified multiplatform water environment method was used to generate a mouse model of CSD. The mice were divided into three groups: the control (CON) group (ad libitum sleep), the CSD group (subjected to sleep deprivation), and the CSD+AKK group (CSD mice were supplemented with A. muciniphila at 3 × 10⁸ CFU per mouse, three times per week). After an 8-week intervention, glucose metabolism was assessed. Serum concentrations of lipopolysaccharide (LPS), interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were measured. The mRNA expression and protein expression of mucin 2 (MUC2) and zonula occludens-1 (ZO-1) in the colon tissue were analyzed. Goblet cells in colon tissues were quantified using Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining. Additionally, changes in gut microbiome diversity and composition among groups were compared.

RESULTS: CSD induced significant glucose intolerance and insulin resistance, evidenced by increased area under the curve (AUC) of the oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), and fasting insulin levels compared to the CON group (all p < 0.05). This was accompanied by a marked impairment of the colonic mucosal barrier, characterized by a profound loss of goblet cells and downregulation of key barrier components, MUC2 and ZO-1, at both the mRNA and protein levels (all p < 0.05). Intervention with A. muciniphila significantly ameliorated CSD-induced glucose intolerance, insulin resistance and colonic barrier damage. Furthermore, CSD elevated serum levels of LPS, IL-6, TNF-α, and IL-1β (all p < 0.05), which were effectively mitigated by A. muciniphila intervention. 16S rDNA sequencing confirmed the successful colonization of A. muciniphila, as its absolute abundance was significantly greater in the CSD+AKK group than in the CSD group. In addition, A. muciniphila intervention affected the abundance of Burkholderiales bacterium, Lactococcus garvieae, and other bacterial strains in the intestine.

CONCLUSION: A. muciniphila supplementation effectively ameliorated CSD-induced glucose intolerance, reduced the serum levels of LPS and proinflammatory cytokines (IL-6, TNF-α, and IL-1β), and restored intestinal barrier integrity by upregulating MUC2 and ZO-1 expression in colon tissues.}, } @article {pmid41608923, year = {2025}, author = {Polena, H and Callejon, S and Salvert, M and Abric, E and Buisson, A and Cadars, B and Giraud, F and Scalia, J and Remoue, N and Ardiet, N and Sayag, M and Trompezinski, S and Prestat-Marquis, E and Dreno, B and Graizeau, C}, title = {An innovative ecobiological wound repair cream that restores the microbiome.}, journal = {European journal of dermatology : EJD}, volume = {35}, number = {6}, pages = {508-518}, doi = {10.1684/ejd.2025.4979}, pmid = {41608923}, issn = {1952-4013}, mesh = {Humans ; *Wound Healing/drug effects ; *Microbiota/drug effects ; *Skin Cream/pharmacology/therapeutic use ; *Skin/microbiology/drug effects ; Male ; Female ; Middle Aged ; Adult ; Aged ; }, abstract = {Small everyday wounds would benefit from optimal healing conditions, and the role of the microbiome in this process is being increasingly discussed. Objectives: To evaluate a wound repair cream (Cicabio Crème+, NAOS Ecobiology Company, Bioderma, France), assessing its effects on the skin microbiome and wound healing. The impact on the microbiome was evaluated by monitoring restoration of diversity after disinfection. The efficacy of the repair complex was assessed ex vivo using a 3D wound-healing human skin model to analyse closure and protein expression. Short-term evaluation of adherence, gas permeability, wound protection, and hydration was assessed. In vivo efficacy was examined through two clinical studies: one on healing erosive areas and another after chemical peel. After disinfection, the cream accelerated restoration of microbiome diversity (+31%, p=0.001) without promoting pathogenic/commensal bacteria or altering the level of Staphylococcus epidermidis (p=0.193). In a 3D wound-healing model, the repair complex enhanced wound closure, promoting protein expression (Ki67, loricrin, CD44, collagen XVII, VII, III) and re-epithelialisation. The cream adhered to the skin, allowed gas exchange, and provided protection and hydration. In vivo, the cream reduced transepidermal water loss (day 4: p=0.016; day 7: p=0.014), erythema (day 7: p=0.023), and functional signs (day 4: p=0.032) of erosive wounds. Following chemical peels, the cream reduced inflammation (day 7: p=0.037), visible damage (day 7: p=0.029), and skin pH (day 1: p<0.001). We demonstrate, for the first time, protection of microbiome diversity, stimulation of wound closure, and preservation of skin pH using a wound repair cream.}, } @article {pmid41608868, year = {2026}, author = {Mahen, KK and Massey, WJ and Orabi, D and Brown, AL and Jaramillo, TC and Burrows, A and Horak, AJ and Dutta, S and Mrdjen, M and Mouannes, N and Varadharajan, V and Osborne, LJ and Ye, X and Yarbrough, DM and Grubb, T and Zajczenko, N and Hohe, R and Banerjee, R and Linga, P and Laungani, D and Hajjar, AM and Sangwan, N and Dwidar, M and Buffa, JA and Swanson, GR and Wang, Z and Brown, JM}, title = {Gut microbe-derived trimethylamine shapes circadian rhythms through the host receptor TAAR5.}, journal = {eLife}, volume = {14}, number = {}, pages = {}, pmid = {41608868}, issn = {2050-084X}, support = {R01 DK130227/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; P50 AA024333/AA/NIAAA NIH HHS/United States ; RF1 NS133812/NS/NINDS NIH HHS/United States ; 10.58275/aha.24post1178494.pc.gr.190863//American Heart Association/ ; }, mesh = {*Methylamines/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; *Circadian Rhythm/physiology ; Mice ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Mice, Inbred C57BL ; Male ; Mice, Knockout ; }, abstract = {Elevated levels of the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) are associated with cardiometabolic disease risk. However, the mechanism(s) linking TMAO production to human disease are incompletely understood. Initiation of the metaorganismal TMAO pathway begins when dietary choline and related metabolites are converted to trimethylamine (TMA) by gut bacteria. Gut microbe-derived TMA can then be further oxidized by host flavin-containing monooxygenases to generate TMAO. Previously, we showed that drugs lowering both TMA and TMAO protect mice against obesity via rewiring of host circadian rhythms (Schugar et al., 2022). Although most mechanistic studies in the literature have focused on the metabolic end product TMAO, here we have instead tested whether the primary metabolite TMA alters host metabolic homeostasis and circadian rhythms via trace amine-associated receptor 5 (TAAR5). Remarkably, mice lacking the host TMA receptor (Taar5[-/][-]) have altered circadian rhythms in gene expression, metabolic hormones, gut microbiome composition, and diverse behaviors. Also, mice genetically lacking bacterial TMA production or host TMA oxidation have altered circadian rhythms. These results provide new insights into diet-microbe-host interactions relevant to cardiometabolic disease and implicate gut bacterial production of TMA and the host receptor that senses TMA (TAAR5) in the physiologic regulation of circadian rhythms in mice.}, } @article {pmid41608696, year = {2025}, author = {Liu, Y and Rong, L and Cheng, Y and Wang, M and Min, S and Xiao, F and Zhang, Z and Yang, Z and Zhang, Q and Zheng, X}, title = {Topographic controls on soil organic carbon partitioning and enzyme dynamics in nutrient-poor soils.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1735665}, pmid = {41608696}, issn = {1664-302X}, abstract = {INTRODUCTION: Understanding the dynamics of soil organic carbon (SOC) in sloping farmlands is critical, as they play a vital role in the global carbon cycle and soil health. Although prior research has focused on physical carbon loss due to erosion, the biological mechanisms by which slope gradients affect microbial carbon cycling remain poorly understood.

METHODS: Soil samples were collected from maize fields with three slope gradients (30°, 45°, and 60°) across different growth stages. Key indicators were determined as follows: SOC by potassium dichromate oxidation (external heating method); DOC by ultrapure water extraction (1:5 ratio) and organic carbon analyzer; POC by sodium hexametaphosphate dispersion, 53-μm sieving, and chromic acid oxidation; soil Ca[2+], Mg[2+], and Cl[-] by EDTA complexometric titration and silver nitrate titration, respectively; invertase (SUC) by 3,5-dinitrosalicylic acid colorimetry; polyphenol oxidase (SPPO) and peroxidase (SPOD) by commercial kits with L-dopa as substrate. Statistical analyses were performed using IBM SPSS 26 (One-way ANOVA with LSD post-hoc test, Pearson correlation analysis) and Origin 2024 (Principal Component Analysis, PCA). Normality of data was verified prior to analysis, and significance was set at P < 0.05.

RESULTS: Results showed that SOC levels decreased with increasing slope steepness, while DOC peaked at 45°. SPPO and SPOD activities (involved in recalcitrant carbon decomposition) were significantly elevated at 60°. SUC activity was positively correlated with DOC, while oxidase activities were positively associated with POC and negatively with Mg[2+].

DISCUSSION: This study identifies a critical slope threshold (30°-45°) for DOC loss: DOC availability on steeper slopes stimulates microbial synthesis of SPPO and SPOD, enhancing recalcitrant carbon degradation and potentially intensifying long-term SOC depletion. The identification of this threshold provides insights for designing microbiome-informed strategies to mitigate soil degradation and safeguard ecological security.}, } @article {pmid41608689, year = {2025}, author = {Yan, W and Du, N and Zhang, K and Yang, P and Guo, J and Xu, L}, title = {Bilirubin-microbiota interaction: molecular mechanisms and therapeutic strategies in neonatal jaundice.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1749152}, pmid = {41608689}, issn = {1664-302X}, abstract = {Recent studies have revealed a complex interplay between bilirubin metabolism and the gut microbiota. Bilirubin functions as a potent antioxidant and signaling molecule in humans, and its concentration-dependent effects on distinct microbial taxa indicate that the compound exerts selective pressure on the gut ecosystem. The gut microbiota modulates bilirubin metabolism by altering intestinal pH, producing and activating Bilirubin metabolic enzyme, and bile acids. Because perturbations in bilirubin handling are especially common-and potentially neurotoxic-in neonates, a concise synthesis of recent progress is warranted. Here we review how microbial communities reshape bilirubin flux, how bilirubin and its conjugates, in turn, sculpt microbial ecology, and how the dynamic equilibrium between conjugated and unconjugated bilirubin in hyperbilirubinaemia is influenced by the microbiome. Regulating gut microbiota to accelerate bilirubin clearance or attenuate its toxicity may therefore offer a tractable therapeutic avenue.}, } @article {pmid41608686, year = {2025}, author = {Sun, Y and Ding, M and Zheng, W and Zhang, H and Lu, Z and Zhang, J and Zhao, G}, title = {Manganese-oxidizing Exiguobacterium acetylicum 4-3-1 reduces cadmium accumulation in spinach.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1734825}, pmid = {41608686}, issn = {1664-302X}, abstract = {Cadmium (Cd) accumulation in edible plants is a significant global concern. This research explores the potential of a manganese-oxidizing rhizobacterium, Exiguobacterium acetylicum 4-3-1, to promote spinach growth while reducing Cd uptake. The bacterium produces indole-3-acetic acid and siderophores and effectively removed 73.74% of free CdCl2. Under Cd stress (10.5 mg/kg), E. acetylicum 4-3-1 significantly increased spinach biomass by 184.3% (dry weight) and chlorophyll content by 33.99%, while decreasing the Cd concentration in spinach leaves by 53.07% through both intrinsic and extrinsic mechanisms. Intrinsically, E. acetylicum 4-3-1 inoculation up-regulated pathways related to photosynthesis and energy metabolism in spinach, while down-regulating genes linked to heavy metal transport. Extrinsically, it oxidizes Mn(II) to form manganese oxides that may immobilize Cd. Moreover, inoculation with strain 4-3-1 altered the rhizosphere microbiome of spinach, increasing the presence of beneficial bacteria like Bacillales. A synthetic community (SynCom) composed of Bacillus subtilis and E. acetylicum 4-3-1 demonstrated synergistic effects on spinach growth under Cd stress. Thus, E. acetylicum 4-3-1 has the potential for Cd bioremediation in crops and promotes sustainable agriculture.}, } @article {pmid41608653, year = {2026}, author = {Yang, RL and Lu, Q and Liang, EM and Luo, HC}, title = {Strengthening causal inference and analytical rigor in the Wumei Pills-Lactobacillus reuteri-intestinal stem cell axis for chemotherapy-induced mucositis.}, journal = {World journal of stem cells}, volume = {18}, number = {1}, pages = {114114}, pmid = {41608653}, issn = {1948-0210}, abstract = {A recent preclinical study reported that Wumei Pills (WMP) and Lactobacillus reuteri (L. reuteri) mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell (ISC)-mediated repair via Wnt/β-catenin signaling. The mechanistic interpretation rests largely on systemic inflammation readouts, correlative microbiota changes, and immunohistochemistry of pathway markers. From a clinical standpoint, chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions, treatment delays, and infection risk; current care is largely supportive and does not directly restore ISC-mediated repair. This unmet need motivates rigorous appraisal of the proposed "WMP → L. reuteri → ISC/Wnt" axis. To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed "WMP → L. reuteri → ISC/Wnt" pathway. This letter critically appraises the study's design, endpoints, and analyses against current best practices in mucositis biology, microbiome causality testing, Wnt/β-catenin pathway validation, and preclinical statistics, and synthesizes concrete, literature-grounded remedies. Six issues with potential impact on interpretation were identified: (1) Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation, with limited tissue-level indices (e.g., myeloperoxidase, interleukin-1β, immune-cell infiltration); (2) Absence of necessity/sufficiency tests to verify microbiota mediation (e.g., L. reuteri depletion, WMP-donor fecal microbiota transplantation, probiotic add-back); (3) Pathway evidence tiering - Wnt/β-catenin activation not confirmed by β-catenin nuclear translocation or downstream targets (Axin2, c-Myc, cyclin D1), and Lgr5 quantification/specificity insufficient; (4) Statistical design under-specified (power justification, blinded assessment, control of multiple comparisons) and potential cage effects unmodeled; (5) Limited dose-response and safety profiling for WMP/L. reuteri; and (6) Constrained generalizability (single sex/strain/age, lack of ABX-only controls, single time-point). The reported benefits of WMP and L. reuteri in chemotherapy-induced mucositis are promising, but stronger causal and analytical foundations are needed. Incorporating tissue-level inflammation readouts, microbiota loss-/gain-of-function designs, definitive Wnt/β-catenin activation assays, rigorous statistical practices (including mixed-effects models for cage clustering and multiplicity control), dose-response/safety evaluation, and broader experimental scope (sex/age/strain, ABX-only controls, time-course) will yield more robust and translationally relevant conclusions.}, } @article {pmid41608632, year = {2026}, author = {Zhang, X and Zhang, Z and Peng, Q and Huang, X and Liu, M and Bai, D and Yang, R and Zhang, Y and Yang, C}, title = {The Immunogenetic Landscape of Allergic Rhinitis: from Cellular Effectors to Gene Regulation and Targeted Therapies.}, journal = {International journal of biological sciences}, volume = {22}, number = {3}, pages = {1322-1345}, pmid = {41608632}, issn = {1449-2288}, mesh = {Humans ; *Rhinitis, Allergic/genetics/immunology/therapy ; Animals ; Signal Transduction ; Gene Expression Regulation ; }, abstract = {Allergic Rhinitis (AR) is a highly prevalent type 2 inflammatory disease driven by a complex immunogenetic background. This review aims to systematically delineate the immunogenetic landscape of AR, elucidating the complete knowledge chain from macroscopic cellular interactions and microscopic molecular regulation to precision targeted therapies. The article first dissects the two core immune axes driving the pathological process of AR: one is the classic adaptive immune pathway, centered on Th2 cells, which mediates IgE production, eosinophil infiltration, and mucus hypersecretion through the secretion of cytokines such as IL-4, IL-5, and IL-13; the other is the innate immune initiation pathway, in which nasal epithelial cells act as "sentinels" by releasing "alarmins" like TSLP and IL-33, leading to the rapid activation of type 2 innate lymphoid cells (ILC2s). The review then delves into the sophisticated signaling networks that regulate these immune responses, with a particular focus on the classic IL-4/STAT6/GATA3 signaling axis and its negative regulatory mechanisms. Building on this, the article further elaborates on the genetic susceptibility architecture of AR, highlighting key risk loci identified by genome-wide association studies (GWAS), such as variants in antigen presentation genes (HLA), epithelial barrier genes (FLG), and genes related to cytokine signaling pathways. To connect genetics with the environment, this review systematically summarizes epigenetic regulatory mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs), and discusses the long-range immunomodulatory effects of nasal and gut microbiota dysbiosis on AR via the "gut-nasal axis". Finally, from a translational medicine perspective, the article demonstrates how a profound understanding of these pathophysiological mechanisms has successfully spurred the development of highly effective targeted biologics, such as omalizumab (targeting IgE), dupilumab (targeting the IL-4Rα receptor, thus blocking IL-4/IL-13 signaling), and tezepelumab (targeting TSLP). This review integrates the latest multidimensional research advances in immunology, genetics, epigenetics, and microbiome studies of AR, providing a comprehensive theoretical framework for understanding its complex pathogenesis and for the development of future personalized treatment strategies.}, } @article {pmid41608628, year = {2026}, author = {Jang, HR and Kim, HJ and Kim, BY and Jeong, JH and Kim, JK and Won, JA and Yoo, HH and Lee, YG and Yim, H}, title = {Combining sorafenib with spermine and sphingosine synergistically enhances anticancer efficacy by modulating metabolic pathways and gut microbiome in hepatocellular carcinoma.}, journal = {International journal of biological sciences}, volume = {22}, number = {3}, pages = {1082-1102}, pmid = {41608628}, issn = {1449-2288}, mesh = {*Sorafenib/pharmacology/therapeutic use ; *Spermine/pharmacology/therapeutic use ; *Carcinoma, Hepatocellular/drug therapy/metabolism/microbiology ; Humans ; *Liver Neoplasms/drug therapy/metabolism/microbiology ; Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Sphingosine/pharmacology/therapeutic use ; Cell Line, Tumor ; *Antineoplastic Agents/pharmacology/therapeutic use ; Drug Synergism ; Xenograft Model Antitumor Assays ; Mice, Nude ; Apoptosis/drug effects ; Male ; }, abstract = {Hepatocellular carcinoma (HCC), which makes up about 90% of liver cancer, is the third leading cause of cancer-related death. Recent studies suggest that metabolites derived from the gut microbiome may offer new therapeutic opportunities for HCC. In this study, we explored whether microbial metabolites could enhance the effectiveness of sorafenib, a first-line multi-kinase inhibitor used in advanced HCC. Through a screen of a microbiome metabolite library, we identified spermine and sphingosine as potential candidates that boosted anticancer effects of sorafenib in HepG2, Huh7, and SK-Hep-1 cells. These metabolites worked synergistically with sorafenib to suppress tumor growth in cultured HCC cells, patients-derived HCC organoids, and a xenograft mouse model. Mechanistically, spermine triggered cell cycle arrest at the S phase, while sphingosine and sorafenib induced G1 arrest, contributing to an increased sub-G1 population and apoptosis when combined. Notably, sorafenib treatment led to the downregulation of SMOX (a key catabolic enzyme for spermine), as well as SPHK1 and CERS1 (critical enzymes involved in sphingosine metabolism), whose high expression levels are associated with poorer survival outcomes in liver cancer patients according to TCGA data. A 16S rRNA sequencing analysis revealed that combination of sorafenib with spermine or sphingosine alters the gut microbiome, increasing the relative abundance of Faecalibaculum, inversely correlated with tumor sizes in a xenograft mouse model. Therefore, we propose that combining sorafenib with spermine or sphingosine could enhance its anti-HCC effects by promoting apoptosis and reducing the expression of metabolic enzymes. Moreover, Faecalibaculum may serve as a potential microbiome-based prognostic marker for HCC.}, } @article {pmid41608560, year = {2026}, author = {Wang, N and Ma, L and Huang, Y and Zhou, X and Rong, Y and Long, F and Qiu, W and Wu, S and Hu, Y and He, X and He, J and Tian, S and Hu, W and Yuan, C and Wang, F}, title = {Tumor microbiome-transcriptome crosstalk identifies Prevotella as an immunotherapeutic predictor in NSCLC.}, journal = {Theranostics}, volume = {16}, number = {7}, pages = {3426-3446}, pmid = {41608560}, issn = {1838-7640}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/microbiology/immunology/drug therapy/genetics/therapy ; *Lung Neoplasms/microbiology/immunology/genetics/drug therapy/therapy ; *Microbiota/immunology/genetics ; *Transcriptome ; Tumor Microenvironment/immunology/genetics ; *Prevotella/isolation & purification/immunology/genetics ; Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Prognosis ; Female ; Male ; Middle Aged ; Aged ; ErbB Receptors/antagonists & inhibitors ; }, abstract = {Background: The tumor-resident microbiome plays a pivotal role in shaping the tumor immune microenvironment; however, its relationship with the host transcriptome and the response to immune checkpoint inhibitors (ICIs) remains largely uncharacterized in non-small cell lung cancer (NSCLC). This study aimed to elucidate the relationship between tissue-resident microbiota, host transcriptomic alterations, and immunotherapy response in NSCLC. Methods: Paired tumor (T) and paracancerous tissue (PT) samples from patients with NSCLC were analyzed using 2bRAD-M and bulk RNA sequencing to generate comprehensive microbiome and transcriptome profiles. The conditional mutual information algorithm was employed to systematically investigate intratumoral microbe-host interactions. Associations between key microbes and patient prognosis, ICI response, and response to epidermal growth factor receptor (EGFR)-targeted therapy were assessed across four independent local clinical cohorts. Results: Higher microbial richness, α-diversity, and β-diversity were observed in PT samples than in T samples. Specifically, PT-resident Bradyrhizobium and Prevotella were identified as key bacterial taxa significantly associated with immune cell populations, including CD8[+] T cells, natural killer cells, and activated dendritic cells. Among these, PT-resident Prevotella, but not Bradyrhizobium, was independently associated with improved prognosis of patients with NSCLC and ICI response in both local clinical sets and public datasets. Furthermore, a combined diagnostic model integrating PT-resident Prevotella abundance with routine clinical blood indicators demonstrated markedly superior predictive performance for ICI response compared with the conventional biomarker PD-L1. By contrast, PT-resident Prevotella exhibited no association with treatment response in the EGFR-targeted therapy cohort. Conclusion: PT-resident Prevotella is strongly associated with the prognosis and ICI response in patients with NSCLC. Moreover, integration of PT-resident Prevotella with routine clinical blood indicators holds promise as a potential auxiliary diagnostic tool to facilitate personalized immunotherapy in NSCLC.}, } @article {pmid41608437, year = {2025}, author = {De Laffolie, J and Hauer, AC}, title = {Editorial: Advances towards precision medicine in pediatric-onset inflammatory bowel disease.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1765757}, pmid = {41608437}, issn = {2296-858X}, } @article {pmid41608298, year = {2026}, author = {Aldoori, J and Mitra, S and Davie, A and Toogood, GJ and Edwards, C and Hull, MA}, title = {The effect of omega-3 polyunsaturated fatty acids on short-chain fatty acid production and the gut microbiome in an in vitro colonic fermentation model.}, journal = {Gut microbiome (Cambridge, England)}, volume = {7}, number = {}, pages = {e1}, pmid = {41608298}, issn = {2632-2897}, abstract = {Oral administration of omega-3 polyunsaturated fatty acids (PUFAs) to rodents and humans is associated with an increase in gut bacteria that are predicted to synthesise short-chain fatty acids (SCFAs). We tested the hypothesis that physiological levels of omega-3 PUFAs in the distal intestinal lumen (1-50 μg/mL) are associated with increased SCFA synthesis in an in vitro fermentation model using faecal slurry from 10 healthy participants (mean age 30 years), with and without exogenous dietary fibres. SCFAs were measured by gas chromatography-flame ionisation detection (n = 10), and changes in bacterial composition were analysed by shotgun metagenomic sequencing (n = 6). In the presence of omega-3 PUFAs, there was a mean 9.3% (no inulin; P = 0.03) and 19.3% (+ 0.01 mg/mL inulin; P = 0.01) increase in total SCFA concentration at 24 h compared with paired control fermentations. Omega-3 PUFAs had a limited effect on the fermentation model microbiome in the absence of inulin. However, omega-3 PUFAs (50 μg/mL) were associated with increased abundance of Bifidobacteriaceae compared with paired control fermentations, if inulin (0.01 mg/mL) was present. Prebiotic activity of omega-3 PUFAs drives SCFA synthesis in an in vitro colonic fermentation model and is augmented by the soluble fibre inulin.}, } @article {pmid41607944, year = {2025}, author = {Gao, YQ and Hou, QY and Hou, XW and Wei, YJ and Shang, KM and Ma, H and Geng, HL and Liu, R and Yang, LH and Elsheikha, HM and Ni, HB and Huang, YF}, title = {Metagenomics-based characterization of fecal microbiome and resistome of laying hens during the production cycle.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1740567}, pmid = {41607944}, issn = {2297-1769}, abstract = {The extensive use of antimicrobials in livestock has accelerated the emergence of antimicrobial resistance (AMR), raising serious global concerns. Poultry feces are recognized as important reservoirs of antibiotic resistance genes (ARGs) and their associated mobile genetic elements (MGEs); however, the microbial community characteristics and ARG profiles of laying hens across different laying stages remain poorly understood. In this study, 40 fecal samples were collected from laying hens at five sampling points, including the early laying stage (HE), three peak laying stages (HPI, HPII, and HPIII), and the late laying stage (HL), with eight randomly selected samples per stage. Shotgun metagenomic sequencing was conducted to characterize the taxonomic structure and functional profiles of the intestinal microbiota and to systematically analyze the diversity and distribution patterns of ARGs. The results showed that most ARGs were harbored by bacteria belonging to the phyla Pseudomonadota and Bacillota, with Escherichia coli serving as the primary carrier of antibiotic resistance genes. Moreover, significant correlations were observed between the co-abundance and co-occurrence of ARGs and MGEs, suggesting that MGEs play a key role in facilitating ARG dissemination. Overall, these findings provide novel insights into the prevalence of ARGs in laying hens across different laying stages and may inform strategies to mitigate the spread of antimicrobial resistance in poultry production systems.}, } @article {pmid41607747, year = {2026}, author = {Luo, L and Huang, G and Yang, H and Chi, H}, title = {Revisiting multi-region 16S sequencing in gastric cancer.}, journal = {World journal of gastrointestinal oncology}, volume = {18}, number = {1}, pages = {114708}, pmid = {41607747}, issn = {1948-5204}, abstract = {Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome, demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches. While the study represents a valuable methodological step forward, it remains limited by single-center design, lack of quantitative calibration, and insufficient control for contamination and inter-laboratory variability. This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized, consensus-driven workflows to ensure reproducibility and clinical reliability. The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration, particularly for recurrence prediction, treatment-response monitoring, and perioperative complication risk assessment. By addressing these methodological, economic, and ethical challenges, the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.}, } @article {pmid41607695, year = {2026}, author = {Dias, HM and Jain, R and Santos, VA and Gonzalez-Hernandez, JL and Solanki, S and Menendez Iii, HM and Graham, C}, title = {Reproducible Emu-Based Workflow for High-Fidelity Soil and Plant Microbiome Profiling on HPC Clusters.}, journal = {Bio-protocol}, volume = {16}, number = {2}, pages = {e5577}, pmid = {41607695}, issn = {2331-8325}, abstract = {Accurate profiling of soil and root-associated bacterial communities is essential for understanding ecosystem functions and improving sustainable agricultural practices. Here, a comprehensive, modular workflow is presented for the analysis of full-length 16S rRNA gene amplicons generated with Oxford Nanopore long-read sequencing. The protocol integrates four standardized steps: (i) quality assessment and filtering of raw reads with NanoPlot and NanoFilt, (ii) removal of plant organelle contamination using a curated Viridiplantae Kraken2 database, (iii) species-level taxonomic assignment with Emu, and (iv) downstream ecological analyses, including rarefaction, diversity metrics, and functional inference. Leveraging high-performance computing resources, the workflow enables parallel processing of large datasets, rigorous contamination control, and reproducible execution across environments. The pipeline's efficiency is demonstrated on full-length 16S rRNA gene datasets from yellow pea rhizosphere and root samples, with high post-filter read retention and high-resolution community profiles. Automated SLURM scripts and detailed documentation are provided in a public GitHub repository (https://github.com/henrimdias/emu-microbiome-HPC; release v1.0.2, emu-pipeline-revised) and archived on Zenodo (DOI: 10.5281/zenodo.17764933). Key features • Implement rigorous quality control (QC) of raw 16S rRNA Nanopore reads and sequencing controls. • Remove plant organelle contamination with a curated Kraken2 database. • Perform high-resolution taxonomic assignment of full-length 16S rRNA reads using Emu. • Integrate downstream statistical analyses, including rarefaction, PERMANOVA, and DESeq2 differential abundance. • Conduct scalable microbiome diversity and functional analyses with FAPROTAX.}, } @article {pmid41607410, year = {2026}, author = {Nouso, K and Wakuta, A and Shiota, S and Fujita, R and Kariyama, K and Hiraoka, A and Atsukawa, M and Tani, J and Tada, T and Nakamura, S and Tajiri, K and Kaibori, M and Hirooka, M and Itobayashi, E and Kakizaki, S and Naganuma, A and Ishikawa, T and Imai, M and Aoki, T and Tanaka, H and Hatanaka, T and Tsuji, K and Kawata, K and Takaguchi, K and Tsutsui, A and Ogawa, C and Ochi, H and Yata, Y and Kuroda, H and Matono, T and Yasuda, S and Toyoda, H and Iijima, H and Kudo, M and Kumada, T}, title = {Effect of Butyrate-Producing Enterobacteria and Proton Pump Inhibitors on Advanced Hepatocellular Carcinoma Treatment With Durvalumab and Tremelimumab.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {10}, number = {1}, pages = {e70346}, pmid = {41607410}, issn = {2397-9070}, abstract = {AIM: The gut microbiome modulates immune responses, and butyrate-producing bacteria have been linked to improved immune checkpoint inhibitor (ICI) efficacy. Conversely, proton pump inhibitors (PPIs) may negatively impact ICI outcomes by altering gut microbiota. This study aims to elucidate their effects in hepatocellular carcinoma (HCC).

METHODS: This retrospective multicenter cohort study included 208 HCC patients treated with durvalumab plus tremelimumab at 25 hospitals in Japan. Patients were classified into a butyric acid group (n = 27), who ingested drugs containing butyrate-producing enterobacteria, and a non-butyric acid group (n = 181), as well as a PPI group (n = 107) and a non-PPI group (n = 101). Overall survival (OS) was analyzed using inverse probability of treatment weighting, and risk factors were assessed with Cox proportional hazards modeling. Tumor response was evaluated by RECIST v1.1.

RESULTS: No significant OS differences were observed between the butyric acid and non-butyric acid groups (p = 0.921), or between PPI and non-PPI groups (p = 0.917). The objective response rate was 3.7% in the butyric acid group versus 15.5% in the non-butyric acid group (p = 0.543) and 15.8% in the PPI group versus 12.1% in the non-PPI group (p = 0.222). Disease control rates were comparable. Multivariate analysis identified ECOG performance status (p = 0.019) and ALBI score (p < 0.001) as independent prognostic factors, while butyrate-producing bacteria and PPI use were not associated with survival outcomes.

CONCLUSION: Neither butyrate-producing bacteria nor PPI use significantly influenced the efficacy of durvalumab plus tremelimumab in HCC. The liver's immunotolerant microenvironment may limit the impact of microbiome modulation on ICI efficacy.}, } @article {pmid41607395, year = {2026}, author = {Uppala, PK and Karanam, SK and Maddi, R}, title = {Science of fecal microbiota transplant: From history to cutting-edge clinical practice.}, journal = {World journal of gastrointestinal endoscopy}, volume = {18}, number = {1}, pages = {113133}, pmid = {41607395}, issn = {1948-5190}, abstract = {Fecal microbiota transplantation (FMT) is a pioneering medical technique designed to re-establish a balanced gut microbiome by transferring processed stool from a rigorously screened donor into the gastrointestinal tract of a recipient. Initially conceived as a last-resort therapy for recurrent Clostridioides difficile (C. difficile) infections - a challenging condition frequently resistant to conventional antibiotics - FMT has achieved impressive clinical response rates, often surpassing 80% in resolving recurrent C. difficile infections. This remarkable success has generated significant enthusiasm for its potential use in addressing a broader spectrum of disorders linked to disrupted gut microbial populations, including inflammatory bowel disease, irritable bowel syndrome, metabolic syndrome, and various autoimmune and neurological conditions. However, the wider clinical integration of FMT is accompanied by several notable challenges. These include the need for optimal donor selection, comprehensive long-term follow-up of recipients, standardization of stool processing and delivery methods, and thorough economic evaluation to establish cost-effectiveness. Safety remains a top priority, with particular attention paid to minimizing the risk of infectious disease transmission and preventing unwanted immune responses. Regulatory standards for FMT vary internationally, with some nations categorizing it as a biologic therapy or experimental treatment, while others have established more formalized approval processes. This article offers a comprehensive examination of FMT, covering its historical evolution, underlying mechanisms, current clinical applications, safety protocols, and regulatory landscape. By consolidating the latest research and clinical guidelines, it aims to educate clinicians, researchers, and policymakers on the expanding role of FMT in modern healthcare.}, } @article {pmid41607348, year = {2026}, author = {Abenavoli, L and Yosypenko, K and Yurchyshena, Y and Savytska, M and Lazarieva, O and Shvets, Y and Scarlata, GGM and Lynchak, O and Falalyeyeva, T}, title = {Effect of supplementation with synbiotics in metabolic syndrome: mechanisms and clinical implications.}, journal = {Minerva gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-5985.25.04054-9}, pmid = {41607348}, issn = {2724-5365}, abstract = {Metabolic syndrome (MetS) is a complex and multifactorial condition that represents a major global health challenge. It is characterized by a cluster of interrelated metabolic abnormalities, including central obesity, insulin resistance, dyslipidemia, and hypertension, all of which substantially increase the risk of developing type 2 diabetes mellitus, cardiovascular diseases, and other related complications. Growing evidence underscores the pivotal role of the gut microbiota in regulating host metabolism, modulating immune responses, and influencing the chronic low-grade inflammatory state associated with MetS. Among emerging therapeutic approaches, synbiotics, defined as synergistic combinations of probiotics and prebiotics, have attracted considerable interest. Therefore, in the present narrative review, we aim to find out the feasibility and effectiveness of synbiotic supplements, as well as to evaluate their impact on people with MetS. By selectively stimulating the growth and activity of beneficial microbial taxa while directly introducing health-promoting strains, synbiotics may restore microbial balance, improve metabolic homeostasis, and attenuate inflammatory pathways. Future research should prioritize personalized nutrition strategies and microbiome-tailored interventions, taking into account individual variability in gut microbial composition and host metabolic responses. Such precision approaches could optimize synbiotic efficacy and safety, positioning them as a viable adjunctive treatment for MetS within an integrated lifestyle and pharmacological framework. Ultimately, large-scale, high-quality randomized controlled trials are essential to confirm current promising findings and to establish clear guidelines for clinical application.}, } @article {pmid41607234, year = {2026}, author = {Nasrah, R and Jagoe, RT}, title = {The gut microbiome and dietary interventions in cancer cachexia.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCO.0000000000001211}, pmid = {41607234}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: The gut microbiome (GM) is altered in cancer cachexia, and it is possible that such GM changes may promote or sustain features of cancer cachexia including changes in host metabolism and anorexia. As a result, there is growing interest in GM-focused interventions to address cancer cachexia. In this review, the factors that likely contribute to changes in GM in cancer cachexia are highlighted. Also, this review presents recent data on GM-derived predictive biomarkers for response to dietary interventions in cachexia.

RECENT FINDINGS: The importance of maintaining or increasing energy intake to combat cancer cachexia has become clearer in recent years. However, there is wide inter-individual variation in response to changes after dietary interventions. Two recent studies have reported GM features which predict response to different types of dietary interventions: enteral feeding in pancreatic cancer patients, and oral nutritional counselling promoting an energy and protein dense diet in a mixed cancer group attending a specialized cancer cachexia clinic. Each study reported that increased abundance of a specific GM taxon predicted a more favourable response to the dietary intervention used.

SUMMARY: GM features may prove to be important in identifying patients with cancer cachexia who are more or less likely to respond well to current dietary interventions. This has clear clinical implications and utility. Further studies will be needed to determine whether GM-targeted interventions can be developed to improve response to dietary interventions and the management of cachexia more generally.}, } @article {pmid41607112, year = {2026}, author = {Vasconcelos, DS and Harris, DJ and Tarroso, P and Simões, C and Rato, C and Santos, X and Xavier, R}, title = {Shaped by Fire: Unravelling the Impact of Fire on Lizard Gut Microbiome.}, journal = {Molecular ecology}, volume = {35}, number = {2}, pages = {e70255}, pmid = {41607112}, issn = {1365-294X}, support = {2022.13485.BD//Fundação para a Ciência e a Tecnologia/ ; 2020.00854.CEECIND/CP1601/CT0001//Fundação para a Ciência e a Tecnologia/ ; 2022.07460.PTDC//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {Animals ; *Lizards/microbiology ; *Gastrointestinal Microbiome/genetics ; Portugal ; RNA, Ribosomal, 16S/genetics ; Male ; Female ; *Fires ; Ecosystem ; *Wildfires ; Diet ; Bacteria/genetics/classification ; }, abstract = {In recent decades, wildfire regimes have changed significantly, with increases in frequency, severity and area affected, leading to major habitat alterations that may impact species ecology. While fire's role in plant ecology is well studied, its effects on animal biotic interactions remain poorly understood. In northern Portugal, where wildfires are common, the native rock-dwelling lizard Podarcis lusitanicus may thrive postfire due to its preference for open rocky outcrops, which expand after fires. This suggests not only resilience but also a capacity for persistence in postfire disturbances driven by habitat preferences. However, changes in prey availability after fire induce dietary shifts in this insectivorous lizard, potentially affecting trophic interactions and, consequently, gut microbiota communities. Gut microbiota influence host fitness through effects on nutrition, immunity and behaviour; on the other hand, gut microbiota are affected by variations in diet and environment. This study assessed how fire history affects P. lusitanicus gut microbiota. Sampling occurred across 12 sites in northern Portugal, representing three fire histories: long-unburned, burned in 2016 and burned in 2022. Cloacal swabs were analysed by metabarcoding the V4 region of the 16S rRNA gene. Results showed that gut bacterial composition varied with fire history, as well as with sex, body size and diet. Females had higher microbial richness despite similar diet richness between sexes. While microbiome composition shifted, predicted microbiome function remained relatively stable, indicating both resilience and ecological flexibility in fire-prone environments. These findings enhance understanding of how lizard microbiomes respond to environmental disturbances and may help predict host and microbiota tolerance under changing fire regimes.}, } @article {pmid41607069, year = {2026}, author = {Yang, M and He, Y and Miao, X and Sun, M and Niu, H and Hua, M and Li, D and Xu, H and Wang, J}, title = {Rhodotorula mucilaginosa JAASSRY1 Ameliorates Cyclophosphamide-Induced Immunosuppression by Regulating Gut Microbiota and Activation of Spleen TLR4/MyD88/NF-κB Pathway.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2510031}, doi = {10.4014/jmb.2510.10031}, pmid = {41607069}, issn = {1738-8872}, mesh = {Animals ; *Cyclophosphamide/adverse effects ; Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Spleen/drug effects/immunology/metabolism ; Myeloid Differentiation Factor 88/metabolism ; *Rhodotorula ; Signal Transduction/drug effects ; *Immunosuppression Therapy ; Cytokines/metabolism ; Immunosuppressive Agents/adverse effects ; Male ; Dysbiosis ; Mice, Inbred BALB C ; }, abstract = {The present study was designed to evaluate the ameliorative effects of Rhodotorula mucilaginosa JAASSRY1 (JAASSRY1) on cyclophosphamide (CTX)-induced immunosuppression in mice. Immunocompromised mice were established by intraperitoneal injection of CTX (80 mg/kg/bw) for three consecutive days, followed by JAASSRY1 orally administered of JAASSRY1 for 21 days. Various immunological parameters, including immune organ indices, spleen cytokine levels, and immunoglobulin profiles, were evaluated. JAASSRY1 prevented CTX-induced immune damage by reversing weight loss and immune organ atrophy, suppressing the expression of IL-6, IL-17, and IFN-γ in the spleen (P< 0.01), and restoring levels of IgA and IgG, while up-regulating IL-4 (P< 0.01). Furthermore, JAASSRY1 attenuated immunosuppressive spleen injury by modulating the TLR4/MyD88/NF-κB pathway and regulating the Bax/Bcl-2 ratio. JAASSRY1 also alleviated CTX-induced dysbiosis by enhancing the abundance of Colidextribacter and reducing the levels of Parabacteroides and Bacteroides. A significant association was observed between specific gut microbiome Bacteroides and immune parameters (P< 0.01). Above all, JAASSRY1 demonstrates efficacy in ameliorating immunosuppression through the modulation of the "gut microbiota-spleen" axis, providing a basis for the development of probiotic formulations with immunomodulatory properties.}, } @article {pmid41607051, year = {2026}, author = {Han, Y and Xie, D and Shan, X and Yang, L}, title = {Glutamine: A spatially precise "GPS Signal" shaping the root microbiota.}, journal = {Journal of integrative plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jipb.70165}, pmid = {41607051}, issn = {1744-7909}, support = {2021YFA1300400//National Key R&D Program of China/ ; 23JCYBJC00540//the Natural Science Foundation of Tianjin, China/ ; No. 32471699//the National Natural Science Foundation of China/ ; }, abstract = {This commentary on Tsai et al. (2025) highlights glutamine's important role in attracting beneficial bacteria to colonize plant roots, deciphers its links to Casparian strip integrity, and explores its dual functions. This finding reveals how plants use chemical signals to shape their root microbiome for better health.}, } @article {pmid41606855, year = {2025}, author = {Yang, J and He, Y and Huang, J and Li, M and Wu, X and Pei, X and Yang, X}, title = {Decoding resistome profiles and horizontal transfer of antibiotic resistance genes across the pork production chain under One Health sectors.}, journal = {Food research international (Ottawa, Ont.)}, volume = {221}, number = {Pt 1}, pages = {117259}, doi = {10.1016/j.foodres.2025.117259}, pmid = {41606855}, issn = {1873-7145}, mesh = {*Gene Transfer, Horizontal ; Animals ; Swine ; Anti-Bacterial Agents/pharmacology ; *Drug Resistance, Microbial/genetics ; *One Health ; *Drug Resistance, Bacterial/genetics ; *Pork Meat/microbiology ; Food Microbiology ; Abattoirs ; Metagenome ; Microbiota/genetics ; Metagenomics ; Bacteria/genetics ; }, abstract = {The emergence of antimicrobial resistance has become a global threat to public health. Intensive antibiotic use in swine farming has accelerated the proliferation of antibiotic resistance genes (ARGs) in animal-derived foods, making the production chain a potential ARG transmission route to humans. However, shared resistome profiles and horizontal gene transfer (HGT) mechanisms along this chain remain unclear. Here, we systematically investigated the resistome profile, ARGs' host, and potential HGT of ARGs across interconnected swine farm, slaughterhouse, and retail market by metagenomic assembly and binning. From 42 metagenomes, 1354 ARG subtypes were identified, with 303 shared across all interfaces. Both microbiome and mobile genetic elements (MGEs) contributed to the variation in ARG profiles. Pseudomonadota were the dominant drivers that shape the resistome through plasmid-mediated HGT. Among the 133 reconstructed ARG-carrying genomes (ACGs), 38 of them carried multiple ARGs, indicating the potential mobility of ARGs. Notably, 3 ACGs taxonomically assigned to Pseudomonas_E alcaligenes, Serratia_J grimesii, and Escherichia coli carrying 9, 13, and 41 ARGs, respectively. Furthermore, MetaCHIP analysis uncovered 445 potential HGT events, and ARGs including CpxR, macB, fusA, and vanR were annotated as potentially transferred subtypes. This study decodes the resistome profiles and tracks horizontal ARG transfer at the community level across the entire pork supply chain - from swine farms to retail outlets. To our knowledge, few studies have explored ARG transmission subtypes and directional flows among humans, pigs, and environmental compartments in the pork production chain using metagenomic approaches. These findings highlight the important role of the pork production chain as a critical transmission vector for ARGs under One Health framework.}, } @article {pmid41606854, year = {2025}, author = {Okoye, CO and Abhadiomhen, SE and Ezenwanne, BC and Chen, X and Jiang, H and Wu, Y and Jiang, J}, title = {Machine learning-based predictive modeling of foodborne pathogens and antimicrobial resistance in food microbiomes using omics techniques: A systematic review.}, journal = {Food research international (Ottawa, Ont.)}, volume = {221}, number = {Pt 1}, pages = {117255}, doi = {10.1016/j.foodres.2025.117255}, pmid = {41606854}, issn = {1873-7145}, mesh = {*Machine Learning ; *Food Microbiology ; *Foodborne Diseases/microbiology ; *Microbiota ; *Drug Resistance, Bacterial/genetics ; Animals ; Genomics/methods ; Metagenomics ; Salmonella/pathogenicity/genetics ; Food Safety ; Humans ; }, abstract = {The globalization of food systems has heightened the risk of foodborne pathogens such as Salmonella, Listeria monocytogenes, and Campylobacter, exacerbated by rising antimicrobial resistance (AMR). Traditional pathogen identification and AMR risk surveillance methods are often labor-intensive and low-throughput, while single-omics approaches fail to capture microbial complexity. Moreover, reliance on individual machine learning (ML) models limits predictive robustness, posing challenges to food safety and public health. This systematic review evaluates ML-based predictive modeling integrated with omics techniques (genomics, metagenomics, and transcriptomics) for foodborne pathogen and AMR risk surveillance. Following PRISMA guidelines, 1245 articles from PubMed, Scopus, and other databases (2015-2025) were screened, selecting 13 relevant studies. These studies applied ML algorithms, including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machines (SVM), to enhance predictive accuracy. The selected studies demonstrated predictive accuracies up to 99 % and AUROC scores above 0.90. Key discoveries include genetic markers for Salmonella virulence, Listeria attribution to fruits and dairy, and 145 mobile antimicrobial resistance genes (ARGs) in poultry. Despite these advancements, limitations such as small sample sizes, inconsistent metadata, overfitting, and computational scalability hinder real-world implementation. This review underscores the potential of ML-driven omics frameworks to revolutionize foodborne pathogen and AMR risk monitoring, paving the way for smarter, more resilient food safety systems. However, methodological inconsistencies necessitate standardized protocols, larger datasets, and explainable AI (XAI) to improve reliability and applicability in global food safety monitoring.}, } @article {pmid41606853, year = {2025}, author = {Zhang, T and Liao, Z and Bi, J and Li, Z and Liu, Y and Liu, Y and Song, Y and Qin, Y}, title = {Multi-omics analysis reveals microbial community succession and aroma enhancement mechanisms during spontaneous oak-barrel fermentation of chardonnay wine.}, journal = {Food research international (Ottawa, Ont.)}, volume = {221}, number = {Pt 1}, pages = {117249}, doi = {10.1016/j.foodres.2025.117249}, pmid = {41606853}, issn = {1873-7145}, mesh = {*Wine/analysis/microbiology ; *Fermentation ; *Odorants/analysis ; *Quercus/microbiology ; *Microbiota ; Volatile Organic Compounds/analysis ; *Food Microbiology ; Bacteria/classification/metabolism ; Oxygen/analysis ; *Food Handling/methods ; Fungi/metabolism/classification ; Metabolomics ; Multiomics ; }, abstract = {Spontaneous oak-barrel fermentation contributes to terroir-associated attributes and enhances aroma complexity in wines; however, the microbial succession dynamics and mechanisms underlying aroma enhancement remain unclear. This study comprehensively analyzed the dissolved oxygen concentrations, physicochemical properties, microbial community structures, and aroma compounds during spontaneous oak-barrel fermentation of Chardonnay wine. The results demonstrated that during spontaneous fermentation, dissolved oxygen concentrations varied among different barrel types, with the highest levels observed in new oak barrels, followed by old oak barrels, and the lowest in stainless-steel barrels. Microbiome analysis indicated that the predominant microorganisms included Saccharomyces, Hanseniaspora, Metschnikowia, Fructobacillus, Lactobacillus, and Gluconobacter, all of which were closely associated with aroma compounds formation. The differences in bacterial community composition between different oak barrels were minimal, while the differences in fungal composition were more pronounced. Metabolome analysis identified 15 key differential aroma compounds among the different barrel types, mainly esters, higher alcohols, and acids. Fermentation in new oak barrels exhibited higher concentrations of ester and acid compounds, while fermentation in stainless-steel barrels showed higher levels of higher alcohol compounds. This study elucidates for the first time various oak barrel types influence aroma differentiation during spontaneous fermentation primarily through the interaction between dissolved oxygen and microbial communities. These findings provide valuable insights for optimizing oak barrel usage and enhancing Chardonnay wine quality.}, } @article {pmid41606850, year = {2025}, author = {Wang, Y and Zhao, L and Huang, S and Peng, J and Wu, K and Wu, M}, title = {High-fat diet-induced obesity disrupts the gut microbiome and mucus secretion to aggravate experimental colitis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {221}, number = {Pt 1}, pages = {117245}, doi = {10.1016/j.foodres.2025.117245}, pmid = {41606850}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Diet, High-Fat/adverse effects ; *Obesity/complications/microbiology ; *Colitis/chemically induced/microbiology/etiology ; Goblet Cells/metabolism ; Mice, Inbred C57BL ; Mice ; *Mucus/metabolism ; Dextran Sulfate ; Male ; Disease Models, Animal ; Intestinal Mucosa/metabolism ; Colon/pathology ; }, abstract = {Obesity and its associated comorbidities have emerged as a major public health crisis. Accumulating evidence indicates that a high fat diet (HFD) may promote intestinal injury. However, the roles of intestinal goblet cells and specific gut microbiota composition in colitis under obesity conditions remain unclear. In this study, we employed a HFD-induced obesity model combined with dextran sulfate sodium (DSS) to induce colitis in mice. Our results reveal that obesity exacerbates DSS-induced colitis in the colon, as evidenced by increased intestinal barrier injury. These changes are associated with impaired goblet cell maturation, reduced mucus production, and a disrupted microbiota composition, notably characterized by an enrichment of pro-inflammatory bacteria Escherichia-Shigella and Helicobacter. In vitro, combined HFD and DSS treatment suppresses mucus secretion and alters the metabolic profile of LS174T cells, particularly affecting amino acid metabolism. Collectively, our findings reveal that HFD-induced obesity aggravates colitis severity, involving disruption of goblet cell function and gut microbial homeostasis, highlighting the importance of dietary intervention in obese individuals to alleviate intestinal inflammation.}, } @article {pmid41606790, year = {2026}, author = {Clutter, CH and Leung, DT}, title = {Tracing MR1 expression across tissues to find the perfect MAIT.}, journal = {Journal of leukocyte biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jleuko/qiag014}, pmid = {41606790}, issn = {1938-3673}, abstract = {Mucosal associated invariant T (MAIT) cells are part of a T cell subset that is activated upon presentation of B2 vitamin (riboflavin) metabolites by the major histocompatibility complex, class I related (MR1) protein. Though there is a clear relationship between microbial production of riboflavin and MAIT cell development and persistence, little is known about the cells that primarily communicate with MAIT cells and other MR1-restricted T cells. Elegant work by Deng et al demonstrates that it is macrophages from the lung and peritoneum that express the highest amount of MR1 and are the most efficient at presenting vitamin B antigens to MAIT cells. This landmark study not only definitively identifies and maps the key antigen presenting cell populations involved in MAIT cell activation, it also reveals a bidirectional relationship between MR1 expression and the host microbiome. While further work on how these findings translate to human MAIT cell biology is needed, this study has provided us with unprecedented insights into the mechanistic interplay and microbial ecology of MR1 presentation of riboflavin metabolites.}, } @article {pmid41606773, year = {2026}, author = {Ross, SM}, title = {Forever Young, Part 3: Urolithin A: A Gut Microbiome-Derived Metabolite and Its Role in Aging.}, journal = {Holistic nursing practice}, volume = {}, number = {}, pages = {}, pmid = {41606773}, issn = {1550-5138}, } @article {pmid41606595, year = {2026}, author = {Luan, J and Zhang, X and Chen, T and Pu, S and Shen, Z and Xu, C and Chen, Z and Zhang, J and Chen, D}, title = {Adolescent exposure to polystyrene nanoplastics induces male reproductive damage via the microbiome-gut-testis axis.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04069-y}, pmid = {41606595}, issn = {1477-3155}, support = {ZDXK202219//Jiangsu Province Capability Improvement Project through Science, Technology and Education/ ; PY2025017//Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University/ ; PY2023002//Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University/ ; 2022ZB730//Jiangsu Funding Program for Excellent Postdoctoral Talent/ ; 82103580//National Natural Science Foundation of China/ ; }, abstract = {Polystyrene nanoplastics (PS-NPs), are increasingly associated with reduced male fertility, yet the underlying mechanisms remain poorly defined. Here, we systematically unraveled a novel microbiome-gut-testis axis mediating PS-NPs-induced reproductive toxicity. Adolescent rats exposed to PS-NPs for 5 weeks induced dose-dependent testicular injury, characterized by disrupted spermatogenesis, and compromised blood-testis barrier. Single-cell atlases revealed spermatogenic arrest, abnormal immune microenvironment, and perturbed testicular cell communication upon exposure to PS-NPs. Furthermore, multi-omics analysis highlighted the activation of NF-κB/IL-17/HIF-1 and inhibition of PPAR-γ signaling, contributing to increased DNA damage and apoptosis, suppressed autophagy, and dysregulated energy-lipid metabolism. Additionally, PS-NPs exposure initiated gut microbial dysbiosis, significantly increasing pro-inflammatory bacteria, while reducing beneficial commensals. This microbial disruption compromised intestinal barrier integrity, leading to elevated circulating LPS levels. Subsequent activation of the TLR4/MyD88/NF-κB signaling pathway propagated inflammatory responses to testes. Crucially, FMT from PS-NPs-exposed donors reproduced the damage in healthy recipients, thus suggesting gut microbiota as a causal mediator. Therapeutically, DI intervention effectively mitigated the reproductive toxicity by restoring gut barrier integrity, rebalancing microbial communities, and suppressing inflammation. Our findings unveil a gut microbiome-centric mechanism for nanoplastic-induced male reproductive toxicity, and identify DI as a promising therapeutic candidate, accordingly providing critical insights for environmental risk assessment.}, } @article {pmid41606550, year = {2026}, author = {Zhang, X and Xu, J and Chen, M and Wu, Y and Chen, D and Xu, X and He, X}, title = {Aspergillus fumigatus in mechanically ventilated pneumonia- independent mortality risk and synergistic microbiome signatures from a multicenter mNGS cohort.}, journal = {BMC pulmonary medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12890-026-04131-3}, pmid = {41606550}, issn = {1471-2466}, support = {2022GYX28//Lishui Public Welfare Technology Application Research Program Project/ ; }, } @article {pmid41606514, year = {2026}, author = {Hu, S and Luo, C and Wan, S and Zhang, S and Li, N and Liu, G and Zhao, LY}, title = {Modulating the gut microbiome to enhance cancer immunotherapy: a systematic review and Meta-Analysis of probiotics and FMT as adjuncts.}, journal = {BMC cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12885-026-15655-6}, pmid = {41606514}, issn = {1471-2407}, } @article {pmid41606319, year = {2026}, author = {Kamitaki, N and Handsaker, RE and Hujoel, MLA and Mukamel, RE and Usher, CL and McCarroll, SA and Loh, PR}, title = {Human and bacterial genetic variation shape oral microbiomes and health.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {41606319}, issn = {1476-4687}, abstract = {Human genetic variation influences all aspects of our biology, including the oral cavity[1-3], through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a person's oral microbiome and potentially promote its dysbiosis[3-5]. We characterized the oral microbiomes of 12,519 people by re-analysing whole-genome sequencing reads from previously sequenced saliva-derived DNA. Human genetic variation at 11 loci (10 new) associated with variation in oral microbiome composition. Several of these related to carbohydrate availability; the strongest association (P = 3.0 × 10[-188]) involved the common FUT2 W154X loss-of-function variant, which associated with the abundances of 58 bacterial species. Human host genetics also seemed to powerfully shape genetic variation in oral bacterial species: these 11 host genetic variants also associated with variation of gene dosages in 68 regions of bacterial genomes. Common, multi-allelic copy number variation of AMY1, which encodes salivary amylase, associated with oral microbiome composition (P = 1.5 × 10[-53]) and with dentures use in UK Biobank (P = 5.9 × 10[-35], n = 418,039) but not with body mass index (P = 0.85), suggesting that salivary amylase abundance impacts health by influencing the oral microbiome. Two other microbiome composition-associated loci, FUT2 and PITX1, also significantly associated with dentures risk, collectively nominating numerous host-microbial interactions that contribute to tooth decay.}, } @article {pmid41606239, year = {2026}, author = {Salem, GM and Azamor, T and Familiar-Macedo, D and Onwubueke, C and Cambou, MC and Chen, W and Nielsen-Saines, K and Foo, SS}, title = {Mechanistic insights into the impact of prenatal viral infections on maternal and offspring immunity.}, journal = {Npj viruses}, volume = {4}, number = {1}, pages = {7}, pmid = {41606239}, issn = {2948-1767}, support = {N/A//Cleveland Clinic/ ; }, abstract = {Global outbreaks of human immunodeficiency virus (HIV) and respiratory viruses - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza, accounted for ~50 million infections in 2024. Prenatal exposure to these viruses poses substantial risks to maternal and fetal health, yet the underlying immunological mechanisms remain incompletely understood. Despite differences in viral biology and transmission, mounting evidence reveals a convergent theme of maternal immune activation during pregnancy. Even without vertical transmission, virus-elicted maternal immune responses alter the maternal-fetal interface and gut microbiome, reshaping fetal immunity and birth outcomes. These immune perturbations increase susceptibility to infections, neurodevelopmental disorders, and immune-mediated diseases later in life. Here, we discuss viral immune evasion strategies that modulate maternal immunity and review current clinical and emerging therapeutic approaches aimed at mitigating long-term consequences in exposed children. Understanding how prenatal viral exposure shapes lifelong health is critical for developing targeted interventions and reducing postnatal disease burden.}, } @article {pmid41606218, year = {2026}, author = {Abdelhameed, A and Hussein, RH and Hatem, ZA and Bağcı, C and Ziemert, N}, title = {From niche to niche: investigating microbial communities and their specialised metabolite gene clusters in human microbiomes.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {2}, pages = {65}, pmid = {41606218}, issn = {1573-0972}, mesh = {Humans ; *Multigene Family ; *Microbiota/genetics ; *Bacteria/genetics/metabolism/classification/isolation & purification ; Metagenomics ; Biosynthetic Pathways/genetics ; Metagenome ; }, abstract = {Diverse microbial communities within the human microbiome perform vital functions which influence both health and disease in hosts. Specialized metabolites produced by microbes via biosynthetic gene clusters (BGCs) drive ecological interactions and offer possibilities for therapeutic application. The biosynthetic capabilities of microorganisms present in human microbiomes are still mostly unexplored despite metagenomics advancements. The study examines the variety of microbial communities and BGC locations through metagenomic data from 1,191 samples across eight human microbiomes taken from the IMG/M database. Kraken2 executed taxonomic classification while antiSMASH v6.1.1 identified BGCs. The study used BiG-SCAPE to build a sequence similarity network while Bracken and Pavian tools analyzed microbial diversity. A total of 25,681 BGCs were identified, of which 97.5%, showed no significant match to existing clusters in MIBIG database, indicating substantial potential for novel biosynthetic discoveries . Showing no match to existing clusters in the MIBiG database which shows huge potential for new biosynthetic discoveries. New strains were discovered that produce unique RiPPs, NRPs, and siderophores primarily within the microbiomes of the large intestine, oral cavity, and skin. The large intestine showed maximum microbial and biosynthetic diversity compared to other areas while the biliary tract and nasal cavity displayed minimal diversity. New BGCs associated with antibiotic, cytotoxic, and immune-modulating functions present potential therapeutic uses. The investigation uncovers essential information about how microbial communities develop specific functions within various body regions. Uncharacterized BGC discoveries present new opportunities for drug development and treatments that target microbiomes.}, } @article {pmid41606121, year = {2026}, author = {Duttagupta, S and Messaoudene, M and Hunter, S and Desilets, A and Jamal, R and Mihalcioiu, C and Belkaid, W and Marcoux, N and Fidelle, M and Suissa, D and Ponce, M and Geiger, M and Malo, J and Piccinno, G and Punčochář, M and Filin, A and Heidrich, V and Rusu, D and Mbaye, B and Durand, S and Ben Aissa, I and Puller, V and de Lahondès, R and Blais, N and Tehfe, M and Owen, S and Bélanger, K and Parvathy, SN and Shieh, B and Raphael, J and Lenehan, J and Breadner, D and Rothenstein, J and Rozza, N and Maillou, J and Nili, S and Prifti, DK and Pinto, F and Armanini, F and Kim-Schulze, S and Marron, TU and Kroemer, G and Derosa, L and Zitvogel, L and Silverman, M and Segata, N and Vareki, SM and Routy, B and Elkrief, A}, title = {Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41606121}, issn = {1546-170X}, abstract = {Immune checkpoint inhibitors (ICI) have improved outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma, yet over half of patients exhibit primary resistance. Fecal microbiota transplantation (FMT) may overcome resistance to anti-programmed cell death protein 1 (PD-1) therapy. The clinical activity and safety of FMT plus anti-PD-1 in NSCLC or anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy in melanoma have not been evaluated. Here we report results from FMT-LUMINate, a multicenter, open-label, phase 2 trial assessing healthy donor FMT plus anti-PD-1 in NSCLC (n = 20) or anti-PD-1 plus anti-CTLA-4 (dual ICI) in melanoma (n = 20), in the first-line setting. Eligible patients received a single FMT via oral capsules prior to ICI initiation. The primary endpoint was objective response rate (ORR) in NSCLC. Secondary endpoints included ORR in melanoma, safety and donor-host microbiome similarity. In NSCLC, the ORR was 80% (16/20), meeting the study primary endpoint. In melanoma, the ORR was 75% (15/20). FMT was deemed safe in both cohorts by an independent data and safety monitoring committee, with no grade 3 or higher adverse events (AEs) in NSCLC and 13 (65%) patients experiencing grade 3 or higher AEs in melanoma. Shotgun metagenomic sequencing revealed that responders developed a distinct post-FMT gut microbiome composition, independent of acquired donor-recipient similarity or strain-level engraftment. Responders exhibited significantly greater loss of baseline bacterial species compared to non-responders, with frequent depletion of Enterocloster citroniae, E. lavalensis and Clostridium innocuum. This finding was reproduced across three published FMT oncology trials. We recolonized antibiotic-treated, tumor-bearing mice with post-FMT stool from two responder patients, and reintroduction of the specific bacterial species that were lost after FMT abrogated the antitumor effect of ICI. Taken together, these findings confirm the clinical activity of FMT in combination with ICI and suggest that the elimination of deleterious taxa is required for FMT-mediated therapeutic benefit. ClinicalTrials.gov identifier: NCT04951583 .}, } @article {pmid41606120, year = {2026}, author = {Fernandes, R and Jabbarizadeh, B and Rajeh, A and Hong, MMY and Baines, KJ and Ernst, S and Winquist, E and Ali, AS and Penny, S and Figueredo, R and Parvathy, SN and Lenehan, JG and Pinto, DM and Silverman, MS and Maleki Vareki, S}, title = {Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41606120}, issn = {1546-170X}, support = {1-MR_2022_4884//Lotte and John Hecht Memorial Foundation (Lotte & John Hecht Memorial Foundation)/ ; 203745/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Immune checkpoint inhibitors (ICIs) improve outcomes in metastatic renal cell carcinoma (mRCC) but are hindered by immune-related adverse events (irAEs). Modulation of the gut microbiome may enhance efficacy and mitigate toxicity, yet the safety and mechanisms of healthy donor fecal microbiota transplantation (FMT) in mRCC remain unexplored. In this phase 1 trial, 20 treatment-naive patients with mRCC received encapsulated healthy donor FMT (LND101) combined with ipilimumab/nivolumab (n = 16), pembrolizumab/axitinib (n = 3) or pembrolizumab/lenvatinib (n = 1). The primary endpoint was safety, defined by the incidence and severity of irAEs. Secondary endpoints included clinical response (Response Evaluation Criteria in Solid Tumors version 1.1), gut microbiome and immune correlates and patient-reported quality of life. The safety endpoint was met with 50% (10/20) of patients experiencing grade 3 irAEs and no serious FMT-related toxicities or grade 4 or 5 irAEs. Among evaluable patients, the objective response rate was 50% (9/18), including two complete responses (11%, 2/18). Notably, most treatment responders did not develop any grade 3 or higher irAEs. Alpha (α) diversity improvement and durable engraftment of taxa and metabolic functions associated with anti-inflammatory properties correlated with reduced toxicity and improved response. Conversely, patients experiencing grade 3 irAEs exhibited expansion of Segatella copri, particularly with ipilimumab/nivolumab, and elevated levels of donor-derived microbial enzymes previously linked to pro-inflammatory activity. Resilience to toxicity correlated with the maintenance of protective metabolites and increased levels of immune regulatory cells, whereas the presence of grade 3 irAEs and S. copri enrichment was associated with high immune dysregulation. These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated mRCC. ClinicalTrials.gov identifier: NCT04163289 .}, } @article {pmid41606119, year = {2026}, author = {Porcari, S and Ciccarese, C and Heidrich, V and Rondinella, D and Quaranta, G and Severino, A and Arduini, D and Buti, S and Fornarini, G and Primi, F and Stumbo, L and Giannarelli, D and Giudice, GC and Damassi, A and Giron Berríos, JR and Punčochář, M and Barbazuk, TB and Piccinno, G and Pinto, F and Armanini, F and Asnicar, F and Schinzari, G and Derosa, L and Kroemer, G and Sanguinetti, M and Masucci, L and Gasbarrini, A and Tortora, G and Cammarota, G and Zitvogel, L and Segata, N and Iacovelli, R and Ianiro, G}, title = {Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41606119}, issn = {1546-170X}, support = {GR-2018-12365734//Ministero della Salute (Ministry of Health, Italy)/ ; PNRR-POC-2023-12377319//Ministero della Salute (Ministry of Health, Italy)/ ; PNRR-POC-2023-12377319//Ministero della Salute (Ministry of Health, Italy)/ ; 30203//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; FIS00001711//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; ERC-StG MicroRestore-101221279//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 101052444//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; microTOUCH-101045015//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 101168810//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; ONCOBIOME-825410//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; IHMCSA-964590//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 1U01CA230551//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {Renal cell carcinoma (RCC) is a common malignancy with limited durable responses to first-line immune checkpoint inhibitor (ICI)-based therapies. Emerging evidence implicates the gut microbiome in modulating ICI efficacy. In the investigator-initiated, randomized, double-blind placebo-controlled phase 2a TACITO trial, we evaluated whether fecal microbiota transplantation (FMT) from complete ICI responders enhances clinical outcomes in treatment-naive patients with metastatic RCC (mRCC) receiving pembrolizumab + axitinib. The primary endpoint was the rate of patients free from disease progression at 12 months after randomization (12-month progression-free survival (PFS)). Secondary endpoints were median PFS and median overall survival, objective response rate (ORR), safety and microbiome changes, after randomization. Forty-five patients randomly received donor FMT (d-FMT) or placebo FMT (p-FMT). Although the primary endpoint was not met (70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053), the secondary endpoint of median PFS was significantly longer with d-FMT (24.0 months in the d-FMT arm versus 9.0 months in the p-FMT arm; hazard ratio = 0.50, P = 0.035). The ORR was 52% of patients in the d-FMT arm and 32% of patients receiving placebo. Microbiome analysis confirmed donor strain engraftment and increased α-diversity and larger microbiome shifts (β-diversity) compared with baseline composition in the d-FMT treatment group. Acquisition or loss of specific strains, but not total engraftment, was associated with the primary endpoint. Our findings support the safety and potential efficacy of selected donor FMT to enhance ICI-based treatment in mRCC, which deserves further investigations. ClinicalTrials.gov identifier: NCT04758507 .}, } @article {pmid41606026, year = {2026}, author = {Rahat, MTI and Sumi, MSA and Nurejannath, M and Ahmmed, R and Kibria, MK}, title = {Identification of bacterial key genes and therapeutic targets in hypertensive patients with type 2 diabetes through bioinformatics analysis.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36467-5}, pmid = {41606026}, issn = {2045-2322}, abstract = {Hypertension (HTN) coexisting with type 2 diabetes (T2D) significantly increases cardiovascular risk, yet most microbiome studies have focused on these diseases separately and have overlooked their combined microbial gene-level mechanisms. The coexistence of HTN and T2D may create a distinct gut microbial environment where metabolic and vascular pathways intersect but the specific bacterial genes and molecular interactions underlying this dual phenotype remain largely unknown. To address this gap, this study aimed to identify bacterial key genes (bKGs) associated with hypertension coexisting with type-2 diabetes (HTNT2D) and to explore therapeutic agents targeting these bKGs through integrated bioinformatics approaches. A total of 124 gut microbiome samples, including 95 healthy controls (HC) and 29 HTNT2D cases were analyzed. Diversity analysis revealed significantly higher microbial richness and distinct clustering in HTNT2D, indicating altered microbial community structure. Differential abundance analysis identified 19 bacterial genera across four dominant phyla, while functional prediction uncovered 195 enriched metabolic pathways and 257 associated genes. To refine these finding, protein-protein interaction analysis highlighted 10 hub genes (acpP, dnaG, fusA, gltB, guaA, gyrB, lacZ, mdh, purF and tktA) as potential drivers of HTNT2D pathogenesis. Molecular docking analysis of these bKGs revealed binding affinities ranging from - 4.109 to -9.961 kcal/mol and three top-ranked drug candidates named Naringin-fusA (-9.961 kcal/mol), Neohesperidin-mdh (-9.818 kcal/mol), and Bromocriptine-gyrB (-9.446 kcal/mol) were selected as potential drugs based on their binding affinities. Subsequent molecular dynamics simulations performed for 100 ns confirmed the stability of their complexes, supporting their biological relevance. Drug-likeness and ADMET evaluations pointed to Bromocriptine as the most suitable compound though further safety validation will be necessary. Overall, this study provides novel insights into the gut microbiome signatures of HTNT2D and identifies bKGs with therapeutic potential. These computationally identified candidates can be prioritized for experimental validation to advance microbiome-based diagnostics and targeted therapies for HTNT2D management.}, } @article {pmid41605941, year = {2026}, author = {Di Grazia, G and Sánchez-Bayona, R and Casals-Pascual, C and Pascual, T and Generali, D and Gennari, A and Vigneri, P and Harbeck, N and Cortés, J and Prat, A and Schettini, F}, title = {Dynamic biomarkers in hormone receptor-positive/HER2-negative breast cancer trials: a new hope for precision oncology.}, journal = {NPJ breast cancer}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41523-026-00904-5}, pmid = {41605941}, issn = {2374-4677}, abstract = {Hormone receptor-positive/HER2-negative breast cancer evolves in response to therapy, demanding smarter, adaptive biomarker-based treatment strategies. We review emerging dynamic biomarkers to guide therapeutic decision-making, spanning tissue and liquid biopsies, metabolic imaging, and microbiome profiling, that capture tumor or host-related changes over time. By contrasting Academic and Industry approaches, we advocate for a cultural shift in clinical trial design and implementation, aiming to move from reactive to proactive Oncology.}, } @article {pmid41605932, year = {2026}, author = {Raethong, N and Patumcharoenpol, P and Vongsangnak, W}, title = {Modeling diet-gut microbiome interactions and prebiotic responses in Thai adults.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00921-z}, pmid = {41605932}, issn = {2055-5008}, support = {N42A660907//National Research Council of Thailand/ ; }, abstract = {The impact of diet on gut microbial metabolism is essential for advancing microbiome-based health interventions. This study introduces a novel systems biology pipeline that integrates genome-scale metabolic models (GSMMs) with Thai dietary intake data to simulate gut microbiome metabolism and assess prebiotic responses. Utilizing metagenomic data from healthy Thai adults and an average Thai diet derived from national surveys, community-scale metabolic models (CSMMs) were developed and simulated under both typical dietary and prebiotic-supplemented condition. Flux variability analysis was employed to assess metabolic capacities, short-chain fatty acids (SCFAs) production in relation to microbial taxonomy. The results promisingly revealed inter-individual variability in SCFA profiles, with Bacteroides and Phocaeicola notably linked to isobutyrate production and Bifidobacterium emerged as a key responder to prebiotic supplementation. This integrative framework offers biological insights into diet-gut microbiome interactions and provides a foundation for the development of precision nutrition strategies tailored to the Thai population.}, } @article {pmid41605865, year = {2026}, author = {Solis, S and Maldonado, EM and Mukhopadhyay, S and Jan, G and Landete, JM and Maluquer de Motes, C and Gutierrez-Merino, J}, title = {Self-aggregating Lactiplantibacillus plantarum enhances type-I interferon responses via the cytosolic sensors NOD2 and cGAS.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2615490}, pmid = {41605865}, issn = {1949-0984}, mesh = {*Interferon Type I/immunology/metabolism/genetics ; *Nod2 Signaling Adaptor Protein/metabolism/genetics/immunology ; Humans ; Gastrointestinal Microbiome ; *Nucleotidyltransferases/metabolism/genetics/immunology ; Macrophages/immunology/microbiology ; *Lactiplantibacillus plantarum/immunology/physiology ; Animals ; Cytosol ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; }, abstract = {The gut microbiome plays a critical role in health, disease and immunity. To date, we have access to large datasets describing how the microbial diversity present in the gut correlates with many clinical conditions. However, the microbiome composition is taxonomically complex; influenced by many environmental factors; and variable between individuals and communities, thereby limiting functional and mechanistic insights into the microbiota‒host interactions. We are still unsure of the molecular mechanisms by which gut commensal microbes intrinsically possess to interact with the immune system and induce beneficial responses. This study has addressed this important question by revealing that only certain members of Lactobacillaceae, a bacterial family very well known for its probiotic properties, interact very intimately with macrophages because of their ability to simultaneously overexpress adhesive cell wall proteins and to self-aggregate, leading to significant production of type I interferon (IFN-I) cytokines. IFN-I cytokines are essential to confer protection against viral infections and auto-immune disorders. Specifically, we have proved that this enhanced IFN-I feature is strain-dependent and predominantly driven by cGAS, a molecule that activates the cytosolic sensor STING upon the recognition of bacterial DNA. Furthermore, another cytosolic sensor, NOD2, seems to be an additional stimulus to amplify IFN-I production, suggesting the involvement of successive molecular events for a prominent probiotic response. Our findings provide insight into how specific molecules of probiotic bacteria modulate or stimulate host responses, providing a better understanding of the molecular crosstalk between the microbiome and immune cells.}, } @article {pmid41605799, year = {2026}, author = {Lee, H and Lee, MH and Seo, SH and Pak, J and Bae, S and Lee, G and Kim, HS and Kim, K and Kim, JH and Son, HS}, title = {Integrated Microbiome and Metabolomic Profiling to Identify Potential Biomarkers of Major Depressive Disorder.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2512014}, doi = {10.4014/jmb.2512.12014}, pmid = {41605799}, issn = {1738-8872}, mesh = {Humans ; *Major Depressive Disorder/microbiology/diagnosis/blood/metabolism ; *Biomarkers/blood/urine ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Male ; *Metabolomics/methods ; Middle Aged ; Female ; Adult ; *Metabolome ; Bacteria/classification/genetics/isolation & purification/metabolism ; Carnitine/analogs & derivatives/metabolism/blood ; Dysbiosis/microbiology ; Gas Chromatography-Mass Spectrometry ; Fatty Acids/metabolism ; Republic of Korea ; }, abstract = {The pathophysiology of major depressive disorder (MDD) remains incompletely understood, hindering the development of objective diagnostic markers. While the microbiota-gut-brain axis is implicated in MDD, the functional link between gut dysbiosis and systemic metabolism remains largely obscure. To address this, we employed an integrated multi-omics approach combining 16S rRNA gene sequencing, GC-MS analysis of urine and plasma, complemented by UPLC-QTOF-MS profiling of plasma, in a Korean cohort (n = 69). We identified distinct taxonomic shifts, specifically the enrichment of the Eubacterium eligens group and Veillonella in MDD patients. Integrated correlation analysis revealed a functional "gut-lipid axis", where these taxa were strongly associated with alterations in host acylcarnitine and fatty acid metabolism. Notably, diagnostic evaluation demonstrated that the plasma metabolic profile yielded superior predictive accuracy (AUC = 0.862) compared to the gut microbiota (AUC = 0.654). Our findings suggest that while the gut microbiome provides mechanistic insights into lipid dysregulation, the circulating metabolome serves as a more robust, proximal diagnostic readout for MDD.}, } @article {pmid41605796, year = {2026}, author = {Park, CK and Bae, SH and Park, HW and Oh, NS and Kim, YJ and Kim, YW and Cho, TJ and Li, Y and Chai, J and Zhao, J and Cho, HT and Jung, JH and Park, J and Kim, TG and Kim, JK}, title = {Development of Large Language Model Specialized into Microbiome Datasets: an Application of Self-Evaluation and Scoring Comparison with Conventional Natural Language Processing Markers.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2511050}, doi = {10.4014/jmb.2511.11050}, pmid = {41605796}, issn = {1738-8872}, mesh = {*Natural Language Processing ; Humans ; Artificial Intelligence ; *Gastrointestinal Microbiome ; *Microbiota ; Computational Biology/methods ; Liver/microbiology/metabolism ; Large Language Models ; }, abstract = {The gut microbiome plays a fundamental role in host metabolism, immune regulation, and disease development. With the rapid accumulation of multi-omics and literature data, the microbiome field now faces the challenge of efficiently extracting scientific insights from massive, heterogeneous datasets. Artificial intelligence (AI) and large language models (LLMs) provide promising tools to address this complexity by enabling integrative analysis and knowledge synthesis across diverse biological sources. In this study, we developed METABOLISM, a microbiome-specialized LLM fine-tuned on 160,000 scientific abstracts to enhance literature-based contextual understanding of microbiome-liver interactions and related biological mechanisms. Using LoRA-based parameter-efficient training, METABOLISM was optimized for domain-specific reasoning and response generation. Model performance was evaluated through both automated Phi-4 scoring (a large language model-based evaluator for relevance, informativeness, and fluency) and structured human expert rubric assessments involving 20 domain specialists. The fine-tuned METABOLISM achieved superior relevance and clarity scores (mean > 7.5 ± 0.06) compared with general-purpose LLMs such as Gemma-3-12B-IT and ChatGPT-4o. Correlation analysis revealed weak to moderate negative relationships (R = -0.65, p < 0.0001) between traditional NLP metrics (BLEU, ROUGE) and human expert rubric scores, with a similar trend observed for correlations with Phi-4-based automated evaluation scores, indicating the limitations of surface-level similarity measures in biomedical contexts. Overall, our findings demonstrate that microbiome-adapted LLMs can effectively distill high-volume scientific data into biologically meaningful insights, supporting more efficient and interpretable research in microbiology and systems biology.}, } @article {pmid41608402, year = {2025}, author = {Roth, W and Lo, E and De Leon, O and Suriya, S and Fakhri, F and Brorson, JR and Polster, S and Kass-Hout, T and Prabhakaran, S and Siegler, JE}, title = {Understanding the Relationship Between Cerebrovascular Disease and the Gut Microbiome.}, journal = {Stroke (Hoboken, N.J.)}, volume = {5}, number = {1}, pages = {e001272}, pmid = {41608402}, issn = {2694-5746}, abstract = {While traditional vascular risk factors (eg, hypertension, dyslipidemia, tobacco use) account for 20% of the explained variance in carotid atherosclerosis, they remain a prominent focus for primary and secondary ischemic stroke prevention strategies. Among other potential contributors to atheroma formation and cerebrovascular disease, the gut microbiome has become increasingly implicated as a mediator of vascular risk. The foods we eat, coupled with our physiology and exposures (eg, antibiotics, supplements), directly contribute to atherosclerotic disease in complex ways that are mediated by gastrointestinal flora and metabolic by-products. Proliferation of "pathogenic" gut microbes such as Enterobacteriaceae and Streptococcus spp, decrement of "commensal" species such as Akkermansia spp and the biodiversity of gut flora are directly related to an individual's dietary intake and exposure history. Each of these components of the gut microbiome correlate with the development or progression of many conditions including atherosclerosis. Moreover, the metabolism of certain substrates found in animal products (notably l-carnitine and choline) and of refined sugars by these microorganisms leads to buildup of circulating metabolites with known links to atherogenesis, platelet activation, atrial fibrillation, and other adverse vascular outcomes. Several of these toxic metabolites, including trimethylamine and trimethylamine N-oxide, have been extensively studied in cardiovascular and cerebrovascular disease. Trimethylamine and trimethylamine N-oxide represent not only biomarkers of gut dysbiosis and cardiovascular risk, but they are increasingly recognized as therapeutic targets for novel interventions in atherosclerotic vascular disease. The individualized targeting of one's microbiome, and perhaps more generalized targeting of toxic microbial metabolites, has the potential to revolutionize the treatment of vascular disease. In this review, we summarize the latest evidence illustrating the impact of the microbiome on cerebrovascular disease and highlight the potential applications of this information on individualized and global scales.}, } @article {pmid41605717, year = {2026}, author = {Zhang, Y and Zhu, SJ}, title = {Role of bile acid metabolites in regulating viral infections.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2025.12.008}, pmid = {41605717}, issn = {1878-4380}, abstract = {Gut microbiota-derived bile acids are emerging as pivotal regulators of viral pathogenesis. They exhibit dual roles by directly blocking or promoting viral entry, while also systemically tuning immune responses. This forum discusses how spatiotemporal mapping of these interactions can address unresolved questions and inspire novel microbiome-based antiviral strategies.}, } @article {pmid41605669, year = {2026}, author = {Shen, X and Li, SB and Gao, MJ and Cao, JJ and Yang, H and Li, WW and Wei, LC and Chen, M and Liu, JY and Shi, YQ}, title = {Relationship Between Fecal Bile Acid Profile and Intestinal Microbiota in Patients With Chronic Radiation Enteritis.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.70029}, pmid = {41605669}, issn = {1751-2980}, support = {82330100//National Natural Science Foundation of China/ ; 82200567//National Natural Science Foundation of China/ ; 2024TD-06//Healthcare lnnovation Capability Enhancement Plan in Shaanxi Province/ ; JSYXM04//Booster Plans of Xijing Hospital/ ; }, abstract = {OBJECTIVE: We aimed to investigate the relationship between fecal bile acid (BA) profile and intestinal microbiota in patients with chronic radiation enteritis (CRE).

METHODS: Altogether 60 patients with cervical cancer (CC) who visited Xijing Hospital between December 2022 and September 2023 were enrolled, including 20 patients who did not undergo any treatment (the CC group), 20 patients who developed CRE after radical radiotherapy (the CRE group), and 20 patients who did not experience CRE after radical radiotherapy (the non-CRE [NRE] group). Patients' characteristics and fecal samples were collected. Fecal BA profiles were quantified, and intestinal microbiota were analyzed by using the 16S rRNA gene sequencing. Differentially expressed BAs and microorganisms were identified across groups, and their correlations were assessed using Spearman's correlation analysis.

RESULTS: In patients with CRE, BA metabolism was characterized by increased proportions of primary BAs and decreased proportions of secondary BAs, particularly lithocholic acid and its isomers. In addition, the abundance of beneficial bacterial genera, such as Bifidobacterium and Megasphaera, was reduced, whereas that of potentially pathogenic genera, including Megamonas and Dorea, was increased. Furthermore, a bidirectional relationship between BA metabolism and intestinal microbiota was observed.

CONCLUSIONS: Patients with CRE present notable alterations in BA metabolism and intestinal microbiota. CRE may trigger a harmful feedback mechanism driven by the interaction between these two factors. Targeted regulation of BA metabolism and intestinal microbiota may be a promising therapeutic approach for the management of CRE.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05728060.}, } @article {pmid41605617, year = {2026}, author = {Vijay-Kumar, M and Yeoh, BS and Gewirtz, AT}, title = {Hydroxylation matters! Microbial bile acid metabolism and colorectal cancer.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-337583}, pmid = {41605617}, issn = {1468-3288}, } @article {pmid41605597, year = {2026}, author = {Murcia-Soriano, LF and Venegas-Sanabria, LC and Arias-Blanco, D and Baracaldo Gomez, SDP and Borda, MG and Sanchez, G and Buitrago-Garcia, D}, title = {Microbes and ageing beyond the gut: the oral microbiome and frailty, sarcopenia and neurocognitive disorders in the elderly - a scoping review protocol.}, journal = {BMJ open}, volume = {16}, number = {1}, pages = {e106590}, doi = {10.1136/bmjopen-2025-106590}, pmid = {41605597}, issn = {2044-6055}, mesh = {Humans ; Scoping Reviews as Topic ; *Sarcopenia/microbiology ; Aged ; *Aging/physiology ; *Frailty/microbiology ; *Microbiota ; *Neurocognitive Disorders/microbiology ; *Mouth/microbiology ; Research Design ; }, abstract = {INTRODUCTION: Population ageing is a global phenomenon that has resulted in an increase in the number of patients with chronic diseases and geriatric syndromes. Frailty, sarcopenia and neurocognitive disorders are among the most prevalent conditions affecting older adults and have a direct effect on their quality of life, and can impact the burden and budgets of health systems. Recently, the oral microbiome has gained attention as it may be a factor that potentially influences the onset and progression of these syndromes. However, this is still a new line of research that has not been deeply explored. This scoping review protocol aims to explore how the oral microbiome may be associated with the onset of prevalent geriatric syndromes, frailty, sarcopenia and neurocognitive disorders, providing a picture of the current evidence and potential gaps for future research.

METHODS AND ANALYSIS: The scoping review will follow the Johanna Briggs Institute (JBI) methodology and will be reported accordit to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines (PRISMA-ScR). Searches will be conducted in Medline, Embase, Cochrane Central, CINAHL, LILACS and Epistemonikos from inception to December 2025. Independent reviewers will perform the study selection and data extraction. A descriptive analysis of information will be conducted, highlighting oral microorganisms associated with these syndromes and emerging trends in the evidence. Original research studies in any language will be included. We will include randomised controlled trials, cohort studies, case-control studies and other relevant designs if they investigate the oral microbiome and its relation to geriatric syndromes in adults aged 65 or older, regardless of geographic location or setting.

ETHICS AND DISSEMINATION: Ethics approval is not required.}, } @article {pmid41605486, year = {2026}, author = {Cai, XX and Zhang, HT and Wang, YX and Li, XJ}, title = {[Role and research progress of dental medicine in physical anthropology studies].}, journal = {Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology}, volume = {61}, number = {2}, pages = {266-272}, doi = {10.3760/cma.j.cn112144-20251013-00401}, pmid = {41605486}, issn = {1002-0098}, support = {2023YFC2506300//National Key R&D Program of China/ ; 2024C03241//Key Research and Development Program of Zhejiang Praince/ ; RD2022DXKB03//Exploration and Development Project of School of Stomatolog, Zhejiang University School of Medicine/ ; 202505/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Physical anthropology is a discipline that studies human physical characteristics and their evolutionary patterns through the analysis of human biological remains. Oral tissues such as teeth and jawbones, serving as crucial or even exclusive materials among human biological remains, establish dental medicine's central role in this field. This paper reviewed the advances in dental medicine's research on key physical anthropology topics and methodologies, including human origins and evolution, paleopathology, paleodietary reconstruction, and paleomicrobiology. In human origins and evolution research, dental morphology provides crucial evidence for identifying population relationships. Paleopathology reflects ancient survival pressures, subsistence economies, and cultural behavioral patterns through oral diseases. Paleodietary research reconstructs ancient dietary structures using dental microwear, trace elements, stable isotopes, and calculus microfossils (e.g., starch grains, ancient DNA, ancient proteins). Paleomicrobiology explores the evolution of health and disease through the oral microbiome. Current research faces limitations including narrow observation of oral diseases, inconsistent diagnostic criteria, and insufficient interdisciplinary integration. Future efforts should enhance multidisciplinary collaboration among dental medicine, archaeology, anthropology, and other fields. This multi-perspective approach will systematically elucidate the evolutionary trajectory of oral health and disease, enrich the historical context of dental medicine, and provide insights for contemporary prevention and treatment of oral diseases.}, } @article {pmid41605365, year = {2026}, author = {Pillay, D and Kuppusamy, UR and Arumugam, B}, title = {Role of terpenes and terpenoids in cross-talk between adipocyte browning and gut microbiome in obesity.}, journal = {Fitoterapia}, volume = {}, number = {}, pages = {107113}, doi = {10.1016/j.fitote.2026.107113}, pmid = {41605365}, issn = {1873-6971}, abstract = {Obesity, a major global health concern, is a complex condition characterized by excessive accumulation of fat that can result in various other health complications like cardiovascular disease, type 2 diabetes, and cancer. The intricate interactions between the gut microbiota and adipocyte browning, the process that transforms white adipose tissue (WAT) into metabolically active beige or brown-like adipose tissue (BAT) have gained considerable attention as a therapeutic strategy against obesity and related metabolic disorders. Terpenes and terpenoids have emerged as promising natural compounds to combat obesity and its associated metabolic complications. Terpenoids have been shown to exert anti-adipogenic effects, thus attenuating adipocyte hypertrophy, adipose tissue inflammation and oxidative stress through various mechanisms. The compounds have also been shown to modulate the composition and activity of gut microbiota, promoting the growth of beneficial bacteria while inhibiting the proliferation of harmful ones. These alterations in gut microbiota composition have been linked to improved metabolic parameters, including enhanced energy expenditure, improved insulin sensitivity, and reduced adiposity. Recent studies have highlighted the potential role of gut microbiota in mediating the effects of terpenoids on adipocyte browning, suggesting a complex interplay between these factors. However, the interplay has not been reviewed thus far. Therefore, this review highlights the role and mechanisms of terpenes and terpenoids in the cross-talk between adipocyte browning and the gut microbiome as potential therapeutic strategies for obesity. Studies were identified and screened through academic database searches and synthesized narratively. The review also includes challenges and future perspectives in introducing the compounds as alternate treatments for obesity.}, } @article {pmid41605326, year = {2026}, author = {Yuasa, H and Bermudez, DA and Konishi, K and Furukawa, M and Nozaki, R and Morita, S and Ozaki, K and Kondo, H and Hirono, I and Koiwai, K}, title = {Bacterial communities in pond water of kuruma shrimp Penaeus japonicus farms with different reported disease histories.}, journal = {Journal of invertebrate pathology}, volume = {}, number = {}, pages = {108555}, doi = {10.1016/j.jip.2026.108555}, pmid = {41605326}, issn = {1096-0805}, abstract = {Penaeid shrimp aquaculture is expanding worldwide, but recurrent infectious diseases remain a major threat to production. Interestingly, some farming environments sustain long-term stable production performance. To investigate the microbial basis of this condition, we performed 16S rRNA gene-based bacterial community analysis of rearing water from two farms with different reported disease histories. The stable production performance farm (Taketomijima) was characterized by a low-diversity bacterial community dominated by unclassified Rhodobacteraceae, whereas the variable production performance farm (Tanegashima) harbored a highly diverse and heterogeneous community. Despite the higher diversity, the variable production performance environment showed less stability across ponds, while the stable production performance farm exhibited a uniform and resilient microbiome structure. These results demonstrate that community composition and dominance of specific taxa, rather than overall diversity, are critical for disease prevalence. Our findings provide new insight into microbial factors of disease outcomes and lay the foundation for microbiome-informed management strategies to improve the sustainability and resilience of shrimp aquaculture.}, } @article {pmid41605325, year = {2026}, author = {Domari, MA and Khani, A and Sahebzadeh, N and Najimi, M and Mehrabadi, M}, title = {Gut microbes modulate Helicoverpa armigera immunity and affect its susceptibility to microbial pathogens.}, journal = {Journal of invertebrate pathology}, volume = {}, number = {}, pages = {108553}, doi = {10.1016/j.jip.2026.108553}, pmid = {41605325}, issn = {1096-0805}, abstract = {Emerging research underscores the critical roles of host-associated microbiota in modulating immunity and disease resistance in insects. However, the interplay between gut microbes and innate immune pathways remains incompletely understood in lepidopteran pests. This study investigates if manipulation of the gut microbiome affects immune responses and pathogen susceptibility in Helicoverpa armigera larvae. To do this, the gut microbiome of the larvae was removed using antibiotic treatment. Subsequently, the expression of antimicrobial peptides (AMPs) including attacin and defensin, and antioxidant genes including superoxide dismutase (SOD), dual oxidase (DUOX) and NADPH oxidase (NOX)were assessed following challenge with Bacillus thuringiensis (Bt) and Beauveria bassiana (Bb). Our results revealed that microbiome depletion reduced the expression of attacin and defensin in fat body and gut, and suppressed SOD gene expression in the gut. The bioassay tests showed that depletion of microbiota resulted in increased larval vulnerability to the pathogens compared to the control larvae. We also tested whether microbial infection affects gut microbiota and found that intrahemocoelic microbial injection induced both humoral and gut immunity, resulting in suppression of gut microbiota, highlighting a crosslink between humoral and gut immunity. Together, these results underscore a conserved requirement for microbiota-derived signals in priming specific innate immune pathways and provide insight into how microbiome manipulation may impact the success of biological control strategies. These findings suggest that targeted manipulation of the gut microbiome could be harnessed to enhance pest susceptibility to biocontrol agents, thereby offering a promising avenue for improving microbial pest control.}, } @article {pmid41605271, year = {2026}, author = {Akhtara, N and Bharali, MK}, title = {Recurrent amoxicillin exposure disrupts colonic homeostasis through oxidative stress, DNA repair dysregulation, and gut dysbiosis-driven inflammation.}, journal = {Chemico-biological interactions}, volume = {427}, number = {}, pages = {111939}, doi = {10.1016/j.cbi.2026.111939}, pmid = {41605271}, issn = {1872-7786}, abstract = {The present study investigated the impact of recurrent amoxicillin exposure on colonic health in a mouse model, applying a multi-parametric approach. Twenty animals were randomly divided into two groups, out of which one group received oral amoxicillin (100 mg/kg BW), administered every other week for twelve weeks. Histological and ultra-structural analyses (SEM and TEM) of colonic tissues revealed crypt degeneration, mucosal thinning, and inflammatory cell infiltration in the treated group. Biochemical assays demonstrated significantly elevated lipid peroxidation along with reduced antioxidant defences, indicative of oxidative stress. Immunohistochemistry confirmed oxidative DNA damage, accompanied by aberrant expression of DNA repair genes, indicating impaired genomic maintenance. Faecal microbiota profiling showed a pronounced loss of microbial load and enrichment of opportunistic pathogens, alongside a paradoxical increase in short-chain fatty acid levels. These alterations correlated with significantly upregulated inflammatory gene expression (TNF-α, IFN-γ, IL-6, IL-17 & IL-1β), indicating microbiome destabilization and heightened inflammatory signalling. Overall, recurrent amoxicillin exposure disrupted colonic homeostasis through dysbiosis, oxidative stress, genotoxicity, and inflammation, underscoring the potential risks of antibiotic therapy.}, } @article {pmid41605131, year = {2026}, author = {Kindtler, NL and Sheikh, S and He, R and Fonseca, RRD and Laursen, KH and Ekelund, F}, title = {Microbial diversity loss affects old and modern barley cultivars differently under varying nitrogen sources.}, journal = {Microbiological research}, volume = {306}, number = {}, pages = {128458}, doi = {10.1016/j.micres.2026.128458}, pmid = {41605131}, issn = {1618-0623}, abstract = {Soil microbial diversity is crucial for plant nutrition and health, yet how its loss affects plant performance remains unclear. We used a dilution-to-extinction approach to test how declining rhizo-microbiome diversity influences two barley cultivars: the modern RGT Planet and the older Babushka. Plants were grown in sterilized systems amended with mineral or organic nitrogen and inoculated with microbiome treatments (10[-][1], 10[-][3], 10[-][5], and 10[-][7] dilutions), plus a no-inoculum treatment. We used amplicon sequencing (16S, ITS, 18S) to profile rhizosphere communities, and quantified plant biomass, shoot nitrogen, and chitin mineralization. Protists and fungi were present in 10[-][1] and 10[-][3] but absent in all others. Microbiome inoculum and nitrogen source explained most variation in rhizo-microbiome composition, with cultivar having a smaller effect. Under organic nitrogen, Babushka showed a marked decline in biomass with decreasing diversity, whereas RGT was largely unaffected, indicating that the older cultivar relied more on a diverse microbiome to maintain growth. At intermediate diversity, when protists and fungi were lost, both cultivars showed improved growth and shoot nitrogen, coinciding with shifts in bacterial composition and loss of potential pathogens. Hence, reduced diversity did not always impair growth, suggesting functional compensation. Under mineral nitrogen, both cultivars were less sensitive to diversity loss. Overall, nitrogen source and cultivar identity modulated plant responses to microbial diversity loss. Diverse microbiomes promoted efficient use of organic nitrogen, particularly for the older cultivar, while the modern cultivar maintained growth at lower diversity. Our results demonstrate that the consequences of diversity loss are context-dependent and cultivar-specific.}, } @article {pmid41605120, year = {2026}, author = {Shakir Shakir, HN and Alias-Castillo, AJ and Bertini-Pérez, D and Rueda-Ruzafa, L and Roman, P and Cardona, D}, title = {Effectiveness of probiotic supplementation in managing depressive symptoms and inflammatory status in patients with depression: A systematic review and meta-analysis.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {58}, number = {}, pages = {106554}, doi = {10.1016/j.clnu.2025.106554}, pmid = {41605120}, issn = {1532-1983}, abstract = {BACKGROUND AND AIMS: Depression is a multifactorial disorder influenced by genetic, biochemical, psychological, and environmental factors, and it significantly impacts quality of life. Probiotics, especially Lactobacillus and Bifidobacterium strains, have been proposed as adjunct therapies due to their capacity to modulate gut microbiota and the gut-brain axis. This systematic review and meta-analysis aimed to evaluate the effectiveness of probiotic supplementation on depressive symptoms and inflammatory status in individuals with depression.

METHODS: Articles were identified through searches in databases including PubMed, Scopus, CINAHL, and Zenodo, using terms related to depression, microbiome, and probiotics. The search, conducted between January and February 2025, yielded 780 articles. After removing duplicates and applying eligibility criteria, 13 studies were included in the systematic review and 7 in the meta-analysis.

RESULTS: Probiotic supplementation was significantly associated with improvement in depressive symptoms (p < 0.00001). However, no significant changes were found in inflammatory biomarkers, including interleukin-6 (p = 0.45) and tumor necrosis factor-alpha (p = 0.21).

CONCLUSIONS: These results suggest that probiotics may help alleviate depressive symptoms, although their effect on inflammation remains uncertain. Further high-quality studies are necessary to clarify underlying mechanisms and determine the clinical relevance of probiotics as adjunctive therapy in depression..}, } @article {pmid41605069, year = {2026}, author = {Vijayasimha, M and Srikanth, M}, title = {From association to action: Advancing microbiome evidence toward decision-grade insights in Japanese encephalitis virus research.}, journal = {Veterinary microbiology}, volume = {314}, number = {}, pages = {110901}, doi = {10.1016/j.vetmic.2026.110901}, pmid = {41605069}, issn = {1873-2542}, } @article {pmid41604931, year = {2026}, author = {Tanunchai, B and Schröder, O and Schädler, M and Noll, M}, title = {Dynamics of the plastisphere microbiome in agricultural soils under changing climatic conditions.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141151}, doi = {10.1016/j.jhazmat.2026.141151}, pmid = {41604931}, issn = {1873-3336}, abstract = {Plastic pollution is a growing environmental concern, particularly in agricultural soils where plastics are widely used. Biodegradable plastics such as polybutylene succinate (PBS) and polybutylene adipate-co-terephthalate (PBAT) are increasingly promoted as sustainable alternatives, yet their environmental fate under changing climate and land-use conditions remains poorly understood. This study investigated the plastisphere microbiome associated with PBS, PBAT, and polyethylene (PE) as a reference, under conventional and organic farming systems and both ambient and simulated future climate scenarios. We assessed microbial colonization, plastic degradation, and bacterial-fungal interactions over one year of soil exposure. Agricultural practices significantly influenced the PBS plastisphere microbiome and PBAT bacterial richness, while climate effects were minor and limited to specific time points. No treatment significantly affected the molar mass loss of biodegradable plastics, although PBS degraded faster than PBAT. Microbial community composition shifted over time, with bacterial and fungal richness peaking at 160 or 270 days, and gene copy numbers highest at 60 or 365 days. Early colonization was dominated by a few genera, including Sphingomonas, Hymenobacter, Massilia, Vishniacozyma, Alternaria, and Mycosphaerella, many of which are known plastic colonizers and potential degraders. Co-occurrence networks revealed positive associations between dominant bacterial and fungal taxa. These findings provide new insights into the temporal dynamics and environmental drivers of plastisphere microbiomes in agricultural soils. Understanding microbial succession and interactions on biodegradable plastics is essential for assessing their degradation potential and environmental risks, particularly regarding microplastic formation and the persistence of plastic residues in terrestrial ecosystems.}, } @article {pmid41604430, year = {2026}, author = {de Jong, MJ and Zhou, J and Derikx, LAAP and Darwish Murad, S and van der Meer, AJ and de Vries, AC}, title = {Management of Inflammatory Bowel Disease Associated With Primary Sclerosing Cholangitis Pre- and Post-liver Transplantation.}, journal = {Transplantation}, volume = {}, number = {}, pages = {}, pmid = {41604430}, issn = {1534-6080}, abstract = {Primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) is considered a distinct IBD phenotype, with probably a distinct pathogenesis according to genome-wide association studies and mucosal immunology and microbiome studies. Management of IBD in patients with PSC presents with specific monitoring and therapeutic challenges. Both IBD-related and treatment-related complications have to be carefully considered in the context of hepatobiliary disease, end-stage liver disease, and liver transplant recipients. Standard IBD drug therapies are generally effective and well-tolerated in PSC-IBD, both pre- and post-liver transplantation. However, evidence of direct benefit on PSC progression is limited and largely based on surrogate endpoints such as alkaline phosphatase reduction. Vedolizumab and adalimumab have shown modest biochemical improvements in selected cohorts, although no therapy has demonstrated consistent disease-modifying effects on PSC. Based on current available data, vancomycin seems promising to improve IBD and PSC outcomes. In patients with an indication for colectomy, counseling on functional outcome in general and on disease-specific risks of recurrent intestinal inflammation, neoplasia, and PSC progression is warranted. Immunosuppressive regimens posttransplant and persistent intestinal inflammation influence graft survival and PSC recurrence. Thus, management in patients with PSC and IBD requires a tailored, risk-adapted approach, integrating control of intestinal inflammation, hepatobiliary monitoring, and cancer surveillance. This contemporary review aimede to elucidate the current understanding regarding the efficacy and safety of medical and surgical therapies used for IBD in light of the pre- and posttransplant course of patients with PSC-IBD.}, } @article {pmid41604220, year = {2026}, author = {Yao, ML and Lin, P and Hua, K and Zhang, W}, title = {The biosynthetic gene cluster landscape of the oral microbiome across health and dental caries.}, journal = {Journal of industrial microbiology & biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jimb/kuag005}, pmid = {41604220}, issn = {1476-5535}, abstract = {Specialized metabolites encoded by biosynthetic gene clusters (BGCs) in the oral microbiome remain largely unexplored in the context of oral health and disease. Previous genome-centric surveys have identified hundreds of uncharacterized BGCs in the oral cavity associated with health and disease, but these studies relied on reference genomes and did not capture strain-level variation or the native distribution of BGCs. Here, we assembled three independently sourced metagenomic datasets from healthy and dental caries samples, extracted BGCs, and quantified their metagenomic abundance and transcriptional activity. We found that aryl polyene, ribosomally synthesized and post-translationally modified peptide (RiPP), and nonribosomal peptide (NRP) encoding BGCs were the most prominent BGCs identified across the three metagenomic datasets. We grouped the identified BGCs into homology-based gene cluster families (GCFs) and found that specific GCFs were consistently associated with either health or caries across diverse taxa, suggesting that some specialized metabolites may perform conserved ecological functions. Conversely, other BGCs showed more restricted taxonomic distributions and were linked to disease-associated taxa, such as Propionibacterium acidifaciens, suggesting niche-specific biosynthetic capacities within the oral environment. Applying elastic-net regression to the metatranscriptomic dataset further identified a subset of 51 BGCs out > 3 000 that distinguished healthy from caries samples, reinforcing the discriminatory power of BGC expression patterns. Together, these results demonstrate that BGCs provide functional resolution beyond taxonomic profiling and that BGC expression, rather than genomic presence alone, differentiates oral microbial community states. This underscores the relevance of specialized metabolism to oral health and supports the use of BGC-centric analyses to interrogate microbial interactions underlying community stability and disease-associated shifts.}, } @article {pmid41604186, year = {2026}, author = {Molasy, B and Wrzosek, M}, title = {The Wound Microbiome in Chronic Wounds: A Biomarker and Therapeutic Target.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxag025}, pmid = {41604186}, issn = {1365-2672}, abstract = {Chronic wounds, including diabetic foot ulcers, venous leg ulcers, and pressure ulcers, remain a major global healthcare challenge, associated with substantial morbidity, risk of limb loss, and high healthcare costs. Increasing evidence indicates that the wound microbiome modulates inflammation, tissue repair, and responses to therapy, thereby influencing clinical outcomes. This review summarizes current knowledge on the composition and function of chronic wound microbial communities and discusses their clinical relevance as prognostic biomarkers and therapeutic targets. Microbiome structure is shaped by wound etiology, chronicity, anatomical site, and host comorbidities. Dysbiosis and biofilm formation contribute to persistent inflammation, antimicrobial tolerance, and delayed healing. Advances in sequencing and multi-omics technologies have improved microbial characterization and enabled the identification of candidate microbial signatures associated with healing trajectories. Emerging microbiome-modulating strategies such as probiotics, bacteriophages, topical oxygen approaches and nanotechnology-based interventions show potential to shift wound ecosystems toward a pro-healing state; however, robust clinical validation remains limited. Further clinical studies are needed to validate microbiome-guided diagnostics and interventions and to establish standardized protocols for their application in clinical practice.}, } @article {pmid41604101, year = {2026}, author = {Nihel, AB and Rania, AD and Hamadou, OH and Ghiles, G and Imen, B and Fatma, A and Ali, A and Basma, M and Hayet, S and Radhouan, G and Leila, AK and Mokdad-Gargouri, R}, title = {Nanopore sequencing of the Tunisian gut microbiome: effect of the DNA extraction methods.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {57}, number = {1}, pages = {47}, pmid = {41604101}, issn = {1678-4405}, support = {952583//H2020 European Research Council/ ; }, } @article {pmid41604057, year = {2026}, author = {Silveira, KA and Ramiro-Garcia, J and Lawless, C and Espinosa-Vazquez, JM and Fermoso, FG and Collins, G and O'Flaherty, V}, title = {Mutual dosing of tungsten, molybdenum and selenium impact anaerobic digestion microbiome.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {}, number = {}, pages = {}, pmid = {41604057}, issn = {1572-8773}, support = {861088//H2020 Marie Skłodowska-Curie Actions/ ; }, abstract = {Metals are critical in anaerobic digestion, but their co-occurrence effects on microbiome structure and function are underexplored. This study hypothesized that exposure of methanogenic granules to a trace element (TE) mixture alongside molybdenum (Mo), tungsten (W) or selenium (Se)-would alter (i) extracellular polymeric substances (EPS) protein and carbohydrate content, (ii) microbial composition and function (iii) methanogenic pathways.To test this, anaerobic batch reactors (n = 35) were set up in a fed batch mode, with sacrificial reactors (n = 14) used to collect biomass for analyses, including DNA: RNA co-extraction, amplicon sequencing, and determination of the concentrations of total and soluble metals, Scanning Electron Microscopy- Energy Dispersive X-ray (SEM-EDX) and EPS extraction over a 24-day period.The results reveal that, Mo and W increased the concentration of soluble Fe in abiotic controls, enhancing Fe and S retention. The presence of W, Mo, W + Se, and Se had a positive effect on methane production, with W + Se and W enhancing acetoclastic methanogenesis. Additionally, Se increased EPS protein and carbohydrate contents in the biomass. Shifts in the microbiome composition were mainly driven by Mo and Se, with typically dominant Anaerolineacaeae, Capriciproducens, Macelibacteroides and Clostridium sensu stricto 5 taxa. Functional potential suggested an enrichment of nucleotide metabolism and, importantly, Vitamin (B12, B6 and B9) metabolic potential.These finding inform Anaerobic digestion (AD) stakeholders about the impacts of Fe, W, Mo, and Se co-dosing on process performance and microbiome structure and function, offering insights to optimize biogas production through tailored metal supplementation combinations, given demonstrations at lab and pilot scales.}, } @article {pmid41603727, year = {2026}, author = {Hoedt, EC and Burns, GL and Kang, S and Bruce, J and Morrison, M and Keely, S and Talley, NJ}, title = {Altered Duodenal Mucosa-Associated Microbiota and Immune Profiles in Functional Dyspepsia: A Study of Host-Microbiome Homeostasis.}, journal = {Neurogastroenterology and motility}, volume = {38}, number = {1}, pages = {e70238}, doi = {10.1111/nmo.70238}, pmid = {41603727}, issn = {1365-2982}, support = {//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Dyspepsia/immunology/microbiology/pathology ; *Gastrointestinal Microbiome/immunology/physiology ; Female ; Male ; Homeostasis/immunology ; Middle Aged ; Adult ; *Intestinal Mucosa/microbiology/immunology/pathology ; *Duodenum/microbiology/immunology/pathology ; Leukocytes, Mononuclear/immunology ; }, abstract = {BACKGROUND: Recent work suggests an altered duodenal mucosa-associated microbiota (d-MAM) in patients with functional dyspepsia (FD) when compared to controls. This may reflect alterations in host-microbiome homeostasis. Given the specific mucosal immune signatures identified in FD, we hypothesize that these signatures are associated with specific microbial changes. We aim to profile the d-MAM to identify microbes associated with known changes in FD mucosal and peripheral immunity.

METHODS: Upper gastrointestinal biopsies were collected from 11 outpatient controls and 17 FD patients. Specific biopsies were collected for 16S rRNA sequencing, histology, and mucosal lamina propria mononuclear cell (LPMC) isolation. Where available, peripheral blood mononuclear cells (PBMC) were isolated. PBMC and LPMC populations were analyzed for T-cell populations by flow cytometry.

KEY RESULTS: Comparing the histological and immune measures between FD and controls revealed significant differences with decreased villi goblet cells and increased LPMC CD4 Central Memory, LPMC CD8, and PBMC CD4+ Central Memory Th17 in FD patients. Specific microbiome associations found that in controls, villi goblet cells positively correlated with Massilia and negatively with Exiguobacterium. Additionally, controls had a negative correlation between LPMC CD4 Central Memory and Veillonella. Notably, FD patients demonstrated a significant negative correlation between LPMC CD8 and Sulfophobococcus, and a positive correlation between PBMC CD4+ Central Memory Th17 and both Gemella and Fusobacterium.

CONCLUSIONS AND INFERENCES: Our findings contribute to a growing body of evidence, indicating FD patients exhibit distinct alterations in d-MAM and immune profiles compared to controls. Furthermore, the immune-microbiome associations within control populations were absent in FD patients, suggesting a loss of host-microbiome homeostasis that may contribute to FD pathophysiology.}, } @article {pmid41603631, year = {2026}, author = {Díaz, S and Eisfeld, AJ and Palma-Cuero, M and Dinguirard, N and Owens, LA and Ciuoderis, KA and Pérez-Restrepo, LS and Chan, JD and Goldberg, TL and Hite, JL and Hernandez-Ortiz, JP and Kawaoka, Y and Zamanian, M and Osorio, JE}, title = {Gut microbiota and parasite dynamics in an Amazonian community undergoing urbanization in Colombia.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0078825}, doi = {10.1128/msphere.00788-25}, pmid = {41603631}, issn = {2379-5042}, abstract = {Studies on human gut microbiota have recently highlighted a significant decline in bacterial diversity associated with urbanization, driven by shifts toward processed diets, increased antibiotic usage, and improved sanitation practices. This phenomenon has been largely overlooked in the Colombian Amazon, despite rapid urbanization in the region. In this study, we investigate the composition of gut bacterial microbiota and intestinal protozoa and soil-transmitted helminths (STHs) in both urban and rural areas of Leticia, located in the southern Colombian Amazon. Despite their geographic proximity, the urban population is predominantly non-indigenous, while indigenous communities mostly inhabit the rural area, resulting in notable lifestyle differences between the two settings. Our analyses reveal a reduction in bacterial families linked to non-processed diets, such as Lachnospiraceae, Spirochaetaceae, and Succinivibrionaceae, in the urban environment compared to their rural counterparts. Prevotellaceae, typically associated with non-processed food consumption, shows a significantly higher abundance in urban Leticia. STH infections were primarily detected in rural Leticia, while intestinal protozoa were ubiquitous in both rural and urban areas. Both types of parasites were associated with higher gut bacterial richness and diversity. Additionally, microbial metabolic prediction analysis indicated differences in pathways related to unsaturated fatty acid production and aerobic respiration between rural and urban bacterial microbiomes. This suggests a tendency toward changes in the urban microbiota that may lead to increased susceptibility to non-communicable chronic diseases. These findings provide new insights into the impact of urbanization on gut microbiota dynamics in the Amazonian context and underscore the need for further research into any associated health outcomes.IMPORTANCEChanges in the diversity and composition of gut microbiota in urban populations have been linked to the rise of non-communicable chronic diseases, such as autoimmune conditions, diabetes, and cancer. As developing countries undergo a demographic shift toward increased urbanization, accompanied by changes in diet, housing, and medication use, there is a concerning loss of microbial diversity. Therefore, it is essential to investigate microbiota changes in overlooked populations, such as indigenous communities in the Colombian Amazon basin. A better understanding of local and generalizable changes in gut microbial composition through urbanization may facilitate the development of targeted programs aimed at promoting lifestyle and diet changes to prevent diseases that healthcare systems may be ill-equipped to effectively address.}, } @article {pmid41603538, year = {2026}, author = {Retherford, SA and Woodruff, KL and Harstine, BR and Dittoe, DK and Block, J}, title = {The Bull Reproductive Microbiome: A Comparative Analysis of Microbial Communities within Semen and Organs of the Bull Reproductive System†.}, journal = {Biology of reproduction}, volume = {}, number = {}, pages = {}, doi = {10.1093/biolre/ioag025}, pmid = {41603538}, issn = {1529-7268}, abstract = {Semen from mature, healthy bulls contains commensal microbes. Potential internal sources of seminal microbes have not been extensively evaluated. Objectives were to 1) assess whether the testes of the bull contain commensal microbes and to compare the composition of the putative testicular microbiome to that of semen and rumen fluid and 2) determine whether other organs of the bull reproductive system contain microbial populations. Here, we demonstrate that the testes of the bull contain a low biomass, yet diverse, microbiome. Interestingly, the microbial composition of rumen fluid, semen and testicular tissue were each dissimilar from one another, indicating that each source contains a unique microbiota. Only four core amplicon sequence variants, Acinetobacter, Enterobacteriaceae (E. coli), Jeotgalicoccus, and Kiritimatiellae WCHB1-41, were shared between semen and the testes. Along with the testes, microbial populations were also present within the penile and pelvic urethra, seminal vesicles and epididymis of mature bulls. Of these anatomic niches, the microbial populations within the penile and pelvic urethra were the most diverse and shared the greatest number of core taxa (n = 72). The microbiota of the seminal vesicles, epididymis and the testes were significantly dissimilar from each other. Only one core taxa, Mycoplasma, was shared between the testes and epididymis. Collectively, our results demonstrate that semen and organs of the bull reproductive tract contain unique microbial populations. Further research is necessary to determine whether the microbial composition of organs of the bull reproductive system, such as the testes and epididymis, influence sperm viability and bull fertility.}, } @article {pmid41603371, year = {2026}, author = {McAbee, GN and Morse, AM}, title = {Symptomatic Vitamin and Nutrient Deficiencies of Autism Spectrum Disorder and the Potential for Treatment.}, journal = {Journal of child neurology}, volume = {}, number = {}, pages = {8830738251413826}, doi = {10.1177/08830738251413826}, pmid = {41603371}, issn = {1708-8283}, abstract = {Autism spectrum disorder (ASD) is a heterogeneous neurobehavioral disorder. Children with ASD often have restrictive diets that can be due to food aversion, sensory sensitivities, ritualistic behavior, or comorbid gastrointestinal issues. Diet and nutritional status play a critical role in the health of neurodevelopment, and the microbiome, and can affect cognition, motor and sensory status, behavior, and sleep. Children with ASD are 5 times more likely to develop eating problems and secondary vitamin and nutritional deficiencies. Such dietary restriction has been causative of vitamin and nutritional deficiencies that can lead to permanent sequelae if not adequately identified and treated. Symptoms of these deficiencies can be subtle and misleading and, thus, underrecognized. This review discusses various symptomatic vitamin and nutrient deficiencies associated with dietary restrictions that can occur in children and adolescents with ASD of which clinicians need to be aware. With treatment, symptoms can be reversible. Without timely treatment, sequelae can be permanent.}, } @article {pmid41603333, year = {2026}, author = {Tiwari, P and Gupta, A and Kaushik, M and Dwivedi, R and Tripathi, M and Dada, R}, title = {Association of yoga with cognitive and gut microbiome changes in Alzheimer's disease: An exploratory case-control study.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877261415612}, doi = {10.1177/13872877261415612}, pmid = {41603333}, issn = {1875-8908}, abstract = {BackgroundAlzheimer's disease (AD) is marked by cognitive decline, depressive symptoms, and gut microbial dysbiosis. Yoga may support cognitive and emotional health while modulating gut microbiota, but integrative clinical evidence is limited.ObjectiveTo evaluate the effects of a 12-week yoga intervention on cognition, depressive symptoms, and gut microbial diversity, composition, and function in Indian patients with mild AD.MethodsIn this hospital-based case-control study, 16 AD patients and 17 cognitively healthy controls (HCs) were recruited at AIIMS, New Delhi. AD diagnosis followed NIA-AA criteria, supported by Montreal Cognitive Assessment (MoCA) and Patient Health Questionnaire-9 (PHQ-9) assessments. AD participants underwent 60-min supervised yoga sessions daily for 12 weeks. Cognitive performance, depressive symptoms, and stool microbiota were assessed pre- and post-intervention. Metagenomic sequencing enabled taxonomic and functional profiling, with alpha diversity, beta diversity (Bray-Curtis distance), and differential abundance analyses performed using standard bioinformatics tools.ResultsYoga was associated with improved cognition (MoCA: 22.33 ± 2.34 → 25.44 ± 2.01; p = 0.001) and reduced depressive symptoms (PHQ-9: 5.78 ± 3.11 → 2.22 ± 1.71; p = 0.007). Alpha diversity remained stable, while beta diversity shifted post-yoga AD samples toward the HC cluster. Beneficial taxa (Faecalibacterium prausnitzii, Roseburia intestinalis, Bifidobacterium, Akkermansia) increased, whereas pro-inflammatory taxa (Collinsella aerofaciens, Klebsiella spp.) decreased. Functional analysis showed partial recovery of metabolic and short-chain fatty acid pathways.ConclusionsA 12-week yoga intervention was associated with cognitive and mood improvements and partial normalization of gut microbial function in mild AD. Larger randomized trials with lifestyle monitoring and multi-omics integration are warranted to confirm causal mechanisms.}, } @article {pmid41602763, year = {2025}, author = {Xu, J and Li, J and Kong, X and Zhang, C and Qi, B and Zhu, X and Zhu, Y and Xu, Y}, title = {Dysbiosis and metabolic pathway shifts in the gut microbiome of children with sepsis: a comparative analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1715990}, pmid = {41602763}, issn = {1664-302X}, abstract = {BACKGROUND: The newly published Phoenix Sepsis Score in 2024 for assessing sepsis in children mainly focuses on respiratory, cardiological, coagulation and neurological indicators, whereas the gut microbiome also plays key roles in the occurrence and progression of sepsis. Additionally, emerging evidence suggests that specific biomarkers in gut microbiome are associated with disease progression. This study aimed to explore the differences in gut microbiome diversity, composition and function between septic and healthy children, and to establish correlations with clinical indicators and outcomes, providing new possibilities for the diagnosis and treatment of sepsis.

RESULTS: Analysis of gut microbiome was performed in 20 sepsis children and 9 healthy controls aged between 3 and 18 years old. The anal swab samples were analyzed by metagenomic next-generation sequencing. Significant differences were observed in α and β diversity of gut microbiome between sepsis group and healthy controls groups. Especially, Shannon diversity was significantly correlated with white blood cell count, serum lactate, length of pediatric intensive care unit stay and length of hospital stay (all R > 0, p < 0.05). Firmicutes and Bacteroidetes were both dominant in most of children in SG and HC groups, while three in SG showed extremely low combined abundances of Firmicutes and Bacteroidetes (<10%), which might be associated with chemistry therapy and death outcome. Bacteria associated with nosocomial infections, including genus taxa Acinetobacter, Prevotella, Escherichia, Klebsiella, Bacteroides, and Corynebacterium, can be dominant (relative abundance>70%) in sepsis group, which were absent in healthy control group. Enterococcus abundance not only predicted sepsis risk (AUC = 0.85) but also was correlated with 28-day mortality (R > 0, p = 0.004). Gene function prediction based on Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significant differences profile in SG and sepsis-deaths groups. The enriched gut microbiome genes were related to cellular proliferation, energy metabolism, signal transduction, the oxidative stress response and arginine metabolism.

CONCLUSION: Significant differences in diversity, taxa composition and gene function in the gut microbiome existed between septic and healthy children. The associations between gut microbiome dysbiosis and clinical indicators were identified. Enterococcus could be a biomarker to predict sepsis risk.}, } @article {pmid41602754, year = {2025}, author = {Deng, L and Chen, X and Pan, S and Huang, W and Yin, Y and Wei, X and Zhang, H and Zhu, C}, title = {The developmental changes of fecal microbial composition and diversity in emu (Dromaius novaehallandiae) at early growth stages.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1744168}, pmid = {41602754}, issn = {1664-302X}, abstract = {The early postnatal period plays a crucial role in the establishment and maturation of the gut microbiome in avian hosts, significantly influencing their metabolic processes and overall health. This study was carried out to characterize the ontogenetic development of fecal microbiota in emus (Dromaius novaehollandiae) during critical early growth stages from days 7 to 28 post-hatch using 16S rRNA gene sequencing. The results indicated that rank abundance and rarefaction curves confirmed adequate sequencing depth for capturing microbial diversity across all age groups. The dominant phyla of fecal microbiota in emus included Firmicutes, Proteobacteria, and Bacteroidetes, with successional shifts observed at order, family, and genus levels. As emus advanced in age, fecal microbiota underwent significant changes in microbial community, diversity, and function. The α-diversity indices (Observed species, Shannon, PD whole tree, Chao1, and ACE) in the feces of emus peaked significantly at d 21 (p < 0.05). The β-diversity analysis revealed significant structural differences in microbial communities between different ages, particularly between d14 and d7, d21 vs. d7, and d14 vs. d28 (p < 0.05). Linear discriminant analysis Effect Size (LEfSe) identified 26 discriminative biomarkers with stage-specific enrichments, including Turicibacter (d7/d28), Erysipelotrichaceae (d7/d14), Bacteroidetes (d21), and Corynebacteriaceae as well as Actinobacteria (d28). T-test validation confirmed significant temporal variations in phylum (Firmicutes, Actinobacteria, and Bacteroidetes) and genus-level abundances (e.g., Bacteroides and Lactobacillus) in the feces of emus (p < 0.05). PICRUSt functional prediction indicated age-dependent metabolic pathway enrichment, including amino and nucleotide sugar metabolism (d7), oxidative phosphorylation (d14), ABC transporters and cysteine metabolism (d21), and genetic information processing pathways (d28). These results demonstrated dynamic, stage-specific restructuring of the fecal microbiota and its metabolic potential during early development in emus. This research presented the initial longitudinal assessment of fecal microbiota development in emus throughout their crucial early developmental stage, revealing age-dependent alterations in microbial composition and metabolic activity that could guide enhanced nutritional and health approaches for ratites.}, } @article {pmid41602751, year = {2025}, author = {Wu, Y and Zhou, M and Wan, Y and Wei, K and Ma, S and Cheng, L and Lin, T and He, L and He, Y and Zhou, F}, title = {The microbial conductor of cancer hallmarks: intratumoral microbiome as a multidimensional oncogenic modulator.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1695187}, pmid = {41602751}, issn = {1664-302X}, abstract = {The intratumoral microbiome, comprising diverse bacteria, fungi, and viruses residing within tumor tissues, is increasingly recognized as a multidimensional oncogenic modulator, acting akin to a "microbial conductor" orchestrating key cancer hallmarks. Its compositon exhibits substantial heterogeneity across individuals and is closely associated with the host immunity, the tumor microenvironment (TME), and therapeutic efficacy. Specific microbial species can "conduct" pro-tumorigenic processes by producing carcinogenic metabolites, dysregulating inflammatory signaling, or facilitating immune evasion. Conversely, other microorganisms may exert anti-tumorigenic effects by stimulating anti-tumor immunity or directly inhibiting cancer cell proliferation. Furthermore, the intratumoral microbiome can influence therapeutic outcomes by modulating the metabolism of chemotherapeutic agents or altering the efficacy of immunotherapies. Therefore, a deeper understanding of the intratumoral microbiome and its complex interplay with tumors holds immense potential to unravel fundamental mechanisms of cancer development and progression, while simultaneously revealing novel avenues for precision oncology strategies. This review outlines the biological roles of the microbiota in modulating the hallmarks of cancer hallmarks, summarizes current knowledge on its multidimensional interactions driving tumor progression, and discusses the translational potential of targeting or leveraging the intratumoral microbiome based on recent advancements. Future research integrating multi-omics profiling, spatial technologies, and functional validation will be essential for resolving methodological limitations and accelerating the clinical translation of microbiome-based interventions.}, } @article {pmid41602744, year = {2025}, author = {Karpe, AV and Hegde, P and Bletotu, C and Qiu, Z}, title = {Editorial: Antimicrobial resistance: causes, mechanisms and mitigation strategies for gut dysbiosis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1765239}, pmid = {41602744}, issn = {1664-302X}, } @article {pmid41602620, year = {2025}, author = {Yang, SB and Moon, JH}, title = {Microbial therapeutics for canine periodontal disease: current status and future perspectives.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1748968}, pmid = {41602620}, issn = {2297-1769}, abstract = {Periodontal disease in dogs arises from ecological disruption of the oral microbiome. Sequencing-based studies and quantitative molecular analyses reveal characteristic dysbiotic transitions in affected dogs, with coordinated increases in Porphyromonas gulae, Prevotella, and Treponema, along with Treponema denticola and Tannerella forsythia, together with a loss of commensal-dominated genera such as Moraxella, Capnocytophaga, and members of the Neisseriaceae family. Rather than being driven by a single dominant pathogen, accumulating evidence indicates that canine periodontitis is driven by polymicrobial synergy within dysbiotic biofilms. This ecological perspective has stimulated growing interest in microbial therapeutics aimed at modulating community structure and function instead of relying solely on broad-spectrum antibiotics. Probiotics and postbiotics show potential in reducing halitosis and modulating epithelial innate immune responses. Bacteriophage-based approaches and predatory bacteria exhibit strain-specific antimicrobial activity in preclinical human or in vitro models, although their relevance to canine oral disease remains unvalidated. Synthetic biology and CRISPR-based antimicrobial systems provide conceptual frameworks for genotype-targeted modulation of virulence. Remaining challenges include transient microbial persistence, limited veterinary clinical evidence, biosafety concerns, and the absence of standardized regulatory pathways. Collectively, emerging microbial therapeutics highlight the potential but also the current limitations of ecology-guided, non-antibiotic strategies for canine periodontal therapy.}, } @article {pmid41602541, year = {2025}, author = {Adkar-Purushothama, CR and Chettimada, A and Murali, TS and Muthusamy, A and Bouarab, K and Perreault, JP}, title = {Non-chemical control of fungal pathogens in crops: a one-health perspective on strategies, mechanisms, and future directions.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1746521}, pmid = {41602541}, issn = {1664-462X}, abstract = {Fungal pathogens threaten global crop production, food security, and environmental and human health. Though the reliance on chemical fungicides has provided effective control, but raises concerns over environmental contamination, toxic residues, and the rapid emergence of fungicide-resistant strains. These challenges, along with regulatory pressures, highlight the need for safer, more sustainable disease-management strategies. This review incorporates advances in non-chemical approaches for controlling fungal plant diseases, including cultural practices, biological control agents, natural plant metabolites, RNA-based technologies, nanotechnology, and microbiome engineering. We evaluate each strategy's mechanisms, strengths, limitations, and remaining knowledge gaps. An integrated pest management framework is proposed to combine complementary methods, reduce dependence on chemical inputs, enhance crop resilience, and support human and ecosystem health.}, } @article {pmid41602533, year = {2025}, author = {Vieira, CK and Rozmoš, M and Kotianová, M and Hršelová, H and Bukovská, P and Jansa, J}, title = {Low spatial mobility of associated microbes along the hyphae limits organic nitrogen utilization in the arbuscular mycorrhizal hyphosphere.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1706684}, pmid = {41602533}, issn = {1664-462X}, abstract = {BACGROUND: Arbuscular mycorrhizal (AM) fungi enhance plant nutrient acquisition from soil; however, their ability to exploit organic nutrient forms in the absence of associated microbes capable of mineralization remains unclear.

METHODS: To test if the AM fungi carry their beneficial bacterial partners into nutrient-rich zones, we conducted three controlled experiments manipulating the microbial inputs, diversity and composition in plant-AM fungus-soil systems, ranging from open pots to semi-sterile mesocosms. We manipulated soil microbial diversity by imposing a microbial diversity gradient (complex communities fractionated by size, resulting in fractions passing through 1 µm to 1000 µm sieves) and cultivated Andropogon gerardii in previously sterilized substrate together with a bacterial-free Rhizophagus irregularis. In each experiment, [15]N-labeled chitin or mineral nitrogen (N) compartments were installed in the root-free zone of each mesocosm.

RESULTS: With decreasing microbial inputs into the root-free zone, the N uptake from chitin to plants, facilitated by the AM fungal hyphae, decreased. Upon complete absence of microbes in the root-free zone, AM hyphal foraging preferences assessed by quantitative PCR indicated that exploration of the mineral N compartments was more effective than that of the chitin compartments. The AM fungal hyphae were ineffective in priming mineralization of organic N even if provided with complex soil microbiomes at a distance from the compartment.

CONCLUSIONS: In summary, chitin-enriched compartments become attractive for the AM fungi only when previously mineralized by competent microbes. Such microbes, however, were not effectively transported to spatially restricted organic resources in soil via AM hyphal highways in our experiments.}, } @article {pmid41602516, year = {2026}, author = {Badero, OJ and Meribole, ES and Omokore, O and Quadri, IO and Kingdom, P and Ifeanyichukwu, OC and Ogunnoiki, SO and Samuel-Ogunnoiki, PM and Adeyoola, O and Osibowale, B and Chima-Ogbuiyi, N and Buari, MO and Umeh, J and Adeyemi, A}, title = {Gut Microbiota and Colorectal Cancer: Is Microbial Dysbiosis in Carcinogenesis an Emerging Risk Factor?.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102283}, pmid = {41602516}, issn = {2168-8184}, abstract = {The gut microbiome has emerged as a critical factor in colorectal cancer (CRC) development, offering significant potential for early diagnosis and novel approaches. Current screening methods like colonoscopy and faecal immunochemical tests (FIT), while effective, face limitations in accessibility and patient compliance. Recent research has identified distinct microbial signatures associated with CRC, including elevated levels of Fusobacterium nucleatum and specific metabolic byproducts, which could serve as non-invasive diagnostic biomarkers. The integration of microbiome analysis with existing screening techniques shows promise for improving early detection rates, particularly in underserved populations. Furthermore, advances in multi-omics technologies are revealing novel mechanistic insights into how gut dysbiosis contributes to CRC progression, opening new avenues for targeted therapies and personalised prevention strategies. However, significant challenges related to standardisation and clinical implementation must be addressed to realise the full potential of these microbiome-based approaches in routine CRC care.}, } @article {pmid41602199, year = {2026}, author = {Luo, L and Yang, B and Zhao, J and Li, X and Qiao, W and Zhang, M and Tian, L and Chen, L}, title = {Regulation of infant gut microbiota and metabolic pathways by human milk oligosaccharides: a multi-omics investigation.}, journal = {RSC advances}, volume = {16}, number = {6}, pages = {5641-5651}, pmid = {41602199}, issn = {2046-2069}, abstract = {The third-most solid component in breast milk is human milk oligosaccharides (HMOs)-crucial for the growth and development of infants. HMOs are divided into three main categories: fucosylated, nonfucosylated, and sialylated HMOs. However, comparative studies evaluating the variations of the impact of in vitro fermentation of these typical or dominant HMOs on the metabolic functions of an infant's gut microbiome remain limited. Therefore, we systematically analyzed the role of three typical HMOs-2'-fucosyl lactose, lactose-N-tetrose, and 3'-sialyllactose-in the structural reshaping of the infant intestinal flora; we also explored their impact on short-chain fatty acid (SCFA) production and metabolism, as well as their overall metabolic spectrum. We found that HMOs aided the growth of beneficial microorganisms, such as Bifidobacterium, Lactobacillus, and Enterococcus, while also reducing the number of harmful bacteria, including Escherichia-Shigella. Further, HMOs had a substantial impact on amino acid, purine, and lipid metabolic pathways and significantly increased SCFA levels. Correlation analyses revealed significant associations between Bifidobacterium and multiple lipid metabolites. Positive correlations between Lactobacillus and amino acid derivatives, as well as close links between Bacteroides and acetate production, were detected. Overall, these findings indicate that the gut flora-metabolite interplay is central to HMO function, and different HMOs variably regulate the gut microbiota composition and metabolic pathways. This study provides a theoretical basis for optimizing HMOs' fortification strategies in infant formulas.}, } @article {pmid41602156, year = {2025}, author = {Andrusiów, S and Dratwa-Kuzmin, M and Łacina, P and Bochen, P and Gładysz, K and Szponar, B and Koszewicz, M and Bogunia-Kubik, K}, title = {Genetic and metabolic inflammation signatures in chronic inflammatory demyelinating polyneuropathy: the role of IL18 polymorphisms and short-chain fatty acids.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1738817}, pmid = {41602156}, issn = {1662-5099}, abstract = {INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) remains diagnostically challenging, with limited biological markers to aid phenotyping and differential diagnosis, particularly at the CIDP-diabetes mellitus (DM) interface.

METHODS: We investigated inflammatory genetic and metabolic readouts in CIDP by integrating interleukin 18 (IL-18) promoter variation with cytokines and short-chain fatty acids (SCFAs). 32 untreated CIDP patients and 15 controls underwent clinical scoring, nerve-conduction studies (NCS), IL-18 genotyping (rs187238, rs1946518, rs1946519), serum cytokine profiling (IL-2, tumor necrosis factor α (TNF-α), IL-18), and SCFA quantification in stool, serum, and cerebrospinal fluid (CSF).

RESULTS: No group-level differences emerged for IL-2, TNF-α, or IL-18 in serum or CSF, and CIDP subgroups (DM+ vs DM-; classical vs atypical) did not differ in NCS severity or electromyography (EMG) denervation. In contrast, IL18 promoter variation showed various associations: rs1946518 G allele correlated with peroneal nerve shorter compound motor action potential (CMAP) distal latency and lower ulnar nerve sensory nerve action potential (SNAP) amplitude. Additionally, carriers of the rs187238 C allele showed significantly higher CSF protein concentrations, whereas the rs1946518 G allele was associated with a trend toward lower CSF protein levels. Moreover, the rs187238 C and rs1946518 T alleles were associated with lower CSF butyrate levels. A haplotype analysis indicated that GGG (rs187238, rs1946518, rs1946519) aligned with shorter peroneal nerve CMAP distal latency, lower disability (INCAT), and a lower CSF protein, whereas CTT associated with higher CSF protein and lower CSF butyrate concentrations. We confirmed the presence of acetate, propionate, and butyrate in human CSF and demonstrated serum-CSF equivalence for these SCFAs, while stool concentrations were higher, as expected.

DISCUSSION: Collectively, IL18 polymorphisms and SCFAs readouts emerge as biologically grounded candidates for patient stratification in CIDP; these findings warrant validation in larger, multicenter cohorts integrating electrophysiology with CSF/serum biomarkers and microbiome profiling.}, } @article {pmid41602129, year = {2025}, author = {Gautam, AK and Kumar, V and Sonkar, AB and Singh, A and Yadav, D and Rajan, N and Kumar, P and Singh, S and Saha, S and Mahalingam Rajamanickam, V}, title = {Metabolites involvement in the growth and spread of liver cancer.}, journal = {Liver research (Beijing, China)}, volume = {9}, number = {4}, pages = {286-297}, pmid = {41602129}, issn = {2542-5684}, abstract = {Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a leading cause of cancer-related mortality worldwide, primarily attributed to changing lifestyles and dietary habits. HCC arises from liver cirrhosis, hepatic fibrosis, or hepatitis B virus infection, and is caused by disruptions in protein and lipid metabolism. These metabolic alterations, recognized as a hallmark of cancer, are pivotal in the progression of chronic liver disease to HCC. Due to its asymptomatic nature in early stages, HCC is often diagnosed at advanced stages when treatment options are limited. Despite being a potentially curative option, liver transplantation remains hindered by high costs and donor scarcity, further compounded by suboptimal long-term success rates. This review examines the critical metabolites that play a part in developing HCC, focusing on their roles as possible biomarkers for disease progression and therapeutic targets. Additionally, the influence of the gut microbiome on HCC development is discussed, highlighting its interplay with metabolic pathways. Understanding the roles of metabolites and the gut microbiome in HCC progression underscores the importance of their potential use in early detection and the development of targeted therapies, offering new avenues for improving patient outcomes.}, } @article {pmid41602108, year = {2025}, author = {Mehta, SD and Zulaika, G and Osire, E and Agingu, W and Paul, S and Akinyi, C and Green, SJ and van Eijk, AM and Bhaumik, RK and Otieno, FO and Phillips-Howard, PA}, title = {Sub-optimal menstrual materials and vaginal microbiome disruption in women relying on sex for livelihood.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1662237}, pmid = {41602108}, issn = {2235-2988}, mesh = {Humans ; Female ; *Vagina/microbiology ; Cross-Sectional Studies ; *Microbiota ; Adult ; Young Adult ; Sexual Behavior ; *Menstruation ; Vaginosis, Bacterial/microbiology/epidemiology ; Sexually Transmitted Diseases/microbiology/epidemiology ; *Menstrual Hygiene Products/adverse effects ; RNA, Ribosomal, 16S/genetics ; Adolescent ; }, abstract = {BACKGROUND: Sub-optimal menstrual materials (MM), such as using cloths, cotton balls, or tissues, can adversely affect the vaginal microbiome (VMB). Women who rely on sex for economic livelihood often use sub-optimal materials to conceal menstruation and avoid loss of income. We hypothesized that among women who rely on sex for economic livelihood, those using sub-optimal MM would be more likely to have non-optimal VMB than those with adequate MM.

METHODS: This cross-sectional analysis used baseline data from women participating in a trial assessing the impact of reusable menstrual discs on the VMB, Bacterial vaginosis (BV), and sexually transmitted infections (STIs). Data on sociodemographics, menstrual materials, and sexual practices were collected via interviewer-administered survey. Clinician-collected vaginal samples were tested for BV, STI, and VMB. VMB was assessed via 16S rRNA gene amplicon sequencing. A suite of statistical approaches identified factors associated with sub-optimal MM (use of cotton balls, tissue, or cloth) and VMB composition.

RESULTS: 407 women were enrolled February through October 2023, with median age 27 years, 24.7% were HIV-positive, 42.2% had BV, and 21.9% had STI (composite of chlamydia, gonorrhea, trichomoniasis). Vaginal community state type (CST) was primarily diverse (CST-IV; 63.5%), or Lactobacillus iners dominated (CST-III; 28.1%), while CST-I (L. crispatus dominated) was uncommon (7.9%). Sub-optimal MM was reported by 42.0% of participants and in multivariable modeling, was more common among women with indicators of economic strain. In multivariable analyses, alpha diversity was higher with sub-optimal MM and indicators of economic strain. Sub-optimal MM was associated with CST-IV in crude analyses but was attenuated and non-significant when adjusted for age, educational attainment, amount paid at last sexual encounter, number of sex partners, and HSV-2. Non-targeted machine learning algorithms identified non-optimal VMB taxa with greater relative abundance among women with sub-optimal MM.

DISCUSSION: Sub-optimal menstrual materials were used commonly and associated with non-optimal VMB composition. Reusable menstrual discs that may be worn during sex may address the economic factors driving sub-optimal MM that are associated with non-optimal VMB.}, } @article {pmid41602101, year = {2025}, author = {Deng, Q and Liu, Y and Zhang, J and Zhang, H and Zhang, Y and Wang, M and Jia, M and Ding, D and Fang, Y and Wang, Y and Gu, H and Wang, H}, title = {Clinical validation and utility of targeted nanopore sequencing for rapid pathogen diagnosis and precision therapy in lung cancer patients with pulmonary infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1730098}, pmid = {41602101}, issn = {2235-2988}, mesh = {Humans ; *Lung Neoplasms/complications/microbiology ; *Nanopore Sequencing/methods ; Male ; Female ; Middle Aged ; Aged ; Sputum/microbiology ; *Precision Medicine/methods ; High-Throughput Nucleotide Sequencing ; *Respiratory Tract Infections/diagnosis/microbiology/drug therapy ; Metagenomics/methods ; Microbiota ; Bacteria/genetics/isolation & purification/classification ; Sensitivity and Specificity ; Adult ; Aged, 80 and over ; }, abstract = {BACKGROUND: Pulmonary infections are common in patients with lung cancer (LC), complicating diagnosis and treatment. This study explored the diagnostic performance and clinical utility of targeted nanopore sequencing (TNPseq) for detecting pathogens in LC-related pulmonary infections.

METHODS: A total of 143 patients with LC or benign pulmonary diseases complicated by pulmonary infections were included and stratified into diagnostic and therapeutic cohorts. Sputum samples underwent conventional culture, metagenomic next-generation sequencing (mNGS), and TNPseq analyses. Microbiota profiles were compared across disease groups and correlated with tumor therapy responses. In the therapeutic cohort, clinical outcomes were assessed between empirical therapy and TNPseq-guided therapy.

RESULTS: TNPseq identified a significantly higher proportion of clinically relevant pathogens compared to mNGS (48.76% vs. 16.80%, p < 0.001) and demonstrated superior sensitivity (81.25% vs. 68.75%), with a 40.7% reduction in turnaround time (16 hours vs. 27 hours). Both sequencing methods revealed an enrichment of Lactobacillus species in non-initial diagnosis lung cancer (NDLC) patients (p < 0.01). Patients exhibiting partial response or stable disease (PR/SD) showed increased abundance of Neisseria, Veillonella, and Prevotella species (p < 0.05). Clinical remission was achieved in all patients; however, 68.4% of those initially receiving empirical therapy subsequently required a switch to TNPseq-guided treatment due to its ineffectiveness. Compared to this empirical-to-TNPseq group, the median treatment duration was significantly shorter under direct TNPseq guidance (total: 6 days vs. 13 days, p < 0.01; LC subgroup: 5 days vs. 15.5 days, p < 0.05), thereby reducing unnecessary antibiotic exposure.

CONCLUSIONS: By enabling rapid pathogen detection and profiling of the pulmonary microbiome, TNPseq facilitates targeted therapy and reduces antibiotic overuse in LC patients. These findings highlight the potential of TNPseq as a promising, rapid, and non-invasive diagnostic candidate for first-line use, offering a comprehensive view of both infection and host-microbe interactions in immunocompromised patients.}, } @article {pmid41601983, year = {2025}, author = {Zhang, Y and Zhang, Y and Wang, L and Liu, B and Zheng, J and Cao, J and Xie, L and Shen, N and Wang, J}, title = {Serum valeric acid stimulates lung epithelial cilia assembly and improves prognosis in patients with severe respiratory infections.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1761517}, pmid = {41601983}, issn = {1663-9812}, abstract = {INTRODUCTION: Globally, respiratory infections remain a leading cause of mortality, with treatment efficacy increasingly challenged by antimicrobial resistance. This study aimed to investigate the role of serum metabolites in the prognosis of severe human pneumonia.

METHODS: Untargeted and targeted serum metabolomics were performed on intensive care unit (ICU) patients. Experimental validation was conducted in a murine bacterial infection model and cellular models. RNA sequencing was used for mechanistic exploration to identify the signaling pathways regulated by the key metabolite.

RESULTS: Valeric acid, a short-chain fatty acid, was significantly elevated in survivors compared with non-survivors of severe pneumonia. In the murine Klebsiella pneumoniae model, valeric acid treatment alleviated infection severity, reduced body weight loss, lung inflammation, and bacterial load. Mechanistically, RNA sequencing revealed that valeric acid suppresses IL-17-associated inflammation and upregulates pathways related to mucociliary clearance. We further delineated the underlying mechanism, finding that valeric acid acts as a histone deacetylase (HDAC) inhibitor, specifically targeting HDAC3. This inhibition activates the canonical Wnt/β-catenin signaling pathway, leading to the upregulation of the master transcriptional regulator Foxj1 and subsequent promotion of cilia assembly and function in airway epithelia.

DISCUSSION: The findings establish a protective role for the gut microbiome-derived valeric acid in respiratory infections via the novel HDAC-Wnt-FOXJ1 axis, revealing its potential as a therapeutic agent to improve clinical outcomes.}, } @article {pmid41601696, year = {2025}, author = {Yi, S and Luo, L and Dong, Z and Wang, K and Zhu, Z and Gao, Q and Jiang, Y and Yang, X and Hei, F}, title = {Study on the characteristics and correlation of fecal microbiota and metabolites in patients with acute lung injury after cardiopulmonary bypass based on 16S rRNA sequencing and non-targeted metabolomics analysis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1713650}, pmid = {41601696}, issn = {1664-3224}, mesh = {Humans ; Male ; Female ; *Cardiopulmonary Bypass/adverse effects ; Metabolomics/methods ; *Feces/microbiology ; Middle Aged ; *Acute Lung Injury/metabolism/etiology/microbiology ; Aged ; *Gastrointestinal Microbiome ; *RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Prospective Studies ; *Metabolome ; *Bacteria/genetics/classification ; }, abstract = {Acute lung injury (ALI) is a severe complication following cardiopulmonary bypass (CPB), associated with high mortality and impaired patient prognosis. At present, there is no effective therapeutic strategy for ALI after CPB. Although the gut microbiota has been implicated in ALI, the biological significance of these associations remains largely elusive. A prospective, single-center, case-control design was adopted. A total of 53 post-CPB patients were enrolled, including 21 in the ALI group and 32 in the non-ALI (NALI) group. Postoperative fecal samples were collected for microbiome and metabolomic analyses, which were subsequently correlated with clinical data. Results revealed that β diversity analysis indicated distinct differences in microbial community structure (Anosim: R = 0.14, P = 0.004; Permanova: R[2] = 0.058, P = 0.008). ALI patients exhibited a significant increase in the Bacillota, alongside reductions in Bacteroidota and Actinomycetota. At the genus level, Streptococcus and Enterococcus were enriched in the ALI group, while Bacteroides and Akkermansia were diminished. Metabolomics analysis identified 130 differentially expressed metabolites, 109 of which were significantly reduced in the ALI group, primarily involving amino acid metabolic pathways such as phenylalanine, tryptophan, and tyrosine. A random forest model identified genera such as Bacteroides, Corynebacterium, and Lactobacillus as having high predictive value for ALI (AUC > 0.7). Combined microbiota-metabolite analysis revealed significant correlations between specific genera and differentially expressed metabolites, suggesting a potential role for the gut-lung axis in the development of ALI following CPB. Patients with postoperative ALI following CPB exhibit marked gut microbiota structural disruption and metabolic dysfunction, both closely associated with adverse clinical outcomes. Genera such as Bacteroides and their associated metabolites may serve as early predictive biomarkers, offering novel therapeutic targets for the prevention and management of ALI.}, } @article {pmid41601648, year = {2025}, author = {Pan, S and Cui, W and Lin, J and Wang, Z and Li, Z and Liu, B}, title = {The infection-microbiome-immunity axis in bladder cancer: mechanistic insights and therapeutic perspectives.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1716230}, pmid = {41601648}, issn = {1664-3224}, mesh = {Humans ; *Urinary Bladder Neoplasms/immunology/microbiology/therapy/etiology ; Animals ; Tumor Microenvironment/immunology ; Dysbiosis/immunology ; *Microbiota/immunology ; Gastrointestinal Microbiome/immunology ; }, abstract = {Bladder cancer (BC) represents a paradigm of infection-associated malignancy in which microbial dysbiosis, immune aging, and tumor microenvironmental remodeling converge to shape disease progression. Increasing evidence highlights the dual role of the urinary and gut microbiota in modulating bladder carcinogenesis through infection-driven inflammation and immune dysfunction. Chronic exposure to uropathogens and microbial imbalance disrupts epithelial integrity, promotes extracellular matrix degradation, and reprograms local immune signaling, collectively fostering a tumor-permissive niche. Concurrently, immunosenescence exacerbates microbial persistence and impairs antitumor immunity, reinforcing a pathogenic feedback loop between infection and immune decline. This review integrates current insights from microbiome research, tumor immunology, and microbial pathogenesis to delineate the mechanistic continuum linking infection, dysbiosis, and immune remodeling in BC. Finally, we discuss emerging microbiome-targeted and immunomodulatory strategies aimed at restoring microbial-immune equilibrium and improving therapeutic efficacy. Together, these perspectives provide a refined conceptual framework for understanding infection-driven oncogenesis and guiding precision interventions in BC.}, } @article {pmid41601564, year = {2025}, author = {Alavian, F and Safaeian, M}, title = {How the gut microbiome shapes learning and memory: A comprehensive review.}, journal = {IBRO neuroscience reports}, volume = {19}, number = {}, pages = {491-506}, pmid = {41601564}, issn = {2667-2421}, abstract = {Cognitive functions, such as learning and memory processes, are closely related to the gut microbiome. The gut-brain axis (GBA), a complex network of bidirectional communications between the central nervous system and the gastrointestinal tract, plays an important role in regulating these functions. This study aims to investigate the impact of the gut microbiome on learning and memory and to provide new insights into the role of the GBA in these cognitive processes. This narrative review explores various mechanisms through which the gut microbiome affects cognitive functions by reviewing scientific articles related to the gut microbiome, GBA, learning, and memory. The focus is on studies that have investigated the relationship between the gut microbiome, changes in microbial composition, and cognitive functions. The results indicate that the gut microbiome influences brain function and behavior through various mechanisms, such as vagus nerve signaling, effects on the enteric nervous system, the production of neurotransmitters, the regulation of inflammation and the immune system, and the production of metabolites such as short-chain fatty acids (SCFAs). Dysbiosis of the gut microbiota affects hippocampal function, learning, and stress regulation. Additionally, probiotics and prebiotics, along with nutritional status, affect the composition and function of the gut microbiome; therefore, maintaining the balance of the gut microbiome and paying attention to the GBA may lead to improved cognitive functions and the prevention of learning and memory-related disorders. Microbiome-based interventions, such as probiotics and dietary changes, have the potential to increase performance.}, } @article {pmid41601555, year = {2025}, author = {Yang, H and Gong, W and Hou, Y and Wang, Y and He, P and Yu, Q}, title = {Genetically predicted immune cell-mediated causal associations between 473 gut microbiome species and neurodevelopmental disorders.}, journal = {IBRO neuroscience reports}, volume = {19}, number = {}, pages = {894-902}, pmid = {41601555}, issn = {2667-2421}, abstract = {BACKGROUND: Neurodevelopmental disorders (NDD) are a class of complex diseases whose underlying pathogenesis has not been fully elucidated. Previous observational studies have reported that gut microbiota dysbiosis may be one of the potential risk factors for the development of NDD, however, causal relationships and the potential mediating role of immune cells have yet to be established.

METHODS: Bidirectional two-sample Mendelian randomization (TSMR) and two-step Mendelian randomization (two-step MR) methods, mainly using inverse variance weighting (IVW), were used to explore the potential associations between gut microbiota and NDD, as well as the mediating role of immune cells in the causal pathway. Bayesian weighted Mendelian randomization (BWMR) method was additionally used to validate positive causality. Sensitivity analyses under different statistical assumptions were conducted to assess association robustness.

RESULTS: Based on the IVW and BWMR methods, we identified 5 and 4 gut microbiota taxonomic units exhibiting significant causal associations with ADHD and ASD, respectively. These included the negative modifying effect of family Syntrophorhabdaceae abundance on ADHD risk (OR: 0.4440, 95 % CI = 0.2620-0.7523, P = 0.0025), the significant protective effect of species ER4 sp002437735 on ASD (OR: 0.2996, 95 % CI = 0.1504-0.5968, P = 0.0004) and the stimulatory effect of species Agathobacter sp000434275 on ASD (OR: 1.7426, 95 % CI = 1.1496-2.6415, P = 0.0089). P values derived from Cochran's Q test, Egger's regression intercept test, and global test for pleiotropy and outliers did not suggest statistical significance. Further two-step MR revealed that Syntrophorhabdaceae could reduce the risk of ADHD, with Unswitched memory B cell %lymphocyte mediating 6.35 %. Additionally, 2.49 % and 1.91 % of the causal associations between ER4 sp002437735 and Agathobacter sp000434275 with ASD were mediated by BAFF-R⁺ switched memory B cells and activated/secreting CD4 regulatory T cell percentage of CD4 regulatory T cells, respectively.

CONCLUSION: Our study reveals direct evidence that NDD is influenced by specific gut microbiota, while its causal effects may be mediated by immune cell traits.}, } @article {pmid41601518, year = {2025}, author = {Sgarbossa, C and Chinna Meyyappan, A and Forth, E and Bromley, H and Milev, R}, title = {Assessing the long-term effects of microbial therapeutics as treatment within psychiatry: a systematic review.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1663719}, pmid = {41601518}, issn = {1664-0640}, abstract = {BACKGROUND: The management and treatment of psychiatric disorders by manipulating the gut microbiome and utilizing microbial therapeutics, via modulation of the gut-brain-axis, has been a rapidly growing field of research. Given the novelty of using microbial therapeutics within psychiatry, a growing number of studies have investigated their use as treatment for various psychiatric disorders and symptoms. However, few studies have explored the longitudinal efficacy of these treatments. This review aims to summarize the findings of any studies assessing the long-term effects of gut-related interventions on mood and psychiatric symptoms.

METHODS: A systematic search of 4 databases (Embase, PsycINFO, Medline, Web of Science) from inception to May 28, 2025, informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and using key words relating to microbial therapeutics, psychiatric disorders, and long-term effects was conducted. Findings were included or excluded using pre-determined eligibility criteria such as being been written in English and published by a peer-reviewed journal, assessed for quality using the Cochrane Handbook for Systematic Reviews of Interventions Risk of Bias tool, and qualitatively evaluated.

RESULTS: The search yielded 4175 studies, of which 1274 duplicates were removed. All remaining studies underwent abstract screening, from which 70 records were full-text screened and a total of ten clinical studies (n = 10) met eligibility criteria and were included in the review. The majority of studies explored the effects of microbial therapeutics such as fecal microbiota transplant and probiotics, as treatment for disorders of the gastrointestinal tract as the primary scope, with additional outcome measures assessing psychiatric well-being. The review presented with mixed findings: many studies reported a sustained improvement in symptoms of depression and anxiety ranging from 3- to 18-months post-treatment, while others reported the opposite with no sustained long-term improvement in mood-related symptoms. There was also a lack of consistency across follow-up duration between studies, making it difficult to compare findings.

CONCLUSIONS: Overall, this review highlighted the need for more placebo-controlled studies with larger sample sizes to effectively evaluate the longitudinal potential of microbial therapeutics as treatment for mood-disturbances and psychiatric symptoms. With consideration for the limitations of this field, these results provide evidence that there may be long-term benefits of targeting the gut microbiome as treatment for mood-related disturbances.}, } @article {pmid41601370, year = {2025}, author = {Tu, S and Zhang, Y and Zhang, L and Zhu, SJ}, title = {Commensal bacteria play a fundamental role in maintaining gut immune homeostasis.}, journal = {Journal of Zhejiang University. Science. B}, volume = {27}, number = {1}, pages = {101-104}, pmid = {41601370}, issn = {1862-1783}, support = {323B200243, 32172864 and U21A20261//the National Natural Science Foundation of China/ ; 2022YFD1800804//the National Key Research and Development Plan of China/ ; }, mesh = {*Homeostasis/immunology ; Humans ; *Gastrointestinal Microbiome/immunology ; T-Lymphocytes, Regulatory/immunology ; Inflammatory Bowel Diseases/immunology/microbiology ; Animals ; Intestinal Mucosa/immunology/microbiology ; Immune Tolerance ; Symbiosis ; }, abstract = {The intestinal microbiome, which is a key factor in the maintenance of host gut homeostasis, enhances intestinal mucosal barrier function and immune tolerance (Rooks and Garrett, 2016; Skelly et al., 2019). However, the specific immunomodulatory functions of microbiota-derived metabolites in mucosal inflammatory responses remain largely unknown. The effects of microbial metabolites may vary across different immune cell types and host homeostasis (Hu et al., 2023; Zhao et al., 2023). Hence, it is fundamental to understand how specific intestinal microbes and their metabolic small molecules cause or mitigate gut-related diseases like inflammatory bowel disease (IBD). It has been uncovered that during the pathogenesis of IBD, excessive T helper 1 cell (Th1)/Th17 activation and impaired function of colonic regulatory T cells (Tregs) occur (Subramanian, 2020). Given that colonic Tregs play an important role in inhibiting IBD via secreting immunosuppressive cytokines, the molecular mechanisms linking certain intestinal microbes and their metabolites to Treg-mediated immune tolerance are yet to be fully understood.}, } @article {pmid41601318, year = {2026}, author = {Muñoz-Hernández, J and Peralta-Maraver, I and Cavieres, G and Gutiérrez-Cortés, I and Rezende, EL and Rivera, DS}, title = {Phylosymbiosis and functional redundancy in the Drosophila (Diptera: Drosophilidae) gut microbiome and its implications for host fitness.}, journal = {Journal of insect science (Online)}, volume = {26}, number = {1}, pages = {}, pmid = {41601318}, issn = {1536-2442}, support = {11190637//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 21241747//Universidad Mayor Doctoral Fellowship and the ANID National Doctoral Fellowship/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Drosophila/microbiology/physiology/genetics/growth & development ; *Symbiosis ; RNA, Ribosomal, 16S/analysis ; Chile ; *Genetic Fitness ; Female ; Phylogeny ; }, abstract = {The gut microbiome plays a fundamental role in host ecophysiology. Numerous studies have examined microbiome composition and functionality to understand the ecological and evolutionary factors shaping host-microbe interactions. However, the consequences of these patterns for animal ecology remain poorly understood. Here, we examined how variations in the gut microbiome influence fitness differences among Drosophila species sharing a common dietary niche. Using 16S rRNA gene sequencing, we analyzed the gut microbial taxonomy and predicted functional profiles of 4 Drosophila species collected in central Chile. Our results revealed a strong signal of phylosymbiosis in the microbial taxonomy, while functionality was highly redundant across the studied fly species. Functional biomarkers analysis indicated that the gut microbiome supports the nutritional requirements of D. simulans (Sturtevant), D. hydei (Sturtevant), and D. repleta (Wollaston); whereas, this was less evident in D. melanogaster (Meigen). To assess the potential contribution of the microbiome to host performance, we compared egg-to-adult viability between 2 species with the greatest physiological divergence: D. simulans and D. hydei. Notably, D. simulans exhibited significantly higher egg viability and shorter development time than D. hydei. Strikingly, the D. simulans microbiome contained more taxonomic and functional biomarkers previously demonstrated to enhance fly fitness, whereas the D. hydei microbiome harbored taxa and functions potentially detrimental to host performance. These findings suggest that the gut microbiome contributes to host fitness and may shape the evolutionary ecology of Drosophila species, with broader implications for community dynamics, including interspecific competition and species displacement.}, } @article {pmid41601294, year = {2026}, author = {Song, CH and Kim, N and Nam, RH and Choi, H and Jin, I and Kim, EH and Ha, S and Kang, K and Lee, W and Choi, H and Kim, YR and Seok, YJ and Lee, HK and Shin, CM and Lee, DH}, title = {Sex-Dependent Microbial and Host Profiles Following Fecal Microbiota and Bifidobacterium longum Treatment in Stress-Induced Gut Dysbiosis.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl250440}, pmid = {41601294}, issn = {2005-1212}, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder influenced by stress, microbial dysbiosis, and immune activation. Microbiota-directed therapies, including fecal microbiota transplantation and probiotics, show promise, but their sex-specific effects remain unclear. We compared the therapeutic effects of lyophilized fecal microbiota (LFM) with Bifidobacterium longum BBH016 in male and female Wistar rats subjected to repeated water avoidance stress.

METHODS: Fecal pellet output (FPO), colonic mast cell infiltration, and fecal short-chain fatty acids were measured. Gut microbial composition and function were analyzed by 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway prediction.

RESULTS: Both interventions significantly reduced FPO and mast cell infiltration in males but had less pronounced effects in females. Microbiota analyses revealed sex-dependent responses, with distinct microbial trajectories in each treatment group. Using linear discriminant analysis effect size, we identified seven key taxa with treatment- or sex-specific enrichment. Alistipes onderdonkii and Bacteroides uniformis consistently increased in both LFM- and B. longum-treated groups, regardless of sex. Bacteroides finegoldii and Barnesiella intestinihominis were specifically enriched in the LFM group. In males, Blautia faecis and Fusicatenibacter saccharivorans were enriched following the interventions, whereas Parabacteroides goldsteinii appeared exclusively in stressed males. Functional predictions revealed the enrichment of estrogen signaling and bile acid pathways in males and the attenuation of proinflammatory pathways in females following LFM. Correlations between microbial taxa and host outcomes were predominantly observed in male rats.

CONCLUSIONS: These findings highlight sex-specific microbial and host responses to microbiota-targeted therapies in a stress-induced IBS model, emphasizing sex as a biological variable in designing personalized microbiome-based treatments.}, } @article {pmid41601223, year = {2025}, author = {Liu, ZY and Zhao, XC and Chen, L and Wu, RG and Yuan, MQ and Chen, XH and Zhao, J and Xu, QY and Liu, CH and Sun, HY and Liu, C}, title = {[Recommendations for the Standardization of Forensic Microbiological Analysis].}, journal = {Fa yi xue za zhi}, volume = {41}, number = {5}, pages = {482-493}, doi = {10.12116/j.issn.1004-5619.2025.550501}, pmid = {41601223}, issn = {1004-5619}, mesh = {Humans ; *Forensic Medicine/standards/methods ; Reproducibility of Results ; *Microbiological Techniques/standards/methods ; Reference Standards ; *Bacteria/isolation & purification ; *Microbiota ; }, abstract = {With advances in microbiome research and the continuous advancement of detection technologies, the application of microorganisms in forensic medicine has become increasingly widespread, covering areas such as individual identification, body fluid source inference, biogeographical analysis, postmortem interval estimation, and determination of the cause and location of death. However, due to the lack of a comprehensive standardized system, batch effects and inter-laboratory differences have led to low reproducibility of analysis results. This problem is particularly evident in low-quality forensic samples, which compromise the reliability and evidential value of forensic microbiological analyses. Therefore, based on domestic and international research progress and practical experience, this paper systematically summarizes and discusses the standardization of forensic microbiological analysis, aiming to improve the reliability of results and promote the standardization of forensic microbiological analysis.}, } @article {pmid41601221, year = {2025}, author = {Zou, HY and Lei, YL and Xia, RC and Shi, Y and Li, CT}, title = {[Exploring Microbial Detection of Psychoactive Substances in Wastewater Based on Micobiome Analysis].}, journal = {Fa yi xue za zhi}, volume = {41}, number = {5}, pages = {468-476}, doi = {10.12116/j.issn.1004-5619.2025.550803}, pmid = {41601221}, issn = {1004-5619}, mesh = {*Wastewater/microbiology/chemistry ; RNA, Ribosomal, 16S/genetics ; *Psychotropic Drugs/analysis ; Tandem Mass Spectrometry/methods ; Chromatography, Liquid/methods ; *Microbiota/genetics ; *Bacteria/genetics/classification/isolation & purification ; *Water Pollutants, Chemical/analysis ; DNA, Bacterial/genetics ; }, abstract = {OBJECTIVES: To explore the potential wastewater microbiome analysis for detecting psychoactive substances by using full-length 16S rRNA gene sequencing with liquid chromatography - tandem mass spectrometry (LC-MS/MS).

METHODS: LC-MS/MS was used to qualitatively detect psychoactive substances in 21 wastewater samples suspected to contain such compunds. Based on the results, the samples were categorized into two groups: a positive group (containing psychoactive substances) and a negative group (free of psychoactive substances). Subsequently, bacterial communities in all samples were analyzed using full-length 16S rRNA gene sequencing. This analysis characterized the species composition, α diversity (Shannon and Simpson indices), and β-diversity (PCoA and NMDS). Significantly different operational taxonomic units (OTUs) were screened using linear discriminant analysis effect size (LEfSe), and optimal OTU features were iteratively selected via recursive feature elimination (RFE). A random forest prediction model was built with these two OTU subsets as input features.

RESULTS: The composition and structure of the bacterial communities showed marked differences between the two groups. The sample diversity in the positive group was higher than that in the negative group. The permutational ultivariate analysis of variance (PERMANOVA) revealed a statistically significant difference in β-diversity between the two groups. Random Forest models achieved a prediction accuracy of 83.3%, with areas under the ROC curve of 0.89 and 0.83, respectively.

CONCLUSIONS: Integrating wastewater bacterial community analysis with chemical analysis techniques may provide a more comprehensive approach for monitering the presence of psychoactive substances.}, } @article {pmid41601220, year = {2025}, author = {Chen, J and Zhao, YR and Huang, X and Qu, YL and Lu, YF and Xing, Y and Zhang, H and Zeng, JY and Li, SL and Zhang, SH}, title = {[Effect of Temperature on Microbial Succession in Different Tissues of Cadavers and Estimation of Postmortem Interval].}, journal = {Fa yi xue za zhi}, volume = {41}, number = {5}, pages = {456-467}, doi = {10.12116/j.issn.1004-5619.2025.450404}, pmid = {41601220}, issn = {1004-5619}, mesh = {*Postmortem Changes ; Animals ; RNA, Ribosomal, 16S/genetics ; Male ; *Temperature ; Rats ; Cadaver ; *Microbiota ; Female ; Rectum/microbiology ; Lung/microbiology ; Time Factors ; Rats, Sprague-Dawley ; *Bacteria/genetics/classification/isolation & purification ; Testis/microbiology ; Uterus/microbiology ; Proteobacteria/isolation & purification/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {OBJECTIVES: To explore the distribution characteristics of microbial communities in various rat tissues under different temperature conditions and their dynamic changes over the postmortem interval(PMI), and to analyze the effects of temperature and tissue type on microbial succession in cadavers.

METHODS: A total of 96 rats were sacrificed by cervical dislocation and then placed under room temperature (20 ℃, n=48), high temperature (40 ℃, n=24), and low temperature (-20 ℃, n=24) conditions. Tissue samples from the diaphragm, lung, rectum, testis, and uterus were collected at various PMIs. Microbial community composition was analyzed using 16S rRNA high-throughput sequencing of the 16S rRNA gene V3-V4 regions. α-diversity, β-diversity, phylum- and genus-level species distributions, PMI-associated biomarkers analysis and species differential analysis were employed to systematically compare the effects of temperature and tissue type on microbial succession.

RESULTS: Under room temperature, microbial diversity exhibited a nonlinear trend, initially increasing and then decreasing. High temperature condition accelerated microbial succession and resulted in a significant decrease in microbial diversity within 24 hours. Low temperature slowed the succession, maintaining relatively high diversity and stable species distribution. The rectal microbial community differed significantly from those in other tissues. The phylum Proteobacteria, especially the genus Proteus, showed a significant increase in relative abundance in various tissues after 48 hours at room temperature and 24 hours at high temperature.

CONCLUSIONS: The dynamic succession patterns of microbial communities in multiple tissues under different temperature conditions confirm the significant regulatory effect of temperature on microbial diversity and species distribution, providing an important basis for optimizing microbiome-based PMI estimation methods.}, } @article {pmid41601219, year = {2025}, author = {Zhang, H and Huang, X and Chen, AQ and Chen, J and Lu, YF and Zeng, JY and Wang, X}, title = {[Skin Microbiome: Expanding Dimensions and Challenges in Forensic Evidence].}, journal = {Fa yi xue za zhi}, volume = {41}, number = {5}, pages = {443-455}, doi = {10.12116/j.issn.1004-5619.2025.550403}, pmid = {41601219}, issn = {1004-5619}, mesh = {Humans ; *Skin/microbiology ; *Microbiota/physiology ; *Forensic Medicine/methods ; *Forensic Sciences/methods ; Skin Microbiome ; }, abstract = {The skin microbiome, characterized by its vast abundance, high diversity, pronounced individual specificity, and dynamic traceability, serves as a significant biological marker of the host. Its composition and variation are influenced by both the host's physiological states and external environmental factors, exhibiting a close "mirror" relationship with host phenotypes. This unique "microbial fingerprint" not only expands the sources of forensic evidence but also offers new perspectives and opportunities for the advancement of forensic research and practice. This paper reviews the physiological and structural foundations underlying skin microbial diversity and the mechanisms that shape individual specificity, analyzes its unique advantages and technical approaches in forensic applications, outlines recent research progress, explores the future potential and major challenges of using skin microbiome markers in forensic science, and proposes practical recommendations.}, } @article {pmid41601145, year = {2026}, author = {Jiao, Y and Liu, Y and Sun, F and Wang, W and Li, H and Gao, Q and Li, Y and Lu, N and Tian, X and Ding, X and Du, J}, title = {Genetically Modified Plant Beneficial Microorganisms: A Sustainable Solution or a New Challenge for Agriculture.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c14342}, pmid = {41601145}, issn = {1520-5118}, abstract = {Plant diseases significantly impact crop yield and quality, while conventional pesticide treatments often disrupt beneficial plant microbiota essential for pathogen prevention and immune regulation. Although plant beneficial microorganisms (PBMs) show promise as disease control agents, their effectiveness is constrained by strain-dependent variations, survival challenges, and inconsistent immune responses. Recent advances in genetic engineering, particularly CRISPR-Cas systems combined with complementary technologies like RecE/T, enable precise modifications of PBMs to enhance their protective potential. Enhanced PBMs improve functionality via multiple mechanisms: targeted gene-expression-mediated colonization, specific antimicrobial activity, and immune regulation. Studies demonstrate that genetically modified PBMs can prevent and control plant diseases through competitive exclusion, antibiotic production, barrier reinforcement, and immune modulation. We analyzed the considerations for the environmental release of engineered PBMs to reduce risks. Future research should focus on optimizing PBMs for specific applications while addressing biosafety concerns, thereby unlocking their full potential in safeguarding plant health.}, } @article {pmid41601032, year = {2026}, author = {Wang, X and Yan, W and Fan, G and Han, Z and Xia, M and Liu, J and Wang, Y and Rensing, C and Augustyniak, M and Zhang, Z and Wu, H}, title = {Earthworms reduce the accumulation of soil-borne pathogens in strawberry by altering the gut microbiome and physiological characteristics.}, journal = {Ecotoxicology and environmental safety}, volume = {309}, number = {}, pages = {119595}, doi = {10.1016/j.ecoenv.2025.119595}, pmid = {41601032}, issn = {1090-2414}, mesh = {*Oligochaeta/physiology/microbiology ; Animals ; *Fragaria/microbiology ; *Gastrointestinal Microbiome ; *Soil Microbiology ; Fusarium/physiology ; Alternaria/physiology ; *Plant Diseases/microbiology/prevention & control ; Soil/chemistry ; }, abstract = {Pathogenic fungi cause economic loss to many crops including strawberry, highlighting the need for control using sustainable eco-friendly strategies. Earthworm casts effectively reduce the occurrence of soil-borne diseases. However, the interactions between earthworms and soil-borne pathogenic fungi and their underlying mechanisms remain insufficiently understood in strawberry. This study investigated the effects of the pathogenic fungi Fusarium oxysporum and Alternaria alstroemeriae on the structure and composition of the microbial communities in the drilosphere soil and earthworm gut using high-throughput sequencing. The impact of these pathogenic fungi on functional gene expression in earthworms was determined using transcriptomic analysis. Applying F. oxysporum and A. alstroemeriae with earthworms significantly altered the physicochemical properties of the drilosphere soil, reduced the fungal alpha diversity therein, and increased the abundance of potentially beneficial Pseudomonas spp. and Bacillus spp. The presence of the pathogenic fungi increased the alpha diversity and habitat niche breadth of the fungal community in the earthworm gut. However, there was a significant reduction in the relative abundance of potentially pathogenic fungi to plants and animals in the earthworm gut. Earthworms had a positive legacy effect on the abundance of beneficial bacteria in the rhizosphere and enhanced strawberry biomass. Transcriptomic analysis demonstrated that earthworms activated α-linolenic acid and glycerophospholipid metabolism but downregulated the Toll-like receptor pathway, mitigating excessive immune responses. In summary, earthworms suppress soil-borne pathogenic fungi in strawberry via an integrated mechanism involving the restructuring of the gut microbiota, enrichment of biocontrol agents in the drilosphere, and coordination of host immunity, offering a novel paradigm for pest management and sustainable means for strawberry cultivation.}, } @article {pmid41600738, year = {2026}, author = {Yachida, M and Itoh, M and Morita, Y}, title = {Comparative Effects of Raw Milk and Milk Replacer Feeding on Gut Microbiota Diversity and Function in Cryptosporidium parvum-Infected Neonatal Dairy Calves on a Japanese Farm.}, journal = {Veterinary sciences}, volume = {13}, number = {1}, pages = {}, pmid = {41600738}, issn = {2306-7381}, support = {24K09209//Japan Society for the Promotion of Science/ ; 5 chiku-ni-kyo hatsu dai 27//Japan Association for Livestock New Technology/ ; }, abstract = {Neonatal diarrhea is a major health concern in the livestock industry, and Cryptosporidium parvum is a key pathogen responsible for this condition in calves. Milk management and gut microbiome regulation may play important roles in preventing cryptosporidiosis symptoms. This study analyzed the gut microbiota of neonatal calves fed raw milk (BM) or milk replacer (MR) using a total of 58 fecal samples collected on the same farm in 2022 and 2024. In milk replacer-fed calves, alpha diversity was significantly higher in C. parvum-positive (P) calves without diarrhea (N) (PN, n = 5) than in C. parvum-positive calves with diarrhea(D) (PD, n = 18) (Shannon p = 0.0358; Chao1 p = 0.0598). Beta diversity also differed between PN and PD (PERMANOVA, R[2] = 0.1763, p = 0.0092). Predicted microbial taxa such as Faecalibacterium (ALDEx2, effect size = 2.31, p = 0.00003) and Butyricicoccus (effect size = 1.31, p = 0.0041) were enriched in PN calves in MR. Comparison between milk types (BM vs. MR) further showed higher species richness in PN calves in MR than in those (n = 5) in BM(Chao1, p = 0.0088), along with significant differences in beta diversity (R[2] = 0.4112, p = 0.0069). These findings suggest that microbial diversity and the presence of specific taxa may be associated with reduced diarrheal symptoms. Predicted metabolic pathway profiling using a computational functional profiling approach showed the distinct metabolic pathways, including amino acid, carbohydrate, lipid, and vitamin biosynthesis, were enriched in healthier calves in both groups. These results suggest certain functional features of the microbiome could be associated with anti-inflammatory activity and short-chain fatty acid production, potentially mitigating diarrheal symptoms.}, } @article {pmid41600714, year = {2026}, author = {Jin, A and Zhou, S and Cheng, S and Yang, Y and Sun, Y and Sun, Z and Zhao, Y and Chen, X}, title = {Effects of Dietary Supplementation with Whole Lamb Omasum on Gut Health and Metabolism in Shiba Inu Dogs.}, journal = {Veterinary sciences}, volume = {13}, number = {1}, pages = {}, pmid = {41600714}, issn = {2306-7381}, support = {CSTB2025TIAD-KPX0079//Chongqing Key Special Project for Technological Innovation and Application Development/ ; CQMAITS202513//Chongqing Herbivorous Livestock Industry Technology System/ ; }, abstract = {The growing pet economy boosts demand for fiber-enriched functional foods to improve canine gut motility and metabolic health. However, low-bioavailability commercial fibers often falter in high-energy diets. Whole lamb omasum-from grass-fed sheep omasum and gastric contents-repurposes a discarded byproduct for waste reduction and sustainable livestock production. This study evaluated the short-term effects of WLO supplementation on gut health and metabolism in healthy adult Shiba Inu dogs. Twelve dogs were randomly assigned to control or WLO groups in a randomized controlled trial. WLO supplementation significantly reduced fecal scores by 8.91% (p < 0.05), increased apparent crude fat and fiber digestibility by 3.70% and 11.55% (p < 0.05), and elevated serum IgA by 35.79-36.15% and T-AOC by 30.53-35.71% (p < 0.05). Serum metabolome revealed 13 between-group and 8 within-subject differences related to lipid and endocrine modulation. Fecal microbiota analysis indicated enrichment of the Bacillota phylum and Blautia genus (p < 0.05). These findings support WLO as a functional food that enhances gut and metabolic health in small-breed dogs.}, } @article {pmid41600684, year = {2025}, author = {Mgeni, MS and Zhang, L and Chen, Y and Dong, X and Xiu, Z and Zhang, J and Chen, J and Sun, Y}, title = {Effects of Dandelion Extracts on the Ruminal Microbiota, Metabolome, and Systemic Inflammation in Dairy Goats Fed a High-Concentrate Diet.}, journal = {Veterinary sciences}, volume = {13}, number = {1}, pages = {}, pmid = {41600684}, issn = {2306-7381}, support = {22532J//This research was funded by chongqing performance incentive guide special project 22532J/ ; }, abstract = {This study examined the effect of dandelion extracts on the ruminal microbiota, metabolome, and inflammatory response in dairy goats fed a high-concentrate diet. Eighteen Guanzhong dairy goats were assigned to three groups: low-concentrate diet group (L group, F:C = 60:40), high-concentrate diet group (H group, F:C = 35:65), and dandelion group (D) with 1% dandelion extracts based on the H group. Over six weeks, milk, blood, and ruminal fluid were collected to analyze pH, volatile fatty acids (VFAs), inflammatory markers, microbiome, and metabolome. Feed intake was significantly higher in the H and D groups than in the L group. Ruminal pH decreased in the H group, acetate was significantly higher in the L and D groups, and serum IgA was higher in D group. Bacteroidetes and Firmicutes were dominant rumen phyla, and dandelion supplementation significantly increased Proteobacteria. Prevotella abundance was enriched in the L and D groups and showed a positive correlation with acetate. Dandelion extracts also increased the production of trans-3-Hydroxy-L-proline and 7-Ethyl-5,6-dihydro-1,4-dimethylazulene in the rumen while improving amino acid and lipid metabolism. Overall, supplementation of dandelion extracts positively influenced rumen microbiota, enhanced production of beneficial metabolites, and positively influenced immune function in dairy goats fed high-concentrate diet.}, } @article {pmid41600605, year = {2026}, author = {De Rosa, M and Canepari, S and Tranfo, G and Giampaoli, O and Patriarca, A and Smolinska, A and Marini, F and Massimi, L and Sciubba, F and Spagnoli, M}, title = {Unveiling the Metabolic Fingerprint of Occupational Exposure in Ceramic Manufactory Workers.}, journal = {Toxics}, volume = {14}, number = {1}, pages = {}, pmid = {41600605}, issn = {2305-6304}, support = {BRIC ID 52//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {In this study, for the first time urinary NMR-based metabolomics was applied to investigate the physiological alterations associated with occupational exposure in ceramic manufacturing workers. Multivariate analysis revealed a distinctive metabolic signature with exposure, characterized by a depletion of both aliphatic and aromatic amino acids and a concomitant accumulation of branched-chain amino acid catabolites. Alterations in tricarboxylic acid (TCA) cycle intermediates, including citrate and succinate, suggest an involvement of mitochondrial energy metabolism, reflecting adaptive responses to oxidative stress and increased protein turnover. Notably, glycine levels were found increased, consistent with its central role in antioxidant defense and xenobiotic detoxification. Furthermore, changes in urinary host-microbiome co-metabolites, such as 4-hydroxyphenylacetate and phenylacetylglycine, indicate the potential modulation of gut microbial activity in response to occupational exposure. While limited by the small cohort, this study demonstrates the feasibility of NMR-based urinary metabolomics for the non-invasive biomonitoring of workers and suggests its potential as a useful tool for detecting subtle metabolic perturbations associated with complex occupational exposures.}, } @article {pmid41600411, year = {2026}, author = {Tiwari, AK and Gupta, MK and Mishra, SK and Meena, R and Patolsky, F and Narayan, RJ}, title = {Nanobiosensors: A Potential Tool to Decipher the Nexus Between SARS-CoV-2 Infection and Gut Dysbiosis.}, journal = {Sensors (Basel, Switzerland)}, volume = {26}, number = {2}, pages = {}, pmid = {41600411}, issn = {1424-8220}, mesh = {*Dysbiosis/diagnosis/virology/microbiology ; Humans ; *COVID-19/diagnosis/virology/complications ; *Biosensing Techniques/methods ; *SARS-CoV-2/isolation & purification/pathogenicity ; *Gastrointestinal Microbiome ; *Nanotechnology/methods ; }, abstract = {The emergence of SARS-CoV-2 posed a great global threat and emphasized the urgent need for diagnostic tools that are rapid, reliable, sensitive and capable of real-time monitoring of SARS-CoV-2 infections. Recent investigations have identified a potential connection between SARS-CoV-2 infection and gut dysbiosis, highlighting the sophisticated interplay between the virus and the host microbiome. This review article discusses the eminence of nanobiosensors, as state-of-the-art tools, to investigate and clarify the connection between SARS-CoV-2 pathogenesis and gut microbiome imbalance. Nanobiosensors are uniquely advantageous owing to their sensitivity, selectivity, specificity, and reliable monitoring capabilities, making them well-suited for identifying both viral particles and microbial markers in biological samples. We explored a range of nanobiosensor platforms and their potential use for concurrently monitoring the gut dysbiosis induced by different pathological conditions. Additionally, we explore how advanced sensing technologies can shed light on the mechanisms driving virus-induced dysbiosis, and the implications for disease progression and patient outcomes. The integration of nanobiosensors with microfluidic devices and artificial intelligence algorithms has also been explored, highlighting the potential of developing point-of-care diagnostic tools that provide comprehensive insights into both viral infection and gut health. Utilizing nanotechnology, scientists and healthcare professionals may gain a more profound insight into the complex interaction dynamics between SARS-CoV-2 infection and the gut microenvironment. This could pave the way for enhanced diagnostic and prognostic approaches, treatment courses, and patient care for COVID-19.}, } @article {pmid41600136, year = {2026}, author = {Song, X and Xia, X and Yang, S and Hao, C and Sun, H and Li, F and Xu, X and Zhang, H and Lu, X}, title = {The Influence of Transgenic Insect-Resistance and Herbicide-Tolerance Soybean KM2208-23 on the Rhizosphere Micro-Biome.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/plants15020329}, pmid = {41600136}, issn = {2223-7747}, support = {2023ZD04062//Biological Breeding-Major Projects/ ; 2024LZGC010//the Agricultural Variety Improvement Project of Shandong Province/ ; ZR2021QC207//Shan-dong Province Natural Science Foundation Young Project/ ; }, abstract = {The consequences of stacking multiple insect-resistance and herbicide-tolerance genes, particularly across the entire plant life cycle, remain inadequately understood. This study investigated the impact of stacked-trait transgenic soybeans on rhizosphere microbial communities across five growth stages (pre-sowing, V3, R3, R5, R8). Using 16S rRNA and ITS sequencing, we compared the rhizosphere microbiome of the transgenic modified soybean (GMO) with its non-transgenic control check (CK). Results showed transient but significant shifts in soil properties (e.g., available nitrogen) and microbial beta diversity during the V3 stages. However, plant developmental stage was the predominant factor shaping microbial succession, with its effect outweighing that of the transgene. No persistent changes in microbial alpha diversity were observed. We conclude that the influence of this stacked-trait soybean on the rhizosphere is growth-stage-specific and represents a minor, recoverable perturbation rather than a sustained ecological impact. These findings contribute to the ecological safety assessment of multi-gene transgenic crops.}, } @article {pmid41599966, year = {2026}, author = {Nedeva, I and Assyov, Y and Duleva, V and Karamfilova, V and Kamenov, Z and Naydenov, J and Handjieva-Darlenska, T and Denchev, V and Kolevski, A and Pencheva, V and Vodenicharov, V}, title = {Distinct Gut Microbiome Profiles Underlying Cardiometabolic Risk Phenotypes in Individuals with Obesity.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599966}, issn = {2072-6643}, support = {contract D-300/18.12/2023//Stimulating Excellence in Scientific research, Medical university Sofia/ ; 2025//National program " For Women in Science 2025"/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Obesity/microbiology/complications ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; Phenotype ; *Metabolic Syndrome/microbiology ; Cardiometabolic Risk Factors ; *Cardiovascular Diseases/microbiology ; }, abstract = {Background: Obesity-related cardiometabolic disorders have been linked to alterations in selected gut microbiome components, yet clinically relevant microbial signatures remain incompletely defined. Objectives: This study investigated associations between selected gut bacterial taxa and cardiometabolic risk phenotypes in individuals with obesity. Methods: In this cross-sectional study, 100 adults with obesity were stratified according to metabolic syndrome status. Gut microbiome composition was assessed using targeted multiplex real-time PCR of functionally relevant bacterial taxa. Associations with anthropometric and cardiometabolic parameters were examined using correlation analysis, ROC curves, and multivariable logistic regression models. Results: Reduced relative abundance of Lachnospiraceae was associated with metabolic syndrome, lower Faecalibacterium abundance with arterial hypertension, and increased Prevotella abundance with dyslipidemia. ROC analyses identified cohort-specific discriminative thresholds with moderate accuracy. Conclusions: Selected taxon-specific gut microbiome signatures are associated with cardiometabolic risk phenotypes in obesity. These findings are exploratory and require validation in longitudinal and independent cohorts.}, } @article {pmid41599961, year = {2026}, author = {Lietz, A and Dapprich, J and Fischer, T}, title = {Carnivore Diet: A Scoping Review of the Current Evidence, Potential Benefits and Risks.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599961}, issn = {2072-6643}, mesh = {Humans ; Animals ; }, abstract = {Background: The Carnivore Diet (CD) is an almost exclusively animal-based dietary pattern that has gained increasing popularity on social media. Despite numerous health-related claims, a standardized definition is lacking, and scientific evidence regarding the long-term effects of this diet remains unclear. Methods: The literature search for this scoping review was conducted in accordance with PRISMA guidelines (PRISMA-ScR) using the databases PubMed, LIVIVO, Web of Science, and the Cochrane Library. Results: Nine human studies were included. Individual publications reported positive effects of the CD, such as weight reduction, increased satiety, and potential improvements in inflammatory or metabolic markers. At the same time, potential risks of nutrient deficiencies, particularly in vitamins C and D, calcium, magnesium, iodine, and dietary fiber, as well as elevated low-density-lipoprotein (LDL-) and total cholesterol (TC) levels, were identified, along with one case describing a deterioration in health status. Overall, the quality of evidence is very limited due to small sample sizes, short study durations, and the absence of control groups. Conclusions: The CD may offer short-term health benefits but carries substantial risks of nutrient deficiencies, reduced intake of health-promoting phytochemicals, and the development of cardiovascular disease. At this time, long-term adherence to a CD cannot be recommended.}, } @article {pmid41599910, year = {2026}, author = {Park, SH}, title = {Recent Research on the Role of Lactobacilli Probiotics in Cancer Management.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599910}, issn = {2072-6643}, mesh = {*Probiotics/therapeutic use ; Humans ; *Neoplasms/therapy/microbiology ; *Lactobacillus ; Gastrointestinal Microbiome ; Animals ; Apoptosis ; }, abstract = {Lactobacilli strains are one of the major groups belonging to probiotics. Lactobacilli strains are known to be beneficial microbes widely studied and utilized for their health benefits and applications in various fields. Recently, Lactobacilli strains have emerged as promising agents in cancer management due to their ability to influence various physiological processes. Lactobacilli strains have shown potential in producing tumor-suppressive compounds, enhancing immune responses, and reshaping gut microbiota balance for the management of various cancer types. Lactobacilli strains demonstrated tumor-suppressive activity through mechanisms including induction of apoptosis, inhibition of migration, and regulation of key oncogenic signaling pathways. However, the effects of Lactobacilli strains appear to be strain- and cancer-type-dependent, necessitating further research to identify the most effective strains for the proper cancer type with the optimal treatment regimens. In this review article, we focus on Lactobacilli strains studied between 2021 and 2025 that have demonstrated tumor-suppressive properties in various experimental models. In addition, this article explores the current limitations in research methodologies and proposes potential avenues for future investigations in this area of study.}, } @article {pmid41599902, year = {2026}, author = {Plaza-Diaz, J and Herrera-Quintana, L and Olivares-Arancibia, J and Vázquez-Lorente, H}, title = {Personalized Nutrition Through the Gut Microbiome in Metabolic Syndrome and Related Comorbidities.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599902}, issn = {2072-6643}, mesh = {Humans ; *Metabolic Syndrome/microbiology/prevention & control/diet therapy/therapy ; *Gastrointestinal Microbiome/physiology ; Exercise ; *Precision Medicine/methods ; Comorbidity ; Diet ; }, abstract = {Background: Metabolic syndrome, a clinical condition defined by central obesity, impaired glucose regulation, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol across the lifespan, is now a major public health issue typically managed with lifestyle, behavioral, and dietary recommendations. However, "one-size-fits-all" recommendations often yield modest, heterogeneous responses and poor long-term adherence, creating a clinical need for more targeted and implementable preventive and therapeutic strategies. Objective: To synthesize evidence on how the gut microbiome can inform precision nutrition and exercise approaches for metabolic syndrome prevention and management, and to evaluate readiness for clinical translation. Key findings: The gut microbiome may influence cardiometabolic risk through microbe-derived metabolites and pathways involving short-chain fatty acids, bile acid signaling, gut barrier integrity, and low-grade systemic inflammation. Diet quality (e.g., Mediterranean-style patterns, higher fermentable fiber, or lower ultra-processed food intake) consistently relates to more favorable microbial functions, and intervention studies show that high-fiber/prebiotic strategies can improve glycemic control alongside microbiome shifts. Physical exercise can also modulate microbial diversity and metabolic outputs, although effects are typically subtle and may depend on baseline adiposity and sustained adherence. Emerging "microbiome-informed" personalization, especially algorithms predicting postprandial glycemic responses, has improved short-term glycemic outcomes compared with standard advice in controlled trials. Targeted microbiome-directed approaches (e.g., Akkermansia muciniphila-based supplementation and fecal microbiota transplantation) provide proof-of-concept signals, but durability and scalability remain key limitations. Conclusions: Microbiome-informed personalization is a promising next step beyond generic guidelines, with potential to improve adherence and durable metabolic outcomes. Clinical implementation will require standardized measurement, rigorous external validation on clinically meaningful endpoints, interpretable decision support, and equity-focused evaluation across diverse populations.}, } @article {pmid41599892, year = {2026}, author = {Guraka, A and Lush, M and Zouganelis, G and Waldron, J and Mekapothula, S and Masania, J and Cave, GWV and Conway, ME and Tripathi, G and Kermanizadeh, A}, title = {Investigating the Role of Diet-Manipulated Gut Bacteria in Pathogenesis of Type 2 Diabetes Mellitus-An In Vitro Approach.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599892}, issn = {2072-6643}, support = {NA//University of Derby/ ; NA//Animal Free Research UK/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/etiology/metabolism ; Humans ; Feces/microbiology ; Insulin/metabolism ; Diet, High-Fat/adverse effects ; Dietary Fiber ; Cell Line, Tumor ; *Limosilactobacillus fermentum/metabolism/isolation & purification ; *Diet ; Bacteroides/metabolism/isolation & purification ; Insulin Resistance ; Glucose/metabolism ; Insulin Secretion ; Male ; }, abstract = {Background: The human gut microbiome is highly complex, and its composition is strongly influenced by dietary patterns. Alterations in microbiome structure have been associated with a range of diseases, including type 2 diabetes mellitus. However, the underlying mechanisms for this remain poorly understood. In this study, a novel in vitro approach was utilized to investigate the interplay between gut bacteria, dietary metabolites, and metabolic dysfunction. Methods: Two representative gut bacterial species-Bacteroides thetaiotaomicron and Lactobacillus fermentum-were isolated from human faecal samples and subjected to controlled dietary manipulation to mimic eubiotic and dysbiotic conditions. Metabolites produced under these conditions were extracted, characterized, and quantified. To assess the functional impact of these metabolites, we utilized the INS-1 832/3 insulinoma cell line, evaluating insulin sensitivity through glucose-stimulated insulin secretion and ERK1/2 activation. Results: Our findings demonstrate that metabolites derived from high-carbohydrate/high-fat diets exacerbate metabolic dysfunction, whereas those generated under high-fibre conditions significantly enhance insulin secretion and glucose-dependent ERK1/2 activation in co-culture compared to monocultures. Conclusions: This work systematically disentangles the complex interactions between gut microbiota, diet, and disease, providing mechanistic insights into how microbial metabolites contribute to the onset of metabolic disorders.}, } @article {pmid41599868, year = {2026}, author = {Allegretti, JR and Kassam, Z and Kelly, CR and Grinspan, A and El-Nachef, N and Van Den Elzen, C and Jäger, R and Feuerstadt, P}, title = {A Randomized, Placebo-Controlled Trial Evaluating Multi-Species Synbiotic Supplementation for Bloating, Gas, and Abdominal Discomfort.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599868}, issn = {2072-6643}, support = {N/A//Seed Health Inc./ ; }, mesh = {Humans ; *Synbiotics/administration & dosage ; Double-Blind Method ; Male ; Female ; *Abdominal Pain/therapy ; Adult ; Middle Aged ; *Flatulence/therapy ; Quality of Life ; *Dietary Supplements ; Probiotics/administration & dosage ; Gases ; Treatment Outcome ; Plant Extracts/administration & dosage ; Young Adult ; }, abstract = {Background: Bloating, gas, and abdominal discomfort are common in healthy individuals but lack effective interventions. Probiotics can alleviate some gastrointestinal (GI) symptoms; however, evidence for their impact on bloating, gas and abdominal discomfort in otherwise healthy populations remains limited. Mechanistic studies suggest that synbiotics may influence the underlying mechanisms of bloating, including increased gas production, impaired gut motility, and visceral hypersensitivity, but there is a paucity of data from large trials evaluating clinical outcomes. Accordingly, we evaluated the effects of a multi-species synbiotic on GI symptoms. Methods: In a randomized, double-blind, placebo-controlled, decentralized trial, participants (n = 350) with self-reported bloating/indigestion received either a multi-species synbiotic (53.6 billion AFU multi-species probiotic and 400 mg pomegranate extract; DS-01) or placebo daily for 6 weeks. Outcomes included GI quality-of-life (DQLQ), bloating and gas (PROMIS-GI 13a), abdominal discomfort (PROMIS-GI 5a), constipation, regularity, mood-related symptoms, and safety. Results: The multi-species synbiotic improved GI quality-of-life compared to placebo (0.80 vs. 1.20; p < 0.05) at Week 6. Bloating and gas were reduced in the synbiotic arm compared to placebo (16.0 vs. 21.0; p < 0.01), with more participants reporting never/rarely bloating (72.3% vs. 55.9%; p < 0.001). Abdominal discomfort also decreased (8.0 vs. 10.0; p < 0.01). Additionally, there was a statistically significant improvement in constipation symptoms and regularity in the synbiotic arm relative to placebo. Conclusions: Daily supplementation with this multi-species synbiotic significantly improved GI quality-of-life, bloating, gas, abdominal discomfort, and bowel habits. This is the first synbiotic to demonstrate meaningful improvements in bloating and gas in a generally healthy, diverse, real-world population.}, } @article {pmid41599863, year = {2026}, author = {Baek, HI and Kwon, SY and Noh, HJ and Park, SJ}, title = {Efficacy and Safety of CKDB-322, a Combination of Lactiplantibacillus plantarum Q180 and Phaeodactylum tricornutum, for Reducing Body Fat and Abdominal Adiposity in Overweight Adults.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599863}, issn = {2072-6643}, support = {20020268//Ministry of Trade, Industry and Energy/ ; 2025-RISE-13-WSU//Ministry of Education/ ; }, mesh = {Humans ; Female ; Male ; Adult ; Middle Aged ; Double-Blind Method ; *Probiotics/administration & dosage/adverse effects/therapeutic use ; *Overweight/therapy ; *Lactiplantibacillus plantarum ; *Adiposity ; *Abdominal Fat ; Aged ; Young Adult ; *Obesity, Abdominal/therapy ; *Diatoms ; Body Mass Index ; Treatment Outcome ; Adipose Tissue ; Waist Circumference ; }, abstract = {BACKGROUND: CKDB-322, a combination of Lactiplantibacillus plantarum Q180 and Phaeodactylum tricornutum, has shown anti-obesity potential in preclinical models, although human evidence is still limited. This randomized, double-blind, placebo-controlled, 12-week trial evaluated the efficacy and safety of CKDB-322 in overweight adults.

METHODS: Participants were aged 19-65 years; had a body mass index (BMI) of 25-30 kg/m[2], and a waist circumference of ≥90 cm for men or ≥85 cm for women. They were randomly assigned to receive either CKDB-322, which provided 1.0 × 10[9] CFU of L. plantarum Q180 and 200 mg of P. tricornutum daily (n = 50), or a placebo (n = 50).

RESULTS: CKDB-322 supplementation resulted in statistically significant reductions in body fat mass and body fat percentage, as measured by dual-energy X-ray absorptiometry (DEXA), compared to the placebo group (p < 0.05). Computed tomography (CT) analyses also revealed significant reductions in abdominal fat area in the CKDB-322 group (p < 0.05). Additional improvements were observed in body weight and anthropometric parameters. Among metabolic biomarkers, serum triglycerides and leptin levels decreased significantly in the CKDB-322 group compared to the placebo. Exploratory microbiome analyses indicated an increase in the relative abundance of Lactobacillus, suggesting potential modulation of the gut-adipose axis. CKDB-322 was well tolerated, with no clinically significant adverse events or laboratory abnormalities.

CONCLUSIONS: Collectively, CKDB-322 demonstrated a favorable safety profile and produced statistically significant improvements in multiple adiposity-related outcomes, including reductions in body fat mass, abdominal adiposity, and key anthropometric measures, supporting its potential as a functional ingredient for body fat reduction and metabolic health.}, } @article {pmid41599842, year = {2026}, author = {Adibi, S}, title = {A Conceptual Digital Health Framework for Longevity Optimization: Inflammation-Centered Approach Integrating Microbiome and Lifestyle Data-A Review and Proposed Platform.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599842}, issn = {2072-6643}, mesh = {Humans ; *Longevity ; *Inflammation ; Diet, Mediterranean ; *Life Style ; *Gastrointestinal Microbiome ; Biomarkers/blood ; Aged, 80 and over ; C-Reactive Protein/metabolism ; Male ; Artificial Intelligence ; Digital Health ; }, abstract = {Chronic low-grade inflammation, or "inflammaging," represents a central mechanism linking dietary patterns, gut microbiome composition, and biological aging. Evidence from Blue Zone populations and Mediterranean diet studies demonstrates that specific nutritional interventions are associated with up to 23% lower all-cause mortality, with analyses suggesting that part of this association may be mediated by measurable improvements in inflammatory biomarkers. This paper synthesizes published evidence from Mediterranean diet trials, centenarian microbiome studies, and digital health platforms to propose a comprehensive digital health framework that integrates quarterly inflammation and microbiome monitoring with continuous lifestyle tracking to deliver personalized longevity interventions. This paper introduces the Longevity-Inflammation Index (L-II), a composite score combining high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and microbiome-derived markers, with scoring algorithms derived from centenarian population studies. The proposed platform leverages artificial intelligence to generate evidence-based recommendations adapted from centenarian and Mediterranean dietary patterns. Published evidence from multiple randomized controlled trials demonstrates that Mediterranean dietary interventions reduce hs-CRP by 18-32%, increase microbiome diversity by 6-28%, and improve metabolic markers including HOMA-IR and TG/HDL ratios. Digital health platforms demonstrate sustained engagement rates of 58-84% at 12 months, with dietary logging frequencies of 4-6 days per week. Cost-effectiveness analyses of dietary interventions show incremental cost-effectiveness ratios of USD 2100-4800 per quality-adjusted life year gained. This inflammation-centered digital health framework offers a scalable approach for translating longevity research into practical interventions for healthy aging, with validation studies needed to confirm the integrated platform's efficacy and real-world implementation feasibility.}, } @article {pmid41599822, year = {2026}, author = {De Beul, E and Heyse, J and Jurgelewicz, M and Baudot, A and Vu, LD and Van den Abbeele, P}, title = {N-Acetylglucosamine and Immunoglobulin Strengthen Gut Barrier Integrity via Complementary Microbiome Modulation.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599822}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Acetylglucosamine/pharmacology ; Adult ; Animals ; Caco-2 Cells ; *Immunoglobulins/pharmacology ; Fatty Acids, Volatile/metabolism ; *Intestinal Mucosa/drug effects/microbiology/metabolism ; Cattle ; Male ; Female ; Coculture Techniques ; }, abstract = {Background: Gut barrier dysfunction and altered gut microbial metabolism are emerging signatures of chronic gut disorders. Considering growing interest in combining structurally and mechanistically distinct bioactives, we investigated the individual and combined effects of serum-derived bovine immunoglobulin (SBI) and N-acetylglucosamine (NAG) on the gut microbiome and barrier integrity. Methods: The validated ex vivo SIFR[®] (Systemic Intestinal Fermentation Research) technology, using microbiota from healthy adults (n = 6), was combined with a co-culture of epithelial/immune (Caco-2/THP-1) cells. Results: While SBI and NAG already significantly improved gut barrier integrity (TEER, transepithelial electrical resistance, +21% and +29%, respectively), the strongest effect was observed for SBI_NAG (+36%). This potent combined effect related to the observation that SBI and NAG each induced distinct, complementary shifts in microbial composition and metabolite output. SBI most selectively increased propionate (~Bacteroidota families) and health-associated indole derivatives (e.g., indole-3-propionic acid), while NAG most specifically boosted acetate and butyrate (~Bifidobacteriaceae, Ruminococcaceae, and Lachnospiraceae). The combination of SBI_NAG displayed effects of the individual ingredients, thus, for instance, enhancing all three short-chain fatty acids (SCFA) and elevating microbial diversity (CMS, community modulation score). Conclusions: Overall, SBI and NAG exert complementary, metabolically balanced effects on the gut microbiota, supporting combined use, particularly in individuals with gut barrier impairment or dysbiosis linked to lifestyle or early-stage gastrointestinal disorders.}, } @article {pmid41599794, year = {2026}, author = {Al Hazaimeh, R and Shackelford, L and Boateng, J}, title = {Effects of Mixed Fruits and Berries on Ameliorating Gut Microbiota and Hepatic Alterations Induced by Cafeteria Diet.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599794}, issn = {2072-6643}, support = {ALAX-012-0918//USDA/NIFA Capacity-Building Grant/ ; ALAX-12-2017//USDA/NIFA Evans-Allen/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Male ; Rats, Sprague-Dawley ; *Fruit ; *Liver/pathology/metabolism ; Rats ; Dysbiosis ; *Fatty Liver/etiology/prevention & control ; Disease Models, Animal ; Metabolic Syndrome/etiology ; *Diet/adverse effects ; }, abstract = {Background/Objectives: The study investigated the potential of mixed fruits and berries (MFB) as a dietary intervention to mitigate cafeteria (CAF) diet-induced gut microbiome dysbiosis and hepatic dysfunction associated with metabolic syndrome and steatohepatitis (MASH) in an adolescent rat model. Methods: Forty-eight adolescent male Sprague-Dawley rats (n = 3 cages per group (two rats per cage)) were divided into eight experimental groups, where NC received the normal AIN-93G basal diet, PC received the CAF diet and normal AIN-93G basal diet, T1 and T2 received MFB supplementation (3% and 6% levels) without CAF exposure, P1 and P2 received a MFB (3% and 6% levels) supplementation initiated at the onset of CAF feeding, and I1 and I2 received MFB supplementation initiated 2 weeks after CAF feeding. After 6 weeks, cecal 16S rRNA, hepatic histopathology, Oil Red O staining, and metabolic dysfunction-associated steatotic liver disease (MASLD)-related biomarkers (liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) were analyzed. Results: AST: ALT ratio was the highest in the PC group (3.63, p < 0.05) compared to the MFB groups. Oil Red O staining showed lower hepatic lipid accumulation, and histological analysis demonstrated a marked reduction in portal inflammatory cell infiltration in MFB. Alpha diversity (Simpson Index) decreased in PC (Kruskal-Wallis, p = 0.043). CAF increased Lactobacillus johnsonii (+75%, p < 0.05), while reducing L. murinus and L. intestinalis (~90%, p < 0.05). MFB supplementation restored Bifidobacterium Pseudolongum and increased Akkermansia muciniphila levels in the P2, I1, and I2 groups (~20-fold, p < 0.05). Bacteroides dorei was present in all groups except the PC group. These bacteria presented a positive correlation with key SCFAs. Conclusions: The results from this study indicated that MFB supplementation modulated gut microbiota composition and enhanced SCFA production, thereby strengthening intestinal barrier integrity and reducing gut-derived inflammation. Collectively, these effects attenuated hepatic lipid accumulation and inflammation, highlighting the potential of MFB to restore gut-liver axis homeostasis disrupted by CAF-induced dysbiosis in adolescent rats.}, } @article {pmid41599773, year = {2026}, author = {Mucci, B and Palazzolo, E and Ruberti, F and Ientile, L and Natale, M and Esposito, S}, title = {Advances in the Management of Pediatric Inflammatory Bowel Disease: From Biologics to Small Molecules.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, pmid = {41599773}, issn = {1424-8247}, abstract = {Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO-ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti-tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics-vedolizumab, ustekinumab, risankizumab, and mirikizumab-offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules-including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)-provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host-microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes.}, } @article {pmid41509254, year = {2026}, author = {Ramos, MAA and Gutkin, S and David, M and Shabat, D and Balskus, EP}, title = {Chemiluminescent probes allow for the rapid identification of colibactin-producing bacteria.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41509254}, issn = {2692-8205}, abstract = {The pks (or clb) gene cluster, which produces the genotoxic natural product colibactin, is encoded by human gut Enterobacteriaceae, including many commensal strains of E. coli. Colibactin crosslinks DNA and is implicated in colorectal cancer development, highlighting the importance of identifying colibactin-producing gut bacteria within biological samples. In this study, we develop phenoxy-dioxetane chemiluminescent probes that selectively react with a critical colibactin biosynthetic enzyme, the serine peptidase ClbP. We show that these chemiluminescent probes have superior sensitivity, speed, and detection capabilities compared to previously reported fluorescent ClbP probes. Furthermore, we employ these chemiluminescent probes to detect pks [+] E. coli directly in complex stool suspensions. These probes will enable multiple applications requiring detection of colibactin-producing bacteria, including the identification of ClbP inhibitors and the screening of clinical samples.}, } @article {pmid41454342, year = {2025}, author = {Song, H and Ma, Y and Peng, L and Gao, F and Fan, X and Yang, M and Hua, T and Yang, Y and Fan, R and Li, Z and Yuan, H}, title = {Platinum-doped emodin carbon dots mitigate sepsis-induced lung injury by targeting the gut-lung axis.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {84}, pmid = {41454342}, issn = {1477-3155}, support = {82471239//National Natural Science Foundation of China/ ; JDLCZDZK//Military clinical key specialty project fund/ ; }, abstract = {UNLABELLED: Sepsis-induced acute lung injury is a life-threatening complication with limited therapeutic options. Although the gut-lung axis is crucial in sepsis pathogenesis, effective interventions targeting this pathway remain scarce. Here, we developed multi-enzymatic platinum-doped emodin carbon dots (Pt-ECDs) via a hydrothermal method. Pt-ECDs exhibited superior catalase, superoxide dismutase, glutathione peroxidase and peroxidase-like activities, enabling potent reactive oxygen species (ROS) scavenging. In a murine sepsis model, oral Pt-ECDs significantly improved survival, reduced systemic inflammation, and ameliorated lung injury. Transcriptomic analysis revealed that Pt-ECDs suppressed oxidative stress and macrophage pyroptosis in lung tissues. Mechanistically, integrated metabolomic and microbiome analyses demonstrated that Pt-ECDs modulated the gut microbiota, specifically inhibiting g_Bacteroides-derived palmitic acid (PA) production. We further confirmed that PA exacerbates macrophage pyroptosis and pro-inflammatory polarization by directly binding to NOX2 and NLRP3. Crucially, fecal microbiota transplantation from Pt-ECDs-treated mice attenuated septic lung injury, whereas microbiota depletion abolished the therapeutic benefits. Collectively, our findings identify Pt-ECDs as a promising nanotherapeutic that alleviates septic lung injury by targeting the gut microbiota-palmitic acid-pyroptosis axis.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-025-03972-0.}, } @article {pmid41082399, year = {2026}, author = {Ravenscraft, A and Coon, KL}, title = {Transient Microbes in Insects: Fleeting but Functional.}, journal = {Annual review of entomology}, volume = {71}, number = {1}, pages = {253-273}, doi = {10.1146/annurev-ento-121423-013446}, pmid = {41082399}, issn = {1545-4487}, mesh = {Animals ; *Insecta/microbiology ; *Gastrointestinal Microbiome ; Symbiosis ; }, abstract = {Many insects' gut microbiota derive partly or wholly from environmental sources. These microbes may be transient, passing through in a matter of hours, days, a developmental stage, or a host generation. There is increasing recognition of the presence of transient microbes in the insect gut, but it is often assumed that these microbes are commensal and serve no function for their hosts. Here, we explore different definitions of microbial transience and review results from diverse insect systems showing that transience does not always preclude, and in some cases enables, important contributions of environmentally acquired microbes to host fitness. Moving past the assumption that microbes must always be tightly associated with a host to serve beneficial functions will help us develop a more accurate and nuanced understanding of the functions of the gut microbiota in insects and other animals.}, } @article {pmid40925006, year = {2026}, author = {Hu, Y and Moreau, CS}, title = {Nutritional Symbiosis Between Ants and Their Symbiotic Microbes.}, journal = {Annual review of entomology}, volume = {71}, number = {1}, pages = {35-49}, doi = {10.1146/annurev-ento-121423-013513}, pmid = {40925006}, issn = {1545-4487}, mesh = {*Ants/microbiology/physiology ; *Symbiosis ; Animals ; *Microbiota ; }, abstract = {Nutritional symbioses with microorganisms have profoundly shaped the evolutionary success of ants, enabling them to overcome dietary limitations and thrive across diverse ecological niches and trophic levels. These interactions are particularly crucial for ants with specialized diets, where microbial symbionts compensate for dietary imbalances by contributing to nitrogen metabolism, vitamin supplementation, and the catabolism of plant fibers and proteins. This review synthesizes recent advances in our understanding of ant-microbe symbioses, focusing on diversity, functional roles in host nutrition, and mechanisms of transmission of symbiotic microorganisms. Despite progress, most research has concentrated on a few ant genera, and further exploration of microbial roles in different ant morphs and life stages and across various ant species is needed. Expanding research to include a broader array of ant lineages and integrating genomic data with additional experimental data will provide deeper insights into the metabolic strategies that facilitate ant success across diverse ecological habitats.}, } @article {pmid41599753, year = {2026}, author = {Jin, Y and Wang, L and Lin, R and He, J and Liu, D and Liu, Y and Deng, Y}, title = {Synergistic Effects of Plant Polysaccharides and Probiotics: A Novel Dietary Approach for Parkinson's Disease Intervention.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ph19010157}, pmid = {41599753}, issn = {1424-8247}, support = {Grant Nos. 82003985, 81973712, and 82004030//the National Natural Science Foundation of China/ ; Grant No. 20230204019YY//the Jilin Province Science and Technology Development Plant/ ; Grant No. 2023C027-3//the Jilin Provincial Development and Reform Commission Project/ ; Grant Nos, S202410199012, S202410199095X, andS202510199023//the Undergraduate Innovation and Entrepreneurship Proiects/ ; }, abstract = {Parkinson's disease (PD), the second most common neurodegenerative disorder globally, relies primarily on dopamine replacement therapy for conventional treatment. This approach fails to reverse core pathological processes and is associated with long-term side effects. Recent research on the microbiota-gut-brain axis (MGBA) has revealed that PD pathology may originate in the gut, forming a vicious cycle from the gut to brain through α-synuclein propagation, gut dysbiosis, intestinal barrier disruption, and neuroinflammation. This offers a novel perspective for managing PD through dietary interventions that modulate the gut microbiome. However, single probiotic or prebiotic interventions show limited efficacy. This review systematically introduces the novel concept of "synbiotics combining medicinal plant polysaccharides with probiotics," aiming to integrate traditional "medicinal food" wisdom with modern microbiome science. The article systematically elucidates the pathological mechanisms of MGBA dysfunction in PD and the intervention mechanisms of probiotics and emphasizes the structural and functional advantages of medicinal plant polysaccharide as superior prebiotics. The core section delves into the multifaceted synergistic mechanisms between these two components: enhancing probiotic colonization and vitality, optimizing microbial metabolic output, synergistically reinforcing the intestinal and blood-brain barriers, and jointly regulating immune and neuroinflammation. This approach targets the MGBA to achieve multi-level intervention for PD.}, } @article {pmid41599684, year = {2026}, author = {Bangeppagari, M and Jagadish, P and Srinivasa, A and Choi, W and Tiwari, P}, title = {Natamycin in Food and Ophthalmology: Knowledge Gaps and Emerging Insights from Zebrafish Models.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ph19010086}, pmid = {41599684}, issn = {1424-8247}, abstract = {Natamycin, a polyene macrolide antifungal, has long been used as a food preservative and is the only Food and Drug Administration (FDA)-approved topical treatment for fungal keratitis. While its safety is supported by specific ergosterol interaction and minimal systemic absorption, current research mainly focuses on short-term effects, often overlooking long-term, developmental, and microbiome-related impacts. In food applications, questions remain about cumulative exposure and potential disruptions to gut microbiota. For ophthalmology, advanced delivery methods like nanocarriers and hydrogels enhance drug penetration but may alter pharmacokinetics and pose formulation challenges. Regulatory approvals have historically depended on established safe use and limited toxicological data, emphasizing the need for more systematic evaluations. Zebrafish (Danio rerio) represent a promising yet underutilized model for addressing significant gaps in research, particularly in the realms of microbiome studies, ocular health, developmental processes, and multigenerational effects. When paired with omics technologies, zebrafish facilitate comprehensive system-level mapping of drug-induced outcomes. This review consolidates existing evidence and positions zebrafish as a vital translational link between in vitro assays, mammalian models, and clinical practice. Additionally, it proposes a framework to ensure the effective and scientifically supported use of natamycin in both food and medicinal applications.}, } @article {pmid41599664, year = {2025}, author = {Hwang, JH and Choi, YK}, title = {Herbal and Natural Products for Antibiotic-Associated Diarrhea: A Systematic Review of Animal Studies Focusing on Molecular Microbiome and Barrier Outcomes.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ph19010064}, pmid = {41599664}, issn = {1424-8247}, support = {NRF-2022R1A2C1013518//National Research Foundation of Korea/ ; }, abstract = {Background/Objectives: Antibiotic-associated diarrhea (AAD) arises from antibiotic-induced disruption of microbial diversity, metabolic activity, epithelial integrity, and mucosal immunity. Probiotics are widely used but often show limited efficacy under antibiotic pressure. Herbal and natural products (HNPs) may provide multi-target benefits by modulating microbiota-dependent and host-directed pathways. This review synthesized animal studies evaluating HNP or HNP-probiotic combination (HNP-C) therapies using molecular microbiome endpoints. Methods: Following PRISMA 2020 guidelines, controlled in vivo studies assessing HNP or HNP-C interventions for AAD were searched in Pubmed, EMBASE, Web of Science, Scopus, and CNKI through November 2025. Eligible studies reported microbial diversity, taxonomic shifts, short-chain fatty acids (SCFAs), barrier markers, or immune responses. Risk of bias was assessed using the SYRCLE tool. Due to heterogeneity, findings were narratively synthesized. Results: Twenty-seven studies met inclusion criteria (21 HNP, 6 HNP-C). HNP monotherapies consistently improved α-diversity, shifted β-diversity toward healthy controls, restored SCFA-producing taxa, and increased SCFA levels. They also enhanced tight junction proteins and reduced inflammatory cytokines. HNP-C interventions demonstrated more comprehensive microbial, epithelial, and immune recovery; however, only two studies included direct comparisons among HNP-only, probiotic-only, and combination groups. In these, HNP-C showed greater improvements than individual components, suggesting complementary or potentially complementary or additive effects. Other HNP-C studies were limited by absent comparator arms. Conclusions: HNPs appear to support recovery of microbial diversity, metabolic function, epithelial barrier integrity, and immune regulation by engaging microbiota-dependent and host-mediated mechanisms. HNP-C strategies may offer complementary benefits, although rigorously controlled comparative studies and clinical validation remain needed.}, } @article {pmid41599644, year = {2025}, author = {Machado, EP and Junkert, AM and Lazo, REL and Fernandes, IDC and Tonin, FS and Ferreira, LM and Borba, HHL and Pontarolo, R}, title = {Mapping the Vaginal Metabolic Profile in Dysbiosis, Persistent Human Papillomavirus Infection, and Cervical Intraepithelial Neoplasia: A Scoping Review.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ph19010042}, pmid = {41599644}, issn = {1424-8247}, abstract = {Background/Objectives: This scoping review aimed to map evidence on metabolic alterations in the vaginal environment associated with dysbiosis, transient and persistent human papillomavirus (HPV) infection, and cervical dysplasia, highlighting potential metabolic and protein biomarkers for early detection of cervical cancer. Methods: Systematic searches were conducted in PubMed, Scopus, and Web of Science, following the JBI methodology and PRISMA-ScR guidelines. Studies jointly evaluating vaginal metabolites and proteins in women with HPV and cervical intraepithelial neoplasia (CIN) in the context of dysbiosis were included. Results: After duplicate removal, 196 records were screened, and 41 studies were selected-mostly cross-sectional observational designs-published between 2006 and 2025, predominantly by Chinese research groups. Lactobacillus spp. predominated in HPV-negative women, while HPV infection was associated with a dysbiotic environment enriched with anaerobes such as Gardnerella vaginalis, Atopobium vaginae, Prevotella, and Sneathia. Of 389 metabolic and protein markers associated with HPV infection and CIN, 44 underwent ROC analysis, with prolineaminopeptidase, 5'-O-methylmelledonal, and calonectin showing high diagnostic performance (AUC > 0.90). Conclusions: These results suggest vaginal microbiome and metabolic profiles may represent promising biomarkers for persistent HPV infection. Further, longitudinal studies with larger samples are needed for clinical validation.}, } @article {pmid41599414, year = {2026}, author = {Buendia-Corona, RE and Velasco Dey, MF and Valencia Robles, L and Hernández-Biviano, HJ and Hermosillo-Abundis, C and Castro-Pastrana, LI}, title = {Computational Identification of Blood-Brain Barrier-Permeant Microbiome Metabolites with Binding Affinity to Neurotransmitter Receptors in Neurodevelopmental Disorders.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {2}, pages = {}, doi = {10.3390/molecules31020366}, pmid = {41599414}, issn = {1420-3049}, support = {CVU 921738//SECIHTI/ ; }, mesh = {*Blood-Brain Barrier/metabolism ; Humans ; *Neurodevelopmental Disorders/metabolism/microbiology ; Molecular Docking Simulation ; *Receptors, Neurotransmitter/metabolism/chemistry ; *Gastrointestinal Microbiome ; }, abstract = {The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and receptor-mediated neuromodulation remain unclear. We screened 27,642 microbiome SMILES metabolites for blood-brain barrier permeability using rule-based SwissADME classification and a PyTorch 2.0 neural network trained on 7807 experimental compounds (test accuracy 86.2%, AUC 0.912). SwissADME identified 1696 BBB-crossing metabolites following Lipinski's criteria, while PyTorch classified 2484 metabolites with expanded physicochemical diversity. Following 3D conformational optimization (from SMILES) and curation based on ≤32 rotatable bonds, molecular docking was performed against five neurotransmitter receptors representing ionotropic (GABRA2, GRIA2, GRIN2B) and metabotropic (DRD4, HTR1A) receptor classes. The top 50 ligands across five receptors demonstrated method-specific BBB classification (44% SwissADME-only, 44% PyTorch-only, 12% overlap), validating complementary prediction approaches. Fungal metabolites from Ascomycota dominated high-affinity top ligands (66%) and menaquinone MK-7 showed broad phylogenetic conservation (71.4% of phylum). Our results establish detailed receptor-metabolite interaction maps, with fungal metabolites dominating high-affinity ligands, challenging the prevailing bacterial focus of the microbiome and providing a foundation for precision medicine and a framework for developing microbiome-targeted therapeutics to address clinical needs in neurodevelopmental disorders.}, } @article {pmid41599407, year = {2026}, author = {Cevallos-Fernández, E and Beltrán-Sinchiguano, E and Jácome, B and Quintana, T and Rivera, N}, title = {Fermented Plant-Based Foods and Postbiotics for Glycemic Control-Microbial Biotransformation of Phytochemicals.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {2}, pages = {}, doi = {10.3390/molecules31020360}, pmid = {41599407}, issn = {1420-3049}, mesh = {Humans ; *Phytochemicals/metabolism/pharmacology ; Animals ; *Fermented Foods ; *Glycemic Control ; Biotransformation ; Fermentation ; Gastrointestinal Microbiome ; }, abstract = {Plant-based fermented foods are increasingly promoted for glycemic control, yet their mechanisms and clinical impact remain incompletely defined. This narrative review synthesizes mechanistic, preclinical, and human data for key matrices-kimchi and other fermented vegetables, tempeh/miso/natto, and related legume ferments, kombucha and fermented teas, plant-based kefir, and cereal/pulse sourdoughs. Across these systems, microbial β-glucosidases, esterases, tannases, and phenolic-acid decarboxylases remodel polyphenols toward more bioaccessible aglycones and phenolic acids, while lactic and acetic fermentations generate organic acids, exopolysaccharides, bacterial cellulose, γ-polyglutamic acid, γ-aminobutyric acid, and bioactive peptides. We map these postbiotic signatures onto proximal mechanisms-α-amylase/α-glucosidase inhibition, viscosity-driven slowing of starch digestion, gastric emptying and incretin signaling, intestinal-barrier reinforcement, and microbiota-dependent short-chain-fatty-acid and bile-acid pathways-and their downstream effects on AMPK/Nrf2 signaling and the gut-liver axis. Animal models consistently show improved glucose tolerance, insulin sensitivity, and hepatic steatosis under fermented vs. non-fermented diets. In humans, however, glycemic effects are modest and highly context-dependent: The most robust signal is early postprandial attenuation with γ-PGA-rich natto, strongly acidified or low-glycemic sourdough breads, and selected kombucha formulations, particularly in individuals with impaired glucose regulation. We identify major sources of heterogeneity (starters, process parameters, substrates, background diet) and safety considerations (sodium, ethanol, gastrointestinal symptoms) and propose minimum reporting standards and trial designs integrating metabolomics, microbiome, and host-omics. Overall, plant-based ferments appear best positioned as adjuncts within cardiometabolic dietary patterns and as candidates for "purpose-built" postbiotic products targeting early glycemic excursions and broader metabolic risk.}, } @article {pmid41599227, year = {2026}, author = {Cordero, C and Caballero-Román, A and Martínez-Ruiz, S and Olivo-Martínez, Y and Baldoma, L and Badia, J}, title = {Extracellular Vesicles from Probiotic and Beneficial Escherichia coli Strains Exert Multifaceted Protective Effects Against Rotavirus Infection in Intestinal Epithelial Cells.}, journal = {Pharmaceutics}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/pharmaceutics18010120}, pmid = {41599227}, issn = {1999-4923}, support = {PID2019-107327RB-100//MCIU(MICCIN)/AEI/ ; PID2022-137192OB-I00//MICIU/AEI/10.13039/501100011033/ ; }, abstract = {Background/Objectives: Rotavirus remains a major cause of severe acute gastroenteritis in infants worldwide. The suboptimal efficacy of current vaccines underscores the need for alternative microbiome-based interventions, including postbiotics. Extracellular vesicles (EVs) from probiotic and commensal E. coli strains have been shown to mitigate diarrhea and enhance immune responses in a suckling-rat model of rotavirus infection. Here, we investigate the regulatory mechanisms activated by EVs in rotavirus-infected enterocytes. Methods: Polarized Caco-2 monolayers were used as a model of mature enterocytes. Cells were pre-incubated with EVs from the probiotic E. coli Nissle 1917 (EcN) or the commensal EcoR12 strain before rotavirus infection. Intracellular Ca[2+] concentration, ROS levels, and the expression of immune- and barrier-related genes and proteins were assessed at multiple time points post-infection. Results: EVs from both strains exerted broad protective effects against rotavirus-induced cellular dysregulation, with several responses being strain-specific. EVs interfered with viral replication by counteracting host cellular processes essential for rotavirus propagation. Specifically, EV treatment significantly reduced rotavirus-induced intracellular Ca[2+] mobilization, ROS production, and COX-2 expression. In addition, both EV types reduced virus-induced mucin secretion and preserved tight junction organization, thereby limiting viral access to basolateral coreceptors. Additionally, EVs enhanced innate antiviral defenses via distinct, strain-dependent pathways: EcN EVs amplified IL-8-mediated responses, whereas EcoR12 EVs preserved the expression of interferon-related signaling genes. Conclusions: EVs from EcN and EcoR12 act through multiple complementary mechanisms to restrict rotavirus replication, spread, and immune evasion. These findings support their potential as effective postbiotic candidates for preventing or treating rotavirus infection.}, } @article {pmid41599184, year = {2026}, author = {Caturano, A and Nilo, D and Nilo, R and Sircana, MC and Erul, E and Zielińska, K and Russo, V and Santonastaso, E and Sasso, FC}, title = {Old Drug, New Science: Metformin and the Future of Pharmaceutics.}, journal = {Pharmaceutics}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/pharmaceutics18010077}, pmid = {41599184}, issn = {1999-4923}, abstract = {Metformin, a 60-year-old biguanide and cornerstone of type 2 diabetes therapy, continues to challenge and inspire modern pharmaceutical science. Despite its chemical simplicity, metformin displays highly complex pharmacokinetic and pharmacodynamic behavior driven by transporter dependence, luminal activity, and formulation-sensitive exposure. Originally regarded as limited by low permeability and incomplete absorption, metformin has emerged as a paradigm for gut-targeted therapy, controlled- and delayed-release systems, and personalized pharmaceutics. Growing evidence has repositioned the intestine, rather than systemic plasma exposure, as a major site of action, highlighting the central role of organic cation transporters and multidrug efflux systems in determining efficacy, variability, and gastrointestinal tolerability. Beyond metabolic control, insights into transporter regulation, pharmacogenetics, microbiome interactions, and manufacturing quality have expanded metformin's relevance as a model compound for contemporary drug development. Advances in formulation design, quality-by-design manufacturing, and regulatory control have further reinforced its clinical robustness, while repurposing efforts in oncology, immunometabolism, and regenerative medicine underscore its translational potential. This review integrates mechanistic pharmacology, formulation science, and clinical translation to position metformin not merely as an antidiabetic agent, but as a didactic model illustrating the evolution of pharmaceutics from molecule-centered design to system-oriented, precision-driven therapy.}, } @article {pmid41599092, year = {2026}, author = {Sinhalage, K and Polizel, GHG and Karrow, NA and Schenkel, FS and Cánovas, Á}, title = {Sheep Genetic Resistance to Gastrointestinal Nematode Infections: Current Insights from Transcriptomics and Other OMICs Technologies-A Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/pathogens15010106}, pmid = {41599092}, issn = {2076-0817}, support = {0//Ontario Ministry of Agriculture, Food and Agribusiness (OMAFA), the Ontario Agri-Food Innovation Alliance/ ; 0//Agricultural Research and Innovation Ontario (ARIO)/ ; 0//Ontario Sheep Farmers/ ; 0//the Natural Sciences and Engineering Research Council of Canada (NSERC; Ottawa, Ontario, Canada) and the NSERC - Discovery Grant Established Researchers/ ; 0//Food from Thought, University of Guelph/ ; }, mesh = {Animals ; Sheep ; *Sheep Diseases/parasitology/genetics/immunology ; *Nematode Infections/veterinary/genetics/parasitology/immunology ; *Disease Resistance/genetics ; Transcriptome ; Nematoda ; Genomics/methods ; *Gastrointestinal Diseases/veterinary/genetics/parasitology/immunology ; Host-Parasite Interactions/genetics ; Proteomics ; Gene Expression Profiling ; }, abstract = {Gastrointestinal nematode (GIN) infections are the most prevalent parasitic diseases in grazing sheep worldwide, causing significant productivity losses, high mortality and, as a result, economic losses and emerging animal welfare concerns. Conventional control strategies, primarily relying on anthelmintic treatments, face limitations due to rising drug resistance and environmental concerns, underscoring the need for sustainable alternatives. Selective breeding for host genetic resistance has emerged as a promising strategy, while recent advances in transcriptomics and integrative omics research are providing deeper insights into the immune pathways and molecular and genetic mechanisms that underpin host-parasite interactions. This review summarizes current evidence on transcriptomic signatures associated with resistance and susceptibility to H. contortus and T. circumcincta GIN infections, highlighting candidate genes, functional genetic markers, key immune pathways, and regulatory networks. Furthermore, we discuss how other omics approaches, including genomics, proteomics, metabolomics, microbiome, and multi-omics integrations, provide perspectives that enhance the understanding of the complexity of the GIN resistance trait. Transcriptomic studies, particularly using RNA-Sequencing technology, have revealed differential gene expression, functional genetic variants, such as SNPs and INDELs, in expressed regions and splice junctions, and regulatory long non-coding RNAs that distinguish resistance from susceptible sheep, highlighting pathways related to Th2 immunity, antigen presentation, tissue repair, and stress signaling. Genomic analyses have identified SNPs, QTL, and candidate genes linked to immune regulation and parasite resistance. Proteomic and metabolomic profiling further elucidates breed- and tissue-specific alterations in protein abundance and metabolic pathways, while microbiome studies demonstrate distinct microbial signatures in resistant sheep, suggesting a role in modulating host immunity. In conclusion, emerging multi-omics approaches and their integration strategies provide a comprehensive framework for understanding the complex host-parasite interactions that govern GIN resistance, offering potential candidate biomarkers for genomic selection and breeding programs aimed at developing sustainable, parasite-resistant sheep populations.}, } @article {pmid41599047, year = {2026}, author = {Gioula, G and Exindari, M}, title = {The Airway Microbiome as a Modulator of Influenza Virus Infection: Mechanistic Insights and Translational Perspectives-Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/pathogens15010063}, pmid = {41599047}, issn = {2076-0817}, mesh = {Humans ; *Influenza, Human/microbiology/virology/immunology ; *Microbiota ; Animals ; *Orthomyxoviridae ; *Respiratory System/microbiology ; }, abstract = {Outcomes of influenza virus infection vary widely across individuals, reflecting not only viral genetics and host factors but also the composition and function of the airway microbiome. Over the past few years, mechanistic work has clarified how specific commensals (for example, Staphylococcus epidermidis and Streptococcus oralis) restrict influenza replication by priming epithelial interferon-λ programs, reshaping intracellular metabolite pools (notably polyamines), dampening host protease activity, and maintaining barrier integrity; meanwhile, pathobionts (notably Staphylococcus aureus and Streptococcus pneumoniae) can enhance viral fitness via secreted proteases and neuraminidases that activate hemagglutinin and remodel sialylated glycoconjugates and mucus, setting the stage for secondary bacterial disease. Recent studies also highlight the gut-lung axis: gut microbiota-derived short-chain fatty acids (SCFAs), especially acetate, protect tight junctions and modulate antiviral immunity in influenza models. Together, these insights motivate translational strategies-from intranasal live biotherapeutics (LBPs) to metabolite sprays and decoy/dual neuraminidase approaches-that complement vaccines and antivirals. We synthesize recent evidence and outline a framework for leveraging the airway microbiome to prevent infection, blunt severity, and reduce transmission. Key priorities include strain-level resolution of commensal effects, timing/dosing windows for metabolites and LBPs, and microbiome-aware clinical pathways for anticipating and averting bacterial coinfection. Overall, the airway microbiome emerges as a tractable lever for influenza control at the site of viral entry, with several candidates moving toward clinical testing.}, } @article {pmid41599046, year = {2026}, author = {Plewa, P and Graczyk, P and Figiel, K and Dach, A and Pawlik, A}, title = {Gut and Joint Microbiome and Dysbiosis: A New Perspective on the Pathogenesis and Treatment of Osteoarthritis.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/pathogens15010062}, pmid = {41599046}, issn = {2076-0817}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Osteoarthritis/therapy/microbiology/pathology/etiology ; *Dysbiosis/microbiology/therapy ; Probiotics/therapeutic use ; Animals ; *Joints/microbiology/pathology ; }, abstract = {Osteoarthritis (OA) is one of the most common and burdensome musculoskeletal disorders and a major cause of pain, disability, and reduced quality of life worldwide. In recent years, increasing attention has been paid to extra-articular factors influencing its development and progression, opening new avenues of research into pathophysiological mechanisms and potential therapies. One of the most promising areas concerns the role of the gut-joint axis and related alterations in the gut microbiome. Numerous studies indicate that an imbalance of gut bacteria, increased intestinal permeability, and low-grade inflammation may contribute to the progression of degenerative joint processes. The mechanisms through which the microbiota influences the immune system and host metabolism are becoming increasingly well understood, including pathways involving short-chain fatty acids, tryptophan metabolites, and bile acids. Despite growing evidence linking dysbiosis to the pathogenesis of OA, effective therapeutic strategies based on microbiome modulation remain under active investigation. Among the most frequently studied approaches are probiotics, dietary interventions, and more advanced strategies such as gut microbiota transplantation and targeted modulation of microbial metabolites. However, before these methods can become part of routine treatment, extensive clinical trials and a clearer understanding of causal relationships between the microbiome and joint degeneration are required. This article summarises the current state of knowledge regarding the role of the gut microbiome in osteoarthritis, outlines key research findings, and highlights current and potential therapeutic directions.}, } @article {pmid41599039, year = {2026}, author = {Wang, Z and Chen, G and Yang, M and Wang, S and Fang, J and Shi, C and Gu, Y and Ning, Z}, title = {Host-Filtered Blood Nucleic Acids for Pathogen Detection: Shared Background, Sparse Signal, and Methodological Limits.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/pathogens15010055}, pmid = {41599039}, issn = {2076-0817}, support = {2024-PWXZ-04//New Quality Clinical Specialty Program of High-end Medical Disciplinary Construction in Shanghai Pudong New Area/ ; 2024ZDXK0019//Shanghai Municipal Health Commission, Key Discipline of Shanghai Health System, Cardiology/ ; PW2025D-01//The Scientific Research Program of Shanghai Pudong New Area Health Commission (the Joint Research and Development Program)/ ; }, mesh = {Humans ; *Metagenomics/methods ; *Tuberculosis/microbiology/diagnosis/blood ; Microbiota/genetics ; *Cell-Free Nucleic Acids/blood/genetics ; *Coronary Artery Disease/microbiology/diagnosis/blood ; Mycobacterium tuberculosis/genetics/isolation & purification ; Male ; Female ; Cohort Studies ; }, abstract = {Plasma cell-free RNA (cfRNA) metagenomics is increasingly explored for blood-based pathogen detection, but the structure of the shared background "blood microbiome", the reproducibility of reported signals, and the practical limits of this approach remain unclear. We performed a critical re-analysis and benchmarking ("stress test") of host-filtered blood RNA sequencing data from two cohorts: a bacteriologically confirmed tuberculosis (TB) cohort (n = 51) previously used only to derive host cfRNA signatures, and a coronary artery disease (CAD) cohort (n = 16) previously reported to show a CAD-shifted "blood microbiome" enriched for periodontal taxa. Both datasets were processed with a unified pipeline combining stringent human read removal and taxonomic profiling using the latest versions of specialized tools Kraken2 and MetaPhlAn4. Across both cohorts, only a minority of non-host reads were classifiable; under strict host filtering, classified non-host reads comprised 7.3% (5.0-12.0%) in CAD and 21.8% (5.4-31.5%) in TB, still representing only a small fraction of total cfRNA. Classified non-host communities were dominated by recurrent, low-abundance taxa from skin, oral, and environmental lineages, forming a largely shared, low-complexity background in both TB and CAD. Background-derived bacterial signatures showed only modest separation between disease and control groups, with wide intra-group variability. Mycobacterium tuberculosis-assigned reads were detectable in many TB-positive samples but accounted for ≤0.001% of total cfRNA and occurred at similar orders of magnitude in a subset of TB-negative samples, precluding robust discrimination. Phylogeny-aware visualization confirmed that visually "enriched" taxa in TB-positive plasma arose mainly from background-associated clades rather than a distinct pathogen-specific cluster. Collectively, these findings provide a quantitative benchmark of the background-dominated regime and practical limits of plasma cfRNA metagenomics for pathogen detection, highlighting that practical performance is constrained more by a shared, low-complexity background and sparse pathogen-derived fragments than by large disease-specific shifts, underscoring the need for transparent host filtering, explicit background modeling, and integration with targeted or orthogonal assays.}, } @article {pmid41599006, year = {2025}, author = {Kaminska, D and Ratajczak, M and Nowicka, W and Dlugaszewska, J and Gajecka, M}, title = {New Strategies for Preventing Perinatal Group B Streptococcus (GBS) Infections.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/pathogens15010022}, pmid = {41599006}, issn = {2076-0817}, mesh = {Humans ; *Streptococcal Infections/prevention & control/microbiology ; *Streptococcus agalactiae/drug effects/immunology ; Pregnancy ; Female ; Infant, Newborn ; *Infectious Disease Transmission, Vertical/prevention & control ; *Pregnancy Complications, Infectious/prevention & control/microbiology ; Anti-Bacterial Agents/therapeutic use ; Antibiotic Prophylaxis/methods ; Streptococcal Vaccines/immunology ; Vagina/microbiology ; }, abstract = {Group B Streptococcus (GBS) is a component of the natural human microbiota, colonizing the genitourinary tract and the distal gastrointestinal tract. Due to its production of numerous virulence factors, GBS can cause infections in pregnant women, newborns, and immunocompromised individuals. In newborns, GBS infection may present as severe pneumonia, meningitis, or sepsis. Screening for maternal GBS colonization, combined with intrapartum antibiotic prophylaxis for colonized women, is currently regarded as the most effective strategy for preventing neonatal GBS infections. However, growing concerns regarding antibiotic resistance and the negative impact of antibiotics on the neonatal microbiome have intensified the search for alternative approaches. These include the development of a vaccine and methods to reduce vaginal colonization in pregnant women.}, } @article {pmid41598993, year = {2025}, author = {Wu, X and Zhang, X and Liang, Y and Chen, X and Guo, Y and Zhao, W}, title = {Causal Relationships Between the Oral Microbiome and Autoimmune Diseases: A Mendelian Randomization Study.}, journal = {Pathogens (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/pathogens15010009}, pmid = {41598993}, issn = {2076-0817}, support = {82270965//National Natural Science Foundation of China/ ; 2023B03J1253//Science and Technology Program in Guangzhou/ ; PY2024032//Science Research Cultivation Program of Stomatological Hospital, Southern Medical University/ ; }, mesh = {Humans ; Mendelian Randomization Analysis ; *Autoimmune Diseases/microbiology/etiology/genetics ; *Microbiota ; Genome-Wide Association Study ; *Mouth/microbiology ; Saliva/microbiology ; }, abstract = {The relationship between the oral microbiome and autoimmune diseases (ADs) has attracted considerable research interest. This study employed two-sample Mendelian randomization (MR) to investigate causal relationships between oral microbiota and six ADs, including rheumatoid arthritis (RA), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS). Using genome-wide association study data from oral microbiome features and ADs, we applied inverse-variance weighted estimation complemented by sensitivity analyses and reverse MR to assess robustness and reverse causation. Analysis of 309 tongue dorsum and 285 salivary microbial features identified four tongue dorsum and five salivary taxa with genome-wide significant causal effects. Specific microbial taxa from both oral niches demonstrated protective or risk-enhancing effects for RA, T1D, IBD, and MS, while no causal associations were found for SLE or SS. These findings establish the causal role of specific oral microbiota in autoimmune pathogenesis and highlight priority candidates for further investigation as potential microbial biomarkers.}, } @article {pmid41598945, year = {2026}, author = {Hirata, K and Suzuki, T and Yura, K and Asahi, T and Kataoka, K}, title = {Gut Microbiome Differences Across Mixed-Sex and Female-Only Social Rearing Regimes in Female Field Crickets Teleogryllus occipitalis (Orthoptera: Gryllidae).}, journal = {Insects}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/insects17010091}, pmid = {41598945}, issn = {2075-4450}, support = {24KJ2101//Japan Society for the Promotion of Science/ ; JPJ009237//Cabinet Office/ ; }, abstract = {The insect gut microbiome contributes to various host physiological processes and behaviors, such as digestion, nutrient absorption, immunity, mate choice, and fecundity. The social environment can shape gut microbial communities. Mixed-sex vs. female-only rearing is an important social context because it differs in exposure to the opposite sex and mating opportunities, which may in turn affect female physiology that may influence their gut microbiome. Despite the growing recognition of these social-microbial interactions, most studies have relied on 16S rRNA amplicon sequencing or qPCR, which provide only coarse taxonomic resolution and limited functional insight. In this study, we used whole-genome shotgun metagenomics to examine changes in microbial diversity and functional gene composition in the female field cricket Teleogryllus occipitalis (Serville) (Orthoptera: Gryllidae) reared under two social conditions: mixed-sex rearing and female-only rearing. Species richness and diversity analyses revealed that community composition separated between females from mixed-sex and female-only rearing. Functional profiling indicated higher relative abundances of genes annotated to nutrient processing and inter-bacterial competition in females from mixed-sex rearing, whereas females from female-only rearing showed relative enrichment of genes annotated to stress resistance and nitrogen fixation. These findings provide a genome-resolved foundation for testing how social rearing conditions covary with gut microbiome composition and functional potential in female crickets.}, } @article {pmid41598908, year = {2026}, author = {González-Peña, R and Hidalgo-Martínez, DO and Laredo-Tiscareño, SV and Huerta, H and de Luna-Santillana, EJ and Adame-Gallegos, JR and Rodríguez-Alarcón, CA and Rubio-Tabares, E and García-Rejón, JE and Muñoz-Ramírez, ZY and Tangudu, C and Garza-Hernández, JA}, title = {Characterization of the Bacteriome of Culicoides reevesi from Chihuahua, Northern Mexico: Symbiotic and Pathogenic Associations.}, journal = {Insects}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/insects17010052}, pmid = {41598908}, issn = {2075-4450}, support = {419- 395 24-23//Secretaría de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI)/ ; SIP20250075//Secretaría de Investigación y Posgrado from Instituto Politécnico Nacional/ ; }, abstract = {Culicoides biting midges are vectors of veterinary and zoonotic pathogens, yet the bacteriome of several species remains unexplored. Culicoides reevesi, a poorly studied species in northern Mexico, represents an opportunity to investigate microbial associations that may influence vector biology. Adults of C. reevesi were analyzed using 16S rRNA amplicon sequencing, followed by functional prediction with PICRUSt2. Heatmaps and pathway summaries were generated to highlight dominant taxa and functions. The bacteriome was dominated by Pseudomonadota, followed by Actinomycetota, Bacillota, and Bacteroidota. Symbiotic taxa such as Asaia and Cardinium were identified alongside potentially pathogenic bacteria, including Escherichia coli, Mycobacterium avium, Vibrio parahaemolyticus, and Enterococcus faecalis. Functional predictions indicated metabolic versatility, with abundant pathways related to aerobic respiration, the TCA cycle, amino acid biosynthesis, and quorum sensing. Despite all samples being collected from the same site and date, apparent differences in bacterial composition were observed across pools, suggesting microhabitat or host-related variability. This study provides the first taxonomic and functional baseline of the C. reevesi bacteriome. The detection of both symbiotic and pathogenic bacteria highlights the dual ecological role of the microbiome in host fitness and pathogen transmission potential. In conclusion, we suggest that these microbial associations influence vector physiology and competence, providing a basis for future microbiome-based control strategies. These findings emphasize the importance of integrating microbiome analyses into entomological surveillance and vector control strategies in endemic regions.}, } @article {pmid41598906, year = {2026}, author = {Guo, B and Yi, X and Sun, Q and Sun, K and Guo, L and Guo, Y}, title = {The Honey Bee Body Surface as a Microbial Hub: Connectivity Shaped by Monoculture vs. Polyculture Farming.}, journal = {Insects}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/insects17010053}, pmid = {41598906}, issn = {2075-4450}, abstract = {Honey bees, as vital pollinators and essential contributors to terrestrial ecosystems, play a critical role in maintaining biodiversity and ecological stability. Beyond their role as pollinators, honey bees are increasingly recognized as bioindicators of environmental health, with their microbiomes reflecting habitat quality, agricultural practices, and broader ecological conditions. This study examines the impact of monoculture and polyculture systems on bee-associated microbiomes, focusing on microbial diversity, composition, and functional roles. Microbial communities from floral surfaces, pollen, nectar, foraging bees, hive matrices, and bioaerosols were analyzed across three agricultural plots: a rape monoculture, a pear monoculture, and a polyculture plot. Using 16S rRNA amplicon sequencing, network co-occurrence analysis, and microbial source tracking, the findings reveal that plant species and cultivation methods significantly shape microbial dynamics (Adonis = 0.67 ***). Floral microbiomes exhibit host specificity (Adonis = 0.73 ***), while the honey bee body surface functions as a microbial hub linking environmental, floral, and hive microbial networks (average degree pear: 21.86; rape: 21.96). The polyculture system improves microbial diversity due to the diversity of nectar plants, enhancing ecosystem connectivity and potentially benefiting honey bee health. These results highlight the ecological importance of optimizing agricultural practices to preserve microbial diversity, enhance honey bee health, and maintain ecological stability.}, } @article {pmid41598897, year = {2025}, author = {Nie, Y and Yu, G and Hu, H}, title = {Niche Differentiation and Predicted Functions of Microbiomes in a Tri-Trophic Willow-Gall (Euura viminalis)-Parasitoid Wasp System.}, journal = {Insects}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/insects17010043}, pmid = {41598897}, issn = {2075-4450}, support = {32560120//National Natural Science Foundation of China/ ; }, abstract = {Chalcidoids (Hymenoptera: Chalcidoidea), the most important natural enemies of parasitoids, serve as a pivotal factor in the regulation and management of pest populations. Microbiotas mediate interactions among plants, herbivores, and natural enemies and shape host immunity, parasitoid development, and gall formation; however, the niche-specific diversity and functions of tritrophic parasitoid-host-gall systems remain unclear. Focusing on leaf galls induced on twisted willow (Salix matsudana f. tortuosa) by the willow-galling sawfly Euura viminalis and on two chalcidoids, Eurytoma aethiops and Aprostocetus sp., we profiled bacterial and fungal microbiomes across plant surfaces, gall lumen, host larval tissues, and parasitoids using HTAS. Fungal diversity peaked on parasitoids but was depleted in the gall lumen and host tissues; bacterial richness showed the opposite trend, peaking in the gall lumen and decreasing on parasitoids. In networks contrasted by kingdom, fungi showed positive interface-hub connectivity (Cladosporium, Alternaria), whereas bacteria showed negative hub-mediated associations (Pseudomonas, Acinetobacter), indicating habitat-specific replacements: exposed niches favored transport, two-component, secretion-motility and energy functions, whereas the gall lumen reduced transport/motility but selectively retained N/S metabolism; and in host tissues, information processing and nitrogen respiration were highlighted. These results inform microbiome-guided parasitoid biocontrol.}, } @article {pmid41598765, year = {2026}, author = {Khan, ZE and Dulai, AS and O'Neill, A and Min, M and Lee, J and Dion, C and Afzal, N and Chaudhuri, RK and Lee, A and Sivamani, RK}, title = {Impact of Isosorbide Diesters from Coconut and Sunflower Fatty Acids on Pediatric Atopic Dermatitis and the Skin Microbiome: A Randomized, Double-Blind, Vehicle-Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/jcm15020829}, pmid = {41598765}, issn = {2077-0383}, support = {N/A//Sytheon/ ; }, abstract = {Background/Objectives: Topical application of isosorbide diesters (IDEAS) derived from coconut and sunflower seed oil improve atopic dermatitis (AD) and reduce topical steroid use in adults. This randomized, double-blind, vehicle-controlled trial evaluates topical IDEAS (isosorbide diesters) with colloidal oatmeal for pediatric AD. Methods: Subjects aged 2-17 with mild to moderate AD applied either colloidal oatmeal cream or colloidal oatmeal cream with IDEAS daily. Hydrocortisone 2.5% was used as needed. AD severity, itch, sleep, steroid use, and microbiome data were collected at baseline, week 4, and week 8. Results: More participants in the IDEAS group compared to the control group achieved EASI 50 (81.0% vs. 56.3%, p = 0.10) and EASI 75 (42.9% vs. 18.8%, p = 0.12) and achieved a 4-point reduction in subjective itch at week 4 (45.5% vs. 6.3%, p = 0.0085) and week 8 (42.9% vs. 12.5%, p = 0.045). Use of topical steroids was lower in the IDEAS group (3.4 g vs. 13.3 g, p = 0.012) and the relative abundance of Staphylococcus aureus was reduced after 8 weeks. Conclusions: The addition of IDEAS to colloidal lotion improved AD, improved itch, reduced the use of topical steroids, and reduced the relative abundance of S. aureus in the skin microbiome.}, } @article {pmid41598409, year = {2026}, author = {Passali, GC and Santantonio, M and Passali, D and Passali, FM}, title = {The Diabetic Nose: A Narrative Review of Rhinologic Involvement in Diabetes (1973-2025).}, journal = {Journal of clinical medicine}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/jcm15020472}, pmid = {41598409}, issn = {2077-0383}, abstract = {Background: Although diabetes mellitus is traditionally viewed as a systemic metabolic disorder, growing evidence indicates that it also affects the upper airways through vascular, inflammatory, and neuro-sensory mechanisms. The sinonasal mucosa, highly vascularized and immunologically active, may represent an early target of diabetic microangiopathy and immune-metabolic imbalance. Objectives: Our objectives are to synthesize current evidence on the rhinologic manifestations of DM, with a focus on chronic rhinosinusitis, olfactory dysfunction, and other nasal disorders, and to identify the main pathophysiologic and clinical patterns linking diabetes to sinonasal disease. Results: Evidence suggests that DM, particularly type 2 DM, increases susceptibility to CRSwNP and modulates the sinonasal microbiome toward Gram-negative predominance. Surgical outcomes after endoscopic sinus surgery are generally comparable between diabetics and non-diabetics when perioperative care is optimized. Olfactory dysfunction occurs more frequently and severely in diabetic patients, likely reflecting the combined effects of chronic inflammation, vascular compromise, and insulin resistance. Additional manifestations include recurrent epistaxis, delayed mucociliary clearance, and chronic cough. Allergic rhinitis appears to not be increased, and maybe even inversely related, especially among users of DPP-4 inhibitors. Conclusions: Diabetes intersects with rhinologic health through immune-metabolic, vascular, and epithelial pathways that may shape susceptibility, disease phenotype, and neurosensory decline. Future research should focus on disentangling type-specific mechanisms, metabolic biomarkers, and longitudinal outcomes, with the aim of developing precision-based approaches to rhinologic assessment and management in diabetic patients.}, } @article {pmid41598336, year = {2026}, author = {Faggiani, I and Villaseca, IL and D'Amico, F and Furfaro, F and Zilli, A and Massironi, S and Parigi, TL and Solitano, V and Cicerone, C and Peyrin-Biroulet, L and Danese, S and Allocca, M}, title = {Perianal Crohn's Disease in Inflammatory Bowel Disease: Diagnosis, Assessment and Treatment.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/life16010182}, pmid = {41598336}, issn = {2075-1729}, abstract = {Perianal fistulizing Crohn's disease (pfCD) represents one of the most challenging manifestations of CD, often associated with severe phenotypes, refractory luminal inflammation, and a substantial reduction in quality of life. Its pathogenesis is multifactorial and incompletely understood, involving genetic susceptibility, epithelial and stromal dysfunction, and microbiome-related mechanisms. Diagnosis and monitoring rely on advanced imaging, while management requires coordinated medical-surgical strategies. Significant unmet needs persist regarding standardized treatment targets, optimal imaging follow-up, and personalized therapeutic pathways. In this review, we aim to summarise and provide a comprehensive overview of the most recent evidence across pathogenesis, diagnosis, classification systems, and therapeutic approaches in pfCD. We highlight key advances in understanding epithelial-mesenchymal transition, immune-microbiome interactions, and genetic determinants of disease behaviour. Improvements in diagnostic modalities-including MRI-based scores, ultrasound technologies, volumetric assessment, and AI-enhanced imaging-are discussed alongside modern classification systems such as TOPClass. Evidence guiding medical therapy, seton management, and surgical decision-making is reviewed, emphasising integrated, goal-oriented care. Despite substantial progress, pfCD remains a difficult-to-treat condition with persistent gaps in early diagnosis, objective monitoring, and individualized management. Emerging imaging technologies, standardized treatment targets, and structured classification frameworks offer promising strategies to overcome current limitations and improve long-term outcomes.}, } @article {pmid41598246, year = {2026}, author = {Guo, Y and Zhang, Y and Hui, Q and Zhu, S and Wang, J and Song, L}, title = {Scalp Microbiome Composition in Young Women: Associations with Scalp Type, Sensitivity, and Lifestyle Factors.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/life16010091}, pmid = {41598246}, issn = {2075-1729}, abstract = {BACKGROUND: The scalp represents a distinct ecological niche within the skin, and the structure of its microbiota, together with the factors shaping it, is considered important for the maintenance of scalp health.

METHODS: This study systematically analyzed the bacterial and fungal community structures on the scalps of 63 healthy Chinese women aged 18-25, and examined their associations with scalp type, sensitivity, and lifestyle factors. Scalp samples were collected, questionnaire surveys were administered, scalp physiological parameters were measured, and high-throughput sequencing of 16S rRNA and ITS genes was performed.

RESULTS: The results showed that, in this unique scalp skin niche, the dominant bacterial phylum was Actinobacteria, while the dominant fungal phylum was Ascomycota. The predominant bacterial genera were Cutibacterium and Staphylococcus, and the fungal community was dominated by Malassezia. When scalp types were categorized according to sebum content, dry scalps showed enrichment of Micrococcus, Streptococcus, Delftia, Staphylococcus aureus, and Staphylococcus hominis, whereas oily scalps, on the other hand, are primarily colonized by Cutibacterium and Staphylococcus species. In addition, we observed microbial interactions under different physiological conditions. The relative abundance of Cutibacterium decreased with increasing scalp sensitivity. Higher psychological stress, insufficient sleep, and high-sugar/high-fat dietary patterns tended to coincide with shifts in the relative abundance of Malassezia, implying that these influences may act through fungal rather than bacterial components of the scalp microbiota. Scalp sensitivity showed the strongest association with β-diversity among the variables examined, although the effect size was modest and did not reach conventional significance in the multivariable PERMANOVA.

CONCLUSIONS: In young women, the scalp constitutes a distinct cutaneous niche whose microbiota is jointly shaped by sebum level, barrier sensitivity, and lifestyle factors, with sensitivity emerging as one of the more influential dimensions of community variation. These findings provide guidance for future in-depth research on the scalp microbiome network and offer a foundational reference for preventing suboptimal and pathological scalp conditions.}, } @article {pmid41597776, year = {2026}, author = {Zeng, M and Zhou, H and Wu, Q and Wang, K and Liu, H and Yang, Y and Peng, W and Chen, A and Deng, X and Ji, C and Zhang, X and Han, J}, title = {Diversity Analysis of Fecal Microbiota in Goats Driven by White Blood Cell Count.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010259}, pmid = {41597776}, issn = {2076-2607}, abstract = {The Leizhou goat is a vital indigenous breed, yet its disease resilience can complicate early health monitoring. The white blood cell (WBC) count is a key indicator of immune status, but its relationship with the gut microbiota remains uncharacterized in this breed. This study aimed to characterize the fecal microbiota of Hainan black goats stratified based on their WBC counts. The goats were stratified into Lower, Middle, and High WBC groups based on peripheral WBC counts to compare their fecal microbiota and identify potential associations with systemic immunity. Significant differences in microbial alpha- and be-ta-diversity were observed among the groups, with the High WBC group showing the greatest richness. The microbiota was dominated by Bacillota and Bacteroidota at the phylum level. Linear discriminant analysis Effect Size (LEfSe) identified specific taxa en-riched in each group, such as Ruminococcusin the High WBC group. Critically, Spearman correlation analysis demonstrated significant positive correlations between WBC counts and the relative abundance of genera like unclassified_f_Oscillospiraceae and unclassi-fied_c_Clostridia. These findings demonstrate that WBC counts are significantly associated with distinct shifts in the gut microbial community structure of Hainan black goats. The identified WBC-associated microbial biomarkers suggest a link between the gut microbi-ome and host immune regulation, providing a foundation for future research on microbi-ota-mediated health assessment in goats.}, } @article {pmid41597766, year = {2026}, author = {Raber, J and O'Niel, A and Kasschau, KD and Pederson, A and Robinson, N and Guidarelli, C and Chalmers, C and Winters-Stone, K and Sharpton, TJ}, title = {Diet-Microbiome Relationships in Prostate-Cancer Survivors with Prior Androgen Deprivation-Therapy Exposure and Previous Exercise Intervention Enrollment.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010251}, pmid = {41597766}, issn = {2076-2607}, support = {5T32AG055378//OHSU Knight Cancer Institute; NIA T32/ ; 5T32AG055378//NIA T32/ ; }, abstract = {The gut microbiome is a modifiable factor in cancer survivorship. Diet represents the most practical intervention for modulating the gut microbiome. However, diet-microbiome relationships in prostate-cancer survivors remain poorly characterized. We conducted a comprehensive analysis of diet-microbiome associations in 79 prostate-cancer survivors (ages 62-81) enrolled in a randomized exercise intervention trial, 59.5% of whom still have active metastatic disease. Dietary intake was assessed using the Diet History Questionnaire (201 variables) and analyzed using three validated dietary pattern scores: Mediterranean Diet Adherence Score (MEDAS), Healthy Eating Index-2015 (HEI-2015), and the Mediterranean-Dash Intervention for Neurodegenerative Delay (MIND) diet score. Gut microbiome composition was characterized via 16S rRNA sequencing. Dimensionality reduction strategies, including theory-driven diet scores and data-driven machine learning (Random Forest, and Least Absolute Shrinkage and Selection Operator (LASSO)), were used. Statistical analyses included beta regression for alpha diversity, Permutational Multivariate Analysis of Variance (PERMANOVA) for beta diversity (both Bray-Curtis and Sørensen metrics), and Microbiome Multivariable Associations with Linear Models (MaAsLin2) with negative binomial regression for taxa-level associations. All models tested interactions with exercise intervention, APOLIPOPROTEIN E (APOE) genotype, and testosterone levels. There was an interaction between MEDAS and exercise type on gut alpha diversity (Shannon: p = 0.0022), with stronger diet-diversity associations in strength training and Tai Chi groups than flexibility controls. All three diet-quality scores predicted beta diversity (HEI p = 0.002; MIND p = 0.025; MEDAS p = 0.034) but not Bray-Curtis (abundance-weighted) distance, suggesting diet shapes community membership rather than relative abundances. Taxa-level analysis revealed 129 genera with diet associations or diet × host factor interactions. Among 297 dietary variables tested for cognitive outcomes, only caffeine significantly predicted Montreal Cognitive Assessment (MoCA) scores after False Discovery Rate (FDR) correction (p = 0.0009, q = 0.014) through direct pathways beneficial to cognitive performance without notable gut microbiome modulation. In cancer survivors, dietary recommendations should be tailored to exercise habits, genetic background, and hormonal status.}, } @article {pmid41597765, year = {2026}, author = {Alkaff, AH and Malik, A and Situmeang, PA and Heng, NCK}, title = {Genetic Characteristics Associated with Probiotic Functions in Four Indonesian Skin Microbiome-Derived Bacterial Strains.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010248}, pmid = {41597765}, issn = {2076-2607}, abstract = {The human skin microbiome has gained considerable attention as a resource for the development of innovative probiotics for cosmetic purposes or promoting skin health. However, the evaluation of new probiotic strains to ensure their "generally recognized as safe" (GRAS) status remains challenging. Here, we have subjected the annotated draft genome sequences of four human skin-derived bacterial strains, namely Bacillus subtilis MBF10-19J, Micrococcus luteus MBF05-19J, Staphylococcus hominis MBF12-19J, and Staphylococcus warneri MBF02-19J, to bioinformatic analyses to detect the genes associated with important probiotic traits, as well as undesirable characteristics such as antibiotic resistance, virulence factors, and toxic metabolites. Each bacterium harbors at least one type of adhesin-encoding gene, while only S. hominis MBF12-19J and S. warneri MBF02-19J contain the putative genes encoding enzymes for metabolism improvement. In vitro assays, including antibiotic susceptibility and antimicrobial activity testing, revealed strain-specific safety characteristics that complement the genomic findings. With regard to antibiotic resistance determinants, S. hominis MBF12-19J showed the most favorable profile, S. warneri MBF02-19J and M. luteus MBF05-19J appeared suitable when used with appropriate caution, and B. subtilis MBF10-19J exhibited amoxicillin resistance, i.e., warrants careful evaluation. Further in vivo validation is needed to determine whether these strains do indeed comply with GRAS evaluation frameworks.}, } @article {pmid41597762, year = {2026}, author = {Xiong, Y and Dai, Z and He, F and Liu, R and Wang, J and Zhan, Z and Jia, H and Chen, S and Cai, L}, title = {Effect of Hantavirus Infection on the Rodent Lung Microbiome: Specific Regulatory Roles of Host Species and Virus Types.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010244}, pmid = {41597762}, issn = {2076-2607}, support = {2024JJ9472//The natural science foundation of Hunan provincial/ ; }, abstract = {The lung-targeting characteristic of Hantavirus infection and the unclear mechanism underlying its interaction with the lung microbiome hampers the development of effective prevention and control strategies. In this study, lung tissues from Apodemus agrarius and Rattus norvegicus were collected at Hantavirus surveillance sites in Hunan Province. Metagenomic sequencing was subsequently applied to compare microbiome diversity, community structure, and function between infected and uninfected groups. Then the linear discriminant analysis effect size (LEfSe) was employed to identify key biomarkers. The results indicated that after infection with Hantaan virus (HTNV), Apodemus agrarius exhibited significantly increased evenness but markedly decreased richness of lung microbial communities, as reflected by consistent reductions in the number of observed species, Abundance-based Coverage Estimator (ACE) index, and Chao1 index. In contrast, Rattus norvegicus infected with Seoul virus (SEOV) showed no significant difference in microbial richness compared with uninfected controls, and even a slight increase was observed. These findings suggest that host species and virus type may play an important role in shaping microbial community responses. Furthermore, β-diversity analysis showed that the community structure was clearly separated by the host rodent species, as well as by their virus infection status. LEfSe analysis identified taxa with discriminatory power associated with infection status. Streptococcus agalactiae and Streptococcus were associated with SEOV-infected Rattus norvegicus, while Chlamydia and Chlamydia abortus were relatively enriched in uninfected Apodemus agrarius. This exploratory study reveals preliminary association between specific host-Hantavirus pairings (HTNV-Apodemus agrarius and SEOV-Rattus norvegicus) and the rodent lung microbiome, offering potential insights for future research into viral pathogenesis.}, } @article {pmid41597752, year = {2026}, author = {Mukhtar, F and Guarnieri, A and Naro, MD and Nicolosi, D and Brancazio, N and Varricchio, A and Varricchio, A and Zubair, M and Didbaridze, T and Petronio Petronio, G and Di Marco, R}, title = {Clinical and Immunological Perspectives on the Nasal Microbiome's Role in Olfactory Function and Dysfunction.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010234}, pmid = {41597752}, issn = {2076-2607}, abstract = {The nasal microbiome represents a complex and dynamic microbial ecosystem that contributes to mucosal defense, epithelial homeostasis, immune regulation, and olfactory function. Increasing evidence indicates that this microbial community actively interacts with host physiology, while alterations in its composition are associated with chronic inflammation, oxidative stress, and olfactory impairment. Such changes have been reported in conditions including chronic rhinosinusitis, allergic rhinitis, and post-viral anosmia. Beyond local effects, chronic nasal inflammation has been hypothesized to influence neuroinflammatory processes and protein aggregation pathways involving α-synuclein and tau, potentially linking nasal microbial imbalance to neurodegenerative mechanisms. However, current evidence remains largely indirect and does not support a causal relationship. This narrative review summarizes current clinical and immunological evidence on the role of the nasal microbiome in olfactory function and dysfunction, highlighting limitations of existing studies and outlining future research directions.}, } @article {pmid41597750, year = {2026}, author = {Aljuaid, RS and Alshareef, SA and Jamal, BT and Dhafeer, FH and Alnahari, AA and Ashy, RA}, title = {Spatial and Vertical Stratification of Groundwater Microbial Communities Reveals Proteobacterial Dominance and Redox-Driven Ecological Transitions.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010232}, pmid = {41597750}, issn = {2076-2607}, abstract = {Groundwater microbial communities exhibit pronounced vertical and spatial structuring driven by physicochemical gradients. Here, we investigated microbial assemblages across surface and subsurface layers of three groundwater wells distributed along a 1.26 km transect in the Wadi Awja aquifer system (Jeddah, Saudi Arabia) using high-throughput 16S rRNA gene amplicon sequencing. Across all samples, Pseudomonadota (Proteobacteria) dominated community composition, accounting for ~50-65% of surface assemblages and increasing to ~90% in deeper strata, indicating strong vertical selection. This depth-associated enrichment coincided with reduced community evenness and the prevalence of metabolically versatile, facultatively anaerobic taxa. Although Actinomycetota, Bacteroidota, and Planctomycetota contributed substantially to overall diversity, their relative abundances declined with depth, reinforcing the dominance of Proteobacteria under suboxic conditions. Notably, members of Enterobacteriaceae, particularly Escherichia spp., were consistently enriched in deeper layers, coinciding with simplified community structures. Collectively, these results demonstrate that groundwater microbial communities undergo sharp redox-associated ecological transitions over short spatial scales, emphasizing the role of localized hydrogeochemical heterogeneity in shaping subsurface microbial assemblages.}, } @article {pmid41597728, year = {2026}, author = {de Groen, P and Gouw, SC and Hanssen, NMJ and Nieuwdorp, M and Rampanelli, E}, title = {Early-Life Gut Microbiota: Education of the Immune System and Links to Autoimmune Diseases.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010210}, pmid = {41597728}, issn = {2076-2607}, support = {09150182010020//NWO-VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; 4-SRA-2025-1766-M-B//BREAKTHROUGH T1D Grant/ ; 09150172210050//ZonMw-VIDI grant 2023/ ; }, abstract = {Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization-driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding-deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome-immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases.}, } @article {pmid41597727, year = {2026}, author = {Song, H and Oh, SW and Oh, JH and Unno, T}, title = {Characterization of the Oral and Stomach Microbial Community Structure in Patients with Intestinal Metaplasia, Dysplasia, and Gastric Cancer Through High-Throughput Sequencing.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010209}, pmid = {41597727}, issn = {2076-2607}, support = {EMBRF-2022-07//the Research Institute of Medical Science, The Catholic University of Korea/ ; RS-2023-00285353//the Ministry of Education/ ; }, abstract = {Gastric cancer (GC) is the fifth most common cancer worldwide, with the highest incidence in East Asia. Although H. pylori is a well-known risk factor, carcinogenesis can occur independently of H. pylori infection, and approximately 43% of adults carry H. pylori as part of their native microbiota. This study aimed to identify potential oral and gastric microbial markers across different histological stages of GC in both H. pylori-positive and -negative patients. Buccal swabs and gastric mucosa samples were collected from patients with intestinal metaplasia, low-grade dysplasia, high-grade dysplasia, early GC, or advanced GC. Total DNA was extracted, and 16S rRNA gene amplicon sequencing was performed. Microbiome diversity generally remained stable across histological stages, with no directional shifts in community structure. Differential abundance analysis revealed higher relative abundances of Anaerostipes, Phocaeicola, and Collinsella in the gastric antrum of cancerous samples. Anaerostipes and Phocaeicola are typically enriched in the intestinal microbiota but are rarely observed in the stomach, suggesting their potential ecological and pathological relevance in gastric carcinogenesis. In H. pylori-negative patients, however, a different stage-associated abundance pattern was observed, in which Faecalibacterium, a genus predominantly associated with the intestinal environment, was less abundant in advanced gastric cancer samples than in earlier histological stages within the gastric body. These findings suggest that microbial changes during gastric cancer progression may follow different trajectories depending on H. pylori infection status. In oral samples, Haemophilus and Prevotella were more abundant in intestinal metaplasia than in low-grade dysplasia, and network analysis indicated links between Neisseria and Filifactor at oral and gastric sites. However, as the study population was limited to a single country and ethnicity, the applicability of these microbial markers should be carefully considered.}, } @article {pmid41597726, year = {2026}, author = {Lee, HJ and Park, SH and Han, SY and Lee, JH and Kim, DU and Seo, HI}, title = {Differences in the Biliary Microbiome Between Biliary Tract Cancer and Benign Biliary Disease.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010208}, pmid = {41597726}, issn = {2076-2607}, support = {202100350001//Biomedical Research Institute, Pusan National University Hospital/ ; }, abstract = {Bile contains many bacteria that can contribute to various diseases. Therefore, identifying bile microbiome differences between benign and malignant conditions is essential. In this study, bile samples were collected aseptically from 141 patients with biliary tract cancer (BTC) or benign biliary diseases (BBDs) who underwent endoscopic retrograde cholangiopancreatography or biliary tract surgery. Quality control PCR was performed to amplify the V3-V4 region of the bacterial 16S rRNA gene. Metagenomic sequencing of bile was successfully performed in 35 of 56 samples collected from patients with BTC and 24 of 85 samples from patients with BBD. The mean alpha diversity values comprised 2.788 ± 2.833 and 2.319 ± 1.355 in the BBD and BTC groups, respectively (p = 0.399). The bacterial species (4.7%) were shared between groups, whereas 12.3% and 83% were indicated to patients with BTC and BBD, respectively. Bacteroides coprocola, Prevotella copri, and Bacteroides plebeius were more frequently identified in the bile of patients with BTC, whereas Bacteroides vulgatus and Bacteroides uniformis were more abundant in the bile of patients with BBD. Distinct patterns of microorganism abundance between the two groups of patients suggest association of bile microbiome with disease status, so its diagnostic potential should be validated in further studies.}, } @article {pmid41597719, year = {2026}, author = {van Oppen, MJH and Doering, T and Martins Fernandes, L}, title = {Can Bacterial Manipulation Deliver Reef-Scale Thermal Enhancement of Corals?.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010202}, pmid = {41597719}, issn = {2076-2607}, abstract = {A rapid decline of coral reefs is taking place around the world, with climate warming being the biggest driver behind this deterioration. Efforts to increase coral climate resilience via bioengineering methods have thus become urgent, and there is hope that such interventions can help corals and coral reefs survive until a time when no further climate warming occurs and perhaps a future of climate cooling is imaginable. The manipulation of coral-associated bacterial communities is among the less advanced interventions currently being explored. Nevertheless, early findings provide confidence that some level of thermal enhancement can be achieved via the inoculation of corals with beneficial bacteria. The small number of studies available, however, is limited in terms of the traits used to select candidate bacteria and their ability to ascribe host enhancement to specific bacterial taxa and functions. Further, findings to date are unable to decipher whether candidate bacteria integrate stably within the coral microbiome. These shortcomings prevent assessment of the efficacy of bacterial manipulation to enhance the long-term thermal resilience of corals on the reef. Here we summarise the state-of-play of the field and provide recommendations to fast-track this approach via fine-tuning experimental designs and methods.}, } @article {pmid41597715, year = {2026}, author = {Ruzaini Abdullah, MH and Zainudin, MHM and Aljaberi, MA and Binti Abdul Mutalib, NA and Neoh, HM and Hamat, RA}, title = {First Report of fusF Gene in Staphylococcus kloosii from Virgin Tropical Soil: Expanding the Ecological Reservoirs of Fusidic Acid Resistance.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010197}, pmid = {41597715}, issn = {2076-2607}, support = {FRGS/1/2020/SKK0/UPM/01/2//Ministry of Higher Education (Malaysia)/ ; }, abstract = {Fusidic acid resistance in Staphylococcus spp. has historically been confined to Staphylococcus ureilyticus, with limited data on its environmental distribution. This study presents the first detection of the fusidic acid resistance gene fusF in Staphylococcus kloosii recovered from virgin soil at Kampung Batu 16, Dusun Tua, Hulu Langat, Malaysia. A total of ten Staphylococcus isolates were identified using the VITEK[®]2 system with high confidence (97-99%), comprising seven S. kloosii and three S. ureilyticus. Sequencing of representative isolates further corroborated the species identification. All isolates displayed phenotypic resistance to fusidic acid, while all S. ureilyticus (3/3) exhibited multi-drug resistant (MDR) traits and S. kloosii (7/7) exhibited non-MDR traits. PCR and sequencing confirmed the presence of fusF gene in S. ureilyticus (3/3) and S. kloosii (3/7). In addition, fusB and fusC genes were not detected in both species. The phylogenetic analysis (Maximum Likelihood, Tamura-Nei model) revealed high sequence conservation and clustering between fusF-positive S. kloosii and S. ureilyticus soil isolates, suggesting recent horizontal gene transfer between these two related species. The first detection of fusF gene in S. kloosii from virgin soil signifies the expansion of the ecological and host range beyond S. ureilyticus, establishes virgin soil as a potential antimicrobial resistance (AMR) reservoir, and underscores the One Health risks of resistance dissemination from environmental staphylococci. This baseline study highlights the importance of early AMR surveillance in tropical environments prior to agricultural development.}, } @article {pmid41597703, year = {2026}, author = {Sánchez-Becerra, AE and Peña-Rodríguez, M and Vega-Magaña, AN and García-Arellano, S and Romo-Rubio, HA and Flores-Navarro, S and Escobedo-Melendez, G and Aranda-Romo, S and Zepeda-Nuño, JS}, title = {Oral Microbiome Dynamics in Patients with Acute Lymphoblastic Leukemia and Oral Mucositis.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010185}, pmid = {41597703}, issn = {2076-2607}, abstract = {The oral microbiome of patients with acute lymphoblastic leukemia (ALL) undergoes changes caused by the neoplasia as well as the antimicrobial activity of chemotherapy (CTX), which promotes the development of oral mucositis (OM). This study aimed to analyze the oral microbiome dynamics and salivary cytokine production in pediatric ALL patients before and during CTX, comparing children who did and did not develop OM. We conducted a longitudinal, observational, and analytical study including 32 newly diagnosed pediatric ALL patients (ages 2-16 years) undergoing CTX. Oral rinse and non-stimulated saliva samples were collected at baseline (day 0), day 14, and day 21 of induction of CTX, with an additional sample taken during OM episodes when possible. Microbiome analysis was performed using 16S rRNA sequencing on an Illumina MiSeq platform, and salivary cytokines were measured using a Luminex multiplex assay. The most pronounced microbiome changes occurred on day 14, particularly in patients who developed OM, characterized by higher α diversity, increased abundance of opportunistic taxa, and elevated IL-6 concentrations. In contrast, patients who did not develop OM exhibited a more stable microbial composition. Overall, these findings indicate that temporal oral dysbiosis and increased IL-6 may serve as early markers and potential predictors of OM development during chemotherapy in pediatric ALL patients.}, } @article {pmid41597701, year = {2026}, author = {Mollova, D and Baev, V and Borisova, T and Rusinova, M and Iliev, I}, title = {A Metagenomic Comparison of the Colostrum Microbiome in Bulgarian Mothers by Delivery Mode: A Pilot Study.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010184}, pmid = {41597701}, issn = {2076-2607}, support = {KP-06-M81/6//Bulgarian Science Fund/ ; }, abstract = {Colostrum harbors a highly diverse microbial community, predominantly composed of genera such as Staphylococcus, Streptococcus, Lactobacillus, Bifidobacterium, and Enterococcus. The composition and diversity of this microbiota are influenced by maternal factors-including age, body mass index, lactation activity, stress levels, and gestational diabetes-as well as external factors such as mode of delivery, antibiotic exposure, diet, and geographic location. This microbial community plays a critical role in maternal and neonatal health by contributing to early gut colonization, supporting digestion, promoting immune system development, and protecting against pathogenic microorganisms through mechanisms such as antimicrobial peptide production by lactic acid bacteria. The primary aim of this study was to evaluate the impact of mode of delivery on colostrum microbiota by comparing mothers who delivered vaginally with those who underwent cesarean section. Colostrum samples from 15 mothers were subjected to DNA extraction, high-throughput sequencing, and bioinformatic analyses to characterize microbial composition and predicted functional profiles. Although substantial inter-individual variability was observed, no statistically significant differences were detected in overall microbial diversity or community structure between the two delivery groups. However, distinct bacterial taxa and functional characteristics were identified that were specific to each mode of delivery, suggesting subtle delivery-related influences on colostrum microbiota composition.}, } @article {pmid41597671, year = {2026}, author = {Mihu, ML and Nadăş, GC and Bouari, CM and Fiț, NI and Răpuntean, S}, title = {Klebsiella pneumoniae Infections in Dogs: A One Health Review of Antimicrobial Resistance, Virulence Factors, Zoonotic Risk, and Emerging Alternatives.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010149}, pmid = {41597671}, issn = {2076-2607}, abstract = {Klebsiella pneumoniae is increasingly reported in canine medicine, with growing attention to multidrug-resistant (MDR) and hypervirulent strains. Although its overall prevalence in dogs appears relatively low, published studies indicate that affected animals may harbor clinically important resistance determinants, including extended-spectrum β-lactamases and, less frequently, carbapenemases. Canine isolates described in the literature also carry virulence-associated traits such as hypermucoviscosity and enhanced iron-acquisition systems, which overlap with features of high-risk human lineages and suggest potential, but largely inferred, interspecies links. These observations highlight the relevance of a One Health perspective and the importance of coordinated surveillance that includes companion animals. This narrative review synthesizes available literature on the epidemiology, clinical presentations, antimicrobial resistance, virulence traits, and molecular characteristics of K. pneumoniae in dogs. We critically evaluate evidence suggesting that dogs may function as reservoirs, sentinels, or amplifiers of MDR strains, particularly in clinical settings or following antimicrobial exposure. In addition, we summarize emerging alternative and adjunctive strategies-such as bacteriophage therapy, antimicrobial peptides, anti-virulence approaches, microbiome-based interventions, as well as strengthened antimicrobial stewardship and infection-control practices-that are under investigation as complements to conventional antibiotics. Overall, published evidence indicates that K. pneumoniae infections in dogs represent an under recognized but potentially important clinical and One Health concern. Continued surveillance, responsible antimicrobial use, and rigorous evaluation of non-antibiotic strategies will be essential to inform future veterinary practice and public health policy.}, } @article {pmid41597670, year = {2026}, author = {Soyfoo, M and Sarrand, J}, title = {Plasmablast Storms: Microbial Drivers of Acute and Chronic Autoimmune Flares.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010152}, pmid = {41597670}, issn = {2076-2607}, abstract = {Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts-short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these "plasmablast storms": latent herpesvirus reactivations (Epstein-Barr virus, cytomegalovirus, human herpesvirus-6, varicella-zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease.}, } @article {pmid41597661, year = {2026}, author = {Zavala-Medina, LC and Salas-Leiva, JS and Villegas-Mercado, CE and Arreguín-Cano, JA and Soto-Barreras, U and Santana-Delgado, SA and Larrinua-Pacheco, AD and García-Vega, MF and Bermúdez, M}, title = {Oral Dysbiosis and Neuroinflammation: Implications for Alzheimer's, Parkinson's and Mood Disorders.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010143}, pmid = {41597661}, issn = {2076-2607}, abstract = {BACKGROUND: Growing evidence indicates that oral microbiome dysbiosis contributes to systemic inflammation, immune activation, and neural dysfunction. These processes may influence the onset and progression of major neuropsychiatric and neurodegenerative disorders. This review integrates clinical, epidemiological, and mechanistic findings linking periodontal pathogens and oral microbial imbalance to Alzheimer's disease (AD), Parkinson's disease (PD), depression, and anxiety.

METHODS: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify recent studies examining alterations in the oral microbiota, microbial translocation, systemic inflammatory responses, blood-brain barrier disruption, cytokine signaling, and neural pathways implicated in brain disorders.

RESULTS: Evidence from human and experimental models demonstrates that oral pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, can disseminate systemically, alter immune tone, and affect neural tissues. Their virulence factors promote microglial activation, cytokine release (IL-1β, IL-6, TNF-α), amyloid-β aggregation, and α-synuclein misfolding. Epidemiological studies show associations between oral dysbiosis and cognitive impairment, motor symptoms in PD, and alterations in mood-related taxa linked to stress hormone profiles. Immunometabolic pathways, HPA-axis activation, and the oral-gut-brain axis further integrate these findings into a shared neuroinflammatory framework.

CONCLUSIONS: Oral dysbiosis emerges as a modifiable contributor to neuroinflammation and brain health. Periodontal therapy, probiotics, prebiotics, synbiotics, and targeted inhibitors of bacterial virulence factors represent promising strategies to reduce systemic and neural inflammation. Longitudinal human studies and standardized microbiome methodologies are still needed to clarify causality and evaluate whether restoring oral microbial balance can modify the course of neuropsychiatric and neurodegenerative disorders.}, } @article {pmid41597651, year = {2026}, author = {Colangeli, L and Teofani, A and Desideri, A and Biocca, S and Pacifico, T and Parrotta, ME and Fertitta, V and Fortini, P and Ceccarini, G and Magno, S and Pelosini, C and Santini, F and Novelli, G and Sbraccia, P and Guglielmi, V}, title = {Gut Microbiota in Lipodystrophies and Obesity: A Common Signature?.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010132}, pmid = {41597651}, issn = {2076-2607}, abstract = {Lipodystrophies are rare syndromes characterized by partial or complete loss of subcutaneous adipose tissue leading to ectopic lipid deposition, insulin resistance, and the same metabolic derangements observed in obesity. Given the role of gut microbiota in metabolic disorders, we investigated whether its signature in obesity may be mirrored by that found in lipodystrophies, possibly contributing to their overlapping metabolic abnormalities. In this cross-sectional study, we included 8 individuals with lipodystrophy (LD), 16 individuals with obesity (Ob)-further categorized into 8 metabolically healthy (MHO) and 8 metabolically unhealthy (MUHO)-and 16 normal-weight controls (N). We assessed clinical and metabolic characteristics and performed 16S rRNA sequencing and bioinformatic analyses on fecal samples to characterize the gut microbiome. LD presented significantly lower body mass index (BMI) and waist circumference than Ob, but, from a metabolic perspective, LD showed similarity with MUHO and presented significantly lower levels of HDL-C and higher triglycerides compared to both N and MHO. Gut microbiota analysis revealed reduced α-diversity in LD, MHO and MUHO compared to N, whilst β-diversity and Firmicutes/Bacteroidetes ratio differences were not significant. At the phylum level, differential abundance analysis revealed that LD individuals exhibit similar microbial characteristics to MUHO and higher Verrucomicrobiota levels compared to MHO. The shared gut microbiota signature suggests another potential unexplored link between the pathogenesis of metabolic complications in lipodystrophies and obesity, providing novel insights into the complex interplay between dysbiosis and adiposopathy. Larger longitudinal studies are needed to explore the role of specific taxa and for a more precise characterization of different lipodystrophy subtypes.}, } @article {pmid41597646, year = {2026}, author = {Ali, A and Keelan, JA and Penova-Veselinovic, B and Allentoft, ME and Bunce, M and Christophersen, CT}, title = {Optimising Vaginal Microbiome Profiling for Clinical Translation: A Comparative Assessment of Sample Storage Methods and a Vagina-Specific 16S rRNA Gene Database.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010128}, pmid = {41597646}, issn = {2076-2607}, support = {H1017003370//Telethon-Perth Children's Hospital Research Fund and Western Australia Department of Health/ ; }, abstract = {Vaginal microbiome composition has been linked to risk of preterm birth (PTB), a persistent global health challenge. 16S rRNA microbial profiling has identified specific vaginal community state types (CSTs) that have been associated with PTB risk. Diagnostic profiling requires standardised pre-analytical protocols. We evaluated two storage methods and validated a curated, vagina-specific 16S rRNA gene database (VagDB) to enhance annotation. Paired Copan FLOQ swabs from 22 women at high PTB risk were processed for either (a) dry/immediate freezing or (b) Amies-stabilisation/refrigeration. Amplicon sequence variants were generated via 16S rRNA gene (V4) PCR and Illumina sequencing. We assessed diversity, composition, and community state type (CST) allocation. Amies-stabilised samples yielded significantly higher DNA (p = 0.003), but this did not alter species richness, evenness, or community structure. VagDB enhanced species-level resolution. PCoA showed robust clustering by participant and CST (p < 0.001), irrespective of storage; CST concordance exceeded 90%. Routinely collected vaginal swabs in stabilisation medium with an 8-72 h refrigeration window yield reliable data, supporting the integration of vaginal microbiome profiling into clinical PTB risk assessment.}, } @article {pmid41597613, year = {2026}, author = {Jarrín-V, P and Carrión-Olmedo, JC and Loján, P and Reyes-Barriga, D and Lara, M and Oña, A and Quiroz-Moreno, C and Castillejo, P and Tenea, GN and Díaz, M and Monfort-Lanzas, P and Molina, CA}, title = {Predicted Bacterial Metabolic Landscapes of the Sumaco Volcano: A Picrust2 Analysis of 16S rRNA Data from Amazonian Ecuador.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010094}, pmid = {41597613}, issn = {2076-2607}, support = {NA//National Institute of Biological Resources (NIBR) and the Korea International Cooperation Agency (KOICA) of the Republic of Korea/ ; }, abstract = {The Sumaco volcano in Ecuador, which has a distinct geological origin from the Andes and is located in the Amazon basin, offers an opportunity to study untouched microbiomes. We explored comparative patterns of abundance from predicted functional profiling in soil samples collected along the elevation and sulfur gradients on its slopes. Using 16S rRNA gene metabarcoding, we inferred metagenome functional profiles, contrasting sample groups by altitude or soil sulfur concentration. We inferred that high-altitude communities may have higher predicted abundance for anaerobic metabolism (crotonate fermentation), coenzyme B12 synthesis, and degradation of diverse carbon sources (sugars and octane). High-sulfur soils were associated with an inferred enrichment of pathways for degrading complex organic compounds and nitrogen metabolism, reflecting adaptation to unique geochemical conditions. In contrast, low-sulfur soils are consistent with a higher predicted abundance of glycerol degradation. Within the limitation imposed by the potential weak associations of the applied predicted functional profiling to actual gene content, we propose that the inferred metabolic changes represent different ecological strategies for resource acquisition, energy generation, and stress tolerance, and they are optimized for varying conditions in this unique volcanic ecosystem. Our findings highlight how environmental gradients shape soil microbiome functional diversity and offer insights into microbial adaptation in Sumaco's exceptional geochemistry within the Amazon. Further efforts linking functional predictions back to specific taxa will offer a complete ecological perspective of the microbiome exploration in the Sumaco volcano.}, } @article {pmid41597602, year = {2025}, author = {Freixas-Coutin, JA and Seo, J and Su, L and Hood, S}, title = {Longitudinal Analysis of Vulvovaginal Bacteriome Following Use of Water- and Silicone-Based Personal Lubricants: Stability, Spatial Specificity, and Clinical Implications.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010082}, pmid = {41597602}, issn = {2076-2607}, support = {NA//Reckitt Benckiser (United Kingdom)/ ; }, abstract = {The vulvovaginal microbiome is a complex and dynamic ecosystem of microorganisms. The potential effects of common personal lubricants on its balance, which have implications for reproductive health, are still unknown. This study longitudinally assessed the impact of two commercially available lubricants on the composition and stability of the vaginal and vulvar bacteriome. Paired vaginal and vulvar swabs were collected at baseline and after repeated lubricant use, and the bacteriome was assessed using 16S rRNA gene amplicon sequencing. Alpha and beta diversity were assessed using Shannon entropy and Bray-Curtis dissimilarity, respectively. The results showed that the vaginal bacteriome was dominated by Lactobacillus and Firmicutes, while vulvar communities were more diverse and had higher abundances of Prevotella, Finegoldia, and Peptoniphilus. Both alpha and beta diversity measures indicated that the vaginal and vulvar bacteriome remained largely stable even after repeated lubricant use. Minor and non-significant changes in genus-level composition were observed, particularly in the vulvar samples. A moderate but significant correlation (Mantel r = 0.274, p = 0.001) was also observed between the vaginal and vulvar bacteriome. Overall, this study shows that short-term, repeated use of the water-based lubricant and the silicone-based lubricant tested in this study does not significantly disrupt the vaginal or vulvar bacteriome.}, } @article {pmid41597601, year = {2025}, author = {Wang, H and Ma, W and Malik, MI and Shah, AM and Liu, A and Hu, G and Jing, J and Li, H and Huang, Y and Zhang, Q and Zhou, J and Bai, B and Yang, Y and Wang, Z and Zhang, J and Hao, L}, title = {Effects of Different Feeding Methods on Growth Performance, Enzyme Activity, Rumen Microbial Diversity and Metabolomic Profiles in Yak Calves.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010081}, pmid = {41597601}, issn = {2076-2607}, support = {2024-ZJ-905; 2025KTST04; QHKLYC-GDCXCY-2023-086//Qinghai Provincial Natural Science Fund for Distinguished Young Scholars; Qinghai University Research Ability Enhancement Project; Qinghai University Graduate Supervisor Innovation Team, Leading talent of "Kunlun Talents High-level Innovation and Entrepre/ ; }, abstract = {Yaks are important for the ecology and economy of the Qinghai-Tibetan Plateau. The growth of the yak industry depends on sustainable and accelerated growth of calves, sustaining herd reproduction and production systems. Yak calves born in the summer months of June and July are faced with a heightened risk of winter mortality. Exclusive traditional, natural feeding prolongs the suckling period, and this leads to a series of problems due to the harsh high-altitude environment, such as inadequate nutrition leading to retarded growth and an imbalanced herd structure. To enhance growth performance and breeding efficiency, 12 male calves of similar weights (68.53 ± 6.41 kg) were randomly assigned to a control group (suckle the dam (SU)) or an experimental group (early weaning with full feeding, concentrate and oat hay at a 7:3 ratio (CO)). The results showed that compared with suckling, early weaning with full feeding significantly improved the growth performance, volatile fatty acids and digestive enzyme activity. The abundance of the Firmicutes was reduced, but there was an increased abundance of Bacteroidetes, which affected the rumen metabolome. In conclusion, early weaning with full feeding improves growth performance, promotes rumen fermentation and carbohydrate degradation, reduces the diversity and richness of rumen microbial flora and alters the content and pathways of metabolites in yak calves. These factors contribute to the growth and market readiness of yak calves born in June and July, accelerate herd turnover and enhance the production efficiency of grazing yaks.}, } @article {pmid41597595, year = {2025}, author = {Wang, J and Xu, D and Hu, S and Zheng, B and Chen, Y and Pan, T}, title = {The Impact of Microbiome on Breast Cancer and Regulatory Strategies.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010075}, pmid = {41597595}, issn = {2076-2607}, support = {Grant No. 81602716//National Natural Science Foundation of China/ ; }, abstract = {Breast cancer, the most prevalent malignant tumor in women, is closely linked to the human microbiota. The microbiome participates throughout breast cancer pathogenesis, including its occurrence, progression, response to anti-tumor therapies, and treatment-related complications. This review examines the central hypothesis that microbiome-driven inflammatory and immune mechanisms shape breast cancer progression through two key pathways: systemic immune-inflammatory regulation and local tumor microenvironment remodeling. Furthermore, microorganisms and their metabolites modulate systemic treatments by interfering with drug metabolism and altering systemic or local immune-inflammatory environments. Targeting the microbiota represents a promising strategy for enhancing anticancer efficacy and reducing treatment-related complications. This review aims to advance the understanding of the etiology and disease progression of breast cancer from the perspective of microbial-regulated inflammation and immunity, offering new insights for its prevention and treatment.}, } @article {pmid41597583, year = {2025}, author = {Ashkanani, A and Ashkanani, G and Yousef, M and Rob, M and Al-Marri, M and Naseem, N and Laws, S and Chaari, A}, title = {Microbiome and Skin Health: A Systematic Review of Nutraceutical Interventions, Disease Severity, Inflammation, and Gut Microbiota.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010063}, pmid = {41597583}, issn = {2076-2607}, abstract = {Skin disorders are a major global cause of morbidities, and increasing evidence links several to gut microbiome dysregulation. Because of this the bidirectional gut-skin axis, nutraceuticals have been proposed as therapeutic adjuncts, but their clinical effects across skin conditions remain unclear. To understand how pro/pre/synbiotics can affect health, we conducted a systematic review to investigate disease severity indices, inflammatory and immunological markers, quality of life, and changes in gut microbiota composition. PubMed, Embase, and Web of Science were utilized to identify relevant randomized clinical trials. Selected articles were pre-piloted for in-depth analysis and data extraction. We included 60 randomized controlled trials involving human participants with 5 dermatological conditions, including atopic dermatitis, psoriasis, acne vulgaris, chronic urticaria, and melasma, treated with probiotics, prebiotics, or synbiotics. Risk of bias was generally low across trials, with some having concerns. The SCORAD of the treated group was substantially lower than that of the placebo group in 30 of the 47 trials on atopic dermatitis. Inflammatory markers showed a range of results; some showed significant changes, while others produced contradictory results. Five trials that examined atopic dermatitis and psoriasis independently showed a significant improvement in Quality of Life. The PASI score was considerably lower in psoriasis in three of the five RCTs. Acne vulgaris, melasma, and chronic urticaria were not well documented. Major limitations included heterogeneity in interventions and outcomes, small sample sizes, and inconsistent reporting of microbiome analyses. Nutraceuticals show potential as additional treatments, but further, large scale studies are required.}, } @article {pmid41597581, year = {2025}, author = {Ferreira, FR and Rouvier, GA and Hassib, L and de Andrade Morraye, R and da Silva, YSP and da Gama, LFS and Pereira, IS and Oliveira Gomes, A and Rosa, MJG and de Morais-Scussel, AC and de Molfetta, GA and Silva, WA}, title = {Prebiotic Treatment During Pregnancy Prevents Social Deficits Associated with Autism Spectrum Disorder-like Behavior Induced by Maternal Immune Activation.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010060}, pmid = {41597581}, issn = {2076-2607}, support = {403318/2023-8//CNPq/ ; E-26/SEI-260003/012160/2021//Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro/ ; 88887.923410/2023-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 2023/16731-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, abstract = {Maternal exposure to infectious agents has been associated with an increased risk of mental disorders in offspring, such as autism spectrum disorder. Evidence suggests that maternal immune responses during infection can significantly impact the neurodevelopment of the offspring, potentially affecting central nervous system functions in the future. Inulin is an indigestible soluble fiber that acts as a prebiotic. It promotes the production of short-chain fatty acids, such as butyrate, which can help inhibit the production of pro-inflammatory cytokines. Thus, this study aims to investigate whether inulin treatment during pregnancy can mitigate or reduce the impact of maternal immune activation (MIA) on the neurodevelopment of the offspring. Swiss mice were used in a dose-response study to evaluate the protective effects of inulin against maternal exposure to soluble Toxoplasma gondii antigen. Adult offspring of both sexes underwent behavioral assessments, and their gut microbiota was characterized. Both males and females in the soluble T. gondii antigen (STAg) group exhibited reduced sociability, as evidenced by the three-chamber social interaction test. Moreover, co-treatment with inulin mitigated this effect. Additionally, anhedonia was observed only in female offspring from the MIA group, but treatment with 1% and 3% inulin also mitigated this effect. The analysis of fecal microbiota showed significant differences between the STAg and inulin treatments at both the family and genus levels. Therefore, inulin appears to have a potential protective effect on the neurodevelopment of the offspring exposed to maternal antigenic challenges during pregnancy mediated by offspring microbiome modulations.}, } @article {pmid41597577, year = {2025}, author = {Zhang, Y and Zhang, M and Zhao, Z and Peng, Y and Deng, F and Jiang, H and Zhang, M and Song, B and Kim, JK and Pan, JH and Chai, J and Li, Y}, title = {High-Altitude Extreme Environments Drive Convergent Evolution of Skin Microbiota in Humans and Horses.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010057}, pmid = {41597577}, issn = {2076-2607}, support = {32170430//the National Natural Science Foundation of China/ ; }, abstract = {Unique skin microbial communities have been shaped by the harsh climatic conditions in high-altitude areas, such as intense ultraviolet radiation and low oxygen concentration. However, it is unknown whether high altitude contributes to shaping common microbiota inhabiting the skin across different mammals. The skin microbial communities of humans and horses living in high-altitude (Tibetan) and low-altitude areas were analyzed using full-length 16S rRNA sequencing technology. Alpha diversity differed between high- and low-altitude groups (p < 0.01). Skin microbial community composition also differed between high- and low-altitude areas (p < 0.05). Some of the common taxa present in the skin of humans and horses in high-altitude areas were identified as extreme microorganisms capable of adapting to the harsh high-altitude environment. Five bacterial taxa, including the genera Sphingomonas, Brevundimonas, and Kocuria, as well as the species Acinetobacter guillouiae and Arboricoccus pini, were significantly enriched (p < 0.01) on the skin of both humans and horses in high-altitude areas. Meanwhile, some taxa enriched on the skin surface at the same altitude showed preferences for mammalian species. Acinetobacter johnsonii, Anaerococcus nagyae, and Anaerococcus octavius were significantly enriched (p < 0.05) in the skin of humans at both high and low altitudes, whereas Acinetobacter pseudolwoffii and Armatimonas rosea, Archangium gephyra and Acinetobacter lwoffii were significantly enriched (p < 0.05) in the skin of horses at both high and low altitudes. In the network analyses, a positive correlation (p < 0.01) was shown between the skin taxa enriched in high-altitude areas and each other, while a negative correlation (p < 0.01) was found between the skin microorganisms enriched in high-altitude areas and those enriched in low-altitude areas. Overall, our findings indicate that high-altitude extreme environments drive convergent evolution of skin microbiota across mammals, reflecting the joint effects of environmental selection and host-related filtering on community assembly. This cross-species comparison provides a framework for understanding skin microbiome responses to extreme environments in plateau mammals.}, } @article {pmid41597572, year = {2025}, author = {Li, J and Qi, M and Zhang, J and Zuo, Y}, title = {Plant-Mediated Soil Sickness: Steering the Rhizosphere into a Pathogenic Niche.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010052}, pmid = {41597572}, issn = {2076-2607}, support = {31760360//National Natural Science Foundation of China/ ; 202301AT070007//Natural Science Foundation of Yunnan Province of China/ ; 202101BD070001-078//Natural Science Agricultural Joint Foundation of Yunnan Province of China/ ; }, abstract = {Continuous monoculture of Panax notoginseng leads to severe replant disease, yet the mechanisms by which root exudates mediate rhizosphere microbiome assembly and pathogen enrichment remain poorly understood. Here, we demonstrate that long-term root exudate accumulation acts as an ecological filter, driving the fungal community toward a phylogenetically impoverished, pathogen-dominated state. Specifically, exudates enriched the soil-borne pathogen Fusarium while reducing the abundance of potentially antagonistic fungi. In contrast, bacterial communities exhibited higher resilience, with exudates selectively enriching oligotrophic taxa such as Terrimonas and MND1, but suppressing nitrifying bacteria (e.g., Nitrospira) and plant-growth-promoting rhizobacteria (PGPR). Microbial functional profiling revealed a shift in nitrogen cycling, characterized by suppressed nitrification and enhanced nitrate reduction. Crucially, co-occurrence network analysis identified bacterial taxa strongly negatively correlated with Fusarium, providing a synthetic community blueprint for biocontrol strategies. Our study establishes a mechanistic link between root exudate accumulation and negative plant-soil feedback in monoculture systems, highlighting microbiome reprogramming as a key driver of replant disease. These insights offer novel avenues for manipulating rhizosphere microbiomes to sustain crop productivity in intensive agricultural systems.}, } @article {pmid41597571, year = {2025}, author = {Amirkhanzadeh Barandouzi, Z and Bruner, DW and Lin, Y and Choi, H and Zeki, LR and Akangbe, T and Epari, A and Li, H}, title = {Probiotics for Anxiety and Depressive Symptoms in Cancer: A Systematic Review of Animal and Human Studies with Mechanistic Insights.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010051}, pmid = {41597571}, issn = {2076-2607}, support = {UL1TR002378//National Center for Advancing Translational Sciences of the National Institutes of Health/ ; 5K12ES033593-04//Pediatric and Reproductive Environmental Health Scholars Southeastern Environmental Exposures and Disparities (PREHS SEED) Program/ ; }, abstract = {Probiotics have been increasingly evaluated for their potential effect on anxiety and depression through the modulation of the gut-brain axis. Individuals with cancer experience a high prevalence of these symptoms. However, the effects of probiotics and their underlying mechanisms in this population have not been systematically evaluated. This review synthesizes current evidence regarding probiotic interventions for anxiety and depression in cancer and examines the associated mechanistic pathways. A systematic search for original trials in PubMed, Embase, CINAHL, Web of Science, and PsycINFO was conducted in May 2025. Eligible studies included animal models or adults with cancer who received probiotics alone or in combination with other treatments, with outcomes related to anxiety, depressive symptoms, or depression. Search terms included animal model, cancer, probiotics, anxiety, depressive symptoms, depression, gastrointestinal microbiome, gut microbiome, and microbiota. The review followed PRISMA guidelines. Risk of bias in trials was assessed using the SYRCLE and Cochrane RoB2 tool. Nine studies met the inclusion criteria, including seven human studies, one animal study, and one mixed human-animal study, with human sample sizes ranging from 24 to 266. The animal study reported reductions in depressive and anxiety-like behaviors, paralleled by modulation of the hypothalamic-pituitary-adrenal (HPA) axis, reduced inflammation, rebalancing of the gut microbiota, and improvements in neurotransmitter pathways. Findings from human studies were more variable. Some trials reported improvements in anxiety, and depressive symptoms, while others showed no significant differences compared with control groups. Studies that combined probiotics with antidepressants or exercise demonstrated the most pronounced reductions in anxiety and depression. Mechanistic insights from human studies partially aligned with animal evidence, with several trials showing reductions in inflammatory markers (IL-6, TNF-α), improvements in neuroendocrine measures (serotonin, dopamine, cortisol), stabilization of metabolic markers, and favorable shifts in gut microbiota, although these effects were not consistent across all studies. Probiotics appear to be safe within the intervention periods of the reviewed studies (<24 weeks), as no serious adverse effects were reported. Substantial heterogeneity across studies, including variations in cancer type, intervention duration, probiotic strains, formulations, dosages, and study design combined with small sample sizes, restricts the ability to draw definitive conclusions. Rigorously designed randomized controlled trials with larger sample sizes and mechanistic biomarkers are required to confirm the efficacy of probiotics for relieving anxiety and depression in the cancer population.}, } @article {pmid41597570, year = {2025}, author = {Cesanelli, F and Scarvaglieri, I and De Francesco, MA and Alberti, M and Salvi, M and Tiecco, G and Castelli, F and Quiros-Roldan, E}, title = {The Human Virome in Health and Its Remodeling During HIV Infection and Antiretroviral Therapy: A Narrative Review.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010050}, pmid = {41597570}, issn = {2076-2607}, abstract = {The human virome represents a fundamental yet understudied component of the microbiome, influencing immune regulation and disease. Given the profound immune dysregulation and microbial imbalance associated with HIV infection, understanding virome alterations during HIV and antiretroviral therapy is essential. This narrative review seeks to integrate and discuss the latest evidence regarding the structure and behavior of the human virome in healthy individuals, in the context of HIV infection, and under antiretroviral therapy. A comprehensive literature search was performed in MEDLINE and Google Scholar for peer-reviewed English-language articles published up to November 2025. Studies describing virome composition, diversity, and interactions in people living with HIV, as well as antiretroviral-induced changes, were included. Reference lists of relevant papers were screened to identify additional sources. Data were extracted and synthesized narratively, emphasizing human studies and supported by evidence from primate models where applicable. HIV infection induces profound alterations in the human virome, notably an expansion of eukaryotic viruses such as Anelloviridae, Adenoviridae, and Parvoviridae, accompanied by reduced bacteriophage diversity. Antiretroviral therapy partially restores virome balance but fails to fully re-establish pre-infection diversity, with persistent enrichment of Anelloviridae reflecting incomplete immune reconstitution. Virome perturbations correlate with immune activation, microbial translocation, and inflammation, contributing to comorbidities despite virological suppression. Emerging evidence suggests regimen-specific effects, with integrase inhibitor-based therapies showing more favorable viromic recovery. HIV and antiretroviral therapy profoundly remodel the human virome, with lasting implications for immune homeostasis and chronic inflammation. The ongoing disruption of the virome highlights its promise as both a biomarker and a potential therapeutic target in the management of HIV. Longitudinal, multi-omic studies are needed to clarify the causal role of virome alterations and guide future interventions.}, } @article {pmid41597565, year = {2025}, author = {Li, X and Huang, T and Li, Y and Pang, Z and Zhang, Y}, title = {Multi-Regional Study on the Microbial Community Structure, Core Microbiome and Functional Characteristics in Deep Fracture Waters.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010045}, pmid = {41597565}, issn = {2076-2607}, support = {42502251//National Natural Science Foundation of China/ ; SKL-K202303//the State Key Laboratory of Lithospheric and Environmental Coevolution/ ; }, abstract = {The deep terrestrial subsurface is the largest reservoir of Earth's freshwater resources as well as the largest habitat for prokaryotic life. However, the deep-subsurface microbiome, especially its spatial distribution across countries/continents, is still poorly understood. In this study, we compiled and compared 30 16S rRNA gene amplicon libraries from three deep fractured aquifers in different parts of the world (depth range of tens of meters to 2.4 km below surface) to understand the spatial distribution and functions of deep-subsurface microbial community, and to test for the presence of core taxa. The results revealed spatially heterogenous microbial community composition at both the local and the global scales, even at the phylum level. Environmental filtering was identified as an important driver of the microbial community structure of deep groundwaters. Despite the spatial heterogeneity, the three aquifers share a core microbiome at the genus level. Only one family, Comamonadaceae, was present in all the 30 samples analyzed. Several other families were also prevalent, including Hydrogenophilaceae, Omnitrophaceae, BSV26 (Candidatus Kryptonia), and an unclassified Thermodesulfovibrionia. FAPROTAX functional prediction indicated that chemoheterotrophic functions predominate, and the core microbial genera, together with the dominant genera, collectively govern the functional characteristics. Taken together, our findings provide new insights into the spatial heterogeneity and functional potential of deep-subsurface ecosystems across the globe.}, } @article {pmid41597557, year = {2025}, author = {Domingues, VDSP and Sousa, MP and Waldow, V and Akamine, R and Seldin, L and Jurelevicius, D}, title = {Sulfide Production and Microbial Dynamics in the Water Reinjection System from an Offshore Oil-Producing Platform.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010038}, pmid = {41597557}, issn = {2076-2607}, support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, abstract = {In addition to seawater in the injection header (IH) to enhance oil recovery, oil companies reuse produced water (PW), a byproduct of oil extraction, and implement produced water reinjection systems (PWRI). Although the microorganisms in IH are controlled by biocides, PW is generally treated by flotation to remove oil residues before PWRI. However, IH, PW, and PWRI can be sources of sulfate-reducing bacteria (SRB) related to oil reservoir souring. Here, we evaluated hydrogen sulfide (H2S) production in IH, PW, and PWRI, as well as the microbial dynamics (most probable number-MPN, quantitative PCR, and amplicon sequencing), of a Brazilian oil reservoir. Results revealed that the highest average H2S concentration occurred in PW samples. However, the dissolved H2S threshold concentration of 2 mg L[-1] was exceeded in 18% of PW and ~16% of PWRI samples, respectively. Although MPN showed no correlation between H2S and the number of SRB or total anaerobic heterotrophic bacteria (TAHB), qPCR and microbiome data revealed that the SRB Desulfobacterota was the most abundant in PW and PWRI. Overall, flotation was associated with (i) low microbial control in PW; and (ii) the enrichment of SRB (mainly Desulfobacterota), Thermotogota, and Proteobacteria groups in PWRI.}, } @article {pmid41597554, year = {2025}, author = {Dai, X and Yang, P and Zhou, C and Chen, Z and Li, S and Zhu, T}, title = {Bacillus mojavensis dxk33 Modulates Rhizosphere Microbiome and Suppresses Root Rot in Cunninghamia lanceolata.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010034}, pmid = {41597554}, issn = {2076-2607}, support = {2024NSFSC1193//Natural Science Foundation of Sichuan/ ; }, abstract = {Soil-borne pathogens cause devastating root rot diseases in forest ecosystems, often by inducing dysbiosis in the rhizosphere microbiome. While antagonistic bacteria can suppress disease, their effects frequently extend beyond direct inhibition to include ecological restructuring of resident microbial communities. However, the causal relationships between such microbiome restructuring and disease suppression in tree species remain poorly understood. Here, we show that the antagonistic bacterium B. mojavensis dxk33 effectively suppresses F. solani-induced root rot in C. lanceolata, and that this disease suppression coincides with a partial reversal of pathogen-associated dysbiosis in the rhizosphere. Inoculation with dxk33 significantly promoted plant growth and reduced the disease index by 72.19%, while concurrently enhancing soil nutrient availability and key C-, N- and P-cycling enzyme activities. High-throughput sequencing revealed that dxk33 inoculation substantially reshaped the rhizosphere microbiome, counteracting the pathogen's negative impact on microbial diversity and coinciding with a shift toward a more stable community structure. Under pathogen stress, dxk33 enriched beneficial bacterial taxa such as Pseudomonas and Sphingomonas and suppressed pathogenic fungi while promoting beneficial fungi such as Mortierella. Linear discriminant analysis and functional prediction further indicated that dxk33 remodeled ecological guilds enriched for mycorrhizal and saprotrophic fungi, and reactivated bacterial metabolic pathways and signaling networks that were suppressed by the pathogen. Taken together, our findings are consistent with a multi-tiered mode of action in which direct antagonism by B. mojavensis dxk33 operates alongside associated changes in the rhizosphere microbiome that resemble a disease-suppressive state, although the present experimental design does not allow a strictly causal role for microbiome reconfiguration in disease suppression to be established. This study provides a mechanistic framework for understanding how microbiome engineering may mitigate soil-borne diseases in perennial trees and highlights the potential of targeted microbial interventions for sustainable forest management.}, } @article {pmid41597549, year = {2025}, author = {Komatsu, Y and Furuichi, M and Kokubo, T}, title = {Gastrointestinal Journey of Human Milk Oligosaccharides: From Breastfeeding Origins to Functional Roles in Adults.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010029}, pmid = {41597549}, issn = {2076-2607}, abstract = {Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and play crucial roles in shaping the gut microbiome and promoting infant health. Although their functions during infancy are well established, emerging evidence suggests that HMOs exert region-specific effects throughout the gastrointestinal tract, extending their benefits beyond early life. This review summarizes current findings on HMO activity in the oral cavity, stomach, small intestine, and large intestine, focusing on their microbiota-modulating, barrier-enhancing, and immunoregulatory effects. In the oral cavity, HMOs inhibit pathogen adhesion and biofilm formation, maintaining oral homeostasis. In the stomach, fucosylated and sialylated HMOs act as soluble decoy receptors, preventing Helicobacter pylori infection. In the small intestine, HMOs strengthen epithelial integrity, regulate inflammation, and promote nutrient absorption. In the large intestine, they serve as selective prebiotics for beneficial microbes, enhancing short-chain fatty acid production and improving barrier function. Although preclinical and clinical studies demonstrate their safety and efficacy, further research is required to elucidate their mechanisms in adults. Overall, HMOs represent multifunctional bioactive glycans with promising applications for gastrointestinal health across all ages.}, } @article {pmid41597540, year = {2025}, author = {Yu, J and Ao, Y and Chen, H and Liu, C and Deng, T and Wang, D and Xiang, M and Wan, P and Cheng, L}, title = {Effects of Dietary Supplementation with Dihydromyricetin on Hindgut Microbiota and Metabolite Profiles in Dairy Cows.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010020}, pmid = {41597540}, issn = {2076-2607}, support = {No.2023BBB058//Key Research and Development Program of Hubei Province/ ; No.D20220056//Science and Technology Program of Enshi Tujia and Miao Autonomous Pre-fecture/ ; }, abstract = {High-yielding dairy cows suffer from a high metabolic load and oxidative stress, which lead to systemic inflammation and metabolic disorders, increasing the susceptibility of these cows to various production diseases. Dihydromyricetin (DMY) has demonstrated potent antioxidant and anti-inflammatory physiological functions; however, research into its application in ruminants remains limited. This study investigated whether DMY supplementation is associated with the maintenance of metabolic homeostasis through the regulation of gut microbiota and metabolite profiles. A total of 14 mid-lactation Holstein dairy cows were randomly divided into two groups (n = 7 per group) and supplemented with DMY at 0 or 0.05% in their basal diet for 60 consecutive days. The effects of DMY on the blood biochemical indicators and the antioxidant capacity of the dairy cows were then determined. Alterations to the gut microbiome and the fecal and plasma metabolome were analyzed through 16S rDNA sequencing and untargeted metabolomics. The results showed that DMY significantly improved the activity of serum glutathione peroxidase (GSH-Px) and presented a trend of increasing the total antioxidant capacity (T-AOC). The abundance of multiple fiber-degrading and beneficial commensal bacteria in the gut, including Fibrobacter_succinogenes, Ruminococcus_albus, and Turicibacter, was significantly elevated by the DMY intervention, accompanied by the upregulation of 8,11,14-eicosatrienoic acid, myricetin, dihydro-3-coumaric acid, PGE1, L-leucine, nicotinuric acid, pantothenic acid, and pyruvate in the feces and plasma. Moreover, DMY supplementation notably reduced the abundance of potential pathogenic microbes, such as Chloroflexi, Deltaproteobacteria, RFP12, and Succinivibrio, and downregulated the levels of 12-hydroxydodecanoic acid, 12,13-DHOME (12,13-dihydroxy-9Z-octadecenoic acid), 16-hydroxyhexadecanoic acid, niacin, and glycerol 3-phosphate. These differential metabolites were principally enriched in the mTOR signaling pathway; pantothenate, nicotinate, and thiamine metabolism; glutathione metabolism; and glycolysis/gluconeogenesis. In summary, dietary supplementation with DMY increased the abundance of intestinal fiber-degrading bacteria and multiple metabolites with known anti-inflammatory and antioxidant properties in the feces and plasma, and was associated with alterations in metabolic pathways involving B-vitamins, amino acids, and glutathione. This suggests a potential role for DMY in supporting metabolic homeostasis in dairy cows.}, } @article {pmid41597522, year = {2025}, author = {Tamahara, T and Kouketsu, A and Fukase, S and Sripodok, P and Saito, T and Ito, A and Li, B and Kumada, K and Shimada, M and Iikubo, M and Shimizu, R and Yamauchi, K and Sugiura, T}, title = {Ecological and Functional Landscape of the Oral Microbiome: A Multi-Site Analysis of Saliva, Dental Plaque and Tongue Coating.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010002}, pmid = {41597522}, issn = {2076-2607}, support = {JP24K1310 and JP22K17150//JSPS KAKENHI/ ; }, abstract = {The oral cavity contains several microbial niches, including saliva, dental plaque and tongue coating, each shaped by distinct local environments and host factors. This study compared the ecological and functional characteristics of the microbiomes of these three oral sites within the same individuals and examined host conditions associated with their variation. Saliva, supragingival plaque and tongue coating samples were collected simultaneously from 31 adults without clinical oral lesions. The bacterial 16S rRNA gene (V3-V4 region) was sequenced using the Illumina MiSeq platform, and analyses included α and β diversity, Mantel correlations, differential abundance tests, network analysis and functional prediction. The three sites displayed a clear ecological gradient. Saliva and tongue coating were taxonomically similar but were influenced by different host factors, whereas plaque maintained a distinct, biofilm-like structure with limited systemic influence. Functional divergence was most pronounced on the tongue coating despite its taxonomic similarity to saliva, whereas functional differences between saliva and plaque were modest despite larger taxonomic separation. These findings indicate that microbial composition and function vary independently across oral niches and support the need for multi-site sampling to more accurately characterize oral microbial ecology.}, } @article {pmid41597510, year = {2026}, author = {Boccuzzi, M and Aiuto, R and Lombardo, L and Piasente, M and Bianchi, AE and Clivio, A}, title = {Oral Microbiome and Metabolome Changes During Orthodontic Treatments: A Systematic Review of Limited Clinical Evidence.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {1}, pages = {}, doi = {10.3390/medicina62010224}, pmid = {41597510}, issn = {1648-9144}, mesh = {Humans ; *Microbiota/physiology ; *Metabolome/physiology ; *Mouth/microbiology ; *Orthodontic Appliances/adverse effects ; *Orthodontics/methods ; }, abstract = {Background and Objectives: Recent advances in dentistry include microbiological and metabolomic analyses, which have the potential to improve the understanding of oral microbiome-host imbalances during orthodontic treatment. Fixed appliances, functional devices and, more recently, clear aligners have been associated with several oral health conditions, including enamel demineralization, dental caries, gingivitis, periodontitis and root and bone resorption. In this context, metabolomic approaches may enable the identification of metabolites in biological samples that could potentially serve as biomarkers and reflect functional biological changes within the oral ecosystem. Investigating orthodontic appliances and associated metabolomic alterations may therefore contribute to advancing current knowledge in orthodontics. This systematic review aimed to describe the available evidence on oral metabolomic changes during orthodontic treatment. Materials and Methods: A systematic literature search was conducted in PubMed, Web of Science, Scopus and the Cochrane Library. A total of 1632 records were identified. After duplicate removal and screening, 18 full-text articles were assessed for eligibility. Of these, 15 studies were excluded, and three studies met the inclusion criteria. Risk of bias was assessed using the ROBINS-I and RoB 2 tools, and the GRADE approach was applied to evaluate the certainty of evidence. The review protocol was registered in PROSPERO (CRD420251141544). Results: Three studies met the inclusion criteria. Overall, the available evidence was limited and heterogeneous. The included studies suggested potential differences in oral microbiome composition and metabolomic profiles between patients treated with fixed appliances and those treated with clear aligners. Reported metabolomic findings were exploratory and involved amino acid-related, immune-associated, and acidic metabolic pathways. Limitations: Only three studies were included, all conducted in a single country. The small sample size and methodological heterogeneity limit the generalizability of the findings. In addition, potential confounding variables highlight the need for further standardized longitudinal studies.}, } @article {pmid41597500, year = {2026}, author = {Hendem, E and Koçak, MZ and Çetinkaya, AM and Dinç, G and Çağlayan, M and Uğraklı, M and Çağlayan, D and Araz, M and Eryılmaz, MK and Sakin, A and Eren, OÖ and Tatlı, AM and Geredeli, Ç and Artaç, M}, title = {The Impact of Concurrent Proton Pump Inhibitors on Nivolumab Response in Metastatic Non-Small Cell Lung Cancer: A Multicenter Real-Life Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {1}, pages = {}, doi = {10.3390/medicina62010214}, pmid = {41597500}, issn = {1648-9144}, mesh = {Humans ; *Proton Pump Inhibitors/therapeutic use/pharmacology ; *Carcinoma, Non-Small-Cell Lung/drug therapy/mortality ; Male ; *Nivolumab/therapeutic use/pharmacology ; Female ; Retrospective Studies ; Middle Aged ; Aged ; *Lung Neoplasms/drug therapy/mortality ; Immune Checkpoint Inhibitors/therapeutic use ; Kaplan-Meier Estimate ; Aged, 80 and over ; Antineoplastic Agents, Immunological/therapeutic use ; Drug Interactions ; }, abstract = {Background and Objectives: Clinically meaningful drug-drug interactions may be overlooked in oncology. Proton pump inhibitors (PPIs) may modulate outcomes with immune checkpoint inhibitors (ICIs) by altering the gut microbiome, altering the immune milieu, and affecting transporter interactions. We evaluated whether concomitant PPI use affects survival among patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: We retrospectively included patients with metastatic NSCLC who received second-line nivolumab across five oncology centers (January 2020-June 2023). Patients were grouped as concomitant PPI users vs. non-users. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method and compared with the log-rank test; multivariable Cox models assessed independent associations. Results: A total of 194 patients were screened, of whom 30 were excluded according to predefined criteria. The final analysis included 164 patients-85 PPI users and 79 non-users. Median OS was 26.1 months (95% CI 15.5-36.7) in PPI users and 29.3 months (22.2-36.4) in non-users; this difference was not statistically significant (p = 0.54). Median PFS was 6.2 months (3.7-8.6) in PPI users vs. 10.2 months (7.1-13.2) in non-users (p = 0.04). In multivariable analysis, absence of concomitant PPI use (No vs. Yes) was independently associated with longer PFS (HR = 0.52, 95% CI 0.24-0.89, p = 0.03), whereas PPI use was not associated with OS (HR = 0.96, 95% CI 0.67-1.61, p = 0.83). Conclusions: Concomitant PPI use during nivolumab therapy was associated with significantly shorter PFS and a numerical reduction in OS in real-world metastatic NSCLC. Where clinically feasible, the need for PPIs should be re-evaluated before and during ICI therapy.}, } @article {pmid41597231, year = {2026}, author = {Feng, Y and Geng, Y and Liu, S and Huang, X and Mou, C and Zhao, H and Zhou, J and Li, Q and Deng, Y}, title = {Overwinter Syndrome in Grass Carp (Ctenopharyngodon idellus) Links Enteric Viral Proliferation to Mucosal Disruption via Multiomics Investigation.}, journal = {Cells}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/cells15020157}, pmid = {41597231}, issn = {2073-4409}, support = {2024YFD2401102//National Key R&D ProgramNational Key R&D Program/ ; 2025ZNSFSC1081//Sichuan Provincial Natural Science Foundation/ ; NKYRCZX2025031//Research Initiation Funding from the Sichuan Academy of Agricultural Sciences/ ; SCCXTD-2025-15//Sichuan Freshwater Fish Innovation Team of the National Modern Agricultural Industrial Technology System/ ; }, mesh = {Animals ; *Carps/virology/microbiology ; *Fish Diseases/virology/microbiology/genetics ; *Intestinal Mucosa/virology/pathology/microbiology ; Gastrointestinal Microbiome ; Metagenomics ; Transcriptome ; Multiomics ; }, abstract = {Overwinter Syndrome (OWS) affects grass carp (Ctenopharyngodon idellus) aquaculture in China, causing high mortality and economic losses under low temperatures. Failure of antibiotic therapies shows limits of the 'low-temperature-pathogen' model and shifts focus to mucosal barrier dysfunction and host-microbiome interactions in OWS. We compared healthy and diseased grass carp collected from the same pond using histopathology, transcriptomics, proteomics, and metagenomics. This integrated approach was used to characterize intestinal structure, microbial composition, and host molecular responses at both taxonomic and functional levels. Results revealed a three-layer barrier failure in OWS fish: the physical barrier was compromised, with structural damage and reduced mucosal index; microbial dysbiosis featured increased richness without changes in diversity or evenness, and expansion of the virobiota, notably uncultured Caudovirales phage; and mucosal immune dysregulation indicated loss of local immune balance. Multi-omics integration identified downregulation of lysosome-related and glycosphingolipid biosynthesis pathways at transcript and protein levels, with disrupted nucleotide metabolism. Overall gut microbial richness, rather than individual taxa abundance, correlated most strongly with host gene changes linked to immunity, metabolism, and epithelial integrity. Although biological replicates were limited by natural outbreak sampling, matched high-depth multi-omics datasets provide exploratory insights into OWS-associated intestinal dysfunction. In summary, OWS entails a cold-triggered breakdown of intestinal barrier integrity and immune homeostasis. This breakdown is driven by a global restructuring of the gut microbiome, which is marked by increased richness, viral expansion, and functional shifts, ultimately resulting in altered host-microbe crosstalk. This ecological perspective informs future mechanistic and applied studies for disease prevention.}, } @article {pmid41597223, year = {2026}, author = {Chagas, J and Gilmer, G and Sowa, G and Vo, N}, title = {Impact of Menopause and Associated Hormonal Changes on Spine Health in Older Females: A Review.}, journal = {Cells}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/cells15020148}, pmid = {41597223}, issn = {2073-4409}, mesh = {Humans ; *Menopause/physiology/metabolism ; Female ; *Low Back Pain/physiopathology/metabolism ; *Spine ; *Hormones/metabolism ; Animals ; }, abstract = {Low back pain (LBP) represents a major societal and economic burden, with annual costs in the United States estimated at $90-134.5 billion. LBP disproportionately impacts postmenopausal women relative to age-matched men, suggesting a role for sex-specific biological factors. Although the mechanisms underlying this disparity are not fully understood, hormonal imbalance during menopause may contribute to LBP pathophysiology. This narrative review aimed to elucidate the impact of menopause on LBP, with emphasis on hormonal effects on spinal tissues and systemic processes. A literature search was conducted, followed by screening of titles, abstracts, and full texts of original clinical studies, preclinical research using human or animal samples, and relevant reviews. Rigour and reproducibility were evaluated using the ARRIVE Guidelines and the Modified Downs & Black Checklist. Evidence indicates that menopause is associated with changes in intervertebral discs, facet joint, ligamentum flavum, skeletal muscle, sympathetic innervation, and systemic systems such as the gut microbiome. However, most findings are correlational rather than causal. Evidence supporting hormone replacement therapy for LBP remains inconclusive, whereas exercise and other treatments, including parathyroid hormones, show more consistent benefits. Future studies should focus on causal mechanisms and adhere to rigour guidelines to improve translational potential.}, } @article {pmid41597211, year = {2026}, author = {Böckels, L and Alexa, D and Antal, DC and Gațcan, C and Alecu, C and Kacani, K and Crețu, RA and Piseru, EA and Bîlcu, RV and Cuciureanu, DI}, title = {The Microbiome-Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions.}, journal = {Cells}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/cells15020135}, pmid = {41597211}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/metabolism ; Animals ; Dysbiosis ; Blood-Brain Barrier/metabolism ; }, abstract = {The gut microbiota has emerged as a central regulator of the gut-brain axis, profoundly influencing neural, immune, and metabolic homeostasis. Increasing evidence indicates that disturbances in microbial composition and function contribute to the onset and progression of neurodegenerative diseases (NDs) through mechanisms involving neuroinflammation, oxidative stress, and impaired neurotransmission. Gut dysbiosis is characterized by a loss of microbial diversity, a reduction in beneficial commensals, and an enrichment of pro-inflammatory taxa. These shifts alter intestinal permeability and systemic immune tone, allowing microbial metabolites and immune mediators to affect central nervous system (CNS) integrity. Metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO) modulate blood-brain barrier (BBB) function, microglial activation, and neurotransmitter synthesis, linking intestinal imbalance to neuronal dysfunction and cognitive decline. Disruption of this gut-brain communication network promotes chronic inflammation and metabolic dysregulation, key features of neurodegenerative pathology. SCFA-producing and tryptophan-metabolizing bacteria appear to exert neuroprotective effects by modulating immune responses, epigenetic regulation, and neuronal resilience. The aim of this work was to comprehensively explore the current evidence on the bidirectional communication between the gut microbiota and the CNS, with a focus on identifying the principal molecular, immune, and metabolic mechanisms supported by the strongest and most consistent data. By integrating findings from recent human studies, this review sought to clarify how microbial composition and function influence neurochemical balance, immune activation, and BBB integrity, ultimately contributing to the onset and progression of neurodegenerative processes. Collectively, these findings position the gut microbiota as a dynamic interface between the enteric and CNS, capable of influencing neurodegenerative processes through immune and metabolic signaling.}, } @article {pmid41596956, year = {2026}, author = {Angane, M and Paturi, G and Butts, CA and Quek, SY}, title = {Synergistic Effects of Plant Essential Oils and Extracts on Gut Microbiota in Rats.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/foods15020358}, pmid = {41596956}, issn = {2304-8158}, support = {4200-UOA-48422-A8AN//University of Auckland/ ; }, abstract = {The application of essential oils and plant extracts as natural food preservatives has gained increasing interest; however, their potential impacts on gut health and host physiology remain unknown. This study evaluated the effects of synergistic combinations of peppermint essential oil (EO) + thyme EO and peppermint EO + feijoa peel extract on gut microbiota composition and colonic morphology in a rat model. Sprague-Dawley rats were orally given the synergistic combinations daily for 28 days, and their effects were assessed using 16S rRNA gene sequencing of the caecum microbiota and histological analysis of proximal colon tissues. Alpha diversity metrics showed no significant differences (p > 0.05) between treatment and control groups, and beta diversity indicated no treatment-related shift in the bacterial communities. Taxonomic profiling at the phylum, family, and genus levels showed comparable relative abundances of dominant microbial taxa across all treatments, with no evidence of dysbiosis. Histological examination of proximal colon tissues revealed no significant changes in crypt depth between treated and control groups, confirming the absence of adverse morphological effects on the intestinal epithelium. The results of this study indicate that synergistic combinations of peppermint EO, thyme EO, and feijoa peel extract do not adversely affect the gut microbiota composition and colonic morphology in rats, thereby supporting their application as preservatives in foods.}, } @article {pmid41596857, year = {2026}, author = {Tsouggou, N and Korozi, E and Pemaj, V and Drosinos, EH and Kapolos, J and Papadelli, M and Skandamis, PN and Papadimitriou, K}, title = {Advances in Shotgun Metagenomics for Cheese Microbiology: From Microbial Dynamics to Functional Insights.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/foods15020259}, pmid = {41596857}, issn = {2304-8158}, abstract = {The cheese microbiome is a complex ecosystem strongly influenced by both technological practices and the processing environment. Moving beyond traditional cultured-based methods, the integration of shotgun metagenomics into cheese microbiology has enabled in-depth resolution of microbial communities at the species and strain levels. The aim of the present study was to review recent applications of shotgun metagenomics in cheese research, underscoring its role in tracking microbial dynamics during production and in discovering genes of technological importance. In addition, the review highlights how shotgun metagenomics enables the identification of key metabolic pathways, including amino acid catabolism, lipid metabolism, and citrate degradation, among others, which are central to flavor formation and ripening. Results of the discussed literature demonstrate how microbial composition, functional traits, and overall quality of cheese are determined by factors such as raw materials, the cheesemaking environment, and artisanal practices. Moreover, it highlights the analytical potentials of shotgun metagenomics, including metagenome-assembled genomes (MAGs) reconstruction, characterization of various genes contributing to flavor-related biosynthetic pathways, bacteriocin production, antimicrobial resistance, and virulence, as well as the identification of phages and CRISPR-Cas systems. These insights obtained are crucial for ensuring product's authenticity, enabling traceability, and improving the assessment of safety and quality. Despite shotgun metagenomics' advantages, there are still analytical restrictions concerning data handling and interpretation, which need to be addressed by importing standardization steps and moving towards integrating multi-omics approaches. Such strategies will lead to more accurate and reproducible results across studies and improved resolution of active ecosystems. Ultimately, shotgun metagenomics has shifted the field from descriptive surveys to a more detailed understanding of the underlying mechanisms shaping the overall quality and safety of cheese, thus bringing innovation in modern dairy microbiology.}, } @article {pmid41596745, year = {2026}, author = {Lee, JH and Han, KI and Jeong, E and Moon, J and Kim, MA and Koo, BS and Lee, Y and Baek, S and Kim, HS and Kim, TJ}, title = {Effects and Molecular Mechanisms of Heat-Killed Postbiotic Enterococcus faecalis EF-2001 on Muscle Volume and Grip Strength in Dexamethasone-Induced Muscle Atrophy in SD Rats.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27021105}, pmid = {41596745}, issn = {1422-0067}, support = {RS-2022-00167156//the Ministry of SMEs and Startups (MSS, Republic of Korea)/ ; }, mesh = {Animals ; *Dexamethasone/adverse effects ; *Muscular Atrophy/chemically induced/pathology/metabolism/drug therapy ; *Enterococcus faecalis ; Rats, Sprague-Dawley ; Male ; Rats ; Mice ; *Probiotics/pharmacology ; Muscle Fibers, Skeletal/drug effects/metabolism ; *Hand Strength ; Cell Line ; Muscle, Skeletal/drug effects/pathology ; Hot Temperature ; Proto-Oncogene Proteins c-akt/metabolism ; }, abstract = {The interaction between the gut microbiota and human health has gained increasing recognition, accelerating advances in microbiome research. While early studies have emphasized probiotics, concerns regarding antibiotic resistance and adverse effects, such as sepsis, have shifted research interest towards heat-treated microbial cells or postbiotics. This study investigated the therapeutic potential of heat-killed postbiotic Enterococcus faecalis EF-2001-one of the most widely used postbiotics worldwide-for the prevention and treatment of muscle atrophy. In vitro, mouse C2C12 myotubes were pretreated with heat-killed postbiotic EF-2001 (50-500 μg/mL) for 48 h and then treated with dexamethasone (100 μM) to induce muscle atrophy. In vivo, male Sprague Dawley rats were treated with low-dose (3 mg/kg) and high-dose (30 mg/kg) EF-2001 for efficacy studies. Heat-killed postbiotic EF-2001 attenuated cellular and DNA damage in dexamethasone-induced C2C12 myotubes. Specifically, heat-killed postbiotic EF-2001 increased AKT phosphorylation while suppressing Atrogin-1 expression, thereby alleviating muscle atrophy. In a Sprague Dawley rat model, heat-killed postbiotic EF-2001 significantly reduced dexamethasone-induced muscle loss by regulating muscle atrophy-associated signaling pathways, including Atrogin-1 expression. Collectively, these findings demonstrate that heat-killed EF-2001 alleviates dexamethasone-induced muscle atrophy and support its potential as a postbiotic. This study provides a solid foundation for future human clinical studies by establishing preclinical evidence for the biological activity of heat-killed EF-2001.}, } @article {pmid41596739, year = {2026}, author = {Ottria, R and Mirmajidi, S and Ciuffreda, P}, title = {Gut Microbiota-Derived Short-Chain Fatty Acids in Inflammatory Bowel Disease: Mechanistic Insights into Gut Inflammation, Barrier Function, and Therapeutic Potential.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27021095}, pmid = {41596739}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism/therapeutic use ; *Inflammatory Bowel Diseases/microbiology/metabolism/drug therapy ; Animals ; Intestinal Mucosa/metabolism/microbiology/immunology ; Butyrates/metabolism ; Inflammation/metabolism ; }, abstract = {This review delves into the complex relationship between short-chain fatty acids (SCFAs) produced by the gut microbiota and inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a group of chronic gastrointestinal disorders with an increasing global incidence. Despite extensive research, the exact etiopathogenesis remains elusive, although a complex interplay involving genetic predisposition, environmental influences, and abnormal immune responses against commensal gut microbes is widely recognized. SCFAs, primarily acetate and butyrate, emerge as key microbial metabolites derived from the fermentation of dietary fiber. They exert profound effects on gut homeostasis, notably with butyrate serving as an essential energy source for colonocytes, strengthening epithelial integrity, actively modulating local and systemic immune functions, suppressing the expression of pro-inflammatory cytokines, and enhancing mucosal defense mechanisms. However, clinical trials exploring SCFA administration have frequently yielded variable and inconsistent results due to differences in study design and patient characteristics. This review thoroughly analyzes the diverse roles of SCFAs in the large intestine, focusing on the intestinal barrier, immune modulation, and microbiota. It critically examines the therapeutic potential of SCFAs, including acetate and propionate, in addition to the well-known butyrate, in IBD management.}, } @article {pmid41596659, year = {2026}, author = {Sánchez-Recillas, E and Almanza-Aguilera, E and Bars-Cortina, D and Zamora-Ros, R and Godínez-Santillán, RI and Sánchez-Tusié, AA and Vergara-Castañeda, HA}, title = {Effect of Garambullo (Myrtillocactus geometrizans) Consumption on the Intestinal Microbiota Profile in an Early-Phase Rat Model of Colon Cancer.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27021014}, pmid = {41596659}, issn = {1422-0067}, support = {1560335//Secretaría de Ciencia, Humanidades, Tecnología e Innovación/ ; FME202404//Autonomous University of Queretaro - FONFIVE/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colonic Neoplasms/microbiology/chemically induced/pathology/drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Azoxymethane ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Dextran Sulfate ; *Plant Extracts/pharmacology ; Bacteria/genetics/classification ; }, abstract = {Bioactive compounds in food contribute to reducing the risk of developing colon cancer by modulating the gut microbiota. We have recently demonstrated that garambullo (Myrtillocactus geometrizans), an endemic fruit of Mexico rich in bioactive compounds, attenuates aberrant crypt foci in an animal model. However, its potential to modulate the gut microbiota is unknown. The main objective of this study was to evaluate whether its consumption modulates colon carcinogenesis by altering the microbiota in an in vivo model induced by azoxymethane and dextran sulfate sodium (AOM/DSS). Fecal samples were collected from twelve male Sprague-Dawley rats and analyzed for microbiota composition after 0, 8, and 16 weeks of treatment with saline (control), AOM/DSS, garambullo (G), or residue of garambullo (RG) with AOM/DSS (G+AOM/DSS and RG+AOM/DSS, respectively). Characterization of the microbiome was based on the conserved region of the 16S rRNA V3-V4 gene, and analyzed by the ZymoBIOMICS' Targeted Metagenomics Sequencing (Zymo Research) service. In an animal model induced with AOM/DSS for 8 weeks, consumption of G and its residue increased the bacterial genera Shuttleworthiia, Subdoligranulum, Lactobacillus, Faecalibacterium, and Alloprevotella (p < 0.05). Consumption of G and its residue allowed the proliferation of bacteria that produce short-chain fatty acids and are associated with protective mechanisms of the colon.}, } @article {pmid41596563, year = {2026}, author = {Jäger, E and Peeva, V and Gnad, T and Haange, SB and Rolle-Kampczyk, U and Stäubert, C and Krumbholz, P and Heiker, JT and Gebhardt, C and Krügel, U and Sen, P and Harazin, M and Stab, V and Münzker, J and Hamdani, N and Pfeifer, A and von Bergen, M and Till, A and Fenske, WK}, title = {Antibiotic-Mediated Modulation of the Gut Microbiome Identifies Taurine as a Modulator of Adipocyte Function Through TGR5 Signaling.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020917}, pmid = {41596563}, issn = {1422-0067}, support = {01EO1501//BMBF/ ; AOBJ: 450149205//DFG/ ; AOBJ: 624808//DFG/ ; AOBJ: 432325352//DFG/ ; AOBJ: 335447717//DFG/ ; AOBJ: 624810//DFG/ ; AOBJ: 209933838//DFG/ ; }, mesh = {*Taurine/pharmacology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Mice ; *Adipocytes/metabolism/drug effects ; Lipolysis/drug effects ; Male ; *Signal Transduction/drug effects ; Humans ; *Anti-Bacterial Agents/pharmacology ; Rats ; Thermogenesis/drug effects ; Diet, High-Fat/adverse effects ; Adipose Tissue, Brown/metabolism/drug effects ; Obesity/metabolism ; Mice, Inbred C57BL ; }, abstract = {Gut microbiota has emerged as a modulator of host metabolism and energy balance. However, the precise microbial metabolites mediating thermogenic activation in obesity remain largely undefined. We investigated the effect of antibiotic treatment under a high-fat diet on metabolites and its contribution to lipolysis and thermogenesis. Antibiotic treatment in high-fat diet-fed rats reduced adiposity and enhanced adaptive thermogenesis. Metabolomics revealed elevated taurine levels in the cecum content and plasma of antibiotic-treated animals, correlating with increased expressions of UCP1 and TGR5 in brown adipose tissue. Taurine enhanced lipolysis and oxygen consumption in mouse adipose tissue and human adipocytes. Thereby, taurine modulated lipolysis dependent on TGR5 signaling in adipose tissue. Human data confirmed that taurine promotes browning of white adipocytes and that acute cold exposure leads to a marked drop in circulating taurine, suggesting its rapid recruitment into thermogenic tissues. Besides its synthesis in the liver and dietary uptake, taurine can be a microbiota-derived metabolite that activates adipose thermogenesis and lipolysis through TGR5 and possibly taurine transporter-dependent mechanisms. These findings uncover a gut-adipose axis with therapeutic potential for metabolic disease.}, } @article {pmid41596486, year = {2026}, author = {Sá, L and Machado, E and Ginani, V and Timbó, R and Romiti, R and Kurizky, P and Gomes, C}, title = {Species-Level Comparative Metagenomic Analysis of the Bacterial Abundance of the Gut Microbiome in Psoriasis, Hidradenitis Suppurativa, and Pemphigus Foliaceous Patients Using Shotgun Next-Generation Sequencing.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020838}, pmid = {41596486}, issn = {1422-0067}, support = {00193-00000279/2023-70//Fundação de Apoio à Pesquisa do Distrito Federal (FAP-DF)/ ; 445040/2023-8//National Council for Scientific and Technological Development/ ; 21/2023//Departamento de Ciência e Tecnologia, da Secretaria de Ciência, Tecnologia, Inovação e Com-plexo da Saúde, do Ministério da Saúde (Decit/SECTICS/MS)/ ; }, mesh = {Humans ; *Psoriasis/microbiology ; *Pemphigus/microbiology ; Female ; Male ; *Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; *Metagenomics/methods ; Middle Aged ; Adult ; *Hidradenitis Suppurativa/microbiology ; Feces/microbiology ; *Bacteria/genetics/classification ; Aged ; }, abstract = {Recent studies have revealed a specific relationship between gut bacteria and inflammatory skin profiles. We aimed to perform a species-level comparative metagenomic analysis of the gut microbiome in patients with psoriasis, hidradenitis suppurativa (HS), and pemphigus foliaceus (PF). We included omnivorous nonsmokers and nondrinkers with psoriasis (n = 24), HS (n = 10), and PF (n = 11), as well as healthy controls (n = 10). We collected faecal samples from all patients for classic parasitological analysis. Gut microbiome analysis was conducted using shotgun next-generation sequencing. We used the Deseq2, Limma_voom, LinDA, and MaAMaAsLin 2 bioinformatics tools to evaluate concordance and differential abundance between patients. Thirteen patients (23.64%) were diagnosed with active intestinal parasitosis. The presence of intestinal parasitosis was significantly related to immunosuppression (p = 0.009). The most abundant microorganism species found in the faeces of the patients evaluated was Escherichia coli. Psoriasis patients presented a greater abundance of bacteria from the Veillonellaceae family, whereas PF patients presented a greater abundance of Firmicutes bacteria. Patients with PF showed increased E. coli virulence and antibiotic resistance functional markers. Immunosuppression significantly influenced the presence of intestinal parasitosis as well as increased the virulence of functional markers in patients with PF receiving systemic corticosteroid therapy.}, } @article {pmid41596463, year = {2026}, author = {Sankararaman, S and Liu, R and Sun, X and Retuerto, M and Schindler, T and Roesch, E and Sferra, TJ and Drumm, M and Ghannoum, M and Zhang, L}, title = {Comparison of Stool Microbiome in Children with Cystic Fibrosis Treated with and Without Elexacaftor-Tezacaftor-Ivacaftor-A Pilot Study.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020814}, pmid = {41596463}, issn = {1422-0067}, support = {Pilot Faculty Award - P0598//Rainbow Babies & Children's Hospital/ ; }, mesh = {Humans ; *Cystic Fibrosis/drug therapy/microbiology ; Child ; Male ; Female ; Adolescent ; *Aminophenols/therapeutic use/pharmacology ; Pilot Projects ; Child, Preschool ; *Quinolones/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Feces/microbiology ; Drug Combinations ; *Benzodioxoles/therapeutic use ; *Pyridines/therapeutic use ; *Indoles/therapeutic use ; Prospective Studies ; *Pyrazoles/therapeutic use ; Quinolines ; }, abstract = {Prior studies in people with cystic fibrosis (CF) demonstrated a positive impact of ivacaftor on the stool microbiome. However, studies evaluating the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on gut dysbiosis are limited. In this prospective, observational study, we evaluated the differences in stool microbiome in children (aged 2-17 years) with CF who were treated with ETI for at least two months and compared with children with CF who did not receive ETI. We also included healthy siblings as controls. There were no significant differences in the demographics between the groups. There were no significant differences in alpha diversity between the groups for both bacteriome and mycobiome. Alpha diversity showed a negative trend with the duration of ETI therapy for both bacteriome and mycobiome. Firmicutes and Proteobacteria were the most abundant phyla and core members across all samples, regardless of disease status or treatment. Ascomycota and Basidiomycota were the most abundant and core members across all samples, regardless of disease status or treatment. Alpha diversity showed a negative trend with the duration of ETI therapy for both bacteriome and mycobiome in children with CF treated with ETI. Future studies are needed to confirm or refute our preliminary findings.}, } @article {pmid41596452, year = {2026}, author = {Jandosov, J and Chenchik, D and Baimenov, A and Silvestre-Albero, J and Bernardo, M and Azat, S and Doszhanov, Y and Sabitov, A and Busquets, R and Howell, C and Mikhalovsky, S and Mansurov, Z}, title = {Assessment of Phenolic and Indolic Compounds Removal from Aqueous Media Using Lignocellulose-Derived Surface-Modified Nanoporous Carbon Adsorbents: A Comparative Study.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020804}, pmid = {41596452}, issn = {1422-0067}, support = {AP23485436//Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, mesh = {Adsorption ; *Carbon/chemistry ; *Lignin/chemistry ; *Indoles/chemistry/isolation & purification ; *Nanopores/ultrastructure ; *Phenols/chemistry/isolation & purification ; Cresols/chemistry ; Water Purification/methods ; *Water Pollutants, Chemical/chemistry ; Indoleacetic Acids/chemistry/isolation & purification ; Uremic Toxins/chemistry ; }, abstract = {P-cresol, indole and indole-3-acetic acid (IAA) are catabolites of amino acids, formed by the gut microbiome. Most of these aromatic hydrocarbon derivatives are excreted by the colon before reentering the body to form "exogenous" protein-bound uremic toxins (PBUTs), which aggravate chronic kidney disease (CKD). Removal efficiencies of these PBUT precursors from model phosphate-buffered saline solutions by three different surface-modified nanoporous carbon adsorbents (PCs) were studied. PCs were produced by physicochemical and/or acid base activation of carbonized rice husk waste. Removal rates achieved values of 32-96% within a 3 h contact time. High micro/mesoporosity and surface chemistry of the N- and P-doped biochars were established by N2 adsorption studies, SEM/EDS analysis, XPS and FT-IR-spectroscopy. The ammoxidized PC-N1 had the highest adsorption capacity (1.97 mmol/g for IAA, 2.43 mmol/g for p-cresol and 2.42 mmol/g for indole), followed by "urea-nitrified" PC-N2, whilst the phosphorylated PC-P demonstrated the lowest adsorption capacity for these solutes. These results do not correlate with the total pore volume values for PC-N2 (0.91 cm[3]/g) < PC-P (1.56 cm[3]/g) < PC-N1 (1.84 cm[3]/g), suggesting that other parameters such as the micropore volume (PC-N1 > PC-N2 > PC-P) and the interaction of surface chemical functional groups with the solutes play key roles in the adsorption mechanism. N-doped PC-N1 and PC-N2 have basic functional groups with higher affinity with acidic IAA and p-cresol. The ion-exchange mechanism of phenolic and indolic compound chemisorption by nanoporous carbon adsorbents, modified with surface N- and P-containing functional groups, has been proposed.}, } @article {pmid41596418, year = {2026}, author = {Wang, J and Zeng, NK and Zhang, X}, title = {Tuber Inoculation Drives Rhizosphere Microbiome Assembly and Metabolic Reprogramming in Corylus.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020768}, pmid = {41596418}, issn = {1422-0067}, support = {2019RC185 and 320RC597//Natural Science Foundation of HainanProvince/ ; (2024)171//Project of Science and Technology Programs of Guizhou Province/ ; Gui(2024)TG12//Project of Central Government Financial Fund for Forest Reform and Development/ ; }, mesh = {*Rhizosphere ; *Microbiota ; Mycorrhizae/physiology ; Symbiosis ; Plant Roots/microbiology/metabolism ; Metabolomics/methods ; *Plant Tubers/microbiology/metabolism ; Soil Microbiology ; Metabolic Reprogramming ; }, abstract = {To elucidate the potential of integrated multi-omics approaches for studying systemic mechanisms of mycorrhizal fungi in mediating plant-microbe interactions, this study employed the Tuber-inoculated Corylus system as a model to demonstrate how high-throughput profiling can investigate how fungal inoculation reshapes the rhizosphere microbial community and correlates with host metabolism. A pot experiment was conducted comparing inoculated (CTG) and non-inoculated (CK) plants, followed by integrated multi-omics analysis involving high-throughput sequencing (16S/ITS), functional prediction (PICRUSt2/FUNGuild), and metabolomics (UPLC-MS/MS). The results demonstrated that inoculation significantly restructured the fungal community, establishing Tuber as a dominant symbiotic guild and effectively suppressing pathogenic fungi. Although bacterial alpha diversity remained stable, the functional profile shifted markedly toward symbiotic support, including antibiotic biosynthesis and environmental adaptation. Concurrently, root metabolic reprogramming occurred, characterized by upregulation of strigolactones and downregulation of gibberellin A5, suggesting a potential "symbiosis-priority" strategy wherein carbon allocation shifted from structural growth to energy storage, and plant defense transitioned from broad-spectrum resistance to targeted regulation. Multi-omics correlation analysis further revealed notable associations between microbial communities and root metabolites, proposing a model in which Tuber acts as a core regulator that collaborates with the host to assemble a complementary micro-ecosystem. In summary, the integrated approach successfully captured multi-level changes, suggesting that Tuber-Corylus symbiosis constitutes a fungus-driven process that transforms the rhizosphere from a competitive state into a mutualistic state, thereby illustrating the role of mycorrhizal fungi as "ecosystem engineers" and providing a methodological framework for green agriculture research.}, } @article {pmid41596401, year = {2026}, author = {Zhu, Z and Liu, Z and He, Y and He, X and Zheng, W and Jiang, M}, title = {G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020752}, pmid = {41596401}, issn = {1422-0067}, support = {2023YFC2706500 and 2023YFC2706504//The National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Irritable Bowel Syndrome/metabolism/therapy/microbiology/immunology/drug therapy ; *Receptors, G-Protein-Coupled/metabolism ; Animals ; Gastrointestinal Microbiome ; Signal Transduction ; }, abstract = {Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances in understanding how GPCRs mediate gut immune regulation, microbiota-host crosstalk, metabolic signaling, and pain processing in IBS. Recent studies show that microbial metabolites (e.g., short-chain fatty acids, biogenic amines, and lipid mediators) signal through GPCRs on immune cells, epithelia, and neurons to influence intestinal homeostasis. On immune cells and neurons, GPCRs also mediate signals from external substances (such as fats, sugars, histamine, etc.) to regulate immune and neural functions. And there are challenges and future directions in targeting GPCRs for IBS, including patient heterogeneity and the complexity of host-microbiome interactions. This review provides a mechanistic framework for GPCR-based therapies in IBS.}, } @article {pmid41596399, year = {2026}, author = {Tian, X and Chen, Q and He, Y and Cheng, Y and Zhao, M and Li, Y and Yu, M and Jiang, J and Wang, L}, title = {Berberine: A Negentropic Modulator for Multi-System Coordination.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020747}, pmid = {41596399}, issn = {1422-0067}, mesh = {*Berberine/pharmacology/therapeutic use ; Humans ; Animals ; AMP-Activated Protein Kinases/metabolism ; Lipid Metabolism/drug effects ; Signal Transduction/drug effects ; }, abstract = {Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose-lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR's capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub-axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling.}, } @article {pmid41596382, year = {2026}, author = {Han, L and Yang, Y and Zhang, B and Wang, Y and Ji, Y and Du, S and Zou, Y}, title = {Seed Oil of Lycium barbarum L. from Qaidam Basin Prevents and Treats UV-Induced Photodamage in BABL/c Mice Skin by Modulating Skin Microbiome and Amino Acid Metabolism.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020731}, pmid = {41596382}, issn = {1422-0067}, support = {2025ZY011//Central Government-Guided Local Science and Technology Development Fund Project in Qinghai Province/ ; }, mesh = {Animals ; *Ultraviolet Rays/adverse effects ; Mice ; *Microbiota/drug effects/radiation effects ; *Skin/drug effects/radiation effects/microbiology/metabolism/pathology ; *Amino Acids/metabolism ; *Lycium/chemistry ; Mice, Inbred BALB C ; *Plant Oils/pharmacology/chemistry ; *Seeds/chemistry ; Metabolomics ; *Skin Aging/drug effects/radiation effects ; Cytokines/metabolism ; Skin Microbiome ; }, abstract = {Ultraviolet (UV) radiation is a primary environmental factor responsible for skin photodamage, and exposure to UV rays is strongly linked to a variety of skin diseases. This study examined the prophylactic and therapeutic effects of Seed Oil of Lycium barbarum L. from the Qaidam basin (QLBSO) in a UV-induced skin photodamage model in BALB/c mice, exploring potential mechanisms by analyzing the skin microbiota and metabolites using 16S rDNA sequencing and metabolomics. The results showed that QLBSO effectively alleviated UV-induced histopathological changes in mouse skin. It also significantly increased the activity of superoxide dismutase (SOD) and catalase (CAT) in UV-damaged skin tissue, while reducing levels of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as matrix metalloproteinases-1 (MMP-1) and MMP-3. Omics analysis revealed that QLBSO successfully restored the balance of the skin microbiota and corrected disruptions in amino acid metabolism caused by UV exposure. Notably, Firmicutes_A and Kineothrix, along with cysteine, cystine, glycine, arginine, proline, and choline, were identified as key microbial species and metabolites responsive to QLBSO's prophylactic and therapeutic effects. In conclusion, QLBSO likely protects against UV-induced skin photodamage by modulating the skin microbiota and amino acid metabolism, providing a scientific foundation for its potential use in skin health protection.}, } @article {pmid41596292, year = {2026}, author = {Lagunas-Cruz, MDC and Valle-Mendiola, A and Soto-Cruz, I}, title = {The Vaginal Microbiome and Host Health: Implications for Cervical Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020640}, pmid = {41596292}, issn = {1422-0067}, support = {CBF-2023-2024-1208//Secretaría de Ciencia Tecnología e Innovación/ ; }, mesh = {Humans ; Female ; *Vagina/microbiology/virology ; *Microbiota ; *Uterine Cervical Neoplasms/microbiology/pathology/virology ; Papillomavirus Infections/microbiology/complications/virology ; Lactobacillus ; Disease Progression ; Dysbiosis/microbiology ; }, abstract = {The vaginal microbiome plays a crucial role in maintaining host health by preserving a balanced microenvironment. Nevertheless, the definition of a "normal" vaginal microbiome remains controversial, as its composition varies depending on factors such as ethnicity and geographical origin. In most cases, members of the genus Lactobacillus predominate in healthy vaginal microbiomes, protecting against potential pathogens through specific mechanisms such as the secretion of lactic acid and bacteriocins, among others. A reduction in Lactobacillus abundance, accompanied by an increase in anaerobic organisms, predisposes the host to the development of various pathologies. Among these pathologies is infection with human papillomavirus (HPV) and the subsequent development of cervical cancer. A progressive decline in Lactobacillus has been observed as the lesion advances in different populations worldwide. In the case of the Mexican population, several Lactobacillus have been reported in healthy microbiomes: L. gasseri, L. fermentum, L. rhamnosus, L. jensenii, L. crispatus, L. delbrueckii, L. acidophilus, and L. brevis. In contrast, genera reported in dysbiosis include Sneathia, while Brevibacterium aureum and Brachybacterium conglomeratum have been associated with HPV16 infection and/or SIL. The mere presence of some bacteria is not sufficient to modulate the cellular activity of host cells; therefore, the expression, production and activity of different proteins could be affected by the vaginal microbiome. The impact of the microbiome on host cell function is the result of different metabolites produced by the bacteria, which suppress or activate different signaling and metabolic pathways. The molecular interactions between the host and microbiome, as well as their role in cervical carcinogenesis, are still unknown. In this review, we focus on the vaginal microbiome, HPV, and the impact that the interaction of the microbiome with HPV has in cervical cancer development.}, } @article {pmid41596275, year = {2026}, author = {Paprocka, P and Spałek, J and Daniluk, T and Kaliniak, S and Durnaś, B and Okła, S and Bucki, R}, title = {The Importance of Ear Canal Microbiota and Earwax in the Prevention of Outer Ear Infections.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020622}, pmid = {41596275}, issn = {1422-0067}, support = {SUPB.RN.24.043//This work was supported by Jan Kochanowski University in Kielce, Poland (SUPB.RN.24.043 to B.D.)/ ; }, mesh = {Humans ; *Microbiota ; *Ear Canal/microbiology ; Cerumen ; Animals ; *Otitis Externa/prevention & control/microbiology ; Biofilms ; }, abstract = {This article describes the microbiome of the outer ear and the earwax in the ear canal, which performs various protective functions against bacterial infections. This article is based on an analysis of literature gathered from databases including PubMed, Google Scholar, Web of Science, and Scopus, primarily from the last 15 years. The search strategy included MeSH terms: ear canal, microbiome, earwax, cerumen, antibacterial peptides, ear infections, biofilm. Only peer-reviewed articles were included. The natural ear canal microbiota provides so-called colonization resistance, which protects against invasion by pathogenic microorganisms. Earwax is composed primarily of keratin secreted by epithelial cells and substances secreted by sweat and apocrine glands. It plays a key role in the physiology of the ear canal, maintaining a low pH, limiting moisture, and exhibiting antimicrobial properties. Both an excess and a deficiency of earwax can lead to dysbiosis of the outer ear, and consequently to the development of various infections. In an era of increasing antibiotic resistance and the search for new solutions in the fight against pathogenic microorganisms, understanding the natural properties of earwax is becoming increasingly important.}, } @article {pmid41596220, year = {2026}, author = {Hussain, SA and Sarker, MI and Liu, Y and Jin, TZ}, title = {DNA Methylation and Its Role in Personalized Nutrition: Mechanisms, Clinical Insights, and Future Perspectives.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, doi = {10.3390/ijms27020566}, pmid = {41596220}, issn = {1422-0067}, mesh = {Humans ; *DNA Methylation ; *Precision Medicine/methods ; *Epigenesis, Genetic ; Diet ; Animals ; }, abstract = {DNA methylation is a central epigenetic mechanism that mediates the interaction between nutritional exposures and gene regulation. Emerging evidence demonstrates that diet, bioactive compounds, genetic background, and lifestyle factors collectively shape the human methylome, influencing metabolic function, disease susceptibility, and biological aging. This review synthesizes current knowledge on the molecular and biochemical mechanisms of DNA methylation, the role of nutrients and dietary patterns in modulating methylation dynamics, and findings from human clinical trials evaluating nutritional interventions. Genotype-specific responses, including polymorphisms in one-carbon metabolism and metabolic pathways, are discussed as key determinants of interindividual variation in methylation outcomes. The review further highlights the advances in epigenetic clocks, systems biology, and multi-omics integration that support the development of precision nutrition frameworks. Ethical considerations and future challenges related to data interpretation, accessibility, and the regulation of epigenetic testing are also examined. Collectively, this review provides an integrative perspective on how DNA methylation serves as a dynamic interface between diet and health and outlines opportunities for implementing personalized nutrition strategies to improve metabolic resilience and promote healthy aging.}, } @article {pmid41596178, year = {2026}, author = {Feix, JB and Cheng, G and Hardy, M and Kalyanaraman, B}, title = {Microbial Metabolism of Levodopa as an Adjunct Therapeutic Target in Parkinson's Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/antiox15010120}, pmid = {41596178}, issn = {2076-3921}, support = {1R21NS137244-01A1/NH/NIH HHS/United States ; }, abstract = {Parkinson's disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson's disease.}, } @article {pmid41596119, year = {2026}, author = {Patanè, GT and Moreira, RJ and Almeida-Santos, M and Putaggio, S and Barreca, D and Oliveira, PF and Alves, MG}, title = {Anthocyanins and Metabolic Disease: A New Frontier in Precision Nutrition.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/antiox15010061}, pmid = {41596119}, issn = {2076-3921}, support = {2024.03012.BD//Fundação para a Ciência e Tecnologia/ ; UIDB/50006/2020//Laboratório Associado para a Química Verde/ ; CEECINST/00026/2018//Fundação para a Ciência e Tecnologia/ ; CDL-CTTRI-267-SGRH/2022//Fundação para a Ciência e Tecnologia/ ; UIDB/04501/2020-DOI 10.54499/UIDB/04501/2020 and UIDP/04501/2020-DOI 10.54499/UIDP/04501/2020//iBiMED/ ; }, abstract = {Metabolic syndrome (MetS) represents a global health challenge mainly driven by chronic low-grade inflammation and persistent oxidative stress (OS). Current therapeutic and nutritional strategies often fail to resolve these interconnected core pathologies due to the multifactorial nature of MetS. Anthocyanins (ACNs), a class of potent dietary flavonoids, offer significant promise due to their established pleiotropic effects, including robust antioxidant activity through modulation of the Nrf2/ARE pathway, anti-inflammatory effects via NF-κB suppression, and overall support for glucose and lipid homeostasis. However, the therapeutic efficacy of ACNs is characterized by interindividual variability, which is intrinsically linked to their low systemic bioavailability. This heterogeneity in the response is due to the complex interplay between genetic polymorphisms affecting absorption, distribution, metabolism, and excretion (ADME), as well as the specific biotransformation capacity of the gut microbiome. This review proposes that achieving the full clinical potential of ACNs requires moving beyond conventional nutritional advice. We propose that precision nutrition, which integrates multi-omics data (e.g., genomics, metagenomics, and metabolomics), can determine the individual phenotype, predict functional metabolic response, and tailor safer and effective ACN-rich interventions. This integrated, multifactorial approach is essential for optimizing the antioxidant and metabolic benefits of ACNs for the prevention and management of MetS and its associated pathologies.}, } @article {pmid41595645, year = {2026}, author = {Rusu, M and Ichim, C and Anderco, P and Pălăștea, A and Boicean, A}, title = {Gut-Kidney Axis: Unraveling the Role of the Microbiome in Chronic Kidney Disease.}, journal = {Biomedicines}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/biomedicines14010109}, pmid = {41595645}, issn = {2227-9059}, abstract = {Chronic kidney disease (CKD), which affects over 850 million individuals globally, is increasingly regarded as a systemic condition in which the gut microbiota represents a key pathogenic node. This review provides an integrated overview of mechanistic, translational and clinical data implicating the gut-kidney axis in CKD. The CKD-associated microbiota displays a characteristic dysbiosis, marked by depletion of short-chain fatty acid-producing commensals, overgrowth of proteolytic and urease-expressing taxa and disruption of epithelial barrier integrity. These disturbances favor the generation and systemic accumulation of gut-derived uremic toxins, most notably indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid and trimethylamine-N-oxide, which promote endothelial dysfunction, vascular calcification, fibrosis and chronic inflammation, thereby hastening renal function loss and heightening cardiovascular risk. Microbiome-directed interventions, including dietary modification, prebiotics, probiotics, synbiotics, intestinal dialysis, fecal microbiota transplantation, gut-acting sorbents and nephroprotective phytochemicals, are summarized with emphasis on their effects on uremic toxin burden and clinical surrogates. System-level implications of the gut-kidney axis for cardiovascular disease, immunosenescence and sarcopenia are discussed, together with future priorities for integrating multi-omics profiling and precision microbiome-based strategies into nephrology practice.}, } @article {pmid41595609, year = {2025}, author = {Zimbru, EL and Zimbru, RI and Bojin, FM and Chiriac, SD and Haidar, L and Andor, M and Tănasie, G and Tatu, C and Georgescu, M and Uța, C and Bănărescu, CF and Groza, S and Panaitescu, C}, title = {Microbiota-Driven Immune Dysregulation Along the Gut-Lung-Vascular Axis in Asthma and Atherosclerosis.}, journal = {Biomedicines}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/biomedicines14010073}, pmid = {41595609}, issn = {2227-9059}, abstract = {Background: Asthma and atherosclerosis frequently coexist in clinical populations and share convergent immunometabolic pathways amplified by gut microbial dysbiosis. We propose the gut-lung-vascular axis as a unifying mechanistic framework connecting epithelial and endothelial inflammation providing a foundation for understanding shared inflammatory mechanisms beyond tissue-specific disease boundaries. Methods: A targeted narrative review systematically appraised clinical, experimental and multi-omics studies published over the last five years to delineate microbiota-driven pathways relevant to asthma and atherosclerosis. Particular emphasis was placed on specific microbial taxa, metabolite profiles and immunometabolic networks that connect gut dysbiosis with respiratory and cardiovascular dysfunction. Results: Across human and experimental cohorts, dysbiosis marked by depletion of short-chain fatty acids (SCFAs) producing taxa (Faecalibacterium, Roseburia, Bacteroides) and enrichment of pathobionts (Proteobacteria, Haemophilus, Moraxella, Streptococcus) promotes epithelial and endothelial barrier dysfunction, amplifying Th2/Th17-skewed inflammation and endothelial injury. Key metabolites, including SCFAs, trimethylamine N-oxide (TMAO), secondary bile acids (BA), indole/tryptophan derivatives and lipopolysaccharides (LPS), serve as molecular connectors linking gut, airway and vascular inflammation. Microbial signatures and metabolomic patterns hold emerging diagnostic and therapeutic potential, and several drug classes (e.g., statins, corticosteroids, proton-pump inhibitors (PPIs)) further modulate host-microbiota interactions. Conclusions: Shared microbial taxa and metabolite signatures in asthma and atherosclerosis support microbiota-mediated immune dysregulation along the gut-lung-vascular axis as a common pathogenic framework. Microbial and metabolite profiling may enable improved risk stratification and precise, microbiota-targeted therapies. Integrating microbiome-informed diagnostics and personalized interventions could help reduce systemic inflammation and the burden of these overlapping inflammatory diseases.}, } @article {pmid41595585, year = {2025}, author = {Pasitka, LP and Molnár, T and Urbán, E and Csécsei, P and Hetesi, Z and Mód, J and Bán, Á}, title = {Periodontal Bacteria and Outcomes Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Analysis.}, journal = {Biomedicines}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/biomedicines14010048}, pmid = {41595585}, issn = {2227-9059}, abstract = {Background: Periodontitis has been associated with systemic diseases such as cerebrovascular events. Emerging research highlights the potential role of the microbiome in intracranial aneurysm formation and rupture. Aims: We aimed to explore the associations among periodontal pathogens and the outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Materials and Methods: A total of 43 aSAH patients were enrolled. Clinical probing depth measurement and microbiological culture were performed for all participants. The markers of systemic immune response (IL-6, hsCRP) and brain injury (NSE, S100B) were measured between 24 and 48 h after admission. Development of delayed cerebral ischemia (DCI) as the primary and clinical outcome, based on modified Rankin Scale as secondary endpoints, comprised the chosen metrics. Results: A significant association was observed between patients with periodontal pocket depth PPD ≥ 5 mm (n = 28) and DCI, which developed in 19 patients (p = 0.007). In the subgroup of patients with PPD ≥ 5 mm significant associations were found between certain periodontal pathogens and DCI. Higher hsCRP (p = 0.05), IL-6 (p = 0.037) levels were observed in cases with periodontal pathogens, independent of the depth of the pocket, suggesting systemic inflammation. Conclusions: Elevated hsCRP and IL-6 levels, periodontal pocket depth ≥ 5 mm, and red-complex periodontal pathogens are associated with an increased risk of DCI after aSAH, suggesting a role for periodontal disease-related systemic inflammation in DCI risk stratification.}, } @article {pmid41595535, year = {2026}, author = {Ma, Y and Wang, L and Hu, H and Shieh, AR and Li, E and He, D and He, L and Liu, Z and Paing, TM and Chen, X and Cao, Y}, title = {Composition and Function of Gut Microbiome: From Basic Omics to Precision Medicine.}, journal = {Genes}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/genes17010116}, pmid = {41595535}, issn = {2073-4425}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Precision Medicine/methods ; Animals ; Genomics/methods ; Probiotics ; }, abstract = {The gut microbiome is defined as the collective assembly of microbial communities inhabiting the gut, along with their genes and metabolic products. The gut microbiome systematically regulates host metabolism, immunity, and neuroendocrine homeostasis via interspecies interaction networks and inter-organ axes. Given the importance of the gut microbiome to the host, this review integrates the composition, function, and genetic basis of the gut microbiome with host genomics to provide a systematic overview of recent advances in microbiome-host interactions. This encompasses a complete technological pipeline spanning from in vitro to in vivo models to translational medicine. This technological pipeline spans from single-bacterium CRISPR editing, organoid-microbiome co-culture, and sterile/humanized animal models to multi-omics integrated algorithms, machine learning causal inference, and individualized probiotic design. It aims to transform microbiome associations into precision intervention strategies that can be targeted and predicted for clinical application through interdisciplinary research, thereby providing the cornerstone of a new generation of precision treatment strategies for cancer, metabolic, and neurodegenerative diseases.}, } @article {pmid41595128, year = {2026}, author = {Dovey, Z and Tomas Bort, E and Mechanick, JI}, title = {Adipokine Metabolic Drivers, Gut Dysbiosis, and the Prostate Microbiome: Novel Pathway Enrichment Analysis of the Adiposity-Based Chronic Disease-Prostate Cancer Network.}, journal = {Cancers}, volume = {18}, number = {2}, pages = {}, doi = {10.3390/cancers18020206}, pmid = {41595128}, issn = {2072-6694}, abstract = {Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose tissue (WAT; VAT) and periprostatic adipose tissue (ppWAT). Contributing to systemic inflammation is gut dysbiosis, which itself may be caused by ABCD as well as background local inflammation (prostatitis), which is common in aging men and may be exacerbated by the urinary microbiome. Investigating the molecular biology driving inflammation and its association with increased PCa risk, a recent paper applied a network and gene set enrichment to adipokine drivers in the ABCD-PCa network. It found prominent roles for MCP-1, IL-1β, and CXCL-1 in addition to confirming the importance of exposure to lipopolysaccharides and bacterial components, corroborating the role of gut dysbiosis. To further unravel the mechanistic links between ABCD and PCa risk, this critical review will discuss the current literature on prominent inflammatory signaling pathways activated in ABCD; the influence of gut dysbiosis, the urinary microbiome, and chronic prostatitis; and current hypotheses on how these domains may result in the development of aggressive PCa over a man's life. Moreover, we performed a novel pathway enrichment analysis to further evaluate the associations between ABCD, PCa risk, gut dysbiosis, and the prostate microbiome, the results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular space, there were downstream signals activating chemokine and type 2 interferon pathways, focal adhesion PI3K/Akt/mTOR pathways, as well as the JAK/STAT, NF-κB, and PI3K/Akt pathways. Overall, these findings point to an emerging molecular pathway for PCa oncogenesis influenced by ABCD, gut dysbiosis, and inflammation, and further research, possibly with lifestyle program-based clinical trials, may discover novel biomarker panels and molecular targeted therapies for the prevention and treatment of PCa.}, } @article {pmid41595125, year = {2026}, author = {Turner, L and Sisk, CK and Yusuf, N}, title = {Dietary Fiber and Melanoma: Exploring Microbiome-Driven Immune Modulation.}, journal = {Cancers}, volume = {18}, number = {2}, pages = {}, doi = {10.3390/cancers18020203}, pmid = {41595125}, issn = {2072-6694}, abstract = {Background/Objectives: The gut microbiome influences melanoma biology and response to immune checkpoint inhibitors. Dietary fiber is a key modifiable factor that shapes the microbial composition and metabolite production. This review summarizes mechanistic, preclinical, and clinical evidence describing how fiber and fiber-responsive taxa may affect melanoma immunity and treatment outcomes. Methods: A literature search of MEDLINE, Embase, and Scopus identified studies published within the past five years examining dietary fiber, gut microbiome interactions, immune modulation, or melanoma outcomes. After screening 491 unique records, 49 peer-reviewed mechanistic, preclinical, observational, and interventional studies were synthesized qualitatively in this narrative review. Results: Fiber fermentation produces short-chain fatty acids that regulate dendritic cell activation, T-cell priming, and cytokine signaling. Preclinical melanoma models show that fibers such as inulin and β-glucan enhance IFN-γ-driven antitumor immunity, increase CD8[+] infiltration, and improve checkpoint blockade efficacy in a microbiota-dependent manner. In humans, fiber-rich diets and enrichment of taxa such as Bifidobacterium, Faecalibacterium, and Akkermansia are associated with improved PD-1 inhibitor responses, longer progression-free survival, and possible reductions in ICI-related colitis. Although epidemiologic studies suggest no clear association between fiber intake and melanoma incidence, dietary fiber intake appears to correlate strongly with treatment-related outcomes. Conclusions: Dietary fiber represents a potentially safe and plausible adjunct to melanoma immunotherapy. However, study variability and emerging counterevidence highlight the need for controlled trials to clarify causality and define optimal fiber-based interventions.}, } @article {pmid41594863, year = {2026}, author = {Liang, G and Liu, S and Wang, S and Qin, Y}, title = {Application of Reproductive Toxicity Caused by Endocrine Disruptors in Rotifers: A Review.}, journal = {Biology}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/biology15020128}, pmid = {41594863}, issn = {2079-7737}, support = {No//the 2024 Autonomous Topic Project of Basic Research for Colleges and Universities (General Project), "The Mechanism of the Regulatory Strategy of Benzyl Butyl Phthalate on the Reproduction of Brachionus plicatilis"/ ; XI20230022//the Key Laboratory of Facility Fisheries, Ministry of Education (Dalian Ocean University)/ ; }, abstract = {Endocrine-disrupting chemicals (EDCs), widespread in aquatic environments, interfere with endocrine function in organisms and threaten ecosystem stability. Rotifers, critical live feed for marine fish, shrimp, and crab larvae, link EDC-induced reproductive impairment to marine ecosystem stability and aquaculture sustainability. This PRISMA-compliant review synthesizes key findings, consequences, and gaps in EDC-rotifer reproductive toxicity research. Traditional EDCs (heavy metals, per- and polyfluoroalkyl substances (PFASs), phenols, phthalate esters, polybrominated diphenyl ethers (PBDEs), and steroid hormones) and emerging EDCs (disinfection byproducts, microplastics, pharmaceutical metabolites) induce distinct reproductive harm-e.g., Hg[2+] shows extreme toxicity (24 h LC50 = 4.51 μg L[-1] in Brachionus plicatilis), BDE-47 damages ovaries, and microplastics cause transgenerational delays. Rotifer species and exposure duration affect sensitivity (e.g., BDE-47: 96 h LC50 = 0.163 mg L[-1] vs. 24 h LC50 > 22 mg L[-1] in B. plicatilis). Oxidative stress is a universal mechanism, and combined EDC exposure produces context-dependent synergistic/antagonistic effects. EDC-induced impairment reduces rotifer population density, alters structure, and propagates through food webs, threatening aquaculture and biodiversity; transgenerational toxicity (e.g., 4-nonylphenol: F1 inhibition 28% vs. 12% in F0) weakens resilience. This review supports EDC risk assessment, with gaps including long-term low-concentration data, transgenerational mechanisms, EDC-microbiome interactions, and emerging PFAS toxicity-priorities for future research.}, } @article {pmid41594860, year = {2026}, author = {Carvajal-Rodríguez, A}, title = {Life as a Categorical Information-Handling System: An Evolutionary Information-Theoretic Model of the Holobiont.}, journal = {Biology}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/biology15020125}, pmid = {41594860}, issn = {2079-7737}, support = {ED431C 2024/22//Xunta de Galicia/ ; PID2022-137935NB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; ED431G 2023/07//Centro singular de investigación de Galicia/ ; }, abstract = {Living systems can be understood as organized entities that capture, transform, and reproduce information. Classical gene-centered models explain adaptation through frequency changes driven by differential fitness, yet they often overlook the higher-order organization and causal closure that characterize living systems. Here we revisit several evolutionary frameworks, from the replicator equation to group selection and holobiont dynamics, and show that evolutionary change in population frequencies can be expressed as a Jeffreys divergence. Building on this foundation, we introduce a categorical model of Information Handlers (IHs), entities capable of self-maintenance, mutation, and combination. This abstract architecture illustrates the usefulness of category theory for framing evolutionary processes that range from very simple to highly complex. The same categorical scheme can represent basic allele-frequency change as well as more elaborate scenarios involving reproductive interactions, symbiosis, and other organizational layers. A key feature of the framework is that different levels of evolutionary change can be summarized through a measure that quantifies the information generated, thereby distinguishing diverse types of evolutionary transformation, such as individual and sexual selection, mate choice, or even holobiont selection. Finally, we show that the informational partition associated with host-microbiome pairings in holobionts generalizes the information-theoretic structure previously developed for non-random mating, revealing a common underlying architecture across biological scales.}, } @article {pmid41594852, year = {2026}, author = {Zhao, Q and Li, B and Ma, J and Wei, J and Qin, W}, title = {The Gut Microbiome of the Goitered Gazelle Enables Plasticity by Responding to Environmental Factors in the Qaidam Basin.}, journal = {Biology}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/biology15020118}, pmid = {41594852}, issn = {2079-7737}, support = {32160316//National Natural Science Foundation of China/ ; }, abstract = {The Qaidam Basin on the Qinghai-Tibet Plateau is an extreme arid environment, posing severe survival challenges. The goitered gazelle (Gazella subgutturosa) is a keystone species in this fragile ecosystem, yet the ecological role of its gut microbiota and its associations with environmental drivers remain poorly understood. We collected fecal samples from gazelles across seven regions of the basin. Metagenomic sequencing was employed to characterize the gut microbiome. Statistical analyses (Mantel tests, multiple regression on matrices, co-occurrence networks) were used to link microbial composition and function with key environmental factors. The gut microbiota was dominated by fiber-degrading phyla (Firmicutes, Bacteroidota) and enriched in metabolic pathways, aligning with a high-fiber diet. Regarding environmental drivers of gut microbial composition variations, isothermality and soil organic carbon were significant predictors, likely via vegetation and environmental inoculation. Regarding environmental drivers of gut microbial function variations, winter solar radiation was uniquely associated with metabolic function without altering microbial composition, suggesting a functional plasticity-the capacity to shift metabolic profiles independently of taxonomic turnover-in response to environmental variation. The gut microbiota of the goitered gazelle exhibits a stable core composition alongside environmentally responsive functional modules. This suggests the microbiome may serve as a significant mediator of host resilience, highlighting adaptation as a dynamic interplay between host, microbiome, and environment. These insights are crucial for microbiome-assisted conservation.}, } @article {pmid41594698, year = {2026}, author = {Tempesta, AA and Vertillo Aluisio, G and Di Gregorio, F and Pecora, RL and Mezzatesta, ML and Cafiso, V and Chines, E and Barbagallo, G and Santagati, M}, title = {Antimicrobial and Antibiofilm Activity of a Lactobacillus reuteri SGL01, Vitamin C and Acerola Probiotic Formulation Against Streptococcus mutans DSM20523.}, journal = {Biomolecules}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/biom16010158}, pmid = {41594698}, issn = {2218-273X}, support = {CUP E63C22002090006PE00000007//MUR PNRR Extended Partnership initiative on Emerging Infectious Disease , PE00000007,/ ; CUP E53D23001300006//National Research Project PRIN 2022/ ; }, mesh = {*Limosilactobacillus reuteri/chemistry ; *Streptococcus mutans/drug effects/physiology ; *Ascorbic Acid/pharmacology ; *Biofilms/drug effects/growth & development ; *Probiotics/pharmacology ; Microbial Sensitivity Tests ; *Anti-Bacterial Agents/pharmacology ; }, abstract = {Dental caries is a multifactorial chronic infectious disease that impacts healthcare costs globally, caused by alterations of the plaque microbiome and proliferation of cariogenic Streptococcus mutans. Treatments targeting S. mutans, such as alternative strategies using probiotics, might be effective in preventing the development of dental caries. In this study, the probiotic formulation of Lactobacillus reuteri SGL01, vitamin C, and acerola was tested against S. mutans DSM20523. Antimicrobial activity was assessed by deferred antagonism and spot-on-lawn assays for L. reuteri SGL01. MIC and MBC of L. reuteri SGL01 cell-free supernatant (CFS), vitamin C, and acerola were determined with the microdilution method. Time-kill assays determined the bactericidal kinetics for each compound. The checkerboard method was used to evaluate the potential synergistic activity of CFS-vitamin C or CFS-acerola at scalar dilutions from 1 to 8X MIC. Lastly, antibiofilm activity was tested for each compound. Antimicrobial activity of L. reuteri SGL01 was first assessed by classic methods. MIC and MBC values differed for one dilution for all compounds, with values of 25% and 50% for CFS, 9.3 mg/mL and 18.7 mg/mL for vitamin C, and 18.7 mg/mL and 37.5 mg/mL for acerola, respectively. Moreover, time-kill assays confirmed the bactericidal activity at different timepoints: 4 h for CFS, 6 h for vitamin C, and 24 h for acerola. The fractional inhibitory concentration index (FICI) showed indifference for all combinations, and for associations tested at 2, 4, and 8XMIC. S. mutans biofilm production was impaired for all components, with stronger activity by vitamin C and acerola at lower concentrations. The probiotic formulation containing L. reuteri SGl01, vitamin C, and acerola extract exerts a bactericidal effect, especially strong for the CFS, as well as antibiofilm activity. Thus, the combination of these three components could be advantageous for their complementary effects, with use as a novel treatment against the development of dental caries by S. mutans.}, } @article {pmid41594628, year = {2026}, author = {Tangal, JK and Uchuwittayakul, A and Satapornvanit, K and Srisapoome, P}, title = {Synergistic Effects of Silica Nanoparticles, Chitosan and Bacillus velezensis AAHM-BV2301 on the Growth, Immunity, Gut Microbiota and Disease Resistance of Asian Seabass (Lates calcarifer).}, journal = {Biomolecules}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/biom16010088}, pmid = {41594628}, issn = {2218-273X}, support = {//Department of Science and Technology-Science Education Institute (DOST-SEI), Philippines, through the Foreign Graduate Scholarship Program/ ; }, mesh = {Animals ; *Chitosan/pharmacology/chemistry ; *Bacillus/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Nanoparticles/chemistry ; *Silicon Dioxide/chemistry/pharmacology ; *Disease Resistance/drug effects ; Immunity, Innate/drug effects ; Probiotics/pharmacology ; *Bass/immunology/growth & development/microbiology ; Animal Feed ; }, abstract = {In this study, the synergistic effects of dietary Bacillus velezensis AAHM-BV2301, silica nanoparticles (SiNPs), and chitosan (CS) on the growth performance, innate immunity, gut microbiota, and disease resistance of Asian seabass (Lates calcarifer) fingerlings were evaluated. A total of 400 fish (11.25 ± 2.12 g) were assigned to five dietary treatments for 30 days: control, BV (1 × 10[8] CFU/kg feed), BVSiNP (1 × 10[8] CFU/kg + 2 mg SiNP/kg), BVCS (1 × 10[8] CFU/kg + 15 g CS/kg), and BVSiNPCS (combined additives at the same concentrations). The growth indices (WG, SGR, RGR, and FCR) significantly increased in the fish fed BVSiNPs, whereas the level of innate immunity increased across all the supplemented groups, with BVCS and BVSiNPCS having the strongest respiratory burst and lysozyme activities. The tissue-specific modulation of immune-related genes (α2M, HSP70, Mx, and C3) was most pronounced in BVSiNP-fed fish, particularly in the gills and liver. Gut microbiome profiling revealed enrichment of Cetobacterium somerae in response to BV-based treatments, whereas BVSiNPCS induced the greatest increase in microbial richness and network connectivity. Postchallenge survival against Vibrio vulnificus was significantly greater in the BV and BVSiNP groups (p < 0.05). Overall, SiNPs acted as functional enhancers of the B. velezensis probiotic, supporting improved growth, immune activation, and microbiota restructuring. These results highlight the potential of nanoparticle-integrated synbiotics for microbiome-targeted health management in aquaculture.}, } @article {pmid41594568, year = {2025}, author = {Fu, W and Yang, N and Yan, J and Han, B and Niu, Q and Li, Z and Bai, R and Yu, T}, title = {Oral-Gut Microbial Crosstalk and Therapeutic Applications of Bacterial Extracellular Vesicles.}, journal = {Biomolecules}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/biom16010026}, pmid = {41594568}, issn = {2218-273X}, support = {2022YFA1206100//National Key R&D Program of China/ ; F252067//Beijing Natural Science Foundation/ ; 52373123//National Natural Science Foundation of China/ ; DC20240175//Undergraduate Innovation Experiment Project/ ; BJPSTP-2025-01//Beijing Physician Scientist Training Project/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Gastrointestinal Microbiome ; *Mouth/microbiology ; Probiotics/therapeutic use ; Animals ; Periodontitis/microbiology/therapy ; Inflammatory Bowel Diseases/microbiology/therapy ; }, abstract = {With the accelerating trend of global population aging, oral and gut diseases are imposing a rising socioeconomic burden, both of which have well-known connections to microbial dysbiosis. As the gateway to the human body, the oral cavity exhibits close interactions with the gastrointestinal tract, which includes translocation of bacteria and bacterial extracellular vesicles (BEVs), as well as intermucosal immunity and neural signaling. These oral-gut crosstalk pathways play vital roles in the pathogenesis and progression of oral diseases, such as periodontitis, and gut diseases, such as inflammatory bowel disease (IBD). Focusing on periodontitis and IBD as representative conditions, this review summarizes current understanding of the oral-gut crosstalk and underlying mechanisms. Among diverse interactions, we emphasize BEVs as effective trans-barrier mediators and their therapeutic potentials during oral-gut crosstalk. Beneficial BEVs, notably those from Akkermansia muciniphila (Akk), exert various probiotic roles, including modulating microbial homeostasis, promoting tissue repair and alleviating inflammation, thereby shedding light on the prevention and treatment of oral and gut diseases, even systemic disorders.}, } @article {pmid41594560, year = {2025}, author = {Dissanayaka, DMS and Jayasinghe, TN and Sohrabi, HR and Rainey-Smith, SR and Taddei, K and Masters, CL and Martins, RN and Fernando, WMADB}, title = {Gut Microbial Composition and Short-Chain Fatty Acid Metabolism in Cognitively Unimpaired Adults Stratified by Amyloid-β Status.}, journal = {Biomolecules}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/biom16010018}, pmid = {41594560}, issn = {2218-273X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism ; Female ; Male ; *Amyloid beta-Peptides/metabolism ; Aged ; Feces/microbiology/chemistry ; Middle Aged ; Alzheimer Disease/metabolism ; Cognition ; }, abstract = {Short-chain fatty acids (SCFAs) produced by gut microbial fermentation influence host metabolism and neuroinflammatory processes implicated in Alzheimer's disease (AD). However, the relationship between fecal SCFAs, microbial taxa, and cerebral amyloid-β (Aβ) burden in cognitively unimpaired individuals remains unclear. Fecal SCFAs were quantified using GC-MS, and microbial species were profiled by shotgun metagenomics in 87 participants. Associations between SCFAs, demographics, APOE ε4 status, and Aβ burden were tested using nonparametric statistics and multivariable regression. Microbial-SCFA links were evaluated using Spearman correlations and multivariate ordinations, with mediation analysis exploring potential indirect pathways. Acetate was the predominant SCFA and demonstrated the most robust microbial associations. Higher acetate concentrations were positively associated with Bacteroides ovatus and Faecalibacterium prausnitzii, whereas lower acetate levels were linked to species such as Bifidobacterium animalis and Lachnoclostridium scindens. Stratified analyses indicated that individuals with elevated Aβ burden exhibited more pronounced species-SCFA relationships, including a notable association between Bacteroides thetaiotaomicron and butyrate. Multivariate ordination further identified a significant overall coupling between SCFA profiles and microbial community structure. Mediation analysis suggested that an Oscillospiraceae species may represent a potential intermediary linking valerate concentrations with Aβ status. SCFA concentrations were not strongly influenced by demographic or genetic factors, but specific species demonstrated robust associations with acetate levels. Distinct SCFA-microbial interaction patterns in Aβ High individuals suggest subtle early gut microbial alterations linked to amyloid burden. These findings highlight the potential role of SCFA-related microbial pathways in preclinical AD.}, } @article {pmid41594536, year = {2026}, author = {Flores, RA and Fletcher, PLC and Son, KY and Min, W}, title = {Insights into Non-Antibiotic Alternative and Emerging Control Strategies for Chicken Coccidiosis.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/ani16020348}, pmid = {41594536}, issn = {2076-2615}, support = {RS-2024-00399808//Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries/ ; }, abstract = {Coccidiosis, caused by an obligate intracellular parasite of the genus Eimeria, is the most economically parasitic disease in poultry. Long-term reliance on synthetic anticoccidials and ionophores has accelerated the emergence of drug resistance and intensified the need for effective, residue-free alternatives. This narrative review synthesizes findings from peer-reviewed studies published between 1998 and 2025, summarizing advances in non-antibiotic control strategies encompassing five domains: (i) phytochemicals and botanicals, (ii) functional nutrition and mineral modulators, (iii) microbial and gut modulators, (iv) host-directed immunological and biotechnological approaches, and (v) precision and omics-guided biotherapeutic platforms. These approaches consistently reduce lesion severity, oocyst shedding, oxidative stress, and mortality while improving growth parameters in a variety of Eimeria models. However, translation to field settings remains constrained by variable bioactive composition, limited standardization, inadequate pharmacokinetic data, and the scarcity of large-scale, multi-farm validation studies. This review provides a concise summary of current evidence and delineates critical knowledge gaps to guide the development, optimization, and deployment of next-generation anticoccidial strategies. Together, natural products and emerging biotechnologies provide a promising foundation for sustainable, high-welfare, antibiotic-independent coccidiosis control.}, } @article {pmid41594489, year = {2026}, author = {Kan, WT and Siomko, SA and Rooney, NJ and Wigley, P}, title = {Gut Microbiome Variations in Herring Gulls (Larus argentatus) from Different Environments in the United Kingdom.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/ani16020300}, pmid = {41594489}, issn = {2076-2615}, support = {BB/T008741/1//SWBio BBSRC Doctoral Training Partnership/ ; }, abstract = {Over the last century, anthropogenic activities have contributed to habitat degradation and fragmentation but have also affected the individual health of animals. In this study, we investigated the effect of environmental differences on the gut microbiome of Herring Gulls (Larus argentatus) by collecting fresh faecal samples from ten geographically different populations in the UK, including captive and wild birds, and comparing the resulting gut microbiome diversity and composition. A significantly higher alpha diversity was identified in captive gulls than in urban and suburban gulls for the 46 sequenced samples. When comparing gut microbiome composition, urban inhabitants exhibited a higher abundance of Ligilactobacillus and a lower abundance of Streptococcus than suburban gulls. Such differences could suggest a highly polluted environment for urban-dwelling gulls, while suburban populations could have a wider foraging range and a more diverse diet. In addition, samples from Bristol, West Kirby, Gloucester and Liverpool were all characterised by a significantly higher abundance of one or more of the other bacterial taxa. The high proportion of Mycoplasma could indicate avian mycoplasmosis in the Liverpool population. This study sheds light on the understudied subject of the wild avian gut microbiome and its possible application to wildlife health and disease management.}, } @article {pmid41594435, year = {2026}, author = {Wu, Y and You, X and Huang, S and Chai, J and Zeng, Y and Shi, H and Wang, X}, title = {Utilizing an In Vitro Fermentation Model to Assess Probiotics on Eimeria-Disturbed Cecal Microbiome and Metabolome.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/ani16020245}, pmid = {41594435}, issn = {2076-2615}, support = {32102591//National Natural Science Foundation of China/ ; 2025ZNSFSC0286//Sichuan Science and Technology Program/ ; ZYN2025261//Fundamental Research Funds for the Central Universities of Southwest Minzu University/ ; }, abstract = {Rectifying the microbiome perturbed by Eimeria invasion might alleviate the adverse effects of coccidia on broiler growth. This study employed an in vitro fermentation model to investigate the direct, host-independent effects of two probiotics-Lactobacillus rhamnosus (LR) and Bacillus subtilis (BS)-on the cecal microbiome and metabolome perturbed by Eimeria tenella. Four in vitro fermentation treatments consisted of a healthy control (cecal slurry samples from health broilers), an Eimeria-disturbed control (slurry samples from infected broilers), an LR treatment (Eimeria-infected slurry + 3 × 10[5] of LR cfu/mL), and a BS treatment (Eimeria-disturbed group + 3 × 10[5] of BS cfu/mL). 16S rRNA sequencing and metabolomic analysis revealed that Eimeria infection resulted in an increase in microbial alpha diversity, promoted opportunistic pathogens, including Helicobacter and Bacteroides, and suppressed commensals like Lactobacillus, concurrently altering 530 intracellular metabolites. Probiotic supplementation partially restored microbial composition. Notably, LR inoculation rectified 107 metabolites across pathways including galactose metabolism and phosphotransferase systems, primarily affecting membrane phospholipid balance. In contrast, BS addition restored only 64 metabolites, largely related to secondary metabolism. The current in vitro study indicates that LR can directly modulate key metabolic disturbances in a dysbiotic microbiota, while the BS may be more dependent on host-mediated interactions.}, } @article {pmid41594399, year = {2026}, author = {Kuttappan, VA and Archer, GS and Fournis, Y and Decoux, M}, title = {A Novel Combination of Postbiotics and Essential Oil Compounds Supports a Consistent Improvement in Broiler Performance.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/ani16020209}, pmid = {41594399}, issn = {2076-2615}, abstract = {Recent innovations in poultry feed technology have emphasized the role of postbiotics and phytogenics as promising strategies to strengthen gut health and improve overall performance in broilers. Within this context, the current study evaluated the effectiveness of Biostrong™ Dual (Cargill Inc., Cedar Rapids, IA, USA), a novel product that integrates Saccharomyces cerevisiae fermentation-derived postbiotic products (SCFPs) with a proprietary blend of essential oil compounds (EOCs). The objective was to determine whether this dual formulation could consistently enhance growth, feed efficiency, and carcass quality across multiple production phases. To test this, three independent trials were conducted using commercial broiler strains. Birds were allocated to either a control group (CON) receiving a basal diet or a treatment group (DUAL) receiving the same diet supplemented with 0.4 kg/MT of Biostrong™ Dual. Each trial employed a randomized block design with 24 replicates per treatment and 16-25 birds per replicate. Results consistently demonstrated that DUAL improved (p < 0.05) body weight and the cumulative feed conversion ratio (cFCR) at 42 days. Pooled analysis revealed body weight gains of 5.5%, a cFCR improvement of 5 points, increased feed intake, and a 0.86% rise in breast meat yield. Additionally, one trial showed reduced footpad lesion scores. Collectively, these findings highlight Biostrong™ Dual as a valuable nutritional intervention to optimize productivity and carcass quality in poultry production and further research is needed to understand the mode of action of the product.}, } @article {pmid41594301, year = {2026}, author = {Camatti, J and Bonasoni, MP and Santunione, AL and Cecchi, R and Radheshi, E and Carretto, E}, title = {Postmortem Microbiology in Forensic Diagnostics: Interpretation of Infectious Causes of Death and Emerging Applications.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/diagnostics16020325}, pmid = {41594301}, issn = {2075-4418}, abstract = {Background/Objectives: Postmortem microbiology has traditionally been regarded with caution in forensic practice due to concerns related to contamination, bacterial translocation, and postmortem microbial overgrowth. As a result, microbiological findings obtained after death have often been considered unreliable or of limited diagnostic value. However, growing evidence indicates that, when appropriately interpreted and integrated with autopsy findings, histopathology, and circumstantial information, postmortem microbiology can provide crucial support for cause-of-death determination. This narrative review critically examines the current role of postmortem microbiology in forensic diagnostics, with a focus on its diagnostic applications, interpretative challenges, and future perspectives. Methods/Results: The transition from conventional culture-based techniques to molecular approaches-including polymerase chain reaction, microbiome analysis, and metagenomic methods-is discussed, highlighting both their potential advantages and inherent limitations within the forensic setting. Particular attention is devoted to key interpretative issues such as postmortem interval, sampling strategies, contamination, and bacterial translocation. In addition to cause-of-death attribution, emerging applications-including postmortem interval estimation, trace evidence analysis, and artificial intelligence-based models-are reviewed. Although these approaches show promising research potential, their routine forensic applicability remains limited by methodological heterogeneity, lack of standardization, and interpretative complexity. Conclusions: In conclusion, postmortem microbiology represents a valuable diagnostic tool when applied within a multidisciplinary forensic framework. Its effective use requires cautious interpretation and integration with pathological and contextual evidence, avoiding standalone or automated conclusions. Future progress will depend on standardized methodologies, multidisciplinary collaboration, and a clear distinction between experimental research and routine forensic practice.}, } @article {pmid41594117, year = {2026}, author = {Castagliuolo, G and Notomista, E and Sordillo, A and Barone, L and Antonini, D and Renzi, F and Zanfardino, A and Varcamonti, M}, title = {Study of Human Antimicrobial Peptides Active Against Some Bacteroidota Species of the Oral Cavity.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/antibiotics15010080}, pmid = {41594117}, issn = {2079-6382}, support = {CUP number E65F22000370001.//MUR - PRIN 2020- 3D Customized Hybrid Medical Devices grant for Alzheimer's-disease-related periodontitis./ ; }, abstract = {The increasing problem of antibiotic resistance is a critical global health issue, necessitating the development of alternative therapeutic strategies to manage infections effectively. Among the promising solutions are human antimicrobial peptides (AMPs), naturally occurring molecules known for their broad spectrum of antimicrobial activity. Background/Objectives: This study investigates the potential of some AMPs, selected through a bioinformatic approach, as alternatives to conventional antibiotics, particularly focusing on their efficacy against species within the Bacteroidota phylum. These species, including pathogens such as Porphyromonas gingivalis, Capnocytophaga ochracea, and Capnocytophaga canimorsus, are well known for their roles in various human infections and related diseases. Non-pathogenic environmental species, such as Flavobacterium johnsoniae, are also included in this group, frequently used as a model organism. Methods: By analyzing the antimicrobial efficacy, mechanisms of action, and potential therapeutic applications of human AMPs, this research underscores their significance in addressing the challenge of antibiotic resistance. Results: This study identified three peptides, KTL24, LIR23, and MFP22, as particularly interesting. These peptides are derived from specific human proteins, namely SPI1, NAPSA and SCUB1. Conclusions: Their notable antimicrobial potential suggests that AMPs could serve either as a complementary treatment alongside traditional antibiotics or as a standalone therapy, mitigating the ongoing spread of antibiotic resistance and offering an alternative in global health strategies.}, } @article {pmid41593817, year = {2026}, author = {Bahadir, S and Robinson, JT and Morse, LR and Yoo, PB and Kern, R and Makowski, NS and Kozai, TDY and Fudim, M and Barbe, MF and Lim, HH and Chang, EH and Zanos, S}, title = {The sixth bioelectronic medicine summit: Neurotechnologies for individuals and communities.}, journal = {Bioelectronic medicine}, volume = {12}, number = {1}, pages = {3}, pmid = {41593817}, issn = {2332-8886}, support = {NIH SPARC U41 - NS129436/NH/NIH HHS/United States ; NIH-NIGMS R01GM143362/NH/NIH HHS/United States ; NIH-NINDS 1R01NS136685/NH/NIH HHS/United States ; }, } @article {pmid41593789, year = {2026}, author = {Stapleton, HM and Borges, DS and Trindade, EBSM and Yuan, Q}, title = {Sex-dependent locus coeruleus vulnerability in Alzheimer's disease: gut dysbiosis as a driver and probiotic intervention as rescue.}, journal = {Biology of sex differences}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13293-026-00834-8}, pmid = {41593789}, issn = {2042-6410}, support = {PJT-197770/CAPMC/CIHR/Canada ; }, abstract = {Alzheimer's disease (AD) displays striking sex differences in incidence, progression, and resilience, yet the mechanisms that drive female-biased vulnerability remain incompletely understood. Emerging evidence indicates that gut dysbiosis, increasingly prevalent with ageing, acts as a systemic amplifier of neuroinflammation, vascular instability, and metabolic dysfunction. Here, we synthesize converging findings linking gut microbial alterations to noradrenergic pathology in the locus coeruleus (LC), one of the earliest brain regions affected in AD. We outline how dysbiosis-associated inflammatory signaling, including endotoxin exposure and impaired vagal-neuroimmune regulation, targets LC circuits. In parallel, disruptions in microbial metabolite pathways involving short-chain fatty acids, bile acids, and tryptophan metabolism further promote oxidative stress, tau phosphorylation, and neurodegeneration. We further argue that sex-dependent differences in immune reactivity, autonomic regulation, and hormonal transitions, particularly peri- and post-menopausal estrogen decline, render female LC neurons uniquely vulnerable to microbial and inflammatory perturbation. We propose a mechanistic framework in which gut dysbiosis destabilizes LC integrity through parallel immune-vascular, metabolite, endocrine, and vagal neural pathways, thereby accelerating cognitive decline and AD progression. Understanding how microbial signaling intersects with sex biology and neuromodulatory circuitry may reveal therapeutic windows for early intervention, including microbiome restoration, neuromodulatory tuning, and sex-specific metabolic targeting.}, } @article {pmid41593761, year = {2026}, author = {Tigabu, A and Leung, PHM}, title = {Broad-spectrum antibiotic treatment reshapes the gut microbiome, resistome, and colonization potential of opportunistic pathogens: a metagenomics study.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-026-00795-8}, pmid = {41593761}, issn = {1757-4749}, abstract = {BACKGROUND: The gut microbiota (GM) harbors diverse antibiotic resistance genes (ARGs), which are primarily disseminated through horizontal gene transfer (HGT), contributing to the emergence and spread of multidrug-resistant (MDR) pathogens. Broad-spectrum antibiotics are commonly used to treat a wide range of bacterial infections; however, they also exert collateral effects on non-target microbes. A comprehensive understanding of the impact of broad-spectrum antibiotic treatment on GM composition and the resistome is essential for the effective management of dysbiosis-related complications.

METHODS: Twenty-one fecal samples were collected from randomly selected study participants. Metagenomic sequencing was performed using the Illumina NovaSeq 6000 platform. FastQC v0.12.1, Trimmomatic v0.39, and Bowtie2 were used for quality control, removal of low-quality reads and adapter sequences, and host DNA removal, respectively. Metagenome assembly, gene prediction, and taxonomic annotation were conducted using MEGAHIT v1.2.9, MetaGeneMark-2, and the NCBI non-redundant protein database (nr), respectively. Resistome profiling was performed using the Comprehensive Antibiotic Resistance Database (CARD) v3.3.4. Functional annotation of protein-coding genes was carried out against the KEGG v112.0, eggNOG v5.0, and CAZy databases.

RESULTS: An enrichment of the phylum Bacillota and a depletion of Bacteroidota were observed in fecal samples from antibiotic-treated patients. Specifically, the genus Enterococcus and Streptococcus were the most prominent genera in antibiotic-treated patients, whereas Prevotella, Bacteroides, and Faecalibacterium were more abundant in healthy controls. Notably, the opportunistic pathogen E. faecium was elevated in antibiotic-treated patients. In longitudinal patients receiving augmentin treatment, the genera Escherichia and Enterococcus predominated, with E. coli and E. faecium showing increased prevalence compared with baseline in the first and second longitudinal patients, respectively. Antimicrobial resistance genes associated with antibiotic target alteration and protection were strongly linked to Bacillota, whereas efflux pump-mediated resistance mechanisms were positively associated with Bacteroidota and Pseudomonadota. The genes tetM, tet45, vanHM, vanYM, and vanRM were enriched in antibiotic-treated patients, whereas tetQ, tetW, cfxA6, adeF, vanTG, vanYB, and vanWI were more abundant in controls. Furthermore, PmrF, vanM, and CfxA were identified as principal biomarker genes in the first, second, and third augmentin-treated longitudinal patients, respectively.

CONCLUSIONS: Dysbiosis of the gut microbiota and alterations in the resistome were detected in antibiotic-treated patients. Notably, the opportunistic pathogens E. faecium and E. coli were enriched in antibiotic-treated individuals, suggesting that broad-spectrum antibiotic therapy may facilitate their proliferation and colonization, thereby contributing to dysbiosis-related complications. These findings warrant validation in larger cohorts to better elucidate the dynamics of antibiotic-induced dysbiosis and the dissemination of resistance genes.}, } @article {pmid41593747, year = {2026}, author = {Lin, L and Zheng, X and Tao, Y and Zhu, W and Guan, LL and Mao, S}, title = {Genome-resolved metagenomics uncovers diversity and functional landscapes of the gastrointestinal epithelium-associated microbiome in cattle.}, journal = {Genome biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13059-026-03960-z}, pmid = {41593747}, issn = {1474-760X}, support = {U2202203//NSFC-Regional Innovation and Development Joint Fund/ ; 3236114378//NSFC-International (Regional) Cooperation Research and Exchange Programme/ ; }, abstract = {BACKGROUND: The ruminant gastrointestinal epithelium harbors a diverse and functionally critical remains poorly characterized microbial community due to persistent host-derived DNA contamination in metagenomic studies.

RESULTS: We develop Dilute-MetaSeq (dilution-based metagenomic sequencing), a novel, metagenomic workflow integrating gradient dilution with multiple displacement amplification. Dilute-MetaSeq reduces host DNA interference by 52.4-fold and achieves > 90% microbial sequencing efficiency to assess gastrointestinal epithelium-associated microbiome. This enables the construction of the microbial genome atlas of gastrointestinal epithelium (MGA-GE). This comprehensive resource, comprising 1,907 nonredundant prokaryotic and 5,603 viral genomes, reveals extraordinary microbial diversity and novelty, with 41.4% of prokaryotic and 99.9% of viral genomes representing taxonomically unclassified lineages. Spatial profiling identifies the rumen and reticulum as a biodiversity hotspot dominated by epithelium-adapted Butyrivibrio and methylotrophic Methanomassiliicoccales, while functional annotation uncovers 1,200 biosynthetic gene clusters (primarily RiPPs and NRPSs) and 1,212 viral auxiliary metabolic genes linked to host metabolism modulation. Pangenome analysis of 987 strains, including a novel Butyrivibrio clade with reduced genome sizes, elevated GC content, and butyrate synthesis from amino acid-derived substrates (e.g., glutarate, lysine), highlights metabolic adaptations to the nutrient-scarce epithelial niche compared to digesta-associated microbes.

CONCLUSIONS: Collectively, the MGA-GE provides transformative insights into host-microbe-virus interactions and establishes a foundation for developing microbiome-based intervention strategies to enhance ruminant health, agricultural productivity, and bioactive discovery.}, } @article {pmid41593438, year = {2026}, author = {Wang, X and Tian, D and Han, B and Zhao, K and Hao, W and Du, K and Li, X and Duan, Z}, title = {Exploring the impact of rumen microbiome on ovine flavor-related compounds and comparing flavor profiles between Tibetan sheep and Small-tail Han sheep.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04755-9}, pmid = {41593438}, issn = {1471-2180}, support = {2024YFF0728800//National Key Research and Development Program of China/ ; 2024-ZJ-949//the Natural Science Foundation of Qinghai Province/ ; XDA26040305//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, abstract = {The characteristic 'mutton flavor', primarily attributed to branched-chain fatty acids (BCFAs), is influenced by various factors including rumen microbes. This study aims to elucidate the disparities in meat flavor compounds and their underlying regulatory mechanisms mediated by rumen microbes between two important sheep breeds on the Qinghai-Tibetan Plateau. We used LC-MS/MS to analyze BCFAs and rumen short-chain fatty acids (SCFAs), along with metagenomic sequencing to characterize the rumen microbiome. Compared to Tibetan sheep, Small Tail Han sheep exhibited significantly higher concentrations of BCFAs, including 4-ethyloctanoic acid (EOA) and 4-methyloctanoic acid (MOA), as well as SCFAs such as pentanoate, glutarate, and propionate. In contrast, acetate levels were inversely correlated with these fatty acids. Metagenomics revealed a predominance of Bacteroidota (formerly Bacteroidetes) and Bacillota (formerly Firmicutes) in sheep. Furthermore, random forest and LEfSe analyses identified seven bacterial biomarkers, including Lactobacillus, Ligilactobacillus, Blautia, Anaerovibrio, Selenomonas, Phocaeicola, Sodaliphilus. Functional analysis indicated differences in carbohydrate degradation capabilities of two breeds. Likewise, strong positive correlations of propionate with MOA, and glutarate with EOA were observed, respectively. The findings are expected to provide critical insights into the potential for modulating meat flavor through nutritional strategies targeting rumen microbes.}, } @article {pmid41593136, year = {2026}, author = {Menke, S and Fackelmann, G and Vucetich, LM and Vucetich, JA and Forbey, JS and Sommer, S}, title = {Forage quality shapes physiological and gut microbial responses in moose (Alces alces) of Isle Royale National Park.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {3724}, pmid = {41593136}, issn = {2045-2322}, } @article {pmid41593106, year = {2026}, author = {Elford, JD and Heesbeen, EJ and van der Plaats, NA and Garssen, J and Kraneveld, AD and Groenink, L and Perez Pardo, P}, title = {Gut bacteria composition in animal models of Parkinson's disease: a systematic review and meta-analysis.}, journal = {NPJ Parkinson's disease}, volume = {12}, number = {1}, pages = {31}, pmid = {41593106}, issn = {2373-8057}, abstract = {The gut microbiome is believed to play an important role in the development and onset of Parkinson's disease (PD). While human studies report differences in gut microbiota between PD individuals and healthy controls, it is unclear whether preclinical animal models show similar patterns. We performed a systematic review and Bayesian regularised meta-analysis of preclinical PD studies that assessed both motor function and gut microbiota. Motor deficits were consistently observed across models, but gut bacterial diversity (α-diversity) and changes in key taxa (e.g. Akkermansia, Lactobacillus, Bifidobacterium) were inconsistent and poorly aligned with human data. In contrast, short-chain fatty acids (SCFAs) showed more reproducible changes and greater translatability to human findings. Chronic toxin-based models demonstrated the highest reproducibility. Overall, gut microbiota composition in animal PD models lacks consistency and human relevance, whereas SCFAs may offer a more reliable outcome. Finally, our study makes possible recommendations for reporting to improve future studies.}, } @article {pmid41593069, year = {2026}, author = {Borodovich, T and Buttimer, C and Wilson, JS and Bardy, P and Smith, M and Hill, C and Khokhlova, EV and Harte, M and Govi, B and Fogg, PCM and Hill, C and Shkoporov, AN}, title = {Large-scale capsid-mediated mobilisation of bacterial genomic DNA in the gut microbiome.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68726-4}, pmid = {41593069}, issn = {2041-1723}, support = {101001684//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 220646/Z/20/Z//Wellcome Trust (Wellcome)/ ; }, abstract = {Transducing bacteriophage and gene transfer agents (GTAs) are constrained by the structural limits of their capsids, which determine the maximum length of host DNA they can package. Here, we utilise nanopore sequencing of intact, capsid-packaged DNA molecules to recover full-length reads, thereby enabling the precise identification of encapsidated DNA and its bacterial origin. This approach was validated using well-characterised transducing systems and subsequently applied to faecal viromes from three healthy donors. Our analysis reveals that bacterial DNA encapsidation is widespread in the gut microbiome, with up to 5.4% of capsid-packaged DNA derived from bacterial genomes. Generalised transduction and GTA activity were especially prominent in Oscillospiraceae and Ruminococcaceae (e.g. Faecalibacterium spp.), while lateral transduction was observed in Bacteroides. Additionally, we detected induction of prophages in several highly prevalent gut bacterial taxa. These findings reveal the prevalence of bacterial DNA packaging via virus or virus-like capsids in the human gut, shedding light on the diverse mechanisms that drive this process.}, } @article {pmid41593042, year = {2026}, author = {Perdue, TJ and Newkirk, CE and Beblavy, R and Seppo, AE and Davis, EC and Sohn, MB and Järvinen, KM and Monaco, CL}, title = {The enteric DNA virome differs in infants at risk for atopic disease.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2616066}, doi = {10.1080/19490976.2026.2616066}, pmid = {41593042}, issn = {1949-0984}, mesh = {Humans ; Infant ; *Virome ; Male ; Female ; Feces/virology/microbiology ; *Gastrointestinal Microbiome ; *Bacteriophages/genetics/isolation & purification/classification ; *Hypersensitivity, Immediate/virology/microbiology/epidemiology ; Bifidobacterium/virology/isolation & purification ; }, abstract = {Atopic disease prevalence, including atopic dermatitis, food allergy, asthma, and allergic rhinitis, has risen dramatically in industrialized countries. Traditional, single family farming lifestyles protect against atopic disease, but the mechanisms are incompletely understood. While there are established epidemiologic connections between childhood respiratory viral infections and the infant gut bacterial microbiome with allergic disease development, the influence of the early enteric virome on atopic disease development is unknown. We analyzed the enteric virome in 131 infants from high-atopy-risk urban/suburban environments and low-atopic-risk single-family farming communities. While similar at 12 months, enteric bacteriophage communities significantly differed by farm-life versus urban lifestyle at six weeks and six months of age. A lifestyle protective from atopic disease demonstrated higher colonization rates of Bifidobacterium longum subsp. infantis (B. infantis), an important beneficial commensal, with phageome communities differing in infants colonized by B. infantis at all time points. Simultaneously, Mastadenovirus and Bocaparvovirus were more prevalent in urban infant stools at six months of age. Sparser phage-phage networks were found at all timepoints in infants who later developed atopic disease. These data suggest that the early infant enteric DNA virome develops differently in farming and urban lifestyles and may factor into risk of atopic disease development.}, } @article {pmid41592987, year = {2026}, author = {Chang, G and Zhang, J and Fang, X and Zhang, S and Lu, H and Jiang, Y and Zhu, J}, title = {Corrigendum to "environmental microorganisms as heterogeneous sources and shapers of the fermentation microbiome in Zhejiang rosy vinegar" [Int. J. Food Microbiol. 447 (2026) 111554].}, journal = {International journal of food microbiology}, volume = {}, number = {}, pages = {111656}, doi = {10.1016/j.ijfoodmicro.2026.111656}, pmid = {41592987}, issn = {1879-3460}, } @article {pmid41592670, year = {2026}, author = {López-Tenorio, II and Constantino-Jonapa, LA and Jaimez-Alvarado, S and Reyes-Martínez, S and Escalona-Montaño, AR and Tavera-Alonso, C and Valdez-Gómez, R and Menicatti, M and Bartolucci, G and Niccolai, E and Simone, B and Amedei, A and Ávila-Vanzzini, N and Aguirre-García, MM}, title = {Age-related diversity of the oral and gut microbiome and its correlation with systemic fatty acids and cytokine profiles in healthy subjects.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {113046}, doi = {10.1016/j.exger.2026.113046}, pmid = {41592670}, issn = {1873-6815}, abstract = {BACKGROUND AND AIM: Advances in human microbiome research have highlighted its influence on host health. This study aimed to characterize the oral microbiome (OM) and gut microbiome (GM) and to examine their relationships with systemic fatty acid and cytokine profiles across different age groups in healthy adults.

METHODS: Participants aged 18-76 years without diagnosed diseases were grouped into young (18-29 years), middle-aged (30-49 years), and older adults (≥50 years). Blood, dental plaque, and fecal samples were collected. OM and GM composition were evaluated using 16 rRNA sequencing. Circulating free fatty acids (FFAs) were quantified by gas chromatography-mass spectrometry, and serum cytokines were assessed using flow cytometry.

RESULTS: In the OM, Fusobacterium and Haemophilus were notably abundant in young adults, while Haemophilus and Neisseria predominated in middle-aged adults. In older adults, Neisseria and Capnocytophaga were the most prevalent oral genera. In the GM, Bacteroides was the most prevalent genus across all age groups, followed by Faecalibacterium, Blautia, and Prevotella_9. Additionally, circulating levels of decanoic, hexadecanoic, and octadecanoic acids, as well as the cytokine IP-10, were higher in young adults compared with the other age groups.

CONCLUSION: To our knowledge, this study is the first to characterize and correlate the diversity of both the OM and GM with systemic FFA and cytokine profiles in a cohort of healthy adults, highlighting the critical role of age in shaping microbiome composition and associated metabolites. Integrating microbiota profiling with serum FFA and cytokine measurements enhances our understanding of how the microbiome may influence health and disease risk across the adult lifespan.}, } @article {pmid41592536, year = {2026}, author = {Bogacka, E and Zemelka-Wiącek, M and Agache, I and Jędrzejczak-Czechowicz, M and Groblewska, A and Chełmińska, M and Chałubiński, M and Jutel, M}, title = {Ocular Allergy Within the Framework of the EAACI Nomenclature of Allergic Diseases and Hypersensitivity Reactions.}, journal = {Allergy, asthma & immunology research}, volume = {18}, number = {1}, pages = {6-18}, doi = {10.4168/aair.2026.18.1.6}, pmid = {41592536}, issn = {2092-7355}, support = {SUBK.A020.25.023/MZ/Polish Ministry of Health/Poland ; }, abstract = {Ocular allergy encompasses a heterogeneous group of diseases with overlapping clinical features and complex immunopathological mechanisms. This often creates challenges in classification and, consequently, in optimizing patient management. The nomenclature published in 2023 by the European Academy of Allergy and Clinical Immunology (EAACI) addresses these issues by redefining these conditions and linking clinical phenotypes and environmental modifiers to underlying types of hypersensitivity. This framework enhances diagnostic precision and supports mechanism-guided management. This article applies the EAACI approach based on hypersensitivity types to ocular allergy. The examples addressed include seasonal and perennial allergic conjunctivitis, driven mainly by type I and IV hypersensitivity reactions; vernal and atopic keratoconjunctivitis, involving mixed type I, IVb and IVa pathways; giant papillary conjunctivitis, a tissue-driven type V reaction; and contact blepharoconjunctivitis, a type IVa delayed hypersensitivity reaction with additional components. Distinct endotypes-such as local or acute allergic conjunctivitis, dupilumab-induced ocular disease, and vernal keratoconjunctivitis/atopic keratoconjunctivitis overlap-further illustrate heterogeneity, with the ocular surface microbiome emerging as a modifier. Diagnostics are increasingly aligning with mechanisms, and the EAACI framework translates this complexity into a mechanism-indexed map; this supports the selection of responders for targeted interventions while minimizing overtreatment.}, } @article {pmid41592526, year = {2026}, author = {Chiodelli, P and Papait, A and Agoni, L and Quaglia, F and Silini, AR and Parolini, O}, title = {The tumor ecosystem: Rewiring an open, systemically integrated network for therapeutic gain.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {195}, number = {}, pages = {119047}, doi = {10.1016/j.biopha.2026.119047}, pmid = {41592526}, issn = {1950-6007}, abstract = {Despite the tumor microenvironment (TME) being a major therapeutic focus, the clinical translation of TME-targeted agents has been largely unsuccessful, a paradox that challenges paradigms rooted in a reductionist view of the TME as a self-contained entity. We propose a framework redefining the TME as an open, multi-scalar ecosystem dynamically shaped by systemic host factors. Locally, cancer-associated fibroblasts (CAFs), myeloid cells and the vasculature act not as isolated cell types but as integrated components of functional niches that orchestrate fibrosis, immunosuppression and angiogenesis. Systemically, the gut microbiome and chronic inflammation of ageing ('inflammaging') pre-condition the host terrain and modulate therapeutic responses across this network. Viewed through this systemic lens, resistance emerges not as molecular bypass but as ecological adaptation of a complex, open system. We argue that next-generation therapies will depend on spatial omics to map pathological niches and on rational, multimodal strategies that explicitly target the TME as a systemically integrated network.}, } @article {pmid41592476, year = {2026}, author = {David, J and Gollasch, S and David, M}, title = {International maritime organization, we may have a problem - ballast water treatment triggers global concerns with antimicrobial resistant bacteria.}, journal = {Marine pollution bulletin}, volume = {226}, number = {}, pages = {119277}, doi = {10.1016/j.marpolbul.2026.119277}, pmid = {41592476}, issn = {1879-3363}, abstract = {Vessels sailing worldwide need to treat ballast water to inactivate organisms to comply with the Ballast Water Management Convention. We analysed the phenotypic resistance of isolated unidentified bacteria to antimicrobial substances in the uptake water before treatment and the discharged water after treatment on a vessel in operation with a certified UV based ballast water management system (BWMS). We isolated Escherichia coli on selective media and genotyped the identified isolates. All isolates were categorized into clonal and phylogenetic groups based on Polymerase Chain Reaction (PCR) methods. We examined the presence of Plasmid-mediated Quinolone Resistance (PMQR) genes, betalactamases, adhesins, autotransporters, genes encoding iron uptake proteins, genes associated with immune system evasion, and genotoxins. For all non-clonal isolates, we tested their sensitivity to antimicrobial substances. Resistance to cefotaxime increased after treatment in both intrinsic resistance and E. coli isolates. PCR analyses showed a decrease in the occurrence of qnrS and ompTAPEC genes in the discharged water, and an increase in qnrB, kpsMTII, blaTEM, fyuA, and usp genes. The results of the disk diffusion method indicated an increase in resistance to ampicillin, ceftazidime, and the highest increase occurred in resistance to cefotaxime. The number of multi-drug resistant isolates decreased substantially in the discharged water. BWMS effectively eliminate plankton, while UV water treatment causes different negative changes in bacteria, introducing new threats to human health (microbiome to accumulate resistance genes) and aquaculture (increase diversity and volume of antibiotics used, lower seafood production), hence opening a new issue in global discharges of ballast water.}, } @article {pmid41592132, year = {2026}, author = {Rathod, DR and Silverman, JD}, title = {PCR bias impacts microbiome ecological analyses.}, journal = {PLoS computational biology}, volume = {22}, number = {1}, pages = {e1013908}, doi = {10.1371/journal.pcbi.1013908}, pmid = {41592132}, issn = {1553-7358}, abstract = {Polymerase Chain Reaction (PCR) is a critical step in amplicon-based microbial community profiling, allowing the selective amplification of marker genes such as 16S rRNA from environmental or host-associated samples. Despite its widespread use, PCR is known to introduce amplification bias, where some DNA sequences are preferentially amplified over others due to factors such as primer-template mismatches, sequence GC content, and secondary structures. Although these biases are known to affect transcript abundance, their implications for ecological metrics remain poorly understood. In this study, we conduct a comprehensive evaluation of how PCR-bias influences both within-samples (α-diversity) and between-sample (β-diversity) analyses. We show that perturbation-invariant diversity measures remain unaffected by PCR bias, but widely used metrics such as Shannon diversity and Weighted-Unifrac are sensitive. To address this, we provide theoretical and empirical insight into how PCR-induced bias varies across ecological analyses and community structures, and we offer practical guidance on when bias-correction methods should be applied. Our findings highlight the importance of selecting appropriate diversity metrics for PCR-based microbial ecology workflows and offer guidance for improving the reliability of diversity analyses.}, } @article {pmid41591833, year = {2026}, author = {Barekat, K and Ghosh, S and Herrmann, C and Keat, K and Assenmacher, CA and Tanes, C and Wilson, N and Lordan, R and Mrčela, A and Rauova, L and Sengupta, A and Das, US and Joshi, R and Friedman, E and Ritchie, MD and Bittinger, K and Weljie, A and Cadwell, K and Bushman, FD and Wu, GD and FitzGerald, GA and Ricciotti, E}, title = {Concomitant COX-1 and COX-2 suppression is not sufficient to induce enteropathy associated with chronic NSAID use.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI190575}, pmid = {41591833}, issn = {1558-8238}, abstract = {Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications for the management of chronic pain; however, they are associated with numerous gastrointestinal (GI) adverse events. Although many mechanisms have been suggested, NSAID-induced enteropathy has been thought to be primarily due to inhibition of both cyclooxygenases (COX) -1 and -2, which results in suppression of prostaglandin synthesis. Yet surprisingly, we found that concomitant postnatal deletion of Cox-1 and -2 over 10 months failed to cause intestinal injury in mice unless they were treated with naproxen or its structural analog, phenylpropionic acid, which is not a COX inhibitor. Cox double knockout mice exhibit a distinct gut microbiome composition and cohousing them with controls rescues their dysbiosis and delays the onset of NSAID-induced GI bleeding. In both the UK Biobank and All of Us human cohorts, coadministration of antibiotics with NSAIDs is associated with an increased frequency of GI bleeding. These results show that prostaglandin suppression plays a trivial role in NSAID-induced enteropathy. However, Cox deletion causes dysbiosis of the gut microbiome that amplifies the enteropathic response to NSAIDs.}, } @article {pmid41591701, year = {2026}, author = {Cho, NA and Schlechte, J and Yu, IL and Bains, I and Fahlman, T and Mackenzie, C and McDonald, B}, title = {Impaired systemic antibody response against gut microbiota pathobionts in critical illness and susceptibility to nosocomial infections.}, journal = {Intensive care medicine experimental}, volume = {14}, number = {1}, pages = {9}, pmid = {41591701}, issn = {2197-425X}, support = {173296/CAPMC/CIHR/Canada ; 170746/CAPMC/CIHR/Canada ; JELF grant 40697//Canadian Foundation for Innovation/ ; }, abstract = {BACKGROUND: Critically ill patients in intensive care units (ICUs) experience high rates of hospital-acquired (nosocomial) infections, commonly caused by translocation and dissemination of pathogenic microorganisms that colonize the intestinal tract (pathobionts). Multiple immune barriers protect the host against commensal and pathogenic colonizers, including a repertoire of circulating anti-commensal antibodies. The integrity of this systemic antibody-mediated defense system, its relationship with gut microbiota dysbiosis, and its impact on nosocomial infections in the ICU have not been explored.

RESULTS: We performed a longitudinal cohort study of 46 critically ill patients at day 1 and day 3 of their ICU admission compared to 28 healthy volunteer controls. Circulating IgM, IgG, and IgA responses against 10 common gut and extra-intestinal pathobionts were quantified by flow cytometry, together with high-dimensional analyses of circulating B cell populations, fecal microbiota composition, and clinical outcomes. We observed reduced plasma IgM and IgG reactivity against intestinal pathobionts such as Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis in ICU patients compared to healthy volunteers. Reduced gut pathobiont antibody responses in ICU patients was associated with B cell lymphopenia, and patients with gut microbiota dysbiosis had reduced levels of natural antibody producing B1-like B cells. Reduced IgG and IgM reactivity against gut Gram-negative pathobionts was associated with an increased risk of nosocomial infection or death.

CONCLUSIONS: These findings indicate that the systemic antibody barrier against microbiota pathobionts is compromised in critical illness and associated with increased risk of nosocomial infections.}, } @article {pmid41591389, year = {2026}, author = {Gupta, J and Arora, A and Dogra, S and Chakrabarti, A and Angrup, A and Kumaran, S and Kaur, H and Ghosh, AK and Rudramurthy, SM}, title = {Malassezia and Staphylococcus are associated with scalp seborrheic dermatitis.}, journal = {Medical mycology}, volume = {}, number = {}, pages = {}, doi = {10.1093/mmy/myag005}, pmid = {41591389}, issn = {1460-2709}, abstract = {Seborrheic dermatitis (SD) is a common skin condition affecting the scalp and other sebaceous-rich areas. Most recent studies have focused on the microbiota of individuals with SD and healthy controls, suggesting an association of microbial dysbiosis. The variations in the microbiota at lesional and non-lesional sites of SD patients and healthy controls remain unexplored. The present study aimed to characterize the microbiota in seborrheic dermatitis patients. We conducted a cross-sectional study to analyse microbial composition and diversity of fungi and bacteria on the lesional and non-lesional sites of SD patients (n = 60) and from the scalp of healthy individuals (n = 30) using culture-based methods and high-throughput sequencing (n = 8 each group) of the ITS2 region of fungal rDNA and the V3-V4 region of bacterial 16S rRNA. The culture-based approach revealed a significant association between the combination of 'Malassezia and aerobic bacteria' and lesions in patients, especially in severe cases. Malassezia restricta, Staphylococcus capitis and Staphylococcus epidermidis were the most common isolates. Microbiome results revealed lower species richness of both fungal (observed features, p = 0.0105 and Chao1, p = 0.0487) and bacterial (observed features, p = 0.0016 and Chao1, p = 0.001) communities with higher relative abundance of M. restricta (61%, p < 0.0001) and Staphylococcus (40%, p < 0.0001) and Corynebacterium (16%, p < 0.0001) on lesional sites than on non-lesional sites. A decrease in alpha diversity of both fungal and bacterial flora, on the lesional site compared to the non-lesional site, suggests an association between site-specific dysbiosis and SD.}, } @article {pmid41591312, year = {2026}, author = {Miraeiz, E and Borges Dos Santos, L and Hudson, ME}, title = {Modern Genomics Reshapes Soybean Cyst Nematode Research: Integrating Host Resistance, Nematode Virulence, and Functional Discovery.}, journal = {Molecular plant-microbe interactions : MPMI}, volume = {}, number = {}, pages = {MPMI10250150FI}, doi = {10.1094/MPMI-10-25-0150-FI}, pmid = {41591312}, issn = {0894-0282}, abstract = {The soybean cyst nematode (SCN), Heterodera glycines, remains the most damaging pathogen of soybean worldwide. Genomic advances over the past two decades have transformed our understanding of both the nematode and its host. On the soybean side, genome sequencing, pangenome development, and multi-omics studies have clarified how classical resistance loci such as Rhg1 and Rhg4 function while also revealing a broader and more complex landscape of resistance mechanisms. On the nematode side, effector discovery, high-quality genome assemblies, and evolutionary analyses have shed light on how SCN adapts to resistant cultivars and remodels host cellular processes. Despite these advances, overreliance on a single resistance source, PI 88788, continues to accelerate virulence shifts in SCN populations. This underscores the urgent need for diversified resistance, improved monitoring of nematode adaptation, and deeper mechanistic insight into the interaction. In this review, we integrate current knowledge of soybean-SCN interactions across genomics, transcriptomics, proteomics, cell biology, and microbiome research. We highlight how integrative functional genomics is reshaping the discovery of resistance genes, clarifying nematode virulence strategies, and guiding the development of more durable management approaches. Finally, we outline emerging directions, including pangenomics, dual host-pathogen analyses, and predictive breeding, that are expected to advance innovation in SCN control. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.}, } @article {pmid41590961, year = {2026}, author = {Carlone, J and Rossi, C and Bianco, A and Drid, P and Parisi, A and Fasano, A}, title = {Exploring the Gut Microbiome in Combat Sports: A Systematic Scoping Review.}, journal = {Sports (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/sports14010019}, pmid = {41590961}, issn = {2075-4663}, abstract = {The gut microbiota represents a complex microbial ecosystem with the potential to influence athletic performance, energy metabolism, inflammatory responses, and recovery capacity in athletes. However, the specific relationship between microbiota and performance in combat sport athletes remains poorly characterized. This scoping review systematically maps current evidence on gut microbiota-combat sports performance relationships, identifies microbial response patterns to training and competition, evaluates nutritional prebiotic and probiotic interventions, and highlights methodological gaps to guide future research. Following the PRISMA-ScR framework, 8 studies were identified, which included 247 elite and high-level athletes, comprising 169 males and 78 females, with sample sizes ranging from 12 to 53 across wrestling, mixed martial arts, martial arts, judo, and taekwondo. Associations were observed between gut microbiota characteristics and training intensity, competition level, weight management, and pre-competition psychological states. Limited taxonomic consistency was observed across studies, with most bacterial genera appearing in a single investigation, precluding the identification of robust sport-specific microbial signatures. Preliminary trials demonstrated improvements in gastrointestinal symptoms, aerobic performance, and psychological fatigue with prebiotic and probiotic interventions. However, small sample sizes and methodological heterogeneity across studies limit generalizability and preclude definitive conclusions regarding the role of gut microbiome in combat sports performance.}, } @article {pmid41590860, year = {2026}, author = {Zhang, X and Cheng, L and Zhou, Y and Xie, J and Gui, W and Chen, J and Zhang, Z and Liu, K and Ma, R}, title = {Microbiome-Metabolome Axis in BALF Reveals Novel Diagnostic Biomarkers for Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.}, journal = {Journal of cardiovascular development and disease}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/jcdd13010032}, pmid = {41590860}, issn = {2308-3425}, support = {82460061//National Natural Science Foundation of China/ ; }, abstract = {Background: Early identification of irreversible pulmonary vascular remodeling in congenital heart disease-associated pulmonary arterial hypertension (C-PAH) is critical for optimizing surgical timing. Current noninvasive diagnostic methods are inadequate, and the lung microbiome and metabolome may provide novel insights into disease progression. Methods: We analyzed bronchoalveolar lavage fluid (BALF) from 47 children, including those with C-PAH (n = 15), CHD without PAH (C-NPAH, n = 16), and healthy controls (n = 16), using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified, and their interactions with clinical indicators were assessed via Random Forest (RF) and Mediation Analysis. Results: C-PAH patients exhibited airway microbial dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes (F/B) ratio and increased abundance of g_Lactobacillus. Metabolomic profiling revealed 88 differential metabolites between C-PAH and controls, and 3 between C-PAH and C-NPAH. N1-methylnicotinamide (MNAM) and 2-piperidone emerged as potential biomarkers. Mediation analysis showed that g_Eikenella influenced PAH indirectly through 2-piperidone (β = -0.376, p = 0.026), indicating a microbe-metabolite-host interaction. Conclusions: Integrative microbiome-metabolome profiling of BALF reveals potential biomarkers for C-PAH. These findings provide exploratory evidence that microbial and metabolic biomarkers, particularly 2-piperidone and MNAM, hold potential for the early, noninvasive identification of irreversible pulmonary vascular remodeling, but require further validation in independent cohorts.}, } @article {pmid41590653, year = {2026}, author = {Park, JB and Cho, S and Lee, SJ}, title = {A Comprehensive Review on Medium- and Long-Chain Fatty Acid-Derived Metabolites: From Energy Sources to Metabolic Signals.}, journal = {Metabolites}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/metabo16010045}, pmid = {41590653}, issn = {2218-1989}, abstract = {Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs-producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPARα/γ, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory-metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut-brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability.}, } @article {pmid41590545, year = {2026}, author = {Duduveche, AE and Ocroteala, L and Mirea, AA}, title = {Beyond Oral Health: Personalized Strategies for Managing Oral Infections in Neutropenic Patients.}, journal = {Journal of personalized medicine}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/jpm16010053}, pmid = {41590545}, issn = {2075-4426}, abstract = {Oral infections in neutropenic patients are an underestimated but likely fatal cause of infectious complications, with clinical manifestations often diminished or absent due to immune deficiency. The evaluation and management of these infections requires a personalized multidisciplinary strategy, including prevention through pre-therapy dental assessment, individualized oral hygiene protocols, and rapid treatment of dental lesions. Antimicrobial strategies should be adapted not only to the local resistance profile and individual risk, with a priority on antibiotic stewardship and rapid de-escalation when possible, but also to individual patterns of colonization and comorbidities. Dental procedures can be performed without risk in neutropenic patients with a low complication rate, but further studies are key to stratifying risk. Future research directions include the application of artificial intelligence for infectious risk stratification, the use of salivary or microbiome biomarkers for early detection, and the development of innovative technologies for targeted antimicrobial delivery. This narrative review aims to provide an overview of the common clinical manifestations in neutropenic patients and also the potential progression of dental infections into sepsis in this category of patients.}, } @article {pmid41590540, year = {2026}, author = {Agüera-Sánchez, A and Peña-Ros, E and Martínez-Martínez, I and García-Molina, F}, title = {Comprehensive Landscape of Diagnostic, Prognostic and Predictive Biomarkers in Colorectal Cancer: From Genomics to Multi-Omics Integration in Precision Medicine.}, journal = {Journal of personalized medicine}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/jpm16010048}, pmid = {41590540}, issn = {2075-4426}, abstract = {Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in screening and therapeutic strategies, early detection and individualized treatment remain major challenges. In recent years, an expanding repertoire of biomarkers has emerged, spanning genomic, transcriptomic, proteomic, and metabolomic signatures. Epigenetic features, such as DNA methylation panels, as well as non-coding RNAs and the gut microbiome, hold potential not only for improving early diagnosis but also for refining prognosis and predicting therapeutic responses within the framework of precision oncology. This narrative review provides an updated, integrative overview of CRC diagnostic, prognostic, and predictive biomarkers. We distinguish established markers already in clinical practice, such as RAS and BRAF mutations, HER2 amplification, microsatellite instability/mismatch repair deficiency (MSI/dMMR), and widely investigated molecular alterations including TP53 mutations and immune-checkpoint-related markers, from novel biomarkers with growing translational potential. We also discuss the implementation challenges of these biomarkers in clinical practice, including issues related to validation, standardization, and cost-effectiveness, as well as the multi-modal approach for the development of composite diagnostic panels.}, } @article {pmid41590453, year = {2026}, author = {Zhang, K and Cai, Y and Shi, X and Yan, Z and Huang, Q and Perez-Moreno, J and Liu, D and Yang, Z and Yang, C and Yu, F and Liu, W}, title = {Symbiosis Among Naematelia aurantialba, Stereum hirsutum, and Their Associated Microbiome in the Composition of a Cultivated Mushroom Complex JinEr.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/jof12010041}, pmid = {41590453}, issn = {2309-608X}, support = {202205AD160036//Fuqiang Yu/ ; Yunnan Revitalization Talent Support Program//Jesús Pérez-Moreno, Xinhua He/ ; }, abstract = {The JinEr mushroom ("Golden Ear"), a globally rare edible and medicinal macrofungus, comprises a symbiotic complex formed by the symbiotic association of Naematelia aurantialba (Tremellomycetes) and Stereum hirsutum (Agaricomycetes). However, the interactions between these fungi and their associated microbiome remain poorly understood. This study employed high-throughput amplicon sequencing, in situ microbial isolation and culture, and microbial confrontation assays to analyze microbial diversity, community structure, and potential functional roles of the endomycotic bacterial community within JinEr basidiomata and its cultivation substrate. Molecular analysis confirmed the heterogenous composition of the basidiomata, revealing N. aurantialba constitutes less than 20% of the fungal biomass, while S. hirsutum predominates, accounting for approximately 80%. Endomycotic fungi accounted for 0.33% (relative abundance) of the fungal community. Prokaryotic analysis identified Delftia and Sphingomonas as the dominant endomycotic bacterial genera within basidiomata, comprising 85.42% of prokaryotic sequences. Endomycotic bacterial diversity differed significantly (p < 0.05) between basidiomata and substrate, indicating host-specific selection. Cultivation-based approaches yielded 140 culturable bacterial isolates (spanning four families and seven genera) from basidiomata core tissues. In vitro co-culture experiments demonstrated that eight representative bacterial strains exhibited compatible growth with both hosts, while one Enterobacteriaceae strain displayed antagonism towards them. These findings confirm that the heterogeneous JinEr basidiomata harbor a specific prokaryotic assemblage potentially engaged in putative symbiotic or commensal associations with the host fungi. This research advances the understanding of microbial ecology in this unique fungal complex and establishes a culture repository of associated bacteria. This collection facilitates subsequent screening for beneficial bacterial strains to enhance the JinEr cultivation system through the provision of symbiotic microorganisms.}, } @article {pmid41590435, year = {2025}, author = {Wu, P and Zhu, C and Yu, Z and Ren, C and Fan, Z and Zhang, R and Yue, P and Huang, Y and Deng, G and Zeng, J}, title = {The Compartment and Variety Effects Jointly Shape Pummelo Endophytic Mycobiota.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/jof12010023}, pmid = {41590435}, issn = {2309-608X}, support = {2025TS-1-1//Special Fund for Rural Revitalization Strategy of Guang dong (Improvement of Agricultural Science and Technology Capacity)/ ; 2024-NYP-00-046//Guangdong Province's Seed Industry Revitalization Action Project/ ; CARS-26//National Modern Agricultural (Citrus) Technology Systems of China/ ; }, abstract = {The plant microbiome plays important roles in plant growth and resistance, but its assembly and affecting factors have not been fully studied for most of the agricultural plants. In this study, the endophytic mycobiota of the leaves and roots and the rhizosphere soils of five pummelo varieties were profiled based on the amplicon sequencing of the fungal internal transcribed spacer (ITS). The fungal richness and diversity were significantly different among the compartments, but not among the pummelo varieties. The composition and structure of the endophytic mycobiota of the compartments were significantly different across all five pummelo varieties. These suggest that the variety effect is weaker than the compartment effect, but still significant in shaping the pummelo mycobiota. Specifically, the dominant leaf endophytic fungal taxa (e.g., Fusarium and Zasmidium), and the root selection of fungal genera from the rhizosphere soils, were significantly different among the varieties. And also, the variety effect is more significant in shaping the leaf endophytic mycobiota than those of the roots. Finally, the pummelo varieties also showed some consistent alterations on the endophytic mycobiota, such as the root enrichment of Exophiala species. Our study indicates that the endophytic mycobiota of pummelos is significantly and interactively affected by plant variety and compartment effects, and suggests some fungi of interest for further tests.}, } @article {pmid41590165, year = {2026}, author = {Sato, Y and Watanabe, Y and Ayabe, T and Kokubo, T}, title = {Inhibition of Streptococcus Biofilm Formation by 6'-Sialyllactose and N-Acetylneuraminic Acid.}, journal = {Dentistry journal}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/dj14010041}, pmid = {41590165}, issn = {2304-6767}, abstract = {Background/Objectives: Oral hygiene is crucial for maintaining overall health, as poor oral care can lead to various systemic diseases. Although xylitol is widely used to inhibit plaque formation, more effective agents are needed to control oral biofilms. Herein, we evaluated the inhibitory effects of sialyllactose (SL), a type of human milk oligosaccharide (HMO), and its partial structure N-acetylneuraminic acid (Neu5Ac) against Streptococcus biofilm. Methods: Under a CO2 atmosphere, Streptococcus mutans and mixed Streptococcus species were each cultivated in vitro, and the inhibitory effects of HMOs [2'-fucosyllactose, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL)] and Neu5Ac on biofilm formation were evaluated. Bacterial biofilm formation was quantified using the crystal violet assay. Biofilm architecture and viability were visualized using confocal laser-scanning microscopy (CLSM) with SYTO9/propidium iodide staining. Transcriptomic responses of S. mutans biofilms to the test compounds were analyzed by RNA-Seq. Statistical analysis was performed using one-way analysis of variance followed by Tukey's test. Results: SLs and Neu5Ac at 100 mM significantly inhibited S. mutans biofilm formation, with stronger effects than those of xylitol. The inhibitory effects varied among HMOs, with 6'-SL being more effective than 3'-SL and Neu5Ac being most effective. These effects were consistent in assays targeting biofilms formed by other S. mutans strains and in a mixed biofilm comprising Streptococcus species. Gene expression analysis suggested that the inhibitory mechanism involves the physical inhibition of surface adhesion and stress-induced regulation of gene expression. Conclusions: This study provides insights into the physiological significance of HMOs in the oral cavities of humans. HMOs exhibited potential as functional foods to control oral biofilm formation and reduce the risk of oral and systemic diseases.}, } @article {pmid41590139, year = {2026}, author = {Popa, G and Cocoș, DI and Popa, GV and Iliescu, A and Popescu, CM and Stefanescu, A}, title = {Clinical and Microbiological Effects of Smoking on Lithium Disilicate Endocrowns: An Age-Stratified Cross-Sectional Study.}, journal = {Dentistry journal}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/dj14010015}, pmid = {41590139}, issn = {2304-6767}, abstract = {Background: Smoking alters oral ecological balance, yet its influence on posterior teeth restored with lithium disilicate endocrowns is insufficiently documented. This study assessed the clinical and microbiological impact of smoking on the peri-coronal environment of endocrown-restored teeth, using an age-stratified approach to evaluate cumulative effects. Methods: A cross-sectional study was conducted on 100 adults, equally divided into smokers and non-smokers. Salivary pH, papillary bleeding index, and plaque index were clinically recorded. Subgingival samples collected from endocrown-restored posterior teeth were analyzed using a polymerase chain reaction (PCR) assay targeting major periodontal pathogens. Age-related variation in clinical and microbiological parameters was examined using one-way analysis of variance (ANOVA), followed by Tukey's HSD post hoc test. Results: Smokers showed consistently lower salivary pH and higher plaque accumulation across all age groups. Gingival bleeding was reduced in younger smokers but increased in older individuals. Microbiological analysis identified markedly elevated levels of orange-complex organisms in smokers, including Prevotella intermedia and Fusobacterium nucleatum. Clinically, endocrowns in smokers presented more frequent marginal degradation, localized inflammation, and early signs of recurrent caries. These effects intensified with age. Conclusions: Smoking adversely modifies the peri-coronal biological environment of lithium disilicate endocrowns by increasing acidity, promoting plaque maturation, and supporting dysbiotic microbial communities. Age further amplifies these changes. Considering smoking status and patient age during treatment planning may improve long-term restorative outcomes.}, } @article {pmid41590134, year = {2025}, author = {Alblowi, JA}, title = {Effect of Smoking on Subgingival Microbiome in Chronic Periodontitis: A 16S rRNA Sequencing Study.}, journal = {Dentistry journal}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/dj14010010}, pmid = {41590134}, issn = {2304-6767}, support = {1271018//King Abdulaziz University/ ; }, abstract = {Background: Smoking has a detrimental effect on the periodontal condition. Smoking intensity has recently been considered as a criterion for grading periodontitis cases. However, the influence of smoking intensity on the subgingival microbial community has not been evaluated in depth. This cross-sectional analytical study aims to assess the differences in the subgingival microbiome in adult patients with chronic periodontitis and different smoking habits (heavy smokers versus moderate smokers versus non-smokers). Methods: Sixty patients diagnosed with chronic periodontitis were grouped according to their daily smoking intensity as follows: group I (smoke ≥ 10 cigarettes/day), group II (smoke < 10 cigarettes/day), and non-smokers (group III). For each patient, samples from subgingival plaque were harvested from the deepest three periodontal pockets, and their 16S rRNA was sequenced using the S5 Ion Torrent platform. Sequences were clustered in taxonomic units, and the microbial diversity was expressed using the Shannon index or Simpson index, while the abundance of the microbial species was expressed using the Chao index. Results: Bacterial diversity was lowest in the heavy smoker group (group I) and highest in non-smokers (group III). Veillonella, Streptococcus, Prevotella, Fusobacterium, and Dialister were found to have different prevalences in the three study groups. Campylobacter decreased and Fusobacterium increased as a function of the number of cigarettes smoked per day. The moderate smoker group showed a higher abundance of Spirochaetes. At the species level, the heavy smoker group (group I) showed a higher abundance of Fusobacterium compared to the other two groups. Conclusions: Greater smoking intensity has been associated with higher Fusobacterium abundance, together with decreased diversity of the subgingival microbiome, establishing a more stable putative subgingival bacterial environment.}, } @article {pmid41589915, year = {2026}, author = {Rahman, MM and Gilman, MAA and Hoque, MN}, title = {Mammary and gut microbiome profiles in experimentally induced murine mastitis.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0142825}, doi = {10.1128/mra.01428-25}, pmid = {41589915}, issn = {2576-098X}, abstract = {16S rRNA amplicon sequencing of mammary and gut samples (N = 32) from healthy (n = 3) and experimentally induced mastitis mice (n = 13) revealed Lactobacillus-dominated bacteriomes, low archaeal diversity, and significant mastitis-associated shifts. These results provide a foundational data set for understanding mastitis-causing major pathogen-driven dysbiosis, host-microbiome interactions, and disease-specific microbial community dynamics.}, } @article {pmid41589910, year = {2026}, author = {Kang, M}, title = {AmpliFuse: an amplicon simulation tool with enhanced chimera generation for Illumina platforms.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0143925}, doi = {10.1128/mra.01439-25}, pmid = {41589910}, issn = {2576-098X}, abstract = {PCR-generated chimeric amplicons undermine the accuracy and reliability of subsequent amplicon-sequencing analyses. AmpliFuse, a Python-based tool, simulates realistic amplicon datasets through in silico PCR, chimera formation, and read simulation. By providing biologically relevant chimera-containing amplicon reads, AmpliFuse would facilitate benchmarking of chimera-detection algorithms and workflows, advancing microbiome and AMR research.}, } @article {pmid41589878, year = {2026}, author = {Fricker, AD and Barnes, AL and Henzi, A and Duran, LE and Flores, GE}, title = {Time-resolved growth of diverse human-associated Akkermansia on human milk oligosaccharides.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0207125}, doi = {10.1128/spectrum.02071-25}, pmid = {41589878}, issn = {2165-0497}, abstract = {The infant gut microbiota is strongly influenced by human milk oligosaccharides (HMOs), a set of glycans that comprise a large constituent of milk and reach the large intestine intact. During growth on HMOs, bacteria produce beneficial metabolites, including short-chain fatty acids (SCFAs), that are important for host health. Select gut microorganisms have unique sets of enzymes capable of catabolizing distinct HMOs, leading to host-specific differences in glycan access and ultimately differences in SCFA production. Here, we cultivated three species of human-associated Akkermansia, an early-life commensal that is correlated with a healthy metabolic status in adults, on five individual HMOs in two different media backgrounds. Analysis of growth rates, growth yield, metabolic output, and individual HMO consumption through time revealed differences across species that were influenced by growth media. Most notably, Akkermansia biwaensis CSUN-19 has robust growth in both media backgrounds paired with nearly complete degradation of all HMOs. Across all conditions, overall SCFA production was generally commensurate with growth, but most strikingly, Akkermansia muciniphila MucT and A. biwaensis CSUN-19 produced succinate only when grown in the presence of N-acetyl glucosamine, but not with mucin. The third organism tested, Akkermansia massiliensis CSUN-17, had weaker growth, lower degradation of HMOs, but higher production of propionate in media containing N-acetyl glucosamine. Interactions between Akkermansia and HMOs can influence colonization of other early life commensals, potentially influencing health outcomes throughout life. This study highlights the importance of characterizing the growth of individual Akkermansia species on distinct HMO leading to fermentation into organic acids.IMPORTANCEAkkermansia is a widely distributed bacterial genus found in the healthy human gut that is capable of degrading host-produced glycans, including human milk oligosaccharides (HMOs). Previous endpoint experiments demonstrated varying degradation efficiencies across Akkermansia species, with A. biwaensis displaying enhanced growth on multiple HMOs. However, the temporal dynamics and growth preferences when offered substrate choice across the lineage are unknown. Here, we characterized the temporal growth dynamics, HMO catabolism, and metabolic output of three Akkermansia species across five HMOs and two media backgrounds. Specifically, we demonstrate that one species, A. biwaensis CSUN-19, has robust growth independent of media background with nearly complete degradation of all HMOs tested. Overall, the species-, HMO-, and media-specific response of Akkermansia may impact the colonization success of each species, ultimately influencing host-microbe and microbe-microbe interactions in the developing infant gut microbiome.}, } @article {pmid41589836, year = {2026}, author = {Darlenski, R and Manuelyan, K and Dimova, I and Menzel, P and Schwarzer, R and Fluhr, JW and Bogdanov, I}, title = {Skin surface microbiome dynamics in the extremes: Learnings from Antarctica distinct community.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {}, number = {}, pages = {}, doi = {10.1111/jdv.70324}, pmid = {41589836}, issn = {1468-3083}, support = {80-25-69/3.8.2021//Bulgarian National Program for Polar Research 2017-2021/ ; }, } @article {pmid41589673, year = {2026}, author = {Rosa, A and Gargari, M and Martelli, M}, title = {Gut-Brain-Jaw Axis: The Emerging Role of Gut Microbiota in Temporomandibular Disorders and Orofacial Pain-A Narrative Review.}, journal = {Journal of oral rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1111/joor.70156}, pmid = {41589673}, issn = {1365-2842}, abstract = {BACKGROUND: Temporomandibular disorders (TMDs) and chronic orofacial pain are multifactorial conditions influenced by complex neurobiological and systemic mechanisms. Recent findings emphasise the gut-brain axis as a central modulator of pain, neuroinflammation, and immune signalling. Nevertheless, the role of the gut microbiota in TMD pathogenesis and oral rehabilitation remains insufficiently characterised.

METHODS: A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science up to December 2024 using combinations of keywords including "gut microbiota," "temporomandibular disorder," and "orofacial pain." Eligible publications included clinical studies, systematic and narrative reviews, meta-analyses, and theoretical works addressing microbiota-pain relationships.

RESULTS: Recent Mendelian randomization studies reveal causal associations between specific bacterial genera and TMD risk. Experimental models demonstrate that gut dysbiosis exacerbates temporomandibular joint inflammation and neuroinflammatory responses, while restoring microbial balance through probiotics or faecal microbiota transplantation alleviates pain hypersensitivity. Mechanistic studies suggest that microbial metabolites such as short-chain fatty acids, GABA, and serotonin modulate trigeminal pain pathways via vagal and immune signalling.

CONCLUSION: Current evidence supports a bidirectional gut-brain-jaw communication system influencing both peripheral and central pain mechanisms. Incorporating microbiome-targeted approaches-such as dietary modulation, probiotics, and microbial therapy-may enhance TMD management and promote a more holistic, personalised model of oral rehabilitation.}, } @article {pmid41589626, year = {2026}, author = {Kearns, A and O'Malley, T}, title = {Linagliptan-associated delirium in an older patient.}, journal = {Irish medical journal}, volume = {119}, number = {1}, pages = {11}, pmid = {41589626}, issn = {0332-3102}, mesh = {Humans ; *Delirium/chemically induced/drug therapy/diagnosis ; Aged ; Male ; Diabetes Mellitus, Type 2/drug therapy ; Benzhydryl Compounds/therapeutic use ; Glucosides/therapeutic use ; *Hypoglycemic Agents/adverse effects ; }, abstract = {PRESENTATION: A 77-year-old man with type 2 diabetes, presented to the Emergency Department with an acute onset of confusion for 24 hours. He was on Metformin but due to nausea, this was switched to Linagliptan two days prior to his presentation. All vital signs were stable including blood sugar. Clinical examination was normal.

DIAGNOSIS: Full blood count, renal, liver and C-reactive protein were all normal. CT brain revealed age-related involutional changes, while Chest X-ray and MRI brain was normal. His 4AT score was ten and together with his acute change from baseline, a diagnosis of delirium was made.

TREATMENT: Linagliptan was discontinued and Empagliflozin was commenced with full recovery of the delirium gradually.

DISCUSSION: Linagliptan and delirium may be due to changes to the gut microbiome, disturbing the gut-brain axis increasing inflammation1. Linagliptan associated delirium has not been previously reported, although with effects of delayed gastric emptying and reduced gut motility, more studies are needed.}, } @article {pmid41589442, year = {2026}, author = {Verburgt, CM and van der Kruk, N and Dunn, KA and , and Van Limbergen, JE}, title = {Personalized AZithromycin/metronidAZole + dietary therapy in pediatric Crohn disease: Results of a pilot study.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70357}, pmid = {41589442}, issn = {1536-4801}, support = {585718//Crohn's and Colitis Foundation of America/ ; //CIHR-SPOR-Chronic Diseases/ ; //Canadian Institutes of Health Research [CIHR]-Canadian Association of Gastroenterology- Crohn's Colitis Canada New Investigator Award/ ; }, } @article {pmid41589431, year = {2025}, author = {Şahin, N and Salbaş, E}, title = {The Gut-Joint Connection: Microbiome's Role in Rheumatic Disease.}, journal = {Archives of rheumatology}, volume = {40}, number = {4}, pages = {413-421}, doi = {10.5152/ArchRheumatol.2025.25192}, pmid = {41589431}, issn = {2618-6500}, abstract = {The human gut microbiome is a pivotal regulator of systemic immunity and a central factor in the pathogenesis of rheumatic diseases. An imbalance in this microbial community, known as "dysbiosis," can trigger and perpetuate autoimmune responses through the "gut-joint axis." A key mechanism underpinning this connection is increased intestinal permeability ("leaky gut"), which facilitates the translocation of microbial products like lipopolysaccharide into the systemic circulation, thereby provoking chronic inflammation. Concurrently, dysbiosis disrupts the critical homeostatic balance between pro-inflammatory Th17 cells and regulatory T cells, an immunological hallmark of conditions such as rheumatoid arthritis (RA), ankylosing spondylitis, and systemic lupus erythematosus (SLE). Specific microbial signatures, including the expansion of Prevotella copri in RA and Ruminococcus gnavus in SLE, are emerging as potential diagnostic biomarkers. This deeper understanding is paving the way for innovative therapeutic strategies. Interventions aimed at modulating the gut microbiota, such as targeted diets, probiotics, prebiotics and fecal microbiota transplantation, represent a promising frontier for the personalized management of rheumatic diseases. This review explores the foundational mechanisms linking the microbiome to autoimmunity and discusses the clinical potential of harnessing the gut-joint axis to improve patient outcomes.}, } @article {pmid41589125, year = {2026}, author = {Panyako, PM and Ogada, S and Kuria, SN and Musina, J and Lichoti, JK and Ommeh, SC}, title = {Metagenomic Profiling of Fecal and Cecal Microbiota and Their Antimicrobial Resistance Genes in Indigenous Backyard Poultry.}, journal = {International journal of microbiology}, volume = {2026}, number = {}, pages = {7306065}, pmid = {41589125}, issn = {1687-918X}, abstract = {Indigenous backyard poultry is the predominant type of poultry in developing countries. Rural smallholder farmers in these regions usually adopt the free-range (backyard) production system, which exposes the poultry to diverse environments and a broad spectrum of microorganisms that influence their diet and gut microbiota. In this cross-sectional purposive study, we evaluated the microbial community profiles of indigenous backyard poultry and their antimicrobial resistance genes (ARGs) using both cecal samples, which provide a more accurate representation of the core gut microbiota, and fecal samples, which allow for noninvasive monitoring and pathogen screening. We analyzed 32 pooled fecal and cecal samples using shotgun metagenomics, followed by functional and antimicrobial resistance (AMR) analyses to identify genes and metabolic pathways associated with poultry gut health and production. We report the presence of many commensal microorganisms in indigenous backyard poultry, with the most abundant being Bacteroidetes, Firmicutes, and Proteobacteria. The most dominant genera in the feces were Bacteroides, Methanobrevibacter, and Phocaeicola, while Bacteroides, Methanobrevibacter, and Chlamydia dominated in the ceca. No marked differences in microbial diversity were observed between the fecal and cecal samples. KEGG and COG database analyses revealed significantly enriched pathways associated with metabolism, cellular processes, and information storage and processing. Genes that confer resistance to tetracycline were the most abundant, raising concerns about the risks associated with inappropriate and excessive use of this antibiotic in poultry treatment. These findings deepen our understanding of the poultry gut microbiome, particularly regarding indigenous backyard poultry. Furthermore, the information about ARGs is a valuable indicator of antimicrobial use by rural smallholder farmers who have adopted the free-range production system in Kenya and other developing countries. These insights are crucial for farmers and the national livestock sector to monitor AMR in poultry, thereby enabling improved poultry management practices and informed policy decisions.}, } @article {pmid41589071, year = {2026}, author = {Caserta, MT and Mariani, TJ and Walsh, EE and Gill, SR and Gill, AL and Corbett, A and Harrington, D and Chu, C and Qiu, X}, title = {Nasal Biomarkers of Acute Illness Severity and Predictors of Recurrent Wheeze in Respiratory Syncytial Virus (RSV) Infected Infants.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiag049}, pmid = {41589071}, issn = {1537-6613}, abstract = {BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants and those with RSV disease appear more likely to develop recurrent wheeze. We examined nasal airway gene expression and microbiome composition during acute primary RSV infection to test associations with illness severity and identify infants with recurrent wheeze.

METHODS: Previously healthy infants with confirmed RSV infection were enrolled (Dec 2019 to Dec 2023). Clinical, demographic data, 2 anterior nasal swabs and a nasal wash were collected for metagenome and transcriptome sequencing. Disease severity was measured by the improved Global Respiratory Severity Score (iGRSS). Participants were followed for approximately 1 year after enrollment to identify recurrent wheeze. Multivariate regression models were developed to identify correlates and predictors of disease severity and recurrent wheeze, respectively.

RESULTS: 100 (90 hospitalized) infants were enrolled (mean age 3.2±2.3 months; 61% male). 405 genes (false discovery rate 0.10) were significantly and consistently associated with illness severity (iGRSS), implicating Innate Immune and Interleukin Signaling pathways. An abundance of Dolosigranulum in the nares was inversely associated with iGRSS while the abundance of Haemophilus was directly associated with iGRSS. Predictive models using nasal gene expression during acute infection had the power to classify recurrent wheeze (in-sample AUC=0.992; cross-validated AUC=0.882) while metagenomic features did not improve predictive performance.

CONCLUSIONS: We prospectively followed infants with primary RSV infection and identified associations between nasal gene expression, microbiome composition/function and acute disease severity and recurrent wheeze. Host transcriptional profiles during infection were predictive of recurrent wheeze within the following year.}, } @article {pmid41589020, year = {2026}, author = {Liu, D and Zhang, X and Zhao, X and Che, X and Song, W and Wu, G}, title = {Bacterial vaginosis: advancing insights into microbial dysbiosis.}, journal = {Critical reviews in microbiology}, volume = {52}, number = {1}, pages = {159-175}, doi = {10.1080/1040841X.2025.2537923}, pmid = {41589020}, issn = {1549-7828}, mesh = {Humans ; *Vaginosis, Bacterial/microbiology/diagnosis/therapy/drug therapy ; Female ; *Dysbiosis/microbiology ; *Vagina/microbiology ; Microbiota ; Pregnancy ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Bacterial vaginosis (BV), first identified in the 1950s, is a common vaginal condition characterized by a thin, homogeneous discharge with a fishy odor and minimal inflammation. Its high recurrence rate and associated complications pose significant challenges to patients' physical and mental health. Untreated, BV can result in severe outcomes, including pelvic inflammatory disease and adverse pregnancy complications. A comprehensive understanding of BV's diagnostic criteria, complications, drug resistance, and treatment strategies is essential for improving patient care. This review examines the vaginal microbiome, emphasizing the protective role of healthy flora through physical and immunological mechanisms. Key diagnostic methods, including Amsel's criteria, the Nugent scoring system, BV Blue test, qPCR, and advanced techniques like 16S rRNA sequencing, are discussed. The review also explores the adverse outcomes of BV, such as increased risk of sexually transmitted infections, pregnancy-related complications, and social and psychological impacts. Finally, we highlight advancements in treatment, focusing on polymicrobial biofilms and combination therapies. Emerging approaches include standard antibiotics, probiotics, biofilm-targeting strategies, hormone replacement therapy, and partner treatment. This review underscores the importance of maintaining vaginal microbial balance and offers a detailed perspective on BV's mechanisms, diagnosis, and therapeutic innovations.}, } @article {pmid41589006, year = {2026}, author = {Li, F and Qiao, L and Liang, X and Zhang, Y and Liang, N and Xie, J and Deng, G and Hao, Y and Hu, P and Wu, X and Ding, F and Feng, C and Mu, Y and Zhang, J}, title = {Crosstalk Between Intratumoral Microbes and Tumor Immunity: Implications for Tumor Therapy.}, journal = {Cancer medicine}, volume = {15}, number = {2}, pages = {e71575}, doi = {10.1002/cam4.71575}, pmid = {41589006}, issn = {2045-7634}, support = {ZR2021LSW023//Natural Science Foundation of Shandong Province, China/ ; ZR2021QH356//Natural Science Foundation of Shandong Province, China/ ; }, mesh = {Humans ; *Neoplasms/immunology/therapy/microbiology ; *Tumor Microenvironment/immunology ; *Microbiota/immunology ; Immunotherapy/methods ; Animals ; Bacteria/immunology ; }, abstract = {BACKGROUND: Emerging studies indicate that microbes are present in tumor cells and immune cells. Intratumoral microbiota (ITM) constitute an important component of the tumor immune microenvironment (TIME) and have an important impact on tumor progression and treatment.

OBJECTIVE: Through the general elaboration of ITM represented by bacteria and fungi and the overall summary of their correlation with TIME, we aim to provide new ideas and perspectives for the application of ITM in tumor therapy by this review.

METHODS: This review conducted a literature search using the PubMed database, with no predefined restrictions on the publication time of the included literature. The search terms used included "intratumoral microbiota", "intratumoral microbiome", "intratumoral microbes", "intratumoral microorganisms", "tumor microbiota", "tumor-associated microbiota", "tumor microbiome", "tumor-associated microbiome", "tumor-associated microbes", "intratumoral bacteria", "intratumoral fungi", "cancer", "tumor", "tumor microenvironment", "tumor immune microenvironment", "microbial metabolites", "application", "immunotherapy", "treatment" and "microbial-based cancer therapy". Relevant retrieved literature was screened, prioritizing studies that focused on the distribution characteristics of ITM across different tumors, the mechanistic insights and therapeutic potential.

RESULTS: Studies indicate that bacteria and fungi exhibit distinct distribution patterns in different tumors and interact with the TIME in complex ways, demonstrating either pro-tumor or anti-tumor effects. Proposed hypotheses for the underlying mechanisms include: (1) Antigenic immune responses, including those induced by bacterial peptides or cross-immunity due to similarities between tumor and intratumoral microbial antigens; (2) The activation or inhibition of the function or infiltration of different immune cells; (3) Participating in pattern recognition receptor-mediated signaling pathways; (4) Regulation of immune checkpoints or their inhibitors. ITM can also influence the efficacy of various tumor treatments, including chemotherapy, radiotherapy, and immunotherapy. Several microbial-associated therapeutic approaches, such as engineered bacteria, have already entered clinical application. More treatment strategies are under investigation, although most current research remains at the level of establishing correlations between ITM and tumors, or is confined to preclinical experiments. Further exploration is required to establish causal relationships and achieve precise modulation.

CONCLUSION: Given the significant role of ITM in tumor immunity, it may serve as a potential target for enhancing immunotherapy. Future research must shift its core focus from exploring correlations to intervening based on causality and achieving precise modulation for translational applications.}, } @article {pmid41588971, year = {2026}, author = {Goyal, N and Sharma, S and Bhatia, R and Gupta, S}, title = {Exploring Microbiome-Based Therapy: Bacterial Flavonoid Synthesis as a Novel Approach to PCOS Treatment.}, journal = {Current drug metabolism}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113892002424403251122104355}, pmid = {41588971}, issn = {1875-5453}, abstract = {BACKGROUND: PCOS is a common endocrine disorder characterized by metabolic irregularities, hormonal imbalance, and ovarian dysfunction. Traditional therapies, including dietary changes, herbal remedies, and lifestyle modifications, offer limited efficacy in addressing the complex pathophysiology of PCOS.

METHOD: A literature review was conducted using PubMed, Google Scholar, and ScienceDirect to identify studies on gut microbiota and microbiome-based management strategies for PCOS.

RESULT: Emerging evidence highlights the role of gut bacteria in regulating hormonal and metabolic functions, sparking interest in microbiota-targeted therapies. Microbial flavonoid synthesis by species such as Streptomyces and Escherichia coli may positively influence endocrine and metabolic pathways relevant to PCOS.

DISCUSSION: Modulating the gut microbiome, particularly through microbial flavonoid production, represents a promising therapeutic avenue. However, most evidence remains pre-clinical, with limited clinical validation. Key gaps include mechanistic understanding, safety evaluation, and translational research. Integrating microbiome-targeted interventions with conventional therapies could enhance metabolic and hormonal regulation, offering improved outcomes for women with PCOS.

CONCLUSION: Microbiome-based medicinal approaches, including microbial flavonoid production, may offer novel strategies for PCOS management. Rigorous preclinical studies and well-designed clinical trials are essential to establish their efficacy, safety, and therapeutic potential.}, } @article {pmid41588874, year = {2026}, author = {Nickerson, MN and Tfaily, MM and Meredith, LK and U'Ren, JM}, title = {Fungal Microbiome-Metabolome Relationships in Sphagnum and Two Co-Occurring Alaskan Mosses.}, journal = {Molecular ecology}, volume = {35}, number = {2}, pages = {e70242}, doi = {10.1111/mec.70242}, pmid = {41588874}, issn = {1365-294X}, support = {AGS-1933280//National Science Foundation/ ; DGE-2022055//National Science Foundation/ ; }, mesh = {*Sphagnopsida/microbiology ; *Metabolome/genetics ; Alaska ; *Fungi/genetics/classification ; *Microbiota/genetics ; Ecosystem ; *Bryophyta/microbiology ; *Mycobiome ; Tundra ; }, abstract = {In boreal and tundra ecosystems, mosses are abundant and ecologically important members of the vegetation due to their ability to insulate permafrost and maintain soil moisture. Mosses also harbour diverse bacterial and fungal symbionts that can provide nutrients and protection against environmental stressors. Sphagnum mosses are particularly important due to their significant role in carbon sequestration, which has been attributed in part to the production of antimicrobial metabolites that slow decomposition. Although Sphagnum leachate has been shown to inhibit bacteria, how Sphagnum chemical traits impact fungal communities remains understudied. Here, we used culture-free and culture-based methods to examine the relationship between moss fungal communities and metabolomes in living and senescing tissues of Sphagnum and two co-occurring moss genera across four Alaskan boreal/tundra sites. Although their richness was similar among moss genera, fungal and metabolite composition differed significantly among moss genera, regardless of tissue age. Importantly, mosses with more similar metabolome composition harboured more similar fungal communities, particularly in living tissues. Numerous OTU-metabolite correlations suggest direct interactions whereby fungi may consume, degrade, and/or be inhibited by metabolites; however, in vitro growth of moss-associated fungi showed inhibition in only 25% of replicates with two phenolic metabolites. Overall, our data suggest that metabolites may be a key factor structuring fungal communities in Sphagnum and other mosses, although not solely via inhibitory effects. Given the significance of mosses to ecosystem function and carbon sequestration in northern regions, it is critical to better understand factors that shape fungal communities potentially involved in stress adaptation and decomposition.}, } @article {pmid41588872, year = {2025}, author = {Lai, ZL and Su, YD and Hsu, YY and Hung, YH and Liu, YY and Tai, YA and Lin, HH and Su, HC and Shih, HM and Ho, MW and Cho, DY and Hsueh, PR}, title = {An integrative viro-bacterial signature based on viral load and high-resolution microbiome profiling predicts COVID-19 mortality.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {161}, number = {}, pages = {108153}, doi = {10.1016/j.ijid.2025.108153}, pmid = {41588872}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/mortality/microbiology/virology ; *Viral Load ; *Nasopharynx/microbiology/virology ; Middle Aged ; Male ; *Microbiota ; Female ; SARS-CoV-2 ; Aged ; Machine Learning ; RNA, Ribosomal, 16S/genetics ; Adult ; }, abstract = {BACKGROUND: The nasopharyngeal (NP) microbiota may play a critical role in modulating host immune responses during SARS-CoV-2 infection, yet its utility for predicting clinical outcomes is not fully defined. We aimed to determine if an integrative approach, combining NP microbial profiles with virological and clinical data, could improve mortality prediction in COVID-19 patients.

METHODS: We analyzed nasopharyngeal swabs from 81 COVID-19 patients and 70 non-infected controls. Full-length 16S rRNA sequencing was used for microbiome profiling. Predictive models were developed using machine learning to integrate microbial taxa with viral load and other clinical metadata.

RESULTS: High viral load was identified as the strongest independent predictor of mortality by multivariate logistic regression (OR: 3.80). SARS-CoV-2 infection and its associated viral load were linked to significant reductions in microbial community evenness. Critically, a machine-learning model that integrated viral load, patient age, and specific microbial taxa achieved a high predictive accuracy for mortality (AUC = 0.9046), significantly outperforming models based on clinical data alone.

CONCLUSIONS: Our findings demonstrate that an integrative approach, combining nasopharyngeal microbiota profiles with viral load, provides a robust framework for predicting mortality in COVID-19 patients. This strategy offers a promising, non-invasive tool for improving clinical risk stratification.}, } @article {pmid41588828, year = {2026}, author = {Shaw, D and Gentekaki, E and Tsaousis, AD}, title = {The Microbiome Within a Microbe: Rethinking Blastocystis Biology.}, journal = {The Journal of eukaryotic microbiology}, volume = {73}, number = {1}, pages = {e70056}, doi = {10.1111/jeu.70056}, pmid = {41588828}, issn = {1550-7408}, support = {CA21105//COST/ ; //University of Kent/ ; }, mesh = {*Blastocystis/physiology/microbiology/virology ; Humans ; *Microbiota ; Blastocystis Infections/parasitology ; *Gastrointestinal Microbiome ; }, abstract = {Blastocystis spp., one of the most prevalent microeukaryotes in the human gut, has long puzzled researchers with its ambiguous role in health and disease. Decades-old microscopy studies reported bacterial- and viral-like particles within Blastocystis spp. cells, but these findings have been mainly overlooked. Comparable associations in other protozoa, such as those between Trichomonas vaginalis and Mycoplasma, as well as protozoan-virus interactions, are known to influence metabolism, immune evasion, and ecological fitness. Here, we revisit these neglected observations in Blastocystis spp., framing them within the holobiont concept and proposing that this protist may host its own microbial consortium. We also propose potential mechanisms, ecological implications, and modern experimental strategies-from organ-on-a-chip to single-cell multi-omics-to rigorously test this hypothesis. Recognizing Blastocystis spp. as a possible "microbiome within a microbe" could transform our understanding of its biology and its place in gut microbial ecology.}, } @article {pmid41588774, year = {2026}, author = {de Almeida Brasiel, PG and Luquetti, SCPD}, title = {The Intestine: Development, Functions, and Its Impact on Disease Risk across the Lifespan.}, journal = {Current pediatric reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115733963400365251201134405}, pmid = {41588774}, issn = {1875-6336}, abstract = {The intestine plays a central role in the immune system, continuously interacting with antigens, dietary components, and the microbiota. Intestinal immune processes are increasingly recognized for their influence on the development of both local and systemic diseases, with long-term effects on health and disease progression. This review provides an overview of intestinal development, encompassing its maturation from conception, temporal changes, regenerative capacity, interactions with the microbiota, and involvement in disease. Early life, particularly critical periods such as pregnancy and lactation, may represent a "window of opportunity," establishing lasting conditions that either increase disease risk or confer protection in adulthood. Understanding the regulatory factors, regional and temporal variations, and existing knowledge gaps is essential for guiding clinical practice, as well as for the prevention and treatment of diseases.}, } @article {pmid41588693, year = {2026}, author = {Bhattacharya, D and Nandi, S and Chille, EE and Arroyo, M and Stephens, TG}, title = {The Host Coral Bleaching Response Viewed Through the Lens of Multi-Omics: Multi-Omics Provides the Tools to Understand the Complex Molecular Basis of Coral Bleaching, Which Can Aid Conservation Efforts.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {48}, number = {1}, pages = {e70110}, doi = {10.1002/bies.70110}, pmid = {41588693}, issn = {1521-1878}, support = {23-7825575//Catalyst Science Fund, Revive & Restore, and the National Philanthropic Trust/ ; 2128073//National Science Foundation/ ; NJ01180//USDA National Institute of Food and Agriculture Hatch Formula/ ; }, mesh = {Animals ; *Anthozoa/genetics/physiology ; Symbiosis ; *Coral Bleaching ; Genomics/methods ; Coral Reefs ; Conservation of Natural Resources ; Climate Change ; Oxidative Stress ; Heat-Shock Response ; Multiomics ; }, abstract = {We review recent multi-omics analyses of the coral heat stress response to explore the generality of the Oxidative Theory of Coral Bleaching (OTCB), which posits that algal symbiont release is the final act of defense by the coral host to survive alga-derived oxidative stress. The OTCB is particularly relevant given that ocean warming, which is accelerating under climate change, has proven devastating for corals, leading to the bleaching phenotype and widespread reef loss. Multi-omics results, in combination with other data, such as genome-wide association studies, support the idea that coral bleaching is a multifactorial response that reflects a wide array of causes and effects and is population-specific under most conditions, with coral ploidy and genotype being critical to bleaching sensitivity. This perspective leverages the location, algal and prokaryotic microbiome, and host genotype-specific aspects of coral resilience to promote a new "personal genomics" approach to coral conservation, analogous to that used in human health.}, } @article {pmid41588607, year = {2026}, author = {Meng, Y and Wang, H and Mu, D and Zeng, S and Wang, S}, title = {Host genetic variation and gut microbiome in pediatric diseases.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {41588607}, issn = {2542-5641}, abstract = {Pediatric health is the foundation for people's lifelong health. The co-evolution of host genetics and the gut microbiome fosters a symbiotic relationship that is important for pediatric growth and the pathogenesis of various diseases. However, a comprehensive overview of the human genetic-gut microbiome axis in pediatric diseases remains unavailable. This review summarizes the human genetic variants that are associated with pediatric diseases, affecting the nervous, respiratory, and immune systems, as well as those linked to preterm birth (PTB), as identified by genome-wide association studies (GWAS). As the gut microbiome plays a crucial role in pediatric health, we have systematically discussed microbial biomarkers associated with the onset and progression of pediatric diseases, with an emphasis on their clinical impact across four key axes: the gut-brain, gut-lung, gut-skin, and gut-immune axes. The GWAS on the gut microbiome revealed numerous genetic variants that intricately regulate its composition. These variants predispose individuals to gut microbiome dysbiosis, potentially initiating or exacerbating pediatric disease manifestations, as discussed below. Moreover, the underrepresentation of populations from low- and middle-income countries in existing microbiome-related data, coupled with technical challenges, limits our understanding of the association between microbiome and health. Finally, we emphasize the promising potential of elucidating and modulating host gene-gut microbiome interactions to offer novel insights for advancing precision pediatric medicine and developing innovative therapeutic strategies.}, } @article {pmid41588522, year = {2026}, author = {Huang, G and Tian, C and Liu, Q and Wang, Y and Wang, F and He, Q and Xia, Q and Zhao, P}, title = {Silk-based biomimetic nanocomposite for precision eradication of Helicobacter pylori and gut microbiome preservation.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04050-9}, pmid = {41588522}, issn = {1477-3155}, support = {2022YFD1201600//National Key Research and Development Program of China/ ; 32030103//National Natural Science Foundation of China/ ; 32172798//National Natural Science Foundation of China/ ; }, abstract = {Antibiotics remain the recommended first-line therapy for eradicating Helicobacter pylori infection. However, the harsh gastric physicochemical environment severely limits drug bioavailability, contributing to treatment failure (~10%), gut dysbiosis, and the emergence of antimicrobial resistance. Inspired by H. pylori adhesins binding to gastric epithelial glycan, we developed a biomimetic nanocomposite drug delivery system (BSNG) composed of genetically engineered adhesin-functionalized silk fibroin nanoparticles (BS-NPs) embedded within a fluid silk fibroin hydrogel (FSF-Gel) for targeted anti-H. pylori therapy. BS-NPs exhibit H. pylori-like adhesion to gastric epithelial cells, enabling prolonged gastric retention of over 72 h. FSF-Gel provides conformal coverage of the gastric mucus layer and supports sustained antibiotic release, and prevents acid-induced aggregation of the encapsulated BS-NPs. Upon gastric administration, amoxicillin-loaded BSNG (BSNG@Amo) significantly enhanced both peak drug concentrations and extended therapeutic retention in gastric tissue. In vivo antibacterial studies confirmed that BSNG@Amo achieved superior H. pylori eradication compared to conventional amoxicillin at equivalent doses. Notably, reduced-frequency BSNG@Amo administration maintained therapeutic efficacy while markedly preserving gut microbiota homeostasis. These results highlight BSNG as a precise, long-acting, and microbiota-sparing platform for sustainable gastric antibiotic delivery.}, } @article {pmid41588512, year = {2026}, author = {Yu, S and Wu, Q and Ma, Y and Bano, S and Zhang, X}, title = {Keystone bacterial taxa drive denitrification and N2O emission via adaptive genomic and metabolic strategies in contrasting agricultural soils.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00855-1}, pmid = {41588512}, issn = {2524-6372}, support = {42577128 and 31971526//National Natural Science Foundation of China/ ; (2017YFD0200102)//Key R&D project of the Ministry of Science and Technology/ ; }, abstract = {BACKGROUND: Soil denitrification mediated by microbial communities is a major source of nitrous oxide (N2O), a potent greenhouse gas. However, the regulatory roles of keystone taxa in this process remain poorly understood, particularly under distinct edaphic conditions. Black soil (BS) and fluvo-aquic soil (FS), two representative agricultural soils in China, exhibit contrasting N2O emission potentials, offering an ideal model for exploring microbial mechanisms driving soil-specific denitrification dynamics.

RESULTS: We integrated microbial co-occurrence networks, metagenomics, and functional phenotyping to identify and characterize keystone bacterial taxa involved in denitrification across the two soil types. Structural equation modeling (SEM) and correlation analyses revealed strong associations between keystone taxa and denitrification rates and N2O emission patterns. Ensifer ASV205 was identified as a conserved keystone taxon in both soils and exhibited strain-level niche specialization. Comparative genomic analysis revealed that variations in denitrification gene composition and carbon-nitrogen metabolic pathways enabled Ensifer strains to act either as N2O producers or reducers, depending on environmental conditions.

CONCLUSIONS: Our findings demonstrate that soil-specific denitrification processes and N2O emissions are governed by keystone taxa through adaptive genomic and metabolic strategies shaped by environmental filtering. This study provides new insights into the microbial mechanisms regulating N2O emissions and lays the groundwork for developing microbiome-informed strategies to mitigate greenhouse gas emissions in agricultural soils.}, } @article {pmid41588429, year = {2026}, author = {Myhill, LJ and Jensen, P and Arora, P and Jensen, AM and Zhu, L and Vedsted-Jakobsen, A and Thormar, EA and von Münchow, A and Poojary, MM and Lund, MN and Thamsborg, SM and Limborg, MT and Jensen, BAH and Williams, AR}, title = {Dietary fibre promotes chronic gut parasite infection via direct and time-dependent modulation of innate immunity.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02333-1}, pmid = {41588429}, issn = {2049-2618}, abstract = {BACKGROUND: Dietary fibre is an important regulator of the gut microbiome and is associated with many health benefits. However, high levels of fibre intake have also been reported to exacerbate some diseases.

RESULTS: Here, we show that mice fed semi-synthetic diets supplemented with purified inulin fibre develop chronic infections with the parasitic whipworm Trichuris muris, concomitant with dysregulated innate antimicrobial defences, exacerbated mucosal inflammation, and altered tryptophan metabolism. Inhibition of tryptophan catabolism or neutralizing either IL-27 or IL-18 restored infection resistance. Inulin-fed mice developed gut microbiota dysbiosis during parasite infection, with Proteobacteria becoming dominant. However, despite drastic differences in gut microbiota compositions in control- and inulin-fed mice, microbiota transfer and depletion experiments demonstrated that dietary inulin triggered chronic T. muris infection in a microbiota-independent manner. Importantly, removing inulin from the diet within a critical immune development window rapidly restored anti-parasite immunity, indicating direct, time-dependent modulation of mucosal immune responses.

CONCLUSIONS: These data reveal T. muris-induced dysbiosis as a consequence rather than a causative factor of diet-driven changes in host susceptibility, and establish a direct link between dietary fibre and host defence at mucosal surfaces. Video Abstract.}, } @article {pmid41588382, year = {2026}, author = {Rosato, I and Porcu, G and Donà, D and Batzella, E and Giaquinto, C and Cantarutti, A and Canova, C}, title = {Trajectories of antibiotic prescriptions in Italian children in the first four years of life: a retrospective birth-cohort study.}, journal = {BMC public health}, volume = {26}, number = {1}, pages = {311}, pmid = {41588382}, issn = {1471-2458}, support = {H53D23006110001//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Humans ; Italy ; Retrospective Studies ; *Anti-Bacterial Agents/therapeutic use ; Male ; Female ; Infant ; Child, Preschool ; Infant, Newborn ; *Practice Patterns, Physicians'/statistics & numerical data ; Birth Cohort ; *Drug Prescriptions/statistics & numerical data ; }, abstract = {BACKGROUND: Antibiotics are among the most frequently prescribed medications for pediatric patients. Inappropriate use, particularly in the first years of life, can contribute to the development of antibiotic resistances and impact the maturation of the gut microbiome. Describing prescription patterns using nationally collected data is essential for identifying or monitoring existing strategies for reducing excessive use. This study aims to identify antibiotic prescription trajectories during the first four years of life and to investigate their association with sociodemographic factors.

METHODS: In this retrospective cohort study, we used data collected through the Pedianet registry, a monitoring system involving approximately 200 family pediatricians (FPs) in Italy. We considered children born between 2004 and 2018 with complete follow-up during their first four years of life, excluding those with a birth weight of < 2500 g, gestational age < 37 weeks or genetic disorders. Prescription trajectories over the 16 trimesters of observation were estimated using Group-Based Trajectory Modelling (GBTM), by classifying the included children into homogeneous groups based on their probabilities of membership. The association between trajectories and sociodemographic factors was examined with multinomial logistic regression with random intercepts for FPs.

RESULTS: A total of 143,098 children born between 01/01/2004 and 31/12/2018 were included. Between 0 and 4 years of age, these children received a total of 684,010 antibiotic prescriptions. GBTM identified four different trajectories, defined as: [1] "very low use" of antibiotics (34.9% of children) [2], "low-to-moderate use" (22.8%) [3], "moderate-to-low use" (28.0%) and [4] "high use" (14.3%). Compared to the "very low use" trajectory, male subjects residing in the center and south of Italy and born between 2004 and 2008 had a higher probability of belonging to trajectory groups with "moderate-to-low use" and "high use".

CONCLUSIONS: From 2004 to 2022 in Italy, we observed heterogeneous antibiotic prescription patterns among children aged 0-4 years. Future strategies aimed at reducing the number of prescriptions in this age group should target the subgroups at higher risk.}, } @article {pmid41588328, year = {2026}, author = {Iino, K and Iino, C and Song, S and Sato, M and Nakamura, M and Tanabu, R and Higuchi, T and Tamada, Y and Itoh, K and Sato, N and Imoto, S and Mikami, T and Murashita, K and Yokoyama, Y}, title = {Stability of equol production capability is associated with the diversity of the gut microbiota of the host: a prospective cohort study.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04749-7}, pmid = {41588328}, issn = {1471-2180}, support = {JPMJCE1302, JPMJCA2201, JPMJPF2210//the Center of Innovation Program launched by the Japan Science and Technology Agency/ ; }, } @article {pmid41588320, year = {2026}, author = {Guo, W and Yu, J and Wang, W and Wang, J and Ni, M and Zhou, M and Chen, X}, title = {Multi-kingdom fecal microbiome and virus-host interactions associated with growth performance of indigenous beef calves in Guizhou.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04631-y}, pmid = {41588320}, issn = {1471-2180}, support = {32402705//the National Natural Science Foundation of China/ ; }, } @article {pmid41588237, year = {2026}, author = {Yousefi, A and Mehregan, I and Hamedi, J and Asri, Y and Khan, G and Albach, DC}, title = {Belowground allies, aboveground threats: the vulnerability of the Persian oak (Quercus Brantii Lindl.)- arbuscular mycorrhizal fungi symbiosis in a changing climate.}, journal = {Mycorrhiza}, volume = {36}, number = {1}, pages = {4}, pmid = {41588237}, issn = {1432-1890}, mesh = {*Quercus/microbiology ; *Mycorrhizae/physiology/classification ; *Symbiosis ; *Climate Change ; Iran ; Soil Microbiology ; Plant Roots/microbiology ; Biodiversity ; Droughts ; Microbiota ; }, abstract = {Climate change poses a major threat to ecosystems worldwide, including Iran's ecologically important Zagros oak forests. These forests are experiencing accelerating decline due to climate-related stress and intensified human pressures, despite their key role in sustaining regional biodiversity. Soil health and the crucial symbiotic partnership between oak trees and arbuscular mycorrhizal fungi (AMF) are crucial for resilience in drought-prone Mediterranean environments. Due to a lack of comprehensive studies, this research aimed to analyze the root-associated microbiome of Persian oak (Quercus brantii) across western and southwestern Iran, specifically focusing on AMF diversity and their ecological role. Our study employed Illumina high-throughput sequencing of ITS and 18 S rRNA V4 markers of root-associated fungal communities to assess taxonomic composition and diversity of 160 trees across eight different sites. Analyses revealed dominant fungal groups, including key AMF taxa like Glomeraceae and Claroideoglomeraceae, with significant spatial variation in diversity and community structure, likely influenced by regional and abiotic factors. In addition, the findings highlight the important ecological function of the Persian oak canopy in creating a favorable microclimate and the essential symbiotic partnership with AMF for drought tolerance and nutrient uptake. However, our study ultimately concludes that despite this crucial symbiosis, the Zagros oak forests remain highly vulnerable to increasing pressures from agricultural expansion and the escalating impacts of climate change, seasonal wildfires, and declining groundwater levels, which pose significant threats to their long-term survival.}, } @article {pmid41588169, year = {2026}, author = {Völkerer, A and Wernly, S and Semmler, G and Flamm, M and Ausserwinkler, M and Koch, G and Götz, N and Hofer, H and Aigner, E and Datz, C and Wernly, B}, title = {Proton pump inhibitor use is not independently associated with colonic diverticulosis in an asymptomatic screening population.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-37547-2}, pmid = {41588169}, issn = {2045-2322}, abstract = {Proton pump inhibitors (PPIs) are widely used medications that alter gut microbiota. Given the high prevalence of colonic diverticulosis and its increasing incidence in younger populations, we investigated whether PPI use is associated with diverticulosis prevalence in an asymptomatic screening population. This retrospective observational study analyzed data from 6,153 asymptomatic individuals undergoing colorectal cancer screening in Austria. Colonoscopies assessed diverticulosis presence, while PPI use was determined via structured medical history. Statistical analyses, including Poisson regression models and sensitivity analyses, were conducted to evaluate the association between PPI use and diverticulosis, with adjustments for confounding factors such as age, sex, BMI, comorbidities, and lifestyle characteristics. Among 6,153 participants, 37% were found to have diverticulosis, with a significantly higher prevalence observed in PPI users (48%) compared to non-users (36%, p < 0.001). PPI users were generally older, had a higher BMI, and were more likely to have cardiometabolic comorbidities. Univariate analysis demonstrated a significant association between PPI use and diverticulosis (RR 1.326, 95% CI: 1.199-1.476, p < 0.001). However, this association was not sustained in multivariable models adjusted for age, sex, BMI, comorbidities, and lifestyle factors, indicating that the observed relationship is likely attributable to confounding rather than a direct causal effect. In this large screening cohort, the initially observed association between PPI use and diverticulosis was likely attributable to confounding. These findings suggest that PPI use is not independently associated with diverticulosis.}, } @article {pmid41588163, year = {2026}, author = {Young, V and Dohai, B and Halder, H and Fernandez-Macgregor, J and van Heusden, NS and Hitch, TCA and Weller, B and Hyden, P and Saha, D and Pieren, DKJ and Rittchen, S and Lambourne, L and Maseko, SB and Lin, CW and Tun, YM and Bibus, J and Pletschacher, L and Boujeant, M and Choteau, SA and Bergogne, L and Perrin, J and Ober, F and Schwehn, P and Rothballer, ST and Altmann, M and Altmann, S and Strobel, A and Rothballer, M and Tofaute, M and Kotlarz, D and Heinig, M and Clavel, T and Calderwood, MA and Vidal, M and Twizere, JC and Vincentelli, R and Krappmann, D and Boes, M and Falter, C and Rattei, T and Brun, C and Zanzoni, A and Falter-Braun, P}, title = {Effector-host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41588163}, issn = {2058-5276}, support = {01EA1803//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 101003633//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 210592381//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 403224013//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 11819559//Österreichische Forschungsförderungsgesellschaft (Austrian Research Promotion Agency)/ ; ANR-16-CONV-0001//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-17-HDIM-000//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-16-CONV-0001//Agence Nationale de la Recherche (French National Research Agency)/ ; }, abstract = {Pseudomonadota (formerly Proteobacteria) are prevalent in the commensal human gut microbiota, but also include many pathogens that rely on secretion systems to support pathogenicity by injecting proteins into host cells. Here we show that 80% of Pseudomonadota from healthy gut microbiomes also have intact type III secretion systems (T3SS). Candidate effectors predicted by machine learning display sequence and structural features that are distinct from those of pathogen effectors. Towards a systems-level functional understanding, we experimentally constructed a protein-protein meta-interactome map between human proteins and commensal effectors. Network analyses uncovered that effector-targeted neighbourhoods are enriched for genetic variation linked to microbiome-associated conditions, including autoimmune and metabolic diseases. Metagenomic analysis revealed effector enrichment in Crohn's disease but depletion in ulcerative colitis. Functionally, commensal effectors can translocate into human cells and modulate NF-κB signalling and cytokine secretion in vitro. Our findings indicate that T3SS contribute to microorganism-host cohabitation and that effector-host protein interactions may represent an underappreciated route by which commensal gut microbiota influences health.}, } @article {pmid41588066, year = {2026}, author = {Pániková, L and Ondreičková, K and Pánik, P and Janiga, M and Oxikbayev, B}, title = {Linkages Between Trace Elements and Bacterial Communities in Glacial Freshwater Systems of Zhongar Alatau National Park, Kazakhstan.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-025-02674-2}, pmid = {41588066}, issn = {1432-184X}, abstract = {Glacial ecosystems of Central Asia represent extreme environments where microbial communities are shaped by both physicochemical conditions and hydrological dynamics. In this study, we analysed 21 surface and meltwater samples collected in September 2023 from a lake, river, glacier, glacial river, and sedimentary lake in the Zhongar Alatau National Park (Kazakhstan, 1 040-3 360 m a.s.l.). Bacterial community structure was assessed using ARISA profiling, while spectrometric methods determined concentrations of chemical elements. Alpha diversity indices revealed the highest richness and diversity in lake and sedimentary lake samples, moderate diversity in river samples, and the lowest values in glacier samples. The glacial river samples showed the strongest variability among the samples. Unique operational taxonomic units (OTUs) were most abundant in the lake, but the glacier exhibited the highest relative proportion of habitat-specific OTUs. Principal component analysis revealed that DNA yield, along with heavy metals and other elements (Rb, Fe, Mn, K, Ba), covaried along the major axes, primarily reflecting differences driven by habitat. Overall, our results demonstrate that glacial valley habitats host distinct bacterial assemblages and that the chemical environment is consistent with the observed spatial structuring of microbial communities. These findings highlight the vulnerability and sensitivity of mountain freshwater ecosystems to glacier retreat and associated changes in water chemistry.}, } @article {pmid41587937, year = {2026}, author = {Yoshimoto, Y and Nagata, N and Inoue, R and Yamamoto, Y and Nagaoka, K}, title = {Changes in the microbiome and metabolome in captive red kangaroos (Osphranter rufus) affected by macropod progressive periodontal disease.}, journal = {Australian veterinary journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/avj.70057}, pmid = {41587937}, issn = {1751-0813}, abstract = {Macropod progressive periodontal disease (MPPD) is a severe oral condition frequently observed in captive macropods, particularly red kangaroos (Osphranter rufus), yet its underlying biological features remain poorly understood. In this exploratory descriptive study, we investigated oral and fecal microbiomes and metabolomic profiles in captive red kangaroos to characterise microbial and metabolic patterns associated with MPPD. Oral swabs, fecal samples and serum were collected from clinically healthy individuals and animals diagnosed with MPPD. Microbiome profiling was performed using 16S rRNA gene sequencing, and untargeted metabolomic analyses were conducted using GC-MS. All analyses were conducted in a descriptive manner to summarise observed patterns and trends rather than to support formal statistical inference. Descriptive comparisons suggested differences in the oral microbiome composition of animals with MPPD, including increased representation of several taxa previously associated with periodontal disease in other species. Oral metabolomic profiling indicated variation in multiple metabolites, including lower relative levels of guanosine higher relative levels of suberic acid and lower relative levels of L-octanoylcarnitine and adipic acid in affected animals. In contrast, fecal microbiome and serum metabolome profiles showed comparatively limited variation across groups. Although limited by small sample size, this study provides preliminary, descriptive observations on microbiome and metabolome features associated with MPPD in captive red kangaroos. These findings offer an initial framework to inform future hypothesis-driven investigations using larger cohorts.}, } @article {pmid41587576, year = {2026}, author = {Mburu, D and Kumar, S and Wang, Y and Namagerdi, AA and Bai, K and Ali, B and Minalla, A and Gonzales, KO and Abdelhalim, KA}, title = {The oxalobiome: unraveling the role of gut microbiota in oxalate metabolism and its implications for kidney health and disease management.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {584}, number = {}, pages = {120852}, doi = {10.1016/j.cca.2026.120852}, pmid = {41587576}, issn = {1873-3492}, abstract = {The oxalobiome, comprising microbial communities involved in oxalate metabolism, plays a critical role in maintaining oxalate homeostasis and preventing associated health issues, particularly calcium oxalate nephrolithiasis. Key organisms, notably Oxalobacter formigenes, are essential for degrading oxalate, yet their abundance is influenced by factors such as diet, genetics, and antibiotic use. Recent advances in research have elucidated the complex interactions between the gut microbiome and oxalate metabolism, highlighting the potential for therapeutic interventions. Innovative strategies, including RNA interference therapies (e.g., lumasiran, nedosiran), engineered probiotics, and gene-editing technologies, show promise in managing conditions like primary hyperoxaluria. However, challenges remain, including limitations in oxalate measurement techniques and variability in microbial populations. Multi-omics approaches and metagenomic analyses have enhanced our understanding of the oxalobiome, revealing novel microbial taxa and metabolic pathways involved in oxalate degradation. Despite the potential of emerging therapies, clinical translation is still in its infancy, necessitating further research to establish efficacy and safety. Future studies should focus on mechanistic insights, standardized methodologies, and targeted microbiome-based therapies to optimize management strategies for hyperoxaluria and related systemic diseases. A comprehensive understanding of the oxalobiome is essential for developing precision medicine approaches that effectively address oxalate dysregulation and improve patient outcomes.}, } @article {pmid41587553, year = {2026}, author = {Zecher, BF and Schramm, C}, title = {[Immunopathogenesis and therapy of primary sclerosing cholangitis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {64}, number = {1}, pages = {56-66}, doi = {10.1055/a-2730-4719}, pmid = {41587553}, issn = {1439-7803}, support = {493624519, FOR 5086, TP6, Nr. 429191104, FOR SOMACROSS, TP1, Nr. 445297796, SFB1700, Projekt 530990199//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Cholangitis, Sclerosing/immunology/therapy/diagnosis ; Inflammatory Bowel Diseases/immunology/therapy ; Evidence-Based Medicine ; }, abstract = {Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the biliary tract for which no prognosis-improving therapies are yet available. PSC is characterized by genetic risk factors, alterations in the microbiome and pathological immune activation leading to the development of biliary fibrosis. Cholangiocytes play an active role in the inflammatory processes, as they interact directly with the microbiome and immune cells. The concomitant chronic inflammatory bowel disease has a distinct phenotype and causes a reciprocal modulation of intestinal and hepatic disease activity via changes in the intestinal barrier and the enterohepatic circulation of bile acids. While the currently available drugs and endoscopic treatment options are only symptomatically effective, new pharmacologic therapies are under clinical evaluation. In this review, we aim to provide an insight into the current understanding of the pathogenesis of PSC and new therapeutic developments.}, } @article {pmid41587124, year = {2026}, author = {Berthet, L and Tardiveau, C and Roy, M and Viennois, E}, title = {Oral Gavage in Neonatal Mouse Pups and Functional Assessment of Gut Barrier Integrity Using Ussing Chambers.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {227}, pages = {}, doi = {10.3791/69751}, pmid = {41587124}, issn = {1940-087X}, mesh = {Animals ; Mice ; Animals, Newborn ; Administration, Oral ; *Colon/metabolism/physiology ; Permeability ; *Intestinal Mucosa/metabolism ; Female ; }, abstract = {Growing evidence underscores the importance of the first 1,000 days of life in shaping the gut-microbiome axis. This early-life window is critical in the establishment of long-term physiological trajectories and immunological adaptations, potentially influencing susceptibility to diseases linked to dysbiosis and barrier dysfunction. A deeper understanding of the underlying mechanisms requires a comprehensive assessment of key physiological parameters, including paracellular and transcellular permeability of the neonatal gut. Evaluating these parameters is essential to elucidate how early exposures to exogenous molecules may influence gut integrity and long-term health outcomes. Therefore, the first part of this article describes the oral administration of molecules of interest in mouse pups as early as day of life 6, while minimizing stress, risk of injury, and cannibalism. Lubricated, rounded-tip 24-G feeding needles are used to gavage mouse pups weighing a minimum of 2.5 g. The second part outlines the ex vivo assessment of paracellular and transcellular permeability using Ussing chamber assays on colonic samples from pups between DOL-10 and weaning. Pinless sliders adapted for small biopsies are used in combination with Ussing chambers to mount neonatal colonic samples. The paracellular probe FITC-Dextran 4 kDa and the transcellular marker horseradish peroxidase 44 kDa Type VI are added to the apical compartment of the system at the start of the assay. Samples are collected in the basolateral compartment at 0 min, 30 min, 60 min, 90 min, and 120 min to quantify probe passage. The passage of both markers is quantified directly (FITC) and indirectly (HRP) by a plate reader, calculated using standard curves, and expressed as flux.}, } @article {pmid41586772, year = {2026}, author = {Peh, A and Dinakis, E and Nakai, M and Muralitharan, RR and Rupasinghe, S and Wilson, JL and Wong, CHY and Jama, HA and Barker, CMO and Modarresi, M and Kemp-Harper, BK and Zheng, T and Marques, FZ and Broughton, BRS}, title = {Gut bacteria presence in the brain is increased after ischemic stroke in mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2617694}, doi = {10.1080/19490976.2026.2617694}, pmid = {41586772}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Brain/microbiology/pathology ; *Ischemic Stroke/microbiology ; Male ; *Bacteria/isolation & purification/classification/genetics ; Bacterial Translocation ; Mice, Inbred C57BL ; Blood-Brain Barrier/microbiology ; Disease Models, Animal ; Infarction, Middle Cerebral Artery/microbiology ; Germ-Free Life ; Lipopolysaccharides/metabolism ; }, abstract = {Systemic infections are a common cause of complications and death after stroke. These infections can occur due to the breakdown of the gut epithelial barrier and the translocation of bacteria from the gut to peripheral systemic tissues. However, it remains unclear whether gut bacteria also translocate to the brain and contribute to stroke-induced neuronal damage. In this study, we observed a significant number of peptidoglycan- and lipopolysaccharide-positive bacteria in the ischemic hemisphere of mice subjected to either photothrombotic (PT) stroke or middle cerebral artery occlusion (MCAO). In contrast, no bacteria were observed in the ischemic brains of germ-free mice following MCAO. Absolute quantification via PCR also revealed increased bacteria in the ischemic hemisphere and blood of PT mice. Bacterial translocation to the brain is associated with the breakdown of the gut-epithelial and blood-brain barriers. Although inhibition of sympathetic tone reduces gut-epithelial barrier permeability, the bacterial load in the brain and functional deficits poststroke, it does not affect cerebral apoptosis, neuroinflammation or infarct volume. Collectively, these findings indicate that activation of the sympathetic nervous system after stroke promotes the migration of gut-derived bacteria into the ischemic brain, and this process worsens motor function in mice.}, } @article {pmid41586591, year = {2026}, author = {Sui, X and Shi, C and Song, M and Jiang, W and Li, S and Geng, J and Xu, J and Zhang, Y and Zhu, X and Cai, Y and Li, B and Wang, H and Dong, D and Teng, H and Li, Y and Wang, W}, title = {Sex-biased associations between gut microbiota and hematologic toxicity of neoadjuvant chemoradiotherapy in locally advanced rectal cancer.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000004688}, pmid = {41586591}, issn = {1743-9159}, abstract = {BACKGROUND: Compared to male cancer patients, female patients have a higher incidence and severity of adverse events (AEs) associated with anticancer treatment. The mechanism underlying these disparities is largely unknown, especially in the context of radiotherapy. Notably, the composition and metabolism of the gut microbiota differ between sexes, and such differences have been implicated in multiple physiological and pathological processes. In this study, we aimed to investigate the sex differences in hematologic toxicities during chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and to explore the potential role of the gut microbiota in mediating these differences.

MATERIALS AND METHODS: This real-world study included 329 patients with LARC receiving neoadjuvant chemoradiotherapy (nCRT). Hematologic AEs were evaluated according to Common Terminology Criteria for Adverse Events 5.0. 16S rRNA sequencing, metatranscriptome sequencing, and metabolome detection were performed on longitudinal fecal samples. Mendelian randomization analyses were performed to investigate the correlation between stem cell and gut microbial traits.

RESULTS: In this cohort, females had a higher severity of hematologic AEs than males. Using integrated longitudinal multi-omics data, we identified sex-biased bacterial species (e.g., Parasutterella excrementihominis and Bifidobacterium adolescentis) and microbiota-mediated arginine metabolism associated with hematologic toxicities. Gut microbiome-mediated arginine metabolism is associated with an abundance of hematopoietic stem cells and may be involved in the occurrence of sex-biased radiotherapy-induced hematologic AEs.

CONCLUSION: These results indicate that the differences in gut microbial composition and metabolism between the two sexes are associated with the sex-biased hematologic AEs induced by nCRT. Females require greater attention regarding the hematologic toxicity of chemoradiotherapy, and that gut microbes may serve as potential targets for sex-tailored strategies to restore hematopoietic function following chemoradiotherapy.}, } @article {pmid41586590, year = {2026}, author = {Laursen, MF}, title = {Bifidobacterium infantis-a key (late) colonizer of the infant gut?.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0085125}, doi = {10.1128/msphere.00851-25}, pmid = {41586590}, issn = {2379-5042}, abstract = {Human milk oligosaccharide (HMO)-degrading Bifidobacterium species are key early colonizers of the gut and influence gut and immune maturation. Loss of these taxa, particularly Bifidobacterium infantis, in many industrialized populations has raised concern. O'Brien et al. showed that supplementation with B. infantis EVC001 in exclusively breastfed U.S. infants aged 2-4 months leads to rapid and abundant colonization that persists 1 month after supplementation, demonstrating effective colonization beyond the neonatal period (C. E. O'Brien, S. A. Frese, K. Cernioglo, K. Damian-Medina, et al., mSphere e00518-25, 2025, https://doi.org/10.1128/msphere.00518-25). These findings align with observational cohort data showing that B. infantis can overcome priority effects and dominate the gut microbiome in breastfed infants by 2-3 months of age. Key questions remain regarding colonization in mixed- or formula-fed infants, the HMO thresholds required to sustain dominance during milk- and complementary feeding, and the critical developmental windows of B. infantis colonization for beneficial immune effects. Ongoing clinical trials with B. infantis will further clarify its role in disease prevention.}, } @article {pmid41586525, year = {2026}, author = {Díaz-González, F and Rojas-Villalobos, C and Issotta, F and Reyes-Impellizzeri, S and Hedrich, S and Johnson, DB and Temporetti, P and Quatrini, R}, title = {Trait-based meta-analysis of microbial guilds in the iron redox cycle.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0148825}, doi = {10.1128/msystems.01488-25}, pmid = {41586525}, issn = {2379-5077}, abstract = {UNLABELLED: Microbial iron (Fe) redox cycling underpins key biogeochemical processes, yet the functional diversity, ecological roles, and trait architectures of iron-transforming microbes remain poorly synthesized across global environments. Here, we present a systematic review and trait-based meta-analysis of 387 microbial taxa spanning 314 studies and 76 years of research, integrating phenotypic, genomic, and environmental data to define ecologically coherent microbial iron redox cycle guilds. Rather than relying on taxonomy, our framework delineates first-order functional guilds-Fe(III) reducers, Fe(II) oxidizers, and dual-capacity Fe oxidizers/reducers-and resolves second-order guilds based on trait syndromes, such as acidophily, redox flexibility, or metabolic breadth. Trait profiling revealed that iron-cycling capacities frequently transcend phylogenetic boundaries, with multiple guilds converging in chemically stratified hotspots like hot springs, hydrothermal vents, and acid mine drainages. Dual-capacity Fe oxidizers/reducers (e.g., Acidithiobacillus ferrooxidans and Metallosphaera sedula) emerged as overlooked mediators of "cryptic" iron cycling, possessing genomic repertoires capable of toggling between oxidative and reductive modes in response to redox oscillations. Hierarchical clustering and kernel density analyses of ecophysiological traits highlighted niche partitioning along key environmental filters, including pH, iron availability, salinity, and temperature. Collectively, this work introduces the Guild Exploitation Pattern as a conceptual lens for understanding iron microbiome assembly, providing a data-driven foundation for predicting microbial contributions to iron cycling under changing environmental conditions.

IMPORTANCE: Iron redox reactions shape nutrient turnover, contaminant mobility, and primary productivity, yet the microbes driving these processes are often studied in isolation. By integrating decades of data into a trait-based guild framework, we reveal the ecophysiological diversity and niche differentiation of microbial iron redox cycling taxa across environments. Our synthesis exposes major gaps, such as limited trait data for >80% of dual-capacity Fe oxidizing/reducing species and highlights the need for functional trait surveys to complement metagenomics and cultivation efforts. The guild framework presented here advances predictive microbial ecology by linking metabolic traits with environmental gradients, offering a robust foundation for incorporating iron cycling into ecosystem models and biogeochemical forecasts.}, } @article {pmid41586524, year = {2026}, author = {Bloemen, B and Delvoye, M and Hoffman, S and Marchal, K and Vanneste, K and Fraiture, M-A and Roosens, NHC and De Keersmaecker, SCJ}, title = {Recovery and microbial host assignment of mobile genetic elements in complex microbiomes: insights from a spiked gut sample.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0128225}, doi = {10.1128/msystems.01282-25}, pmid = {41586524}, issn = {2379-5077}, abstract = {UNLABELLED: Mobile genetic elements (MGEs) are major drivers of horizontal gene transfer, including the spread of antimicrobial resistance (AMR) genes. However, determining the microbial host of an MGE in complex microbiomes remains challenging. Here, we spike a niche-aspecific Bacillus velezensis strain carrying a plasmid and linear phage-plasmid into a batch bioreactor simulating the human gut, and use it as a spike-in control to assess the performance of Hi-C sequencing and Oxford Nanopore Technologies (ONT)-enabled DNA methylation detection to identify MGE-host pairs. To improve recovery of low-abundance genomes, we used a novel ONT adaptive sampling (AS) strategy that depletes de novo assembled, sample-specific high-abundance contigs, rather than relying on reference genomes. This approach led to an approximately twofold enrichment of low-abundance replicons, including the spike-in strain. Methylation-based host assignment failed for the B. velezensis MGEs, likely due to the absence of DNA methylation. In contrast, Hi-C successfully linked the phage-plasmid to its host, but not the plasmid, likely due to non-intact cells, and only after removing artefactual signals through bioinformatic processing. For a native Escherichia coli strain, Hi-C and methylation data linked it to two plasmids. Selective isolation and whole-genome sequencing of both the native E. coli and spike-in B. velezensis then confirmed the metagenomic observations. Our results highlight that Hi-C and methylation data can provide powerful insights into MGE-host associations, but their interpretation requires careful computational analysis and biological validation. Moreover, our AS strategy offers a cost-efficient method to boost coverage of low-abundance genomes, improving metagenomic investigation of MGEs in complex microbiomes.

IMPORTANCE: Mobile genetic elements are important contributors to horizontal gene transfer, including of antimicrobial resistance genes. Understanding which microbes carry these mobile elements is vital to assess the spread of resistance. Here, we use a nanopore adaptive sampling approach to increase detection of low-abundance bacteria and mobile elements and use DNA methylation detection and Hi-C sequencing to determine mobile element hosts. By introducing a known bacterium and isolating a native strain, we could evaluate the performance of these methods, indicating that although powerful, they require careful experimental design, interpretation, and validation. However, when combined, these approaches enable a comprehensive investigation of mobile elements and gene transfer dynamics in complex environments.}, } @article {pmid41586522, year = {2026}, author = {Ndlovu, KS and Pavan, RR and Corry, J and Gregory, AC and Mahamed, S and Zotova, N and Tabala, M and Babakazo, P and Funderburg, NT and Yotebieng, M and Klatt, NR and Kwiek, JJ and Sullivan, MB}, title = {The vaginal microbiome of pregnant people living with HIV on antiretroviral therapy in the Democratic Republic of Congo: a pilot study and global meta-analysis.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0059725}, doi = {10.1128/msphere.00597-25}, pmid = {41586522}, issn = {2379-5042}, abstract = {UNLABELLED: Recent studies reveal that a suboptimal vaginal microbiome (VMB), including the enrichment of anaerobic bacteria associated with multiple female genital disorders, is linked to adverse pregnancy and birth outcomes in pregnant people. Problematically, however, the majority of the available data, to date, is biased toward highly developed, Global North countries, leaving underrepresented populations like the Democratic Republic of the Congo (DRC) poorly characterized. Here, we investigate the VMB from a cohort of 82 pregnant people living with human immunodeficiency virus (PLWH) on antiretroviral therapy (ART) from the DRC. Specifically, we explore the associations between the VMB via 16S rRNA gene sequencing and maternal peripheral immune factors. Additionally, we compare the VMB of pregnant PLWH-ART from DRC with publicly available VMB data (5 studies, 1861 samples) in a meta-analysis to elucidate the impact of HIV on the VMB. Combined, these analyses revealed the differences in community structure and predicted function of the microbiota between pregnant PLWH-ART and pregnant people without HIV (PWoH). Taxonomically, the VMB of DRC PLWH-ART were enriched for Lactobacillus iners-dominated VMBs (53%) or a diverse, polymicrobial VMB, that is, bacterial vaginosis (BV) (43%). Functional predictions made from these taxa suggested that protein-coupled receptors, amino sugar and nucleotide sugar metabolism, fatty acid metabolism, and polycyclic aromatic hydrocarbon degradation pathways were differentially abundant between the communities. Correlation with host plasma immune factors revealed putative links between some VMB metrics (e.g., alpha diversity and species abundance) that have been linked to adverse pregnancy and birth outcomes.

IMPORTANCE: Human immunodeficiency virus (HIV) remains prevalent in sub-Saharan Africa, where it has been linked to adverse birth outcomes. Suboptimal vaginal microbiomes (VMBs) have shown similar links. This pilot study fills critical gaps in understanding how HIV interacts with the pregnant VMB in populations underrepresented in microbiome research, like the Democratic Republic of the Congo (DRC). We identified maternal systemic immune factors associated with suboptimal VMBs that have been linked to poor birth outcomes. In a global meta-analysis, we found significant taxonomic and functional differences in the VMBs between pregnant people living with and without HIV, revealing potential biomarkers that increase the risk of adverse birth outcomes. These findings provide crucial insights into VMB features that may influence pregnancy health in PLWH-ART, guiding future research and tailored interventions to support safer pregnancies in the DRC and similar populations.This study is registered with NCT03048669.}, } @article {pmid41586519, year = {2026}, author = {Lubkin, A and Lujan, RA and Pontejo, SM and Oikonomou, V and Fellows, AM and Dos Santos Dias, L and Snarr, BD and MacAlpine, J and Sullivan, KD and Espinosa, JM and Hickman, H and Lionakis, MS}, title = {The Dp16 Down syndrome mouse model does not exhibit oral interferon-gammopathy or susceptibility to oral candidiasis.}, journal = {mBio}, volume = {}, number = {}, pages = {e0387325}, doi = {10.1128/mbio.03873-25}, pmid = {41586519}, issn = {2150-7511}, abstract = {Down syndrome, or Trisomy 21, is associated with excessive interferon (IFN) signaling and concomitant susceptibility to both autoimmunity and immunodeficiency. One of the many clinical phenotypes observed in people with Down syndrome is increased risk for oral candidiasis. Because oral candidiasis can be caused by excessive IFN-γ signaling, we asked whether IFN-gammopathy could be playing a role in susceptibility to oral candidiasis in Down syndrome. We used the Dp16 mouse model of Down syndrome, which displays mild systemic interferonopathy, to model oral candidiasis. We found that the Dp16 model does not exhibit oral IFN-gammopathy and is not susceptible to oral candidiasis. We exposed the Dp16 mice to various inflammatory and infectious stimuli with the goal to induce enhanced local IFN-γ responses, but these did not induce oral IFN-gammopathy or promote susceptibility to oral candidiasis. We conclude that the Dp16 model is not well-suited to study oral IFN-gammopathy or oral candidiasis. Clinical studies of oral candidiasis in people with Down syndrome are warranted.IMPORTANCEDown syndrome, caused by three copies of chromosome 21, presents with different medical conditions in different people. One such condition for some people with Down syndrome is increased susceptibility to oral infection with the fungus Candida albicans. C. albicans is a normal member of the human oral microbiome, but it can also cause painful infections. Down syndrome causes an excess of inflammatory molecules called interferons (IFNs). Excessive inflammation due to one type of IFN, IFN-γ, can cause susceptibility to oral C. albicans infection in certain settings. Thus, we wanted to assess whether excessive IFNs may cause susceptibility to oral C. albicans infection in Down syndrome. We used the Dp16 mouse model of Down syndrome. We found, however, that Dp16 mice did not exhibit excessive IFN-γ oral mucosal responses and were not susceptible to oral C. albicans and thus are not a suitable model for studying this phenomenon.}, } @article {pmid41586429, year = {2025}, author = {Pelton, R}, title = {Postbiotic Metabolites: A Paradigm Shift in Microbiome Science.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {24}, number = {6}, pages = {16-19}, pmid = {41586429}, issn = {1546-993X}, } @article {pmid41586376, year = {2025}, author = {Ramadan, M and Amin, IA and Ali, ME and Abdelbary, ER and Hetta, HF and Alatawy, R and Alanazi, FE and Alattar, A and Alshaman, R and Alatawi, Y and Salah, M}, title = {The gut microbiome in diabetic patients with hepatocellular carcinoma: distinct bacterial compositional shifts after hepatitis C virus eradication.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1693345}, pmid = {41586376}, issn = {1664-302X}, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) poses a major global health burden, and diabetic patients remain at high risk even after achieving a sustained virological response (SVR) to hepatitis C virus (HCV) with direct-acting antivirals (DAAs). Gut microbiome dysbiosis is implicated in this heightened risk, but the microbial characteristics and underlying mechanisms remain poorly understood.

METHODS: We conducted a cross-sectional study of 81 adults divided into three groups (n = 27 each): (1) diabetic patients with HCC after SVR (DHCC), (2) diabetic patients without HCC after SVR, and (3) healthy controls. Stool samples and clinical data were collected approximately 3 years post-SVR. Microbial diversity, taxonomic composition, and predicted metabolic functions were analyzed and correlated with clinical markers of liver disease.

RESULTS: DHCC patients exhibited marked microbial dysbiosis, including reduced alpha diversity (Chao1, p = 0.003) and significant ecological disruption (Kruskal-Wallis, p < 0.001). The key features included enrichment of Treponema_2 (log₂FC = 7.71, padj < 0.001) and Klebsiella (AUC = 0.88) and depletion of the butyrate-producing genus Faecalibacterium (2.08% vs. 9.99% in controls, p = 0.006). Functional analysis revealed a 56% reduction in butyrate synthesis and a 3.2-fold increase in lipopolysaccharide biosynthesis. These shifts correlated with clinical severity: Treponema_2 abundance was associated with hepatic encephalopathy and AST levels, whereas reduced butyrate inversely correlated with FIB-4 scores. Random forest modeling identified Klebsiella, Enterobacter, and Megasphaera as the top predictors of DHCC.

CONCLUSION: Diabetic patients with HCC after HCV eradication exhibit a persistent gut microbiome signature characterized by proinflammatory and carcinogenic features. These findings highlight potential targets for microbiome-based risk stratification and therapeutic interventions in this high-risk population.}, } @article {pmid41586374, year = {2025}, author = {Zhu, FC and Yang, YB and Yin, QJ and Chen, XY and Yu, S}, title = {Comparison of intestinal and environmental microbiota of the snapping shrimp (Alpheus brevicristatus) in a seagrass bed.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1735708}, pmid = {41586374}, issn = {1664-302X}, abstract = {Symbiotic bacteria associated with benthic invertebrates in seagrass beds play an important role in mediating host adaptability and maintaining ecosystem health; however, the taxonomic composition and functional characteristics of the symbiotic microbiota in these invertebrates remain poorly understood. In this study, the intestinal microbiota of seagrass bed-associated snapping shrimp Alpheus brevicristatus was characterized, and their composition was further compared with that of surrounding seawater and sediment using 16S amplicon sequencing. Our results revealed that the intestinal microbiota were dominated by unclassified Alphaproteobacteria and Vibrio. Compared to that of the environment, the microbiota of shrimp intestines showed lower alpha diversity, yet distinct microbial assemblages. Shrimp intestinal microbiota shared more species with sediment than seawater microbiota, suggesting sediment as a primary microbial source. Beta diversity analysis showed marked differences in microbial structure among habitats. The neutral community model and null model analyses indicated that stochastic processes exerted a significant influence on intestinal microbiome assembly. These findings highlight the complex interplay between host physiology and environmental exposure in shaping intestinal microbiota, providing foundational insights into host-microbe-environment interactions in benthic marine invertebrates.}, } @article {pmid41586372, year = {2025}, author = {Fang, L and Luo, B and Danzen, D and Yang, L and Gao, Y and Ni, Z and Wang, J and Duoji, Z and Ci, Y and Suolang, W and Ge, W and Basang, Z}, title = {Investigation into skin physiological parameters and mocroflora characteristics of melasma population in Lhasa China.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1614050}, pmid = {41586372}, issn = {1664-302X}, abstract = {Melasma is a skin disease characterized by symmetrical pigmentation, mainly occurring in the exposed areas of the face, which has some relationship with skin parameters and bacterial diversity. High-altitude regions experience elevated ultraviolet (UV) radiation, potentially influencing skin parameters and microbial characteristics in melasma. To explore the inherent law of the melasma mechanism in high altitude, the hereditary Tibetans at high altitude in Lhasa, Tibet were investigated. Skin physiological parameters such as skin sebum (SM), corneum moisture content (CM), pH, trans epidermal water loss (TEWL), skin erythema index (E), melanin (M), individual typology angle (ITA) and so on, were measured and the microbiome characteristics were sequenced and analyzed. The results showed that among 302 participants, 36 were diagnosed with melasma (mean prevalence: 11.92%). Prevalence was significantly higher in females (16.67%) than males (2.04%), peaking in females aged 31-40 years (37.50%). Melasma patients exhibited significantly lower pH and higher M values compared to controls (p < 0.05). Community diversity analysis of alpha and beta of skin bacteria and fungi showed that the abundance, diversity, and flora composition in melasma population were basically the same as that of control population (p > 0.05). Species analysis of intergroup differences showed that the bacteria were dominated by the genera of Cutibacterium, Staphylococcus and so on, but it was no statistical significance, while Malassezia. Aspergillus, Aureobasidium, and Penicillium were the dominant genera of fungi at the genus level, with Aspergillus and Aureobasidium larger in the melasma group than the control group (p < 0.05). Correlation analysis showed that there were significant differences between the flora characteristics and the parameters of ITA, TEWL, pH, and E, M, SM, which may has the association with the formation of melasma. The ROC analysis assessing fungi such as Aspergillus, Aureobasidium as a predictor of melasma yielded an AUC of 0.798, 0.828, indicating fair discriminatory ability. These findings demonstrate that high altitude hereditary Tibetan melasma population in Tibet has diverse skin parameters and microflora structural features. The strong correlation between microflora characteristics, skin parameters, and melasma prevalence provides a new foundation for research on the prediction, prevention, and treatment of dermatological conditions in high-altitude populations.}, } @article {pmid41586371, year = {2025}, author = {Zimmermann, SD and Taschen, E and Robin, A and Calvo-Polanco, M}, title = {Editorial: Advancing mycorrhizal research for sustainable ecosystem and agricultural practices.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1760087}, pmid = {41586371}, issn = {1664-302X}, } @article {pmid41586370, year = {2025}, author = {Zeng, B and Peng, X and Xiao, P and Nie, K and Zhang, G and Xia, L}, title = {Salt sensitivity potentiates high-salt diet-induced intestinal barrier disruption and gut microbiome dysbiosis in rats.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1718782}, pmid = {41586370}, issn = {1664-302X}, abstract = {INTRODUCTION: The high-salt diet is a prevalent eating habit associated with health risks. This study investigated the impact of high salt on intestinal barrier disruption and gut microbiome dysbiosis using Wistar and Dahl salt-sensitive rat models.

METHODS: Rats were fed a normal diet or a high-salt diet for eight weeks. Body weight and plasma inflammatory cytokines were monitored in the study. Colon tissue damage was assessed via histopathological examination, and metagenomic sequencing was utilized to analyze alterations in microbial composition, functional pathways, and biodiversity.

RESULTS: The results indicated that high salt significantly elevated pro-inflammatory cytokine levels and induced structural damage in the colon. Metagenomic analysis revealed that high salt concentrations resulted in approximately a 15% difference in microbial species composition. And led to a decrease in Alpha diversity, along with an increase in the Firmicutes/Bacteroidetes ratio. Taxon-specific alterations included reduced abundance of Lactobacillus and Clostridium, and increased abundance of Enterobacter and Bifidobacterium. Correlation analyses further revealed a positive correlation between Bifidobacterium abundance and tumor necrosis factor-α level in Dahl salt-sensitive rats.

DISCUSSION: This study illuminates the gut microbiota's role in salt-sensitivity and provides a foundational basis for developing microbiota-targeted interventions for at-risk individuals.}, } @article {pmid41586364, year = {2025}, author = {Garcia-Gutierrez, E and Arbulu, S and Oliver, C and Kumar, S and Dam, SA and Jakobi, B and Pennone, V and Sarda, FAH and Mukherjee, A and Cotter, PD}, title = {GutMicrobiotAware: an international exploratory survey on awareness and understanding of the gut microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1643257}, pmid = {41586364}, issn = {1664-302X}, abstract = {Over the past two decades, scientific understanding of the composition and function of the human gut microbiome has expanded substantially. The recent surge in human gut microbiota-related studies has unveiled the profound influence of the gut microbiota on host nutrition, health, and behavior, bridging biology, medicine, and ecology, among others. The dynamic interaction between daily lifestyle choices, life events, and the gut microbiota makes it understandably, a topic of interest among the lay public. Communicating scientific insights from the laboratory to the population effectively, however, can be challenging, and might involve adapting the delivery of knowledge to different audiences, using precise language in corresponding settings and the use of more accessible concepts in public forums such as science festivals or social media. With the growing interest in gut microbiota beyond academic circles, there is also an increased risk of disseminating information lacking scientific rigor. The current study aimed to assess the general knowledge regarding the gut microbiota among an exploratory pool of participants, primarily accessed via academic and social networks, and evaluate healthcare professionals' understanding of its links to various health conditions, ultimately informing better communication strategies for both groups. Our findings from this exploratory survey indicate that while most participants were familiar with the gut microbiota, instances of partial and even complete misconceptions persisted. The results from our survey further underlined the need for targeted scientific communication to emphasize the microbial diversity of the gut microbiota, the factors influencing it, its links to health conditions, and the realistic scope of current microbiota analyses.}, } @article {pmid41586314, year = {2025}, author = {Schmandt, C and Llukovi, E and Capossela, S and Wettstein, R and Valido, E and Gamba, M and Perret, C and Stoyanov, J and Bertolo, A}, title = {The association between pressure injury microbiome and wound healing: a systematic review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1703418}, pmid = {41586314}, issn = {2235-2988}, mesh = {Humans ; *Wound Healing ; *Pressure Ulcer/microbiology ; *Microbiota ; Bacteria/classification/genetics/isolation & purification ; Bacterial Infections/microbiology ; }, abstract = {INTRODUCTION: Pressure injuries (PIs) are a significant clinical problem, particularly in elderly, bedridden, and spinal cord injury patients. Bacterial infections are a primary complication that often delays or prevents wound healing. This systematic review analysed the current evidence on the role of the PI microbiome in wound healing outcomes.

METHODS: A systematic search was conducted in three online databases, namely Embase, Medline, and Web of Science (latest search October 2024). In total, 20 studies met the inclusion criteria, of which three were interventional (randomised controlled trials (RCTs), n=2; pre-post study, n=1), and 17 were observational study designs (retrospective, n=6; prospective, n=8; and case-control, n=3) comprising 1'015 study participants (with 1'034 PIs). These studies examined the PI microbiome, mostly at PI grades III and IV, using culture-based and next-generation sequencing (NGS) techniques. Data extraction focused on microbial diversity, predominant species, and their association with wound healing. The risk of bias was categorised as moderate, mostly due to the absence of sample size justification, as assessed by the NHLBI tool.

RESULTS: The findings confirmed that Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus spp., and Escherichia coli dominated the PI microbiomes. Microbiome composition varied according to PI severity and anatomical location. Molecular techniques have identified a more diverse microbiome than culture-based methods. Although no specific bacterial taxa have been found to be favourable for wound healing, many taxa were found to be detrimental to PI development, including Anaerococcus, Finegoldia, and Acinetobacter. Antibiotic resistance was common, particularly in S. aureus. Interventions targeting the microbiome, such as debridement and platelet-rich plasma therapy, have been shown to improve healing rates.

DISCUSSION: In conclusion, evidence showed that the composition of the PI microbiome might negatively associate to wound healing, with the dominance of anaerobes associated with delayed healing. Therefore, future PI treatments should prioritise patient-centred approaches that integrate advanced microbial profiling with rigorous clinical evaluation to optimise chronic wound management.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024575143.}, } @article {pmid41586308, year = {2025}, author = {Wang, X and Ye, L and Liu, Y and Li, H and Shi, H and Zheng, L}, title = {Metagenomic analysis reveals severity-dependent microbial succession and correlation with host inflammatory response in oral and maxillofacial space infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1695928}, pmid = {41586308}, issn = {2235-2988}, mesh = {Humans ; Cross-Sectional Studies ; *Metagenomics ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Microbiota/genetics ; Aged ; Severity of Illness Index ; *Bacteria/classification/genetics/isolation & purification ; Adult ; *Inflammation/microbiology ; *Abscess/microbiology ; }, abstract = {BACKGROUND: Oral and maxillofacial space infections (OMSI) vary widely in clinical severity, yet the relationships between microbial community patterns in the abscess niche and host inflammatory responses remain incompletely characterized.

METHODS: We conducted a retrospective, cross-sectional, severity-stratified study of 197 patients diagnosed with OMSI between January 2020 and November 2023. Patients were stratified into mild (n=90), moderate (n=41), and severe (n=66) groups based on established clinical criteria. We performed mNGS on abscess pus samples to characterize the microbial community composition and assessed associations between these features and systemic inflammatory markers.

RESULTS: Although α-diversity did not differ significantly among severity groups, β-diversity analysis revealed distinct microbial communities. Pairwise analyses indicated a threshold-like community shift, characterized by a significant divergence between mild and severe infections, while the moderate group exhibited an intermediate composition that overlapped with both. Severe infections were characterized by an enrichment of Prevotella. Furthermore, analysis of predominant taxa (>30% abundance) revealed considerable microbial heterogeneity, challenging a simple monoinfection model. Notably, a machine learning-identified microbial profile comprising Streptococcus, Corynebacterium, and Pseudomonas was significantly correlated with elevated systemic inflammatory markers.

CONCLUSION: This study characterizes associations between abscess-site microbial communities and host inflammatory profiles across OMSI severity strata. Given the cross-sectional design and the lack of an external validation cohort, the present findings should be interpreted as exploratory and non-causal. Future multicenter prospective studies including independent validation cohorts are warranted to test reproducibility and to evaluate whether any candidate features possess generalizable predictive value.}, } @article {pmid41586247, year = {2025}, author = {Erickson, A and Bellampalli, S and Beyder, A}, title = {Edible evolution: the significance of food additives in shaping human health.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1717352}, pmid = {41586247}, issn = {2296-861X}, abstract = {Human diets have transitioned through distinct stages, from foraging to agriculture, domestication, and industrialization, that progressively altered food composition, availability, and ecological context. While these shifts enhanced food security and shelf life, they also narrowed dietary diversity and layered non-nutritive components ranging from salt and fermentation by-products to synthetic dyes, preservatives, artificial flavors, and non-caloric sweeteners onto ancestral nutritional frameworks. This review traces the historical integration of such compounds, situating them within broader dietary transitions to highlight how technological innovations gradually distanced human diets from their evolutionary origins. Drawing on nutritional anthropology, archaeogenomics, and ecological perspectives, we examine how these changes reshaped gut health, microbial diversity, and long-term disease risk. By framing non-nutritive additives within the long arc of dietary evolution, this perspective provides context for understanding the rise of modern, ultra-processed food systems and underscores the importance of integrating evolutionary and ecological evidence into contemporary nutrition and gastrointestinal research.}, } @article {pmid41586159, year = {2025}, author = {Yang, Y and Hernandez, MC and Chitre, S and Jobin, C}, title = {Emerging Roles of Modern Lifestyle Factors in Microbiome Stability and Functionality.}, journal = {Current clinical microbiology reports}, volume = {12}, number = {}, pages = {}, pmid = {41586159}, issn = {2196-5471}, support = {R01 CA252045/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: It is now evident that the microorganisms living on and inside the human body modulate a myriad of host responses and activities. Particularly, the intestinal microbiota, which comprises diverse bacteria, fungi, archaea, viruses, and eukaryotic entities, forms a close relationship with the host. This relationship is essential for optimal biological function such as maintaining proper immune homeostasis, host metabolism, and prevention of pathogens colonization. The human gut microbiome is relatively stable after 3 years of age but is subjected to influences from diet, environment and lifestyle factors. This review covers recent findings on how lifestyle factors associated with modern society might affect the microbiome.

RECENT FINDINGS: Modern lifestyle factors including circadian rhythm disruption, sleep deprivation, exercise and stress impact the gut bacterial community (bacteriome) composition and function. The resultant gut bacteriome changes contribute to host metabolism dysregulation, inflammatory diseases and cancer development associated with these lifestyle factors.

SUMMARY: Lifestyle factors influence the gut bacteriome to modulate host health and disease risks. Understanding the mechanistic roles of diverse host-associated microorganisms played in lifestyle factors-associated disease risks holds the promise for developing novel approaches to alleviate the detrimental effects.}, } @article {pmid41585896, year = {2025}, author = {Jiang, H and Hu, XW and Deng, X and Huang, XJ and Chen, YL and Yang, YF and Du, Y and Ji, S and Tang, DQ}, title = {Liuwei Dihuang pills ameliorate renal injury in experimental type 2 diabetes mellitus rat by regulating host-gut microbiota interaction.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1715600}, pmid = {41585896}, issn = {1663-9812}, abstract = {BACKGROUND: Liuwei Dihuang pills (LW) are widely used as the traditional tonic prescription for the treatment of diabetes and diabetic kidney disease (DKD). This study aimed to investigate the potential mechanism underlying LW-mediated prevention and treatment of DKD from the perspective of host-gut microbiome co-metabolism.

METHODS: A rat model of DKD was established using high-fat diet and streptozotocin. Levels of type IV collagen (Col IV), fibronectin (FN), laminin (Lam), transforming growth factor-β (TGF-β), SMAD family member 7 (SMAD7), and SMAD3 in the kidneys were determined by real time-polymerase chain reaction and Western blot. Fecal metabolites were profiled using ultra-high-performance liquid chromatography-tandem mass spectrometry. Metagenomic sequencing of the feces was performed using high-throughput sequencing.

RESULTS: When combined with metformin (MET)-based therapy, LW significantly improved serum creatinine and blood urea nitrogen levels, kidney index, 24-h urine volume, urine protein content and excretion rate, and urinary creatinine and cystatin C levels. It also attenuated morphological changes. Correspondingly, LW intervention reduced the renal expression of TGF-β, SMAD3, Col IV, LAM, FN, interleukin (IL)-6, and IL-1β, while increasing SMAD7 expression. Additionally, it normalized metabolic pathway abnormalities in galactose, butyric acid, fructose, mannose, amino sugar, and nucleotide sugar metabolism. Moreover, LW regulated bacterial imbalances, notably in specific species such as Allobaculum unclassified, Escherichia coli, Pseudoflavonifractor capillosus, Desulfovibrio porci, Oscillibacter sp. CU971, Parablautia muri, Phocaeicola dorei, Phocaeicola faecalis, Phocaeicola vulgatus, and Raoultella unclassified.

CONCLUSION: The combination of LW and MET ameliorated renal impairment in DKD rats by regulating the TGF-β/SMAD signaling pathway, metabolic disturbances in endogenous metabolites, and gut microbiota dysbiosis.}, } @article {pmid41585816, year = {2026}, author = {Fang, L and Cheng, S and Zuo, C and Zhang, L}, title = {Alterations of the Gut Microbiome in Psoriasis before and after Treated with Secukinumab.}, journal = {Indian journal of dermatology}, volume = {71}, number = {1}, pages = {36-43}, pmid = {41585816}, issn = {1998-3611}, abstract = {BACKGROUND: Psoriasis is a chronic inflammatory skin disease linked to immune system. Despite its prevalence, the precise aetiology and pathogenesis of psoriasis remain elusive. This study aimed to assess the efficacy and safety of Secukinumab while exploring its impact on the intestinal microbiota in patients with moderate-to-severe plaque psoriasis.

MATERIALS AND METHODS: We recruited 60 healthy controls and 110 patients with moderate-to-severe plaque psoriasis who attended outpatient clinics between June 2022 and June 2023. Clinical data (gender, age, BMI, PASI score, PGA, DLQI, Itch NRS, and STAI score) and faecal samples were collected from all groups. Faecal samples underwent PacBio Full-Length Diversity Sequencing and subsequent informatics analysis.

RESULTS: Patients were randomly assigned to two groups: Before Secukinumab treatment group (BT, n = 55), After 24 weeks of Secukinumab treatment group (AT, n = 55). Control group (Con) consisting of healthy individuals matched for age, sex, and body mass index (n = 60). Following 24 weeks of Secukinumab treatment, significant reductions in PASI score, PGA, DLQI, Itch NRS, and STAI score were observed in psoriatic patients (P < 0.05). The microbial diversity and composition in the AT group exhibited substantial alterations compared to the BT and Con groups, typified by an elevated abundance of Agathobacter and Anaerobutyricum and a diminished presence of Bacteroides and Phocaeicola.

CONCLUSION: The changes in gut microbiota occur at a slower pace than cutaneous manifestations, necessitating prolonged follow-up and microbiome-based investigations in Secukinumab-treated psoriasis patients to substantiate its therapeutic efficacy.}, } @article {pmid41585514, year = {2025}, author = {Wei, C and Chen, Z}, title = {Comprehensive genome analysis uncovers the diversity of jumbo phages in the pig gut microbiome.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1697229}, pmid = {41585514}, issn = {2297-1769}, abstract = {Gut microbiome research has historically focused on bacterial communities. In contrast, the roles of viruses, especially jumbo phages, remain poorly understood. Jumbo phages are of major interest because their large genomes encode unique functions that can influence host metabolism and ecosystem dynamics. This study bridges this gap by identifying 1,545 jumbo phage genomes from 450 pig gut metagenomes. Using CRISPR spacer analysis, we predicted archaeal or bacterial hosts and reconstructed competitive phage networks within this ecosystem. Phylogenetic divergence combined with orthologous protein comparisons supported establishing 14 novel jumbo phage families. Functionally, 10 of these novel families encode auxiliary metabolic genes (AMGs) that enhance host metabolism alongside anti-defense systems including DNA methyltransferases, HNH endonucleases, and glycosyltransferases. Ecological interactions were further elucidated through co-abundance networks (n = 857 pairs) and CRISPR spacer matching (n = 425 pairs), revealing relationships between novel jumbo phages and other jumbo phages. Collectively, this work expands genomic resources for pig gut viromes and delivers new insights into jumbo phages' functional capabilities, host associations, and global prevalence.}, } @article {pmid41585492, year = {2026}, author = {Park, ST and Won, J and Jin, S and Kim, S and Shin, H and Lim, SH and Bang, YJ and Kim, HJ}, title = {Distinct commensal bacteria in human nasopharyngeal lymphoid tissue associated with localized immunological memory.}, journal = {iScience}, volume = {29}, number = {2}, pages = {114579}, pmid = {41585492}, issn = {2589-0042}, abstract = {The nasopharynx (NP) serves as a primary site for localized immune responses that restrict the spread of SARS-CoV-2 to the lower respiratory tract. The microbiome is increasingly recognized as a key modulator of antiviral immunity but whether it shapes immune responses in upper airway remains uncharacterized. Detailed microbial profiles revealed that S. aureus complex abundance was the primary discriminating factor of microbial community in the NP and the enhanced abundance of S. aureus complex correlated with higher frequencies of CD4[+], CD8[+] tissue-resident memory T (TRM), and BRM cells. The abundance of S. aureus complex was closely associated with distinct metabolic pathways, particularly those involved in nitrogen metabolism (e.g., arginine, ornithine, and proline interconversion) and the mevalonate pathway for carotenoid biosynthesis. These findings suggest that S. aureus complex may foster unique metabolic dynamics in the NP in enhancing the tissue-residency of memory cells and localized immune responses in upper airway.}, } @article {pmid41585377, year = {2026}, author = {Tollenaar, SL and Khorasaniha, R and Jovel, J and Ba, I and Voisin, A and Miller, R and Olof, H and Mahmood, R and Marrie, RA and Strachan, E and Soares, LP and Cheng, C and Janveaux, J and Zaidi, D and Bernstein, CN and Bonner, C and Bar-Or, A and Waubant, E and Yeh, EA and Graham, M and Arnold, DL and O'Mahony, J and Banwell, BL and Zhu, F and Mirza, AI and Karimi-Abdolrezaee, S and Tsai, S and Tremlett, H and McGregor, K and Willing, BP and Armstrong, H}, title = {Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage.}, journal = {eGastroenterology}, volume = {4}, number = {1}, pages = {e100296}, pmid = {41585377}, issn = {2976-7296}, abstract = {BACKGROUND: Some people with multiple sclerosis display changes in their gut microbiota with separate evidence suggesting that symptoms may worsen following a high-fibre diet. We hypothesised that in people with multiple sclerosis whose gut microbiota are less able to efficiently ferment dietary fibres, unfermented β-fructans induce inflammation.

METHODS: Diet data (n=48 individuals with multiple sclerosis, n=78 unaffected controls) and stool microbiome data (n=31 individuals with multiple sclerosis, n=61 unaffected controls) were previously collected from participants. Daily fibre subtype intakes were calculated and compared with faecal shotgun metagenomic sequencing in paediatric onset multiple sclerosis and unaffected persons. Response to unfermented β-fructans was examined in a germ-free experimental autoimmune encephalomyelitis (EAE) mouse model (unable to ferment fibres). Mice were fed β-fructans or control fibre diet beginning at symptom onset (day 14). EAE scores and weights were recorded daily. Intestinal and central nervous system tissues were collected at two endpoints to examine inflammatory responses and demyelinating lesions.

RESULTS: Individuals with paediatric onset multiple sclerosis consumed less β-fructans (2.4 g/day±0.3 SD; p<0.05) than unaffected participants (3.6 g/day±0.4), which coincided with differences in the gut microbiota including lower fibre fermenting enzymes. Mice exposed to unfermented β-fructans sustained worsened EAE symptoms (day 20-28; p<0.05), immune activation in the gut and immune activation plus demyelinating lesions in the spinal cord compared with mice on control diet.

CONCLUSIONS: The gut microbiota of individuals with paediatric-onset multiple sclerosis showed reduced fibre fermenting properties, and our animal findings suggest that unfermented β-fructans can worsen demyelination and promote gut-brain axis immune activation. Lower β-fructan consumption was observed among participants with paediatric-onset multiple sclerosis. Future longitudinal studies are warranted to confirm the findings uncovered in this manuscript.}, } @article {pmid41585298, year = {2026}, author = {Ko, S and Oh, K and Won, U and Oh, JA and Kwon, NJ and Park, HS and Ji, YA and Kim, S and Moon, Y and Park, N and Kim, D and Yang, E and Na, K and Kim, Y and Lee, Y and Woo, H}, title = {Development and validation of a multimodal data collection system for adolescent mental health management.}, journal = {Digital health}, volume = {12}, number = {}, pages = {20552076261415916}, pmid = {41585298}, issn = {2055-2076}, abstract = {OBJECTIVE: Adolescence is a critical developmental stage during which mental health vulnerabilities often emerge. Traditional self-report methods are insufficient to capture the complexity of emotional and physiological responses, underscoring the need for data-driven, personalized mental health strategies. This study aimed to develop and validate a structured multimodal data collection system for adolescents to support the future advancement of precision mental health care.

METHODS: This study was conducted as the baseline phase of a longitudinal panel study designed to construct and validate a structured multimodal dataset for adolescent mental health research. A total of 74 adolescents aged 11-15 years from schools and community facilities in Korea was selected through convenience sampling. Multimodal data were collected by integrating six data types: self-reported surveys, electroencephalography (EEG), heart rate variability (HRV), genotyping, microbiome data, and video-based psychological counseling. Data collection was standardized through a three-phase protocol (pre-, on-site, and post-assessment), and participant privacy was protected via pseudonymization based on international standards. Variables were systematically labeled and structured to enable cross-modality analysis. Statistical analyses, including correlation and descriptive statistics, were performed to examine preliminary relationships across modalities.

RESULTS: The study successfully constructed a comprehensive dataset encompassing biological and psychosocial indicators from 74 adolescents. Preliminary analysis revealed statistically significant associations between survey-based BMI and both genomic data (ρ = 0.30, p < 0.01) and microbiome-based obesity indicators (ρ = 0.27, p < 0.05), whereas other psychological constructs (e.g., stress, resilience) showed non-significant cross-modal correlations.

CONCLUSIONS: This study presents a replicable framework for collecting rich, multimodal data from adolescents in real-world settings. By enabling integrative analysis of biological and psychosocial variables, the dataset lays the groundwork for personalized mental health prediction and intervention strategies. Future research should expand longitudinally and optimize context alignment to improve predictive precision and clinical utility.}, } @article {pmid41585255, year = {2025}, author = {Wang, Y and Liu, X and Cui, W and Hu, Y and Song, W and Zhu, L and Wang, Z and Ji, X and Wang, Y}, title = {Visualization of childhood allergic diseases based on VOSviewer and CiteSpace.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1615154}, pmid = {41585255}, issn = {2296-858X}, abstract = {INTRODUCTION: Childhood allergic diseases, such as eczema, allergic rhinitis, bronchial asthma, and cough-variant asthma, are a growing health concern around the world. There is a lot of research about these diseases, but a clear and complete study is still needed to better understand them and help guide future research.

METHODS: This study used a bibliometric analysis of research on childhood allergic diseases from 2014 to 2024. The main goal was to find patterns in publications, main researchers, research focuses, teamwork between groups, and new topics. Data were collected from Web of Science, Scopus, and PubMed. The study included English-language articles and reviews only. The tools VOSviewer and CiteSpace were used to study publication patterns, where research was done, which authors and journals worked together, how often papers were cited together, which papers were cited the most, and how keywords appeared and formed groups.

RESULTS: The amount of research was different for each disease. Eczema got the most attention and kept growing. Cough-variant asthma had fewer studies. The United States and China were the main countries that did most of the work and had well-known authors. The focus of studies changed from general studies about disease spread to more detailed topics like the microbiome, genetics, special treatments, environmental causes, other health problems that happen together, and the effects of COVID-19. The way researchers worked together was not the same for all diseases. This showed that research was more developed and better connected for some diseases and less developed for others, mainly for cough-variant asthma.

CONCLUSION: This study gives a short look at recent research on childhood allergic diseases. It shows that eczema research is growing fast, but cough-variant asthma is still studied much less, with only 110 papers in 10 years. This big difference shows a clear lack of knowledge. These results can help make better research plans and improve medical care in this field.}, } @article {pmid41585184, year = {2026}, author = {Sung, MY and Hsu, PC and Kuo, CY and Chen, LK and Tsai, CC and Hsu, YC}, title = {Characterization of the oral microbiota in zygomatic versus dental implants: Implications for full-mouth rehabilitation.}, journal = {Journal of dental sciences}, volume = {21}, number = {1}, pages = {570-578}, pmid = {41585184}, issn = {2213-8862}, abstract = {BACKGROUND/PURPOSE: Dental implants are widely used to restore oral function and esthetics in patients with tooth loss. General zygomatic implants (GZIs) are a valuable alternative for patients with severely atrophic maxillae or post-oncologic defects. However, implant placement can alter the ecological balance of the oral microbiota, potentially influencing peri-implant and sinus-related diseases. Because GZIs often traverse or adjoin the maxillary sinus, their microbial environment may differ from that of general dental implants (GDIs). This study aimed to compare microbiota taxonomy between GZI and GDI sites.

MATERIALS AND METHODS: Generally healthy adults treated with either general zygomatic implants (GZI group) or general dental implants (GDI group) at a teaching hospital dental clinic were recruited. Biofilm samples were collected from implant surfaces under aseptic conditions. Microbial DNA was extracted and analyzed using 16S rRNA gene amplicon sequencing. Taxonomic classification and diversity analyses were performed through bioinformatic pipelines to identify bacterial genera and compare microbial community composition between groups.

RESULTS: Distinct microbial profiles were observed between the GZI and GDI groups. Rothia, Thermus, and Sphingomonas were significantly more abundant in the GZI group, whereas Capnocytophaga and Leptotrichia predominated in the GDI group, reflecting greater richness in the latter. Notably, Rothia species commonly linked to sinus infections were enriched in the GZI group, suggesting sinus-associated microbiome alterations.

CONCLUSION: Implant type significantly influences peri-implant microbiota composition. Zygomatic implants exhibit distinct microbial communities potentially associated with sinus involvement. Further studies are needed to clarify their role in peri-implant and sinus-related pathogenesis.}, } @article {pmid41585116, year = {2026}, author = {Huang, GT and Huang, YF}, title = {Oral and fecal microbiota in oral lichen planus and xerostomia patients: A preliminary study.}, journal = {Journal of dental sciences}, volume = {21}, number = {1}, pages = {401-409}, pmid = {41585116}, issn = {2213-8862}, abstract = {BACKGROUND/PURPOSE: The human microbiota constitutes a dynamic community of microorganisms inhabiting the body, with the gut and oral microbiotas being the most prominent. Previous studies have shown associations between oral microbiota disruption and various oral and systemic diseases, along with the involvement of the oral-gut microbiome axis. However, further investigation into the relationship between common oral conditions and microbiota changes remains needed. This study hypothesized that the distinct immune environments in oral lichen planus (OLP) and xerostomia patients result in recognizable microbiota compositions, with additional evaluation of fecal microbiota to explore the oral-gut axis.

MATERIALS AND METHODS: Gingival and fecal samples from 8 OLP patients, 19 xerostomia patients, and 10 healthy controls were collected and analyzed using 16S rRNA sequencing with bioinformatic analysis at the phylum level. Statistical comparisons between groups were performed using Student's T-test.

RESULTS: Compared with healthy controls, OLP patients showed significant increases in Campylobacterota and Fusobacteria, and decreases in Actinobacteria and Proteobacteria. Xerostomia patients demonstrated a significant increase in Firmicutes. In fecal samples, both OLP and xerostomia patients exhibited significantly reduced Bacteroidetes compared with controls.

CONCLUSION: OLP and xerostomia are associated with distinct oral microbiota patterns, which may aid in early and non-invasive diagnosis. Fecal samples of both patient groups differed significantly from controls in Bacteroidetes, supporting the oral-gut microbiome axis and providing further evidence that oral conditions can influence systemic microbial communities. A major limitation of this study is the relatively small sample size.}, } @article {pmid41584899, year = {2026}, author = {Zhou, H and Li, L and Gong, Y and Liu, H and Wu, H and Bravo, A and Soberón, M and Zheng, J and Peng, D and Sun, B and Sun, M}, title = {Geographic and seasonal variation of culturable bacteria associated with the diseased silkworm (Bombyx mori).}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100529}, pmid = {41584899}, issn = {2666-5174}, abstract = {The domesticated silkworm, Bombyx mori, is critically impacted by bacterial pathogens, yet the environmental and ecological drivers of their spatiotemporal dynamics remain poorly defined. In this study, 514 bacterial strains were isolated from diseased and healthy silkworm larvae across major sericultural regions in China. Through 16S rRNA gene sequencing and multi-tier pathogenicity assays, 51 isolates were identified as potential novel insect pathogens. Fulfilling Koch's postulates via oral infection tests, the pathogenicity of nine strains belonging to the genera Raoultella, Stenotrophomonas, and Citrobacter were confirmed, while the remaining isolates are considered putative pathogens. All isolates were classified into 33 genera within the phyla Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, with Enterobacter, Bacillus, and Serratia being the most prevalent. Multivariate analysis indicated that geographic and climatic factors-specifically distance from the coastline and key thermal and radiative variables-collectively explained a significant though modest portion of the variance in bacterial community composition. Bacterial diversity correlated positively with cocoon yield. Guangxi presented the highest potential pathogen diversity and co-infection frequency, aligning with its intensive sericulture practices. Seasonal analyses indicated higher bacterial abundance and virulence in spring-summer compared to summer-autumn. Many isolates are taxonomically affiliated with genera containing insect gut microbiota, plant-associated bacteria, and human (opportunistic) pathogens, suggesting diverse environmental and anthropogenic origin. The detection of bacteria related to mulberry phyllosphere microbes underscore the role of host plant ecology in shaping the silkworm microbiome. These findings illuminate the ecological drivers of silkworm-associated bacterial communities and highlight the complex microbial connections within sericulture ecosystems, suggesting potential pathways relevant to a One Health perspective. Furthermore, the repository of 514 identified bacterial isolates from the model lepidopteran B. mori here provides a valuable resources for exploring novel biocontrol agents against other lepidopteran pests.}, } @article {pmid41584842, year = {2025}, author = {Ruchko, E and Chernysheva, M and Sokolov, V and Starinnov, Z and Sabirov, M and Vasiliev, A}, title = {β-cell heterogeneity and molecular plasticity in type 2 diabetes: multi-omics perspectives and the role of gut microbiota.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1698296}, pmid = {41584842}, issn = {2296-634X}, abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder characterized by systemic insulin resistance and progressive deterioration of pancreatic β-cell function. Advances in single-cell transcriptomics, epigenomics, and spatial transcriptomics have delineated marked β-cell heterogeneity, revealing subpopulations with differential secretory capacity, stress resilience, and vulnerability to metabolic and immune-mediated insults. These high-resolution approaches have further identified disease-associated alterations in other islet endocrine cells, as well as in immune, stromal, and exocrine pancreatic compartments, highlighting the central role of intercellular signaling in T2D pathogenesis. Concurrently, microbiome research has elucidated mechanisms by which gut microbial composition and metabolic activity modulate glucose homeostasis and β-cell function through immunoregulatory pathways, maintenance of epithelial barrier integrity, and enteroendocrine signaling, notably via glucagon-like peptide-1 (GLP-1). Therapeutic strategies targeting the gut microbiota include conventional probiotics, prebiotics, and fecal microbiota transplantation, alongside emerging synthetic biology approaches employing genetically engineered probiotic strains to deliver bioactive molecules, including GLP-1, directly in the gut microenvironment. This review integrates current multi-omics and experimental evidence to provide a comprehensive framework for understanding β-cell molecular plasticity, microbiota-mediated metabolic regulation, and their intersection as potential therapeutic targets. Such integrative approaches offer prospects for the development of precision interventions aimed at preserving or restoring β-cell function in T2D.}, } @article {pmid41584828, year = {2026}, author = {Balakrishnan, D and Cromwell, S and Ayayee, PA and Bateman, N and Kariyat, R}, title = {Phenology overshadows seed treatment and cultivar effects on fall armyworm gut microbiome following short-term feeding on rice.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20458}, pmid = {41584828}, issn = {2167-8359}, mesh = {Animals ; *Oryza/parasitology ; *Gastrointestinal Microbiome ; *Spodoptera/microbiology/growth & development ; Larva/microbiology/growth & development ; *Seeds/parasitology ; Herbivory ; }, abstract = {Plants mediate host susceptibility or resistance to infesting insects through various documented ways, and possibly via disrupting insect gut microbiota, an area that is underexplored in rice. The fall armyworm (FAW) (Spodoptera frugiperda (J.E. Smith) is a highly invasive herbivore that infests ∼350 host plant species, including rice (Oryza sativa L.). Exploring the impacts of chemical seed treatments on rice against FAW on the composition and attendant detoxification functionalities of the gut microbiota, as well as the subsequent effect on larval development, could inform the development of more effective management strategies. To test this, we characterized the gut microbiota of FAW 4 th instar larvae exposed to rice cultivars with and without chemical seed treatment (CruiserMaxx plus Vibrance package) at vegetative and reproductive stages for 96-hours. Results did not determine any statistically significant effects of chemical treatments and rice cultivars on larval microbiota composition. However, crop phenology (vegetative and reproductive stages) significantly impacted larval microbiota. Bacterial taxa previously implicated in FAW larval detoxification of plant secondary compounds, as well as FAW growth, and development, were uncovered across larvae. Hence, our findings highlight the importance of considering rice phenology and associated traits in developing management strategies against this highly polyphagous pest.}, } @article {pmid41584608, year = {2025}, author = {Xu, Y and Shen, H and Shang, D and Zhu, C}, title = {Pharmacological strategies to overcome immune checkpoint inhibitor resistance in non-small cell lung cancer.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1665239}, pmid = {41584608}, issn = {2234-943X}, abstract = {Immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm of non-small cell lung cancer (NSCLC), offering durable remission in select patients by reactivating anti-tumor T cell responses. Yet, this clinical triumph is tempered by the reality that most patients experience either primary resistance or relapse due to acquired resistance, underscoring an urgent need for mechanistically grounded solutions. Resistance arises through a complex interplay of tumor-intrinsic mechanisms, including defects in antigen presentation, interferon signaling disruption, and oncogenic pathway activation (EGFR, KRAS, MET), and tumor-extrinsic factors such as immunosuppressive cell populations, inhibitory cytokines, and metabolic rewiring of the tumor microenvironment (TME). This review provides a comprehensive synthesis of emerging pharmacological strategies aimed at reversing ICI resistance in NSCLC. Promising avenues include dual or multi-checkpoint inhibition (targeting LAG-3, TIGIT, TIM-3), integration of epigenetic reprogrammers to resensitize immune-silent tumors, and metabolic interventions that normalize the TME. Additionally, combination regimens with oncogene-directed therapies, engineered cytokine analogs, neoantigen-based vaccines, and adoptive T cell therapies are reshaping the frontier of immunoresistant NSCLC management. We also highlight pivotal clinical trials-both completed and ongoing that illuminate translational breakthroughs and therapeutic pitfalls. Looking ahead, the field must grapple with key challenges: the refinement of predictive biomarkers, stratification of patients through genomic, immunologic, and microbiome-based profiling, and the management of toxicity in complex combination protocols. Ultimately, a shift toward highly personalized, biomarker-guided therapeutic strategies holds the greatest promise for overcoming resistance and extending the reach of immunotherapy in NSCLC.}, } @article {pmid41584317, year = {2026}, author = {Jawed, F and Aziz, R and Mir, SUI and Khan, SA}, title = {Gut microbiota, sarcopenia, and type 2 diabetes: a triangular pathophysiological network.}, journal = {Journal of diabetes and metabolic disorders}, volume = {25}, number = {1}, pages = {41}, pmid = {41584317}, issn = {2251-6581}, abstract = {PURPOSE: Type 2 diabetes mellitus (T2DM), sarcopenia, and gut microbiota dysbiosis are increasingly recognized as interrelated conditions. T2DM accelerates muscle wasting through insulin resistance, inflammation, and oxidative stress, while sarcopenia worsens metabolic dysfunction. This review explores the interconnected conditions of Type 2 Diabetes, sarcopenia, and gut microbiota dysbiosis, highlighting their therapeutic potential and the need for interventions targeting these conditions for metabolic and musculoskeletal health.

METHODS: An extensive literature search was performed in PubMed, EMBASE, Scopus, and Web of Science up to July 2025 using terms related to gut microbiota, sarcopenia, and T2DM. Both preclinical and human studies were included if they addressed microbial composition, metabolites, inflammation, insulin resistance, or muscle protein turnover.

RESULTS: Evidence indicates bidirectional relationships: T2DM patients show higher prevalence of sarcopenia, while reduced muscle mass increases T2DM risk. Gut dysbiosis in T2DM is characterized by depletion of SCFA-producing taxa (e.g., Faecalibacterium prausnitzii) and enrichment of endotoxin-producing bacteria, leading to systemic inflammation and impaired insulin signaling. Germ-free and antibiotic-treated rodent models demonstrate muscle atrophy, whereas probiotic or prebiotic supplementation restores muscle mass and improves glucose metabolism. Limited clinical trials suggest dietary fibre, probiotics, and fecal microbiota transplantation improve glycemic control and inflammatory markers, with potential secondary benefits on muscle function.

CONCLUSION: T2DM, sarcopenia, and gut microbiota are linked through insulin resistance, inflammation, and altered signaling. Targeting gut-muscle-metabolism axis through diet, microbiota modulation, and exercise is promising. Future longitudinal and interventional studies are needed to establish causality and develop precision microbiome-based therapies.

SUMMARY: Type 2 diabetes mellitus (T2DM), sarcopenia, and gut microbiota dysbiosis are interconnected in a triangular pathophysiological network. T2DM accelerates muscle loss through insulin resistance, inflammation, and oxidative stress, while sarcopenia worsens glycaemic control. Gut dysbiosis reduces beneficial short-chain fatty acid (SCFA) production and increases pro-inflammatory metabolites such as lipopolysaccharides, further impairing muscle metabolism and glucose regulation. Preclinical and emerging clinical evidence shows that dietary fibre, probiotics, and fecal microbiota transplantation can modulate this axis. Targeting the gut-muscle-metabolism triad offers promising integrative strategies for preventing and managing diabetic sarcopenia.}, } @article {pmid41583463, year = {2025}, author = {Zha, T and Ding, Y and Xu, X and Zhang, Y and Guo, J and Ge, H and Xu, L}, title = {The oral-gut axis in chronic atrophic gastritis: current perspectives and integrated strategies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1699501}, pmid = {41583463}, issn = {1664-3224}, mesh = {Humans ; *Gastritis, Atrophic/microbiology/therapy/immunology/metabolism/etiology ; *Gastrointestinal Microbiome/immunology ; Helicobacter Infections/microbiology/immunology/complications ; Dysbiosis ; Helicobacter pylori ; *Mouth/microbiology/immunology ; Chronic Disease ; Animals ; }, abstract = {Chronic atrophic gastritis (CAG) is a key precursor to gastric cancer, characterized by progressive mucosal atrophy, inflammation, and microbial dysbiosis. The Correa cascade model highlights Helicobacter pylori as a primary driver, progressing from gastritis to atrophy, intestinal metaplasia (IM), dysplasia, and malignancy. However, 20%-30% of CAG cases lack H. pylori involvement, emphasizing the roles of non-H. pylori microbial dysbiosis, environmental factors, and the oral-gut axis in disease progression. Oral microbes, such as Porphyromonas gingivalis, translocate to the stomach, amplifying inflammation through NF-κB and Wnt/β-catenin pathways and altering metabolites like short-chain fatty acids and trimethylamine N-oxide. Pro-inflammatory cytokines, including IL-1β, IL-6, and IL-17, alongside Th17-driven immune dysregulation, further accelerate carcinogenesis. This perspective integrates multi-omics data to elucidate microbiome shifts, metabolic changes, and immune responses across CAG subtypes. Advanced diagnostics, such as endoscopic imaging, serum biomarkers, and oral microbiota profiling, enable precise risk stratification. Management strategies extend beyond H. pylori eradication to include probiotics, fecal microbiota transplantation, periodontal interventions, and herbal compounds, targeting the oral-gut axis to restore microbial balance and halt carcinogenesis. This framework offers novel avenues for prevention and therapy in high-burden regions.}, } @article {pmid41583462, year = {2025}, author = {Bong, H and Min, J and Kim, S and Lim, W and Lim, D and Eom, H and Her, Y and Jeon, M}, title = {ATOMIC: a graph attention network for atopic dermatitis prediction using human gut microbiome.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1670993}, pmid = {41583462}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dermatitis, Atopic/microbiology/diagnosis/etiology ; Adult ; Dysbiosis ; Female ; Computational Biology/methods ; Male ; }, abstract = {INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by complex interactions among genetic, environmental, and microbial factors; however, its etiology remains unclear. Recent studies have reported the role of gut microbiota dysbiosis in AD pathogenesis, leading to increased interest in microbiome-targeted therapeutic strategies such as probiotics and fecal microbiota transplantation. Building on these findings, recent advances in computational modeling have introduced machine learning and deep learning-based approaches to capture the nonlinear relationships between gut microbiota and diseases. However, these models focus on diseases other than AD and often fail to capture complex microbial interactions or incorporate microbial genomic information, thereby offering limited interpretability.

METHODS: To address these limitations, we propose ATOMIC, an interpretable graph attention network-based model that incorporates microbial co-expression networks to predict AD. Microbial co-expression networks incorporate microbial genomic information as a node feature, thereby enhancing their ability to capture functionally relevant microbial patterns. To train and test our model, we collected and processed 99 gut microbiome samples from adult patients with AD and healthy controls at Kangwon National University Hospital (KNUH).

RESULTS: ATOMIC outperformed baseline models, achieving an AUROC of 0.810 and an AUPRC of 0.927 for KNUH dataset. Furthermore, ATOMIC identified microbes potentially associated with AD prediction and proposed candidate microbial biomarkers that may inform future therapeutic strategies.

DISCUSSION: By identifying key microbial taxa that contributed to the AD classification through its interpretable attention mechanism, ATOMIC provides a foundation for personalized microbiome-based interventions and biomarker discovery. Additionally, to facilitate future research, we publicly released a gut microbial abundance dataset from KNUH. The source code and processed abundance data are available from ATOMIC GitHub repository at https://www.github.com/KU-MedAI/ATOMIC.}, } @article {pmid41583433, year = {2025}, author = {Yang, Q and Yang, Z and Zhao, H}, title = {Lactylation in cancer: mechanistic insights, tumor microenvironment, and therapeutic horizons.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1697008}, pmid = {41583433}, issn = {1664-3224}, mesh = {Humans ; *Tumor Microenvironment/immunology ; *Neoplasms/metabolism/therapy/pathology/immunology/etiology ; *Protein Processing, Post-Translational ; Animals ; *Lactic Acid/metabolism ; Glycolysis ; }, abstract = {The discovery of lactylation, a post-translational modification derived from lactate, has fundamentally altered the perception of cancer metabolism. Once regarded as a metabolic waste product, lactate is now recognized as a central fuel source, a signaling molecule, and an epigenetic substrate capable of reprogramming gene expression and cellular function. Lactylation integrates metabolic reprogramming, tumor plasticity, and immune suppression, thereby orchestrating cancer initiation, progression, and resistance to therapy. This review provides a critical and integrative commentary on recent advances in lactylation biology, drawing from biochemical, epigenetic, and immunological perspectives. It synthesizes mechanistic insights into lactylation, highlights its role in tumorigenesis and the tumor microenvironment (TME), and evaluates therapeutic strategies that target lactate production, transport, and lactylation machinery. By dissecting consensus, controversies, and unresolved questions, we argue that lactylation represents both a hallmark of tumor adaptation and a potential Achilles' heel for intervention. We further discuss future research directions, including comprehensive lactylome mapping, structural biology of lactylated proteins, microbiome-derived lactate, and clinical translation. Ultimately, lactylation is not merely a byproduct of glycolysis but a metabolic language that tumors employ to communicate, adapt, and thrive. Decoding this language may open new frontiers in cancer therapy.}, } @article {pmid41583075, year = {2026}, author = {García-Rios, P and Rodríguez-Lozano, FJ and González-Murcia, R and Murcia, L and Victoria-Montesinos, D and García-Muñoz, AM}, title = {The role of oral dysbiosis in pregnancy complications: a systematic review and meta-analysis of preterm birth.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2617757}, pmid = {41583075}, issn = {2000-2297}, abstract = {OBJECTIVE: To systematically review the association between oral dysbiosis and pregnancy-related complications and to quantitatively assess differences in oral microbial alpha diversity between preterm birth (PTB) and term birth (TB).

MATERIAL AND METHODS: A systematic search was conducted in July 2025 following PRISMA 2020 guidelines and registered in PROSPERO. Studies published between 2015 and 2025 assessing oral microbiota composition, alpha/beta diversity, or taxa abundance in relation to preeclampsia, gestational diabetes mellitus, preterm birth, low birth weight, mental health disorders, or pregnancy loss were included. Due to heterogeneity in study design, microbiome metrics, and outcome definitions, meta-analysis was restricted to studies comparing Shannon alpha diversity between PTB and TB. Study quality was assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute checklist.

RESULTS: Twenty-one studies met the inclusion criteria, including cohort, case-control, and cross-sectional designs; four were included in the meta-analysis. Pregnancy complications were commonly associated with altered oral microbial profiles, characterized by reduced alpha diversity, changes in beta diversity, and increased abundance of genera such as Prevotella, Veillonella, and Porphyromonas. The meta-analysis suggested a directional trend toward altered alpha diversity in adverse pregnancy outcomes.

CONCLUSIONS: Overall, the findings support a potential association between oral dysbiosis and pregnancy-related complications; however, this evidence is limited by the small scale and heterogeneity of the available studies. These results highlight the oral microbiome as a biologically plausible contributor to adverse maternal and neonatal outcomes and a promising focus for future mechanistic and translational research.}, } @article {pmid41583012, year = {2026}, author = {Krausfeldt, LE and Cao, V and Rodrigues, R and Henderson, WA and Eisch, R and Scott, LM and Metcalfe, DD and Komarow, HD}, title = {Evidence for dysbiosis in the gut microbiome of patients with systemic mastocytosis.}, journal = {The journal of allergy and clinical immunology. Global}, volume = {5}, number = {1}, pages = {100578}, pmid = {41583012}, issn = {2772-8293}, abstract = {BACKGROUND: Limited research studies have investigated the role of the gut microbiome in systemic mastocytosis (SM), which is characterized by an aberrant expansion of clonal mast cells in specific tissues including the skin, marrow, liver, and the gastrointestinal tract.

OBJECTIVES: We sought to investigate the relationship between the intestinal microbiome and clinical manifestations of SM.

METHODS: The V4 region of the 16S rRNA gene was sequenced from stool samples of 22 patients with SM and 9 healthy controls. Microbial community composition, diversity, and functional genes inferred from 16S rRNA gene sequences were analyzed. ClinicalTrials.gov Identifier NCT00044122.

RESULTS: Changes in microbial community composition were associated with SM, KIT D816V, and tryptase (PERMANOVA, P = .004, P = .05, P = .005, respectively). The differences with SM were driven by the composition of Firmicutes (P = .04) and an increase in Bacteroidetes abundance (P = .04). Predicted functions of the gut microbiome suggested that there were differences in metabolite profiles, including short-chain fatty acids, increased virulence factors, and decreased bacterial defense mechanisms in patients with SM. Dietary components were associated with symptoms, quality of life, and markers of mast cell activation and inflammation, as well as changes in microbial composition and predicted function in patients with SM.

CONCLUSIONS: Dysbiosis of the gut microbiome is evident in patients with SM and is seemingly associated with mast cell activation. In addition, diet may further alter microbial composition and metabolism in the gut of patients with SM.}, } @article {pmid41582827, year = {2026}, author = {}, title = {The people behind the papers - Longwei Bai and François Leulier.}, journal = {Development (Cambridge, England)}, volume = {153}, number = {2}, pages = {}, doi = {10.1242/dev.205493}, pmid = {41582827}, issn = {1477-9129}, mesh = {Animals ; France ; Drosophila ; *Developmental Biology/history ; History, 21st Century ; History, 20th Century ; Ecdysone/metabolism ; Humans ; }, abstract = {During periods of starvation, some organs and tissues are selectively spared. A recent study in Development shows that microbiome-dependent intestinal sparing in Drosophila is coordinated by the hormone ecdysone. To learn more about this work, we spoke to first author Longwei Bai and corresponding author François Leulier, Director and Group Leader at Institut de Génomique Fonctionnelle de Lyon, France.}, } @article {pmid41582698, year = {2026}, author = {Vallet, M and Staudinger, M and Syhapanha, KS and Meunier, CL and Kirstein, IV and Pohnert, G}, title = {Marine Bacterium Kordia algicida Reshapes Plankton Microbiome and Induces Metabolomic Rewiring, Independent of Heatwave or Worst-Case Climate Scenarios.}, journal = {Journal of natural products}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jnatprod.5c01435}, pmid = {41582698}, issn = {1520-6025}, abstract = {Marine bacteria are integral components of planktonic communities, where they regulate algal growth, induce cell death, and contribute to bloom termination and species succession. They also play a key role in marine biogeochemical cycling by recycling algal-derived organic matter and releasing bioactive metabolites. Despite their ecological importance, bacterial-plankton interactions and their consequences for community structure and chemistry remain poorly understood. We investigated the impact of the algicidal marine bacterium Kordia algicida OT-1 on a natural plankton microbiome collected from a mesocosm experiment simulating present and future climate conditions. Plankton communities were exposed to ambient conditions or to a worst-case climate scenario, with a subset further subjected to a one-week heatwave. After 24 h of incubation, K. algicida significantly altered phytoplankton abundance and phylum-level community composition, independent of the applied abiotic conditions. Chemical changes induced by bacterial interactions were assessed by extracting filtrates from cocultures and analyzing them using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Four natural products, i.e., adenosylhomocysteine, two indole alkaloid derivatives, and 5-bromotryptophan, were identified among metabolites released in response to bacterial exposure. Overall, shifts in the planktonic chemical landscape were primarily driven by bacterial activity, rather than abiotic conditions.}, } @article {pmid41582618, year = {2026}, author = {Wu, X and Lim, KJ and Ma, Y and Gu, J and Jiang, Y and Zhu, L and Chen, Y and Sun, J}, title = {The Effects of Soy Protein-Rich Meals on Muscle Health of Older Adults Are Linked to Gut Microbiome Modifications.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {17}, number = {1}, pages = {e70212}, pmid = {41582618}, issn = {2190-6009}, mesh = {Humans ; Male ; Female ; Aged ; *Gastrointestinal Microbiome/drug effects ; *Soybean Proteins/administration & dosage/pharmacology ; Aged, 80 and over ; *Muscle, Skeletal/physiology ; *Meals ; Feces/microbiology ; Fatty Acids, Volatile/metabolism ; *Sarcopenia/diet therapy ; }, abstract = {BACKGROUND: Sarcopenia is characterized by accelerated muscle mass and function loss in older adults. The role of nutritional interventions in sarcopenia is uncertain. This study investigates whether a soy protein-rich diet can enhance muscle health in older adults via gut microbiota changes.

METHODS: A 12-week randomized controlled trial was conducted with 84 older adults from a long-term care facility. Participants in the intervention group consumed three daily meals containing 10 g of soy protein (totalling 30 g/day), while the control group maintained their usual diets. Faecal samples from 53 participants were collected at Weeks 0, 6 and 12. We assessed changes in muscle function, gut microbiota composition and faecal short-chain fatty acids (SCFA).

RESULTS: The intervention group showed preserved calf circumference, while the control group experienced a decrease (W12-W0: Intervention, 0.56 ± 0.22 cm; Control, -0.91 ± 0.26 cm, p(interaction) < 0.001). Metagenomic analysis revealed significant alterations in gut microbiota among intervention participants who showed improvement in muscle performance parameters. The intervention increased SCFA-producing bacteria (Roseburia faecis, Intervention: 0.42 ± 0.21%, Control: -0.06 ± 0.16, p(interaction) < 0.05; Agathobaculum butyriciproducens, Intervention: 0.02 ± 0.007%, p(time) < 0.01, Control: -0.04 ± 0.01) and decreased species associated with poorer muscle outcomes (Alistipes putredinis, Intervention: -0.88 ± 0.40%, Control: 0.62 ± 0.63, p(interaction) < 0.05; Eubacterium_sp_CAG_38, Intervention: -0.64 ± 0.28%, Control: 0.10 ± 0.22, p(interaction) < 0.05). Functional pathway analysis showed enrichment of anaerobic amino acid degradation pathways and vitamin biosynthesis, with depletion of inflammatory pathways, particularly lipopolysaccharide biosynthesis. Microbiome phenotype prediction revealed a decrease in aerobic bacteria abundance in the intervention group (W12-W0, Intervention: -0.004 ± 0.002; Control: 0.001 ± 0.001, p(interaction) < 0.05). Interaction (group × time) for SCFA was not statistically significant; within-group increases at Week 6 were observed in only the intervention group (butyric acid, Intervention: 0.74 ± 0.34 mg/g, p(time) < 0.05, Control: 0.12 ± 0.43 mg/g; isobutyric acid, Intervention: 0.14 ± 0.08 mg/g, p(time) < 0.05, Control: 0.08 ± 0.10 mg/g; isovaleric acid, Intervention: 0.27 ± 0.14 mg/g, p(time) < 0.05; Control: 0.16 ± 0.20 mg/g), with partial reversal by Week 12. These changes, positively correlated with improved muscle function parameters, suggest intervention benefits on gut health and muscle function.

CONCLUSION: A soy protein-rich intervention improved muscle health in older adults through beneficial gut microbiota. These findings support the gut-muscle axis hypothesis and suggest dietary soy protein may alleviate sarcopenia by promoting a healthier gut microbiome.}, } @article {pmid41582602, year = {2026}, author = {Hernani, R and Albert, E and Hernani-Morales, C and Zúñiga, S and Benzaquén, A and González-Castillo, L and Colomer, E and Morell, J and Català-Senent, JF and Piñana, JL and Giménez, E and Pérez, A and Hernández-Boluda, JC and Arroyo, I and Rivada, M and Barber, T and Alemany, T and Santacatalina, E and Rentero-Garrido, P and Terol, MJ and Díaz, R and Navarro, D and Solano, C}, title = {Microbiome-Based Modeling of CAR-T Therapy Response in Lymphoma: Insights From Shotgun Metagenomics Sequencing.}, journal = {European journal of haematology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ejh.70121}, pmid = {41582602}, issn = {1600-0609}, support = {//Fundación FERO and the Fundación para la Promoción de Acciones Solidarias/ ; //European Union through the Operational Program of the European Regional Development Fund/ ; CA23/00007//bioinformatics technician/ ; //2023 Strategic Action in Health/ ; //Instituto de Salud Carlos III/ ; //European Union/ ; }, abstract = {The interplay between the commensal microbiota and the mammalian immune system may influence the outcomes of T cell-driven cancer immunotherapies. However, clinical studies supporting microbiota-based interventions in chimeric antigen receptor T-cell (CAR-T) therapy remain scarce. This study included 30 adult patients with B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel) or 4-1BB investigational product. Shotgun metagenomics sequencing (SMS) of fecal samples, collected before lymphodepletion and 1 month post infusion, enabled species-level resolution. We also trained 25 microbiome-based machine-learning (ML) models for response prediction. Neither prior "high-risk" antibiotics exposure nor alpha diversity influenced toxicity, response, or survival. However, dysbiosis was observed between 11 healthy controls and patients, particularly in those treated with axi-cel. SMS identified species associated with clinical outcomes. Increased abundance of Alistipes senegalensis and Alistipes onderdonkii correlated with lower neurotoxicity and improved survival, respectively. Bifidobacterium longum was associated with reduced cytokine release syndrome, whereas Bifidobacterium adolescentis, Bifidobacterium bifidum, and Bifidobacterium breve correlated with poorer survival. ML models demonstrated strong predictive performance, with some identifying non-responders using only six species selected by the Boruta method (Bacteroides xylanisolvens, Bifidobacterium bifidum, Bifidobacterium breve, Eubacteriaceae bacterium Marseille-Q4139, Negativibacillus massiliensis, and Sellimonas intestinalis). These findings deepen current knowledge and support prospective microbiota-based strategies in CAR-T therapy.}, } @article {pmid41582394, year = {2026}, author = {Galan, R and Castaño-Vinyals, G and Rubio-Garcia, E and Lopez-Aladid, R and Espinosa, A and Papantoniou, K and Bustamante, M and Bhatti, P and Lassale, C and Márquez, C and Alfaro, A and Casals-Pascual, C and Kogevinas, M and Harding, BN}, title = {The Effect of Night Shift Work on the Gut Microbiome Diversity: The EXPONIT Study.}, journal = {Journal of biological rhythms}, volume = {}, number = {}, pages = {7487304251408152}, doi = {10.1177/07487304251408152}, pmid = {41582394}, issn = {1552-4531}, abstract = {Night shift work may alter the gut microbiome through mechanisms involving circadian misalignment, sleep disturbance, and changes in dietary behavior. However, existing studies on this topic have been limited in sample size and scope. We analyzed stool samples from 240 participants (mean age 42 years, 80% women), of whom 53% were night shift workers. Gut microbiota composition was assessed using 16S rRNA gene sequencing to derive measures of relative abundance, alpha diversity, and beta diversity. Associations between night shift work and microbial composition and alpha diversity were examined using generalized linear models with a Gamma distribution and log link for alpha diversity and Aitchison distance for beta diversity. The effect of night shift work on microbiome genera abundance was evaluated using MaAsLin2 analysis. Models were adjusted for age, sex, and educational level. We also explored potential interactions by sleep quality, diet, and chronotype. There were no overall significant differences in alpha or beta diversity between day and night shift workers, but participants with less than 15 years of night work showed slightly higher Abundance-based Coverage Estimator than non-night workers. Interaction with sleep quality was observed (p-value: 0.01). Among participants with poor sleep quality, night shift work was significantly associated with lower alpha diversity (exp(β): 0.93, 95% CI: 0.87-0.99, p-value: 0.02). Day shift workers showed high relative abundance of Ruminococcus, while night shift workers had increased Escherichia-Shigella at descriptive level, none of which remain statistically significant after false discovery rate. Our findings indicate that night shift work may influence gut microbiome diversity, especially in individuals with poor sleep quality. Future research should explore the long-term health consequences of these microbial changes.}, } @article {pmid41582166, year = {2026}, author = {Jones, BP and Wawman, DC and Johnson, N}, title = {Detection of Bartonella schoenbuchensis and a novel sigmavirus within the microbiome of deer keds (Lipoptena cervi) from the United Kingdom.}, journal = {Parasites & vectors}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13071-025-07208-w}, pmid = {41582166}, issn = {1756-3305}, support = {BB/X018008/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; SE0566//Department for Environment, Food and Rural Affairs, UK Government/ ; }, abstract = {BACKGROUND: Lipoptena cervi is a member of the Hippoboscidae family of insects and is a hematophagous ectoparasite of cervid species, commonly referred to as the deer ked. Lipoptena cervi has a wide geographical distribution and can be found from North America through Europe into East Asia. Deer keds occasionally bite humans and domestic animals and might act as disease vectors. The microbiome associated with this species of biting insect has not been investigated.

METHODS: Mass sequencing of both DNA and RNA extracted from L. cervi specimens collected from two locations in southern England was conducted to characterise the complete microbiome consisting of bacterial, viral and eukaryotic species. Three specimens were collected after landing on humans in Somerset, and three specimens were collected from European roe deer (Capreolus capreolus) in Oxfordshire. Bioinformatic analysis investigated the host and microbial composition of each specimen.

RESULTS: Near-complete mitochondrial genomes were assembled from all six specimens confirming morphological speciation as L. cervi. Bacterial endosymbionts were the most dominant organisms identified with Candidatus Arsenophonus lipoptenae being most abundant. In specimens that had fed on deer, the pathogen Bartonella schoenbuchensis was detected. A novel sigmavirus was also detected in five samples, four of which yielded near-complete genomes. The closest relative of this virus was a sigmavirus found in a sheep ked (Melophagus ovinus) sampled in the Russian Federation.

CONCLUSIONS: The data from this study will allow for a better baseline understanding of the microbiome of L. cervi and provide evidence for their role as vectors of zoonotic pathogens.}, } @article {pmid41581955, year = {2026}, author = {Guan, M and Chang, L}, title = {Biomarkers in Irritable Bowel Syndrome: Rationale and Practical Use.}, journal = {Gastroenterology clinics of North America}, volume = {55}, number = {1}, pages = {91-105}, doi = {10.1016/j.gtc.2025.08.002}, pmid = {41581955}, issn = {1558-1942}, mesh = {Humans ; *Irritable Bowel Syndrome/diagnosis/metabolism/therapy ; *Biomarkers/metabolism/analysis/blood ; Breath Tests ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome ; DNA Methylation ; }, abstract = {Irritable bowel syndrome (IBS) is currently diagnosed based on symptoms and limited diagnostic testing, highlighting the need for noninvasive biomarkers and personalized therapies. Emerging blood-based biomarkers such as cytolethal distending toxin B and antivinculin antibodies, DNA methylation profiles, and intestinal permeability measures, along with stool-based microbiome and metabolite markers, show promise in distinguishing IBS, and its bowel habit subtypes, from other gastrointestinal disorders with overlapping symptoms. Additionally, stool-based biomarkers and breath tests may also predict response to interventions, like the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet, and rifaximin, supporting more personalized treatment strategies.}, } @article {pmid41581948, year = {2026}, author = {Kim, SG and Zhao, MY and Lam, C and Jacobs, JP}, title = {The Current Landscape of Microbial Biomarkers in Gastrointestinal Disease.}, journal = {Gastroenterology clinics of North America}, volume = {55}, number = {1}, pages = {165-184}, doi = {10.1016/j.gtc.2025.10.003}, pmid = {41581948}, issn = {1558-1942}, mesh = {Humans ; Biomarkers/metabolism ; *Gastrointestinal Diseases/microbiology/diagnosis ; *Gastrointestinal Microbiome ; }, abstract = {The intestinal microbiome encompasses a complex network of microorganisms that is now recognized to make wide contributions to health and disease but remains incompletely understood. Recent studies provide new insights into distinct roles of the microbiome in specific gastrointestinal diseases and support the possibility of developing new clinical microbial biomarkers for disease diagnosis, risk stratification for disease progression, and prediction of response to therapeutic interventions. Here, we discuss the various potential taxonomic, metabolic, and serologic biomarkers that have been highlighted in recent studies.}, } @article {pmid41581782, year = {2026}, author = {Chen, F}, title = {Reconsidering the Microbiome and Maintenance Claims in Whole-Food Dietary Trials for Crohn's Disease.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.06.041}, pmid = {41581782}, issn = {1528-0012}, } @article {pmid41581404, year = {2026}, author = {Wang, P and Feng, F and Li, M and Ahmad, F and Wan, Q and Li, Y and Babalola, OO and Mawcha, KT and Ge, J and Yu, X}, title = {Rice recruiting resilience-conferring Enterobacter via enhanced proline and malic acid exudation under thiamethoxam stress.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141176}, doi = {10.1016/j.jhazmat.2026.141176}, pmid = {41581404}, issn = {1873-3336}, abstract = {Although pesticides are essential for ensuring stable agricultural production, how increasing pesticide stress influences crop recruitment of beneficial rhizosphere microorganisms remains unclear. In this study, we investigated how rice reshaped rhizosphere microbiota in response to the insecticide thiamethoxam (THIA) stress, with particular focus on the mechanistic relationship between root exudate chemistry and microbial recruitment. Through integrated transcriptomic and metabolomic analyses coupled with experimental validation, we demonstrate that THIA exposure triggers significant metabolic reprogramming in rice plants, particularly affecting amino acid metabolism and the tricarboxylic acid (TCA) cycle. These changes drive increased secretion of low-molecular-weight organic acids in root exudates, notably malic acid and proline. Chemical profiling revealed these compounds act as chemoattractants, selectively enriching pesticide-degrading and resistant bacterial taxa, with the genus Enterobacter showing particularly pronounced enrichment. Functional characterization of the dominant Enterobacter sp. isolate revealed upregulation of motility-related genes (yqxM, epsA, csgC, fimA, wcaA, and ftsZ) facilitating root colonization, which furthermore enhanced plant growth promotion and THIA stress mitigation upon root association. Notably, this plant-mediated microbial recruitment strategy exhibits dual benefits: environmental detoxification through microbial pesticide degradation and host fitness improvement via stress resilience enhancement. This work advances our understanding of plant-microbe-environment tripartite interactions, with significant implications for agricultural stress management, pollutant remediation strategies and food safety assurance.}, } @article {pmid41581327, year = {2026}, author = {Lamichhane, S and Salihovic, S and Sinioja, T and Virtanen, SM and Vatanen, T and Orešič, M and Knip, M and Hyötyläinen, T}, title = {Prenatal exposure to persistent organic pollutants modulates the metabolism and gut microbiota of the offspring.}, journal = {Environment international}, volume = {208}, number = {}, pages = {110080}, doi = {10.1016/j.envint.2026.110080}, pmid = {41581327}, issn = {1873-6750}, abstract = {Emerging evidence suggests that environmental contaminants can influence both human metabolism and gut microbiota composition. However, the specific effects of prenatal exposure to persistent organic pollutants (POPs) on host-microbiome metabolic interactions remain incompletely understood. In this study, we investigated associations between prenatal exposure to POPs, including organochlorine pesticides, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkyl substances (PFAS), and growth, metabolic profiles, and gut microbiota composition in infants at three months of age. Prenatal POP exposure was strongly associated with alterations in the infant metabolome, particularly affecting lipid metabolism and microbiota-derived metabolites. Among the POPs examined, PCBs showed the most pronounced influence on both metabolic profiles and gut microbial composition. The most affected metabolic pathways included fatty acid metabolism, bile acid transformation, and steroid hormone biosynthesis. Furthermore, prenatal POP exposure significantly altered the composition of the gut microbiome. PCB exposure was linked to reduced Bifidobacterium bifidum and Lactobacillus paragasseri, and increased Erysipelatoclostridium ramosum, along with disruptions in bile acid and amino acid metabolism. These findings suggest that early-life exposure to POPs can disrupt host-microbiome metabolic interactions, potentially through perturbation of lipid- and amino acid-related pathways.}, } @article {pmid41581145, year = {2026}, author = {McCourt, B and Lemr, K and Chakrabarti, S and Woidke, E and Ramaiah, S and Singh, V and Sangwan, N and Brown, JM and Cominelli, F and Rodriguez-Palacios, A and Burberry, A}, title = {C9orf72 in myeloid cells prevents an inflammatory response to microbial glycogen.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116906}, doi = {10.1016/j.celrep.2025.116906}, pmid = {41581145}, issn = {2211-1247}, abstract = {Gut dysbiosis and neural inflammation occur in patients with amyotrophic lateral sclerosis (ALS), including those with a causal mutation in chromosome 9 open reading frame 72 (C9ORF72). How gut commensals interact with common ALS genotypes to impart risk of neural degeneration remains unclear. Here, we identify 10 phylogenetically diverse bacterial strains that promote cytokine release in a C9orf72-dependent manner. Metatranscriptomics implicated the glycogen biosynthesis pathway as a driver of inflammation. Colonization of germ-free C9orf72-deficient mice with Parabacteroides merdae that produced inflammatory glycogen enhanced monocytosis, blood-brain barrier breakdown, and T cell infiltration into the central nervous system. Enzymatic digestion of glycogen in the gut promoted survival of C9orf72-deficient mice and dampened microglial reactivity in the brain. A survey of human fecal samples demonstrated that inflammatory forms of glycogen were present in gut contents from 15/22 patients with ALS, 1/1 patient with C9ORF72 frontotemporal dementia (FTD), and 4/12 healthy controls. Together, the results of this work identify bacterial glycogen as a modifiable mediator of immune homeostasis in the gut and brain.}, } @article {pmid41581110, year = {2026}, author = {Kalu, CM and Ogugua, UV and Udeh, EL and Otun, S and Oladipo, AO and Lebelo, SL and Adriaanse, P and Ntushelo, K and Tekere, M}, title = {Applications of nanoparticles in plant disease identification and control for sustainable crop production.}, journal = {Discover nano}, volume = {21}, number = {1}, pages = {15}, pmid = {41581110}, issn = {2731-9229}, abstract = {Nanotechnology is a vast field applicable in various areas of study, including agriculture. Nanoparticles (NPs) can be used in plant disease control in many ways, including as fungicide delivery systems and to enhance cell-to-cell interactions in plants. Their ease of use can be manipulated not only for disease control in crop production but also for the identification of plant diseases. Information on the use of NPs for plant disease control and disease identification was collated. Mechanisms of action of NPs were outlined and discussed. Through these mechanisms, ZnO-NPs reduced Fusarium wilt symptoms in tomatoes by 28.57% and provided 67.99% protection. Ag-NPs promoted a 49.2% reduction of bacterial leaf blight disease in rice caused by Xanthomonas oryzae pv. oryzae. Various techniques involving NPs have been developed for plant disease identification and have shown promise. To ensure the sustainability of applications of NPs and crop production, several knowledge gaps need to be addressed. These include the timeliness of disease identification, the lack of standardised toxicity assessment protocols for NPs, and the paucity of information on NPs-microbiome-plant tri-interactions under field conditions. Furthermore, integration of NPs biosensing with remote sensing or innovative agricultural tools, and the unclear impact of NPs accumulation on soil enzyme activity and nutrient cycling, needs to be addressed. Further study is required to develop a novel technique for real-time identification of plant disease and to accurately identify and quantify the appropriate NPs for specific plant diseases.}, } @article {pmid41580987, year = {2026}, author = {Zhang, H and Zhang, Y and Kang, Z and Xiong, J and Yang, R and Ning, K}, title = {MGM as a Large-Scale Pretrained Foundation Model for Microbiome Analyses in Diverse Contexts.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e13333}, doi = {10.1002/advs.202513333}, pmid = {41580987}, issn = {2198-3844}, support = {2023YFA1800900//National Key R&D Program of China/ ; 2021YFA0910500//National Key R&D Program of China/ ; 2018YFC0910502//National Key R&D Program of China/ ; 32071465//National Natural Science Foundation of China/ ; 31871334//National Natural Science Foundation of China/ ; 81827901//National Natural Science Foundation of China/ ; }, abstract = {Microbial communities are integral to human health, biotechnology, and environmental systems, yet their analysis is hindered by data heterogeneity and batch effects across studies. Traditional supervised methods often fail to capture universal patterns, limiting their utility in diverse contexts. Here, we present the Microbial General Model (MGM), the first large-scale foundation model for microbiome analysis, pretrained on 260,000 samples using transformer-based language modeling. MGM employs self-attention mechanisms and autoregressive pre-training to learn contextualized representations of microbial compositions, enabling robust transfer learning for downstream tasks. Benchmark evaluations demonstrate MGM's superior performance over conventional methods (average ROC-AUC = 0.99 vs. 0.68-0.97) in microbial community classification, with enhanced generalization across geographic regions. MGM also captures spatial and temporal microbial dynamics, as evidenced by its application to a longitudinal infant cohort, where it delineated delivery mode-specific microbiome trajectories and identified keystone genera such as Bacteroides and Bifidobacterium in vaginal deliveries and Haemophilus in cesarean deliveries. Furthermore, through prompt-guided generation, MGM produced realistic microbial profiles conditioned on disease labels. By integrating self-supervised learning with domain-specific fine-tuning, MGM advances the scalability and precision of microbiome analyses, offering a unified framework for diagnostics, ecological studies, and therapeutic discovery.}, } @article {pmid41580778, year = {2026}, author = {Bai, Y and Kong, X and Wang, J}, title = {Targeting microbiome-driven epigenetic modifications: a new frontier in breast cancer treatment.}, journal = {Clinical epigenetics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13148-025-02046-0}, pmid = {41580778}, issn = {1868-7083}, abstract = {Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with significant heterogeneity in its development and treatment response. Recent advances in understanding the roles of the microbiome and epigenetic regulation have opened new avenues for addressing the complexities of breast cancer progression and therapeutic resistance. This review explores the intricate relationship between the gut and intratumoral microbiomes and epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs. Specifically, we examine how microbial metabolites, particularly short-chain fatty acids (SCFAs), regulate gene expression via epigenetic mechanisms, influencing tumor growth, metastasis, and treatment response. The impact of metabolic diseases, including obesity and type 2 diabetes mellitus (T2DM), on breast cancer risk through microbiome-mediated epigenetic changes is also discussed. Furthermore, the review highlights emerging therapeutic strategies that integrate microbiome modulation with epigenetic therapies, including the use of probiotics, dietary interventions, and fecal microbiota transplantation (FMT), as well as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. These innovative approaches hold promise for overcoming treatment resistance and improving clinical outcomes in breast cancer patients. Future research should focus on elucidating the molecular pathways through which the microbiome influences epigenetic regulation and developing personalized, microbiome-targeted therapies that enhance the efficacy of existing treatments. By targeting both the genetic and epigenetic drivers of breast cancer, microbiome-based interventions represent a novel frontier in the fight against this challenging disease.}, } @article {pmid41580621, year = {2026}, author = {Stanton, WN and Braud, SC and Stack, ER and Davidson, MM and Chait, MG and Feyzjou, N and Golden, KB and Pekarev, M}, title = {Microbial species in deep tissue lesions of Hurley stage III hidradenitis suppurativa: a retrospective observational study.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04744-y}, pmid = {41580621}, issn = {1471-2180}, abstract = {BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses, and sinus tract formation. While dysbiosis of the skin microbiome has been implicated in HS pathogenesis, most studies focus on surface flora, leaving the microbial composition of deep tissue lesions poorly characterized, particularly in surgically managed Hurley stage III disease. This study investigates the culture-based subcutaneous microbiome of stage III HS requiring surgical intervention, with the goal of identifying microbial patterns and their associations with patient-specific clinical features.

METHODS: A retrospective chart review of 83 patients undergoing surgical excision for HS was performed. Intraoperative subcutaneous tissue samples were cultured under aerobic and anaerobic conditions. Demographic, clinical, and treatment data were analyzed for associations with microbial findings.

RESULTS: Streptococcus species and Bacteroides were significantly associated with a history of type 2 diabetes mellitus (T2DM) (p < 0.001 and p = 0.009, respectively). Patients without steroid use within 90 days of culture had lower odds of having an obligate anaerobe present (p = 0.041). Patients without T2DM were less likely to have a facultative anaerobe present (p = 0.031). Microbial profiles did not vary significantly by anatomical site.

CONCLUSIONS: The subcutaneous microbiome in stage III HS remains poorly characterized due to the historical focus on surface lesions and non-surgical populations. Our findings highlight distinct microbial profiles within deep tissue that are influenced by comorbidities and steroid use. Plastic and reconstructive surgeons have a critical role in managing advanced HS. This study provides evidence of the subcutaneous microbiome composition that may be used to tailor perioperative antibiotics based on the surgeon's expertise and clinical factors.}, } @article {pmid41580596, year = {2026}, author = {Warren, PK and Miller, G and Kandlikar, GS and Ng'oma, E}, title = {Persistent effects of dietary selection and inbreeding on microbiome composition and longevity in Drosophila.}, journal = {BMC ecology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12862-026-02493-0}, pmid = {41580596}, issn = {2730-7182}, } @article {pmid41580587, year = {2026}, author = {Fiedorová, K and Obručová, H and Grombiříková, H and Vaněrková, M and Blaštíková, E and Štěpánková, S and Husová, L and Freiberger, T}, title = {Longitudinal analysis of gut bacterial and fungal dynamics after solid organ transplantation.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04753-x}, pmid = {41580587}, issn = {1471-2180}, support = {e-INFRA CZ (ID:90254)//the Ministry of Education, Youth and Sports of the Czech Republic/ ; IG 201802//the Centre of Cardiovascular and Transplantation Surgery (CKTCH)/ ; Programme EXCELES, ID Project No. LX22NPO5104//the European Union, Next Generation EU/ ; Programme EXCELES, ID Project No. LX22NPO5104//the European Union, Next Generation EU/ ; Programme EXCELES, ID Project No. LX22NPO5104//the European Union, Next Generation EU/ ; MUNI/A/1716/2024//Masarykova Univerzita/ ; }, } @article {pmid41580563, year = {2026}, author = {Zhan, MH and Zhan, SH and Han, HQ and Kang, LN and Yang, XG and Chai, AX}, title = {Oxygen-driven nebulization of Clostridium butyricum prevents drug-resistant bacterial pneumonia.}, journal = {Applied microbiology and biotechnology}, volume = {110}, number = {1}, pages = {39}, pmid = {41580563}, issn = {1432-0614}, mesh = {Humans ; *Clostridium butyricum/physiology ; Male ; *Pneumonia, Bacterial/prevention & control/microbiology ; Female ; Middle Aged ; Nebulizers and Vaporizers ; Aged ; Administration, Inhalation ; *Oxygen/administration & dosage ; *Drug Resistance, Bacterial ; Adult ; Sputum/microbiology ; *Probiotics/administration & dosage ; Treatment Outcome ; Anti-Bacterial Agents/pharmacology ; }, abstract = {This study aimed to compare the efficacy of inhaled Clostridium butyricum delivered via oxygen-driven nebulization with oral C. butyricum capsules in preventing drug-resistant bacterial pneumonia, using clinical and microbiological parameters as indicators. A total of 310 patients were randomly assigned to experimental group and control group. In the experimental group, each participant inhaled C. butyricum via oxygen-driven nebulization and orally took a placebo capsule containing glucose powder. In the control group, each participant inhaled sterile water via oxygen-driven nebulization and orally took a C. butyricum capsule daily. Key outcomes included body temperature, white blood cell (WBC) count, high-sensitivity C-reactive protein (hs-CRP) level, chest X ray findings, tracheal tube secretion status, and sputum cultures for Pseudomonas aeruginosa, ESBL-producing Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The incidence of pneumonia was 46.45% (72/155) in the control group, compared to only 1.97% (3/152) in the experimental group (relative risk = 23.54, 95%CI: 7.58-73.08). The experiment group demonstrated significant improvements in clinical parameters, including reduced body temperature, lower WBC counts, and decreased hs-CRP level. Chest X-ray findings and tracheal tube secretion status also improved more markedly in the experiment group. Microbiological analysis revealed a significant reduction in the colonization of pathogenic bacteria in sputum cultures from the experiment group. In conclusion, inhaled C. butyricum delivered via oxygen-driven nebulization appears to be more effective than oral C. butyricum capsules in preventing drug-resistant bacterial pneumonia. These findings suggest that direct delivery of C. butyricum to the respiratory tract via oxygen-driven nebulization may enhance its anti-inflammatory and antimicrobial effects, offering a promising strategy for prevention of drug-resistant bacterial pneumonia. KEY POINTS: • Oxygen-driven nebulization of C. butyricum improved the clinical parameters. • Oxygen-driven nebulization of C. butyricum improved tracheal tube secretion status. • Oxygen-driven nebulization of C. butyricum reduced pathogenic bacteria production.}, } @article {pmid41580562, year = {2026}, author = {Gomes, S and Granja, S and Osório, LA and Mackay, RE and Baltazar, F and Silva, E and Preto, A}, title = {Gut microbiota metabolites positively impacts chemotherapy effects in colorectal cancer.}, journal = {Cell biology and toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10565-026-10147-6}, pmid = {41580562}, issn = {1573-6822}, support = {COVID/BD/152995/2022//Fundação para a Ciência e a Tecnologia/ ; PTDC/QUIQIN/28662/2017,//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide, largely due to late-stage diagnosis and limited efficacy of current therapies. 5-Fluorouracil (5-FU) is the standard chemotherapeutic agent used in CRC treatment; however, its effectiveness is often hampered by resistance, toxicity, and suboptimal outcomes in advanced-stage tumors. Recent evidence suggests that gut microbiota-derived short-chain fatty acids (SCFAs) exert anticancer effects and may hold promise as therapeutic adjuvants. In this study, we investigated the potential of a physiologically relevant mixture of SCFAs to enhance the efficacy of 5-FU against CRC. Using a combination of 2D monolayer cultures, 3D models, and the in vivo chicken chorioallantoic membrane (CAM) assay, we demonstrated that SCFAs positively affect the antitumor effects of low-dose 5-FU. SCFAs contributed to the inhibition of CRC cell growth, proliferation, survival, and migration, with an overall increase of the anti-tumour effects observed across the different models. The combined treatment led to a significant reduction in tumour size in the CAM assay, contributing for an improvement of the effects of 5-FU alone. To our knowledge, this is the first report showing that physiologically relevant SCFA combinations can be harnessed to improve the therapeutic index of 5-FU in CRC, in a context-dependent manner. These findings support the development of microbiota-targeted co-adjuvant strategies to optimize CRC chemotherapy, reduce treatment toxicity, and improve patient outcomes, which is important given the clinical interest in microbiome-chemotherapy interactions.}, } @article {pmid41580554, year = {2026}, author = {Klemets, A and Reppo, I and Krigul, KL and Volke, V and Aasmets, O and Org, E}, title = {Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36318-3}, pmid = {41580554}, issn = {2045-2322}, support = {IUT2041//Eesti Teadusagentuur/ ; PRG1414//Eesti Teadusagentuur/ ; No. 3573//European Molecular Biology Organization/ ; }, abstract = {The gut microbiome has been shown to be affected by the use of many human-targeted medications, and the interaction can be bidirectional. This has been clearly demonstrated for type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described. Considering this, we investigate the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyze whether the pre-treatment gut microbiome can predict the treatment efficacy. In the study, patients with type 2 diabetes donated gut microbiome fecal samples at four timepoints (Baseline, Month 1, Month 3, Month 12) that were studied using 16S ribosomal RNA gene sequencing and analysis. Subjects additionally donated plasma and urine samples for quantitative measurement of clinical markers before treatment initiation and at Months 3 and 12. Repeated measures ANOVA paired with paired t-tests were used to analyze the effects of drug initiation on the gut microbiome. Pearson correlation was used to identify microbial features associated with the change in clinical parameters. First, semaglutide and empagliflozin use is associated with changes in the gut microbiome after treatment initiation, but changes in microbial diversity were not detected. Moreover, the baseline gut microbiome predicted changes in glycohemoglobin for semaglutide and empagliflozin users. Based on the results, our findings suggest that semaglutide and empagliflozin impact the gut microbial community during treatment. In addition, the baseline gut microbiome can predict semaglutide treatment effects.}, } @article {pmid41580488, year = {2026}, author = {Szwed-Georgiou, A and Płociński, P and Włodarczyk, M and Tomaszewska, A and Okła, E and Zadylak, J and Koeman, J and Krupa, A and Williams, MK and Rudnicka, K}, title = {Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-37331-2}, pmid = {41580488}, issn = {2045-2322}, support = {54803/2021/2022//Foundation of the University of Lodz/ ; 54803/2021/2022//Foundation of the University of Lodz/ ; 54803/2021/2022//Foundation of the University of Lodz/ ; 54803/2021/2022//Foundation of the University of Lodz/ ; 54803/2021/2022//Foundation of the University of Lodz/ ; 54803/2021/2022//Foundation of the University of Lodz/ ; 54803/2021/2022//Foundation of the University of Lodz/ ; Grant no. 54803/2021/2022//Ministry of Education and Science (Science Hub UniLodz project)/ ; Grant no. 2016/23/D/NZ6/02553//National Science Centre (NCN), Poland under Sonata 12/ ; }, abstract = {Fulvic acid, a naturally occurring organic compound derived from humic substances, has recently emerged as a multifunctional bioactive agent with potential biological relevance. Here, we evaluated the in vitro bioactivity of various fulvic acid-containing formulations, focusing on cytocompatibility, genotoxicity, anti-inflammatory effects, regenerative potential, and probiotic-stimulating potential microbiome-related activity. Two fossil-based fulvic acid formulations (MLG-50 and alkaline MLG-A50) were assessed in eukaryotic cell models (L929 fibroblasts, LoVo epithelial cells, HepG2 hepatocytes) as well as in vitro and in vivo microbial systems. Both formulations demonstrated high cytocompatibility across a broad concentration range, with genotoxicity levels significantly lower than those induced by reference dietary compounds and no relevant nuclear abnormalities detected. Cell proliferation assays revealed enhanced intestinal epithelial cell growth at sub-toxic concentrations. Wound healing assays indicated a pro-regenerative effect of MLG-A50 in LoVo cells, as reflected by an increased wound closure rate compared with the control. Anti-inflammatory activity was evidenced by the suppression of NF-κB activation in LPS-stimulated monocytes via LPS neutralization and receptor-level inhibition, accompanied by reduced TNF and IL-6 secretion without impairment of IL-10 production. In vitro and in vivo microbiome profiling revealed stimulation of beneficial bacterial taxa, including Lactobacillus and Clostridia spp., alongside reduced growth of pathogenic strains. In vivo supplementation with MLG-50 and MLG-A50 further increased microbial diversity and abundance of health-associated taxa. Overall, fulvic acid-based formulations exhibited a favorable safety profile and measurable bioactivity in cellular and microbiome models. These results support further investigation of fulvic acid as a multifunctional bioactive component, particularly in the context of immunonutrition, microbiome modulation, and regenerative-supportive strategies, while acknowledging the need for future mechanistic and translational studies.}, } @article {pmid41580412, year = {2026}, author = {Draisma, A and Loureiro, C and Louwen, NLL and Kautsar, SA and Navarro-Muñoz, JC and Doering, DT and Mouncey, NJ and Medema, MH}, title = {BiG-SCAPE 2.0 and BiG-SLiCE 2.0: scalable, accurate and interactive sequence clustering of metabolic gene clusters.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68733-5}, pmid = {41580412}, issn = {2041-1723}, support = {OSF.23.1.044//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; }, abstract = {Microbial metabolic gene clusters encode the biosynthesis or catabolism of metabolites that facilitate ecological specialization, mediate microbiome interactions and constitute a major source of medicines and crop protection agents. Here, we present BiG-SCAPE and BiG-SLiCE 2.0, next-generation methods that facilitate scalable, accurate and interactive gene cluster analyses. BiG-SCAPE 2.0 updates its classification, alignment methods, and visualizations, enabling more accurate analysis, up to 8x faster runtimes and halved memory requirements. BiG-SLiCE 2.0 updates its distance metric, pHMM database, and classification logic, resulting in increased sensitivity nearing that of BiG-SCAPE. Analysis of 260,630 biosynthetic gene clusters from publicly available genomes reveals that both tools generate concurring estimates of gene cluster diversity, thus providing significantly extended methodological support for recent evidence indicating that the vast majority of natural product diversity remains unexplored. Together, these updates will facilitate global genome mining efforts for natural product discovery and microbiome analyses scalable with current data sizes.}, } @article {pmid41580244, year = {2026}, author = {Aragón-Barroso, AJ and Gallardo-Altamirano, MJ and Castellano-Hinojosa, A and González-Martínez, A and González-López, J and Osorio, F}, title = {Start-up of novel pilot-scale plant based on two-stage expanded granular sludge bed reactors for pig slurry treatment: Performance and microbial dynamics.}, journal = {Bioresource technology}, volume = {445}, number = {}, pages = {134075}, doi = {10.1016/j.biortech.2026.134075}, pmid = {41580244}, issn = {1873-2976}, abstract = {Pig manure management is an environmental challenge that can be improved through high-rate anaerobic digestion, enabling efficient biogas production and resource recovery. This study evaluated a pilot-scale two-stage expanded granular sludge bed (EGSB) system treating real pig slurry over a 150-day start-up. The reactors, operated in series with different working volumes (100 and 500 L), underwent progressive hydraulic retention times (HRT) reductions (R1: 3-1 d; R2: 12-7 d), increasing organic loading rates (OLR) (R1: 7.6-21.4 kg COD m[-3] d[-1]; R2: 1.0-2.5 kg COD m[-3] d[-1]). General chemical oxygen demand (COD) removal reached 68%, with system sensitivity to high solids, while biogas production and methane yield (MY) remained stable, reaching 264 L/d and 352 L CH4/kg COD removed. Microbial analysis identified Clostridium sensu stricto_1, Methanosarcina, and Methanoculleus as key taxa supporting process stability. These results demonstrate the potential of two-stage EGSB systems for sustainable pig manure valorisation.}, } @article {pmid41580145, year = {2026}, author = {Merrick, B and Cooper, R and Davido, B and Goldenberg, S}, title = {The role of the gut microbiome in MDRO colonisation and infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2026.01.009}, pmid = {41580145}, issn = {1469-0691}, abstract = {BACKGROUND: Colonisation of the gastrointestinal tract by multidrug-resistant organisms (MDROs) is a precursor to endogenous infection and onward transmission. The gut microbiome provides colonisation resistance (CR) - the ability to prevent or limit the establishment of pathogens, including MDROs - through nutrient and niche competition, production of inhibitory metabolites, and immune modulation. However, its integrity is threatened by antibiotics, adverse diet, and healthcare exposures.

OBJECTIVES: To describe mechanistic, epidemiological, and interventional evidence on the role of the gut microbiome in MDRO colonisation and infection, and to highlight implications for clinical practice, policy, and research.

SOURCES: PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from 1 January 2000 to 30 September 2025, supplemented by hand-searching of key international guidelines (EUCIC/ESCMID, WHO, CDC/ECDC, NICE/UKHSA) and reference lists.

CONTENT: CR is shaped by microbial and host factors, including metabolic interactions, immune responses, and environmental exposures. Antimicrobials, non-antimicrobial drugs, diet, travel, and healthcare contact can disrupt the microbiota, predisposing to MDRO acquisition and infection. Observational data link gut microbial composition to risk of colonisation and infection outcomes, but predictive models are imperfect. Interventions to preserve or restore CR - such as diet-based strategies, probiotics, and faecal microbiota transplant - show promise but require robust and repeated, context-specific evaluation.

IMPLICATIONS: Protecting the microbiome must be a clinical and policy priority. Short-course, microbiome-sparing antimicrobial regimens, microbiome-aware diagnostics, and public health measures that support microbiome resilience could reduce MDRO burden and infections. Rigorous trials of microbiota-based therapies and integration of microbiome stewardship into antimicrobial resistance strategies are essential for translating mechanistic insights into patient benefit.}, } @article {pmid41579426, year = {2026}, author = {Mettam, J and Ghumman, NZ and Liu, BT and Annandale, H and Gogoi-Tiwari, J}, title = {Phenylalanine as a biomarker of disease in animals: Current evidence and future perspectives.}, journal = {Research in veterinary science}, volume = {202}, number = {}, pages = {106066}, doi = {10.1016/j.rvsc.2026.106066}, pmid = {41579426}, issn = {1532-2661}, abstract = {Phenylalanine (Phe), an essential aromatic amino acid, is emerging as a potential biomarker of metabolic and health status in animals. Altered Phe concentrations reflect changes in metabolic, inflammatory, and disease processes. In companion animals, shifts in serum or biofluid Phe have been linked to hepatopathies, inflammatory enteropathies, and neoplastic conditions. In livestock, variations in milk or serum Phe accompany mastitis, metabolic stress, lameness, and other production-related disorders. Evidence for cats, horses, poultry, and aquaculture species remains limited. Interpretation is complicated by analytical variability, small sample sizes, and confounding factors such as diet, stress, and microbiome composition. Non-invasive sampling of milk, urine, saliva, and breath, shows promise for Phe monitoring across animal species. Advances in multi-omics, particularly metabolomics, proteomics, and microbiome analyses, can clarify mechanisms and support development of composite biomarker panels. This review evaluates current evidence on Phe as a biomarker across species, highlights gaps in research coverage and methodology, and outlines priorities for future work. Expanding studies to underrepresented species, standardizing measurement protocols, and conducting longitudinal research. Addressing these priorities is essential to establish Phe as a robust biomarker, for veterinary diagnostics, health monitoring, and the optimization of animal welfare and production systems. SHORT SUMMARY: This review looks at phenylalanine (Phe), an amino acid, as a possible health indicator in animals. Changes in Phe levels may show problems with metabolism, inflammation, or disease. Evidence is strongest for dogs and dairy cows, but limited for cats, horses, poultry, and fish. Results vary due to measurement methods and other factors. Future studies should standardize testing, include more species, and combine methods to improve Phe's usefulness in monitoring animal health.}, } @article {pmid41579395, year = {2026}, author = {Johnson, SA and Klimis-Zacas, D and Basu, A and Bolling, BW and Feresin, RG and Hooshmand, S and Joris, PJ and Li, Z and Lila, MA and Stull, AJ and Anandh Babu, PV and Weir, TL}, title = {Wild blueberries and cardiometabolic health: a current review of the evidence.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-22}, doi = {10.1080/10408398.2025.2610406}, pmid = {41579395}, issn = {1549-7852}, abstract = {Wild blueberries (Vaccinium angustifolium Ait.) are North American perennial plants rich in polyphenols, including flavonoids, beneficial to human health. This article provides a summary of the evidence and perspectives presented at an expert symposium that focused on wild blueberries and cardiometabolic health. Topics covered include historical perspectives, food matrix and bioavailability, clinical and translational evidence on blueberries and cardiometabolic health, mechanisms of action, the role of the gut microbiome, knowledge gaps, and future research. Overall, data support that acute and chronic wild blueberry consumption can favorably affect measures of cardiometabolic health and related health outcomes such as the gut microbiota and cognitive function. Mechanistically, data suggest wild blueberry polyphenols, particularly anthocyanins, mediate the cardiometabolic benefits of dietary blueberries by acting on multiple targets. However, the cardiometabolic health benefits of wild blueberry consumption are equivocal, and future research should aim to understand factors and mechanisms contributing to individual and subgroup responses. Future studies should also investigate comprehensive biomarkers of cardiometabolic health and explore standardized methodological and precision nutrition approaches. Finally, evaluation and confirmation of wild blueberry phytochemicals, dosing strategies and food matrix interactions are needed to strengthen clinical trial designs and extend dietary recommendations to broader public health benefits.}, } @article {pmid41579355, year = {2026}, author = {Fan, K and Liu, CC and Beckers, KF and Schulz, CJ and Childers, GW and Sones, JL}, title = {Monitored food intake in early pregnancy modulates the maternal microbiome in the obese BPH/5 mouse model of superimposed preeclampsia.}, journal = {Physiological genomics}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiolgenomics.00213.2025}, pmid = {41579355}, issn = {1531-2267}, support = {1R01HL165467-01A1//HHS | National Institutes of Health (NIH)/ ; }, abstract = {Preeclampsia (PE) is a life-threatening pregnancy disorder strongly associated with maternal obesity, yet the mechanistic links between diet, microbiome, and disease risk remain unclear. The obese BPH/5 mouse, which spontaneously develops PE-like features, provides a model to investigate how maternal nutrition influences microbial and metabolic profiles. Here, we tested the effects of modest caloric restriction (pair-feeding= PF) initiated at embryonic day (e0.5) on maternal microbiota and circulating metabolites at embryonic day 7.5 (e7.5). Microbial communities were profiled by 16S rRNA sequencing across fecal, oral, and vaginal niches, and serum short-chain fatty acids (SCFAs) were quantified by gas chromatography mass spectrometry (GC-MS). The PF BPH/5 dams exhibited a markedly reduced Firmicutes-to-Bacteroidetes (F/B) ratio and increased abundance of Bacteroides and Lactobacillus in fecal samples, which are taxa associated with improved metabolic balance and gut barrier support. In contrast, PF increased Proteobacteria abundance in BPH/5 vaginal and oral sites, a shift linked to inflammation and barrier dysfunction. Serum acetic acid was significantly decreased in PF BPH/5 dams and their offspring, suggesting that restricted intake lowers systemic SCFA availability. These findings demonstrate that early pregnancy caloric restriction produces both beneficial and adverse microbial shifts, suggesting that high-fiber dietary interventions that enhance SCFA production may better support maternal-fetal health than caloric restriction alone.}, } @article {pmid41579169, year = {2026}, author = {Shaik, R and Varikuppala, M and Badampudi, S and Jabeen, A and Hamzah, MA and Zehra, FU and Unnisa, A and Mohammed, JS and Azeeza, S}, title = {Innovative immunotherapy approaches: harnessing synergy of dual checkpoint blockade in oncology.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41579169}, issn = {1432-1912}, abstract = {This review offers a comprehensive assessment of synergistic immune checkpoint inhibitor (ICI) strategies and their evolving combinations for cancer immunotherapy, highlighting dual and strategically designed treatment options. It emphasizes essential insights into checkpoint blockade, the tumor microenvironment (TME), and innovative inhibitory and stimulatory targets, including CTLA-4, PD-1/PD-L1, LAG-3, TIM-3, and TIGIT. It discusses preclinical and clinical data demonstrating how combination therapies, such as chemotherapy, radiation, targeted medications, and adoptive cell transfer, can enhance therapeutic responses and circumvent drug resistance. The review systematically outlines important clinical research and regulatory approvals, highlighting improved results in melanoma, non-small cell lung cancer, renal cell carcinoma, and colorectal cancer. A comprehensive assessment of biomarker development, sequencing and timing optimization, and the management of immune-related adverse events is undertaken, in conjunction with novel methodologies such as AI-driven biomarker identification and the impact of the gut microbiome on the efficacy of immune checkpoint inhibitors. The research indicates that the optimal approach to enhance treatment efficacy and precision in cancer immunotherapy is through the implementation of rational combination strategies that address multiple immune evasion mechanisms and incorporate manipulation of the tumor microenvironment. This will improve long-term survival and clinical outcomes across all cancer types.}, } @article {pmid41579164, year = {2026}, author = {Yao, H and Sun, C and Jiang, L and Zhou, Y and Wang, X and Zhang, Z and Liu, B and Yang, Y and Wang, C and Zhou, C and Song, F and Luo, H}, title = {Responses of skin and salivary microbiome to different environmental exposures.}, journal = {International journal of legal medicine}, volume = {}, number = {}, pages = {}, pmid = {41579164}, issn = {1437-1596}, support = {82371897//National Natural Science Foundation of China/ ; 2024NSFSC0529//Natural Science Foundation of Sichuan Province/ ; }, abstract = {Forensic microbiology allows identification by microbiome analysis when human DNA analysis is limited. However, microbiome-based approaches have not been widely used in forensic medicine. The spatial and temporal stability of microbial communities in response to environmental exposures represents a serious challenge. This study investigates the dynamics of skin and saliva microbial markers in response to environmental exposure to advance their forensic applicability. We selected 8 characteristic microorganisms (Finegoldia magna, Corynebacterium tuberculostearicum, Cutibacterium acnes for skin; Haemophilus parainfluenzae, Streptococcus oralis, Prevotella melaninogenica for saliva; Achromobacter, Pseudomonas as environmental markers) and developed two multiplex amplification systems for capillary electrophoresis detection. A longitudinal exposure model (0-120 days) under controlled indoor and dry environment was applied to 420 skin and saliva samples from 10 subjects. Saliva samples exhibited significant microbial community shifts between environments (R[2] = 0.4137). Dry environment preserved community structure better, evidenced by delayed inflection points in markers' proportions and stronger clustering in PCoA. Redundancy analysis correlated microbial markers with temperature and humidity, and this correlation varied. The microbial markers remained detectable after 120 days of environmental exposure and were able to provide information on community characteristics and deposition time. This study explored the effects of environment and time on microbial communities and the response patterns of microbial markers to temperature and humidity. It is expected to provide help for forensic microbial research related to environmental exposure.}, } @article {pmid41579151, year = {2026}, author = {Gan, T and Zhang, N and Liu, L and Li, W and Ding, M and Chen, J and Zhou, T and Mao, A}, title = {Lactobacillus plantarum CCFM639 Alleviates Hypertension by Reshaping Gut Microbiota and Regulating Key Metabolites.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41579151}, issn = {1867-1314}, support = {82400481//National Natural Science Foundation of China/ ; }, abstract = {A strong association between the gut microbiome and hypertension has emerged. Our previous work demonstrated that supplementation with L. plantarum CCFM639 (CCFM639) reduced blood pressure (BP) in hypertensive mice involving inhibiting the growth of S. aureofaciens Tü117 and conducted an exploratory randomized trial in adults with prehypertension or stage 1 hypertension. Here, we evaluate the effects of CCFM639 supplementation (10[9] CFU/day for 8 weeks) on the gut microbiome and serum metabolome in a subset of these participants (n = 20). Untargeted metabolomic analysis was performed on serum samples, and stool microbiome composition was assessed via metagenomic sequencing. Mono-CCFM639 supplementation altered the metabolomic profile without affecting gut microbiota diversity but reshaped microbial composition. CCFM639 supplementation modulated both the gut microbiome and serum metabolome. Circulating gut-derived metabolites are likely to account for the improvements in BP, suggesting that CCFM639 supplementation could be a key component of nutritional interventions targeting the gut microbiota for hypertension management.}, } @article {pmid41578808, year = {2026}, author = {Warda, M and Adıgüzel, MC and Tekin, S and Çelebi, F and Abd El-Aty, AM}, title = {Hypothesizing the Biotherapeutic Potential of Nitrosotalea devanaterra: Targeting Ammonia Dependency to Disrupt Helicobacter pylori Survival Strategies in Gastritis.}, journal = {The Eurasian journal of medicine}, volume = {58}, number = {1}, pages = {1-4}, doi = {10.5152/eurasianjmed.2026.251203}, pmid = {41578808}, issn = {1308-8734}, abstract = {The increasing antibiotic resistance of Helicobacter pylori (H. pylori) underscores the urgent need for alternative, nonantibiotic therapeutic strategies. This conceptual framework hypothesizes that Nitrosotalea devanaterra (N. devanaterra), an ammonia-oxidizing acidophile, could function as a biological competitor to H. pylori by reducing local ammonia availability, a critical factor for its survival and colonization in the gastric environment. To explore this hypothesis, a stepwise experimental framework is proposed. Initially, in vitro coculture models using gastric epithelial cells under microaerophilic conditions were employed to investigate potential interactions, metabolic competition, and impacts on H. pylori viability. Prospective in vivo validation could subsequently be performed using Mongolian gerbils, a model that closely mimics human gastric physiology, to assess the microbial load, histopathological changes, and host immune responses under controlled conditions. While direct empirical evidence for N. devanaterra survival and activity in the highly acidic gastric milieu is currently lacking, preliminary theoretical analysis suggests that ammonia competition could influence H. pylori persistence and pathogenesis. This hypothesis-driven approach emphasizes a microbiome-inspired strategy that does not rely on antibiotics, potentially reducing selective pressure for resistance. By introducing the concept of targeted nutrient competition as a therapeutic modality, this framework aims to stimulate further research into the feasibility of employing environmental acidophiles as modulators of pathogenicm bacteria in the stomach. The proposed strategy provides a foundation for future studies evaluating N. devanaterra or related ammonia-oxidizing microorganisms as innovative, nonantibiotic interventions against H. pylori infection. Cite this article as: Warda M, Adıgüzel MC, Tekin S, Çelebi F, Abd El-Aty AM. Hypothesizing the biotherapeutic potential of Nitrosotalea devanaterra: targeting ammonia dependency to disrupt Helicobacter pylori survival strategies in gastritis. Eurasian J Med. 2026, 58(1), 1203, doi: 10.5152/eurasianjmed.2026.251203.}, } @article {pmid41578762, year = {2025}, author = {Shen, F and Xu, C and Wang, C}, title = {Gut Microbiome Diagnostic Biomarkers for Colorectal Cancer.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {37}, number = {1}, pages = {62-74}, pmid = {41578762}, issn = {2148-5607}, mesh = {Humans ; *Colorectal Neoplasms/diagnosis/microbiology ; *Gastrointestinal Microbiome/genetics ; Male ; Feces/microbiology ; Female ; Middle Aged ; *Biomarkers, Tumor/analysis ; Aged ; *Adenoma/microbiology/diagnosis ; Case-Control Studies ; Disease Progression ; Early Detection of Cancer/methods ; Fusobacterium nucleatum/isolation & purification ; Adult ; }, abstract = {BACKGROUND/AIMS: Gold standard diagnostic methods, such as invasive procedures and serum biomarkers, have limited sensitivity and specificity for the detection of colorectal cancer (CRC). Thus, the development of more accurate and noninvasive detection approaches is imperative. Emerging research elucidating the intricate role of the gut microbiota in CRC pathogenesis underscores the need for precision screening tailored to high-risk cohorts to improve early detection and intervention strategies and comprehensively address this challenging clinical problem.

MATERIALS AND METHODS: Fecal metagenomic sequencing datasets were employed to identify potential bacterial biomarkers for CRC diagnosis and selected relevant microbial taxa for subsequent validation. A total of 180 participants were enrolled: 65 healthy controls (HC), 65 colorectal adenoma patients, and 50 CRC patients, and fecal samples were analyzed using fluorescence quantitative polymerase chain reaction to confirm biomarker relative abundance, culminating in the establishment of an evolutionary model for CRC progression; furthermore, a treatment efficacy and prognostication model supported by comprehensive statistical methodologies was established.

RESULTS: This study analyzed fecal microbial biomarkers associated with CRC progression and identified differentially abundant bacterial species across HCs, adenoma, and CRC patient groups. Notably, Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (P. anaerobius) showed significant correlations with CRC stage and metastasis, highlighting their potential as diagnostic biomarkers. Among individual microbes, P. anaerobius exhibited the highest diagnostic value when combined with Fn.

CONCLUSION: The results underscore the potential application of fecal microbial markers, particularly Fn and P. anaerobius, for diagnosing CRC and monitoring its progression.   Cite this article as: Shen F, Xu C, Wang C. Gut microbiome diagnostic biomarkers for colorectal cancer. Turk J Gastroenterol. 2026;37(1):62-74.}, } @article {pmid41578632, year = {2026}, author = {Grimsholm, O and Zghaebi, M and Hambrecht, B and Kalic, T and Udoye, CC and Manz, R and Bohle, B and Sitnik, KM and Eckl-Dorna, J and Breiteneder, H}, title = {Allergic Sensitization to Inhalant Allergens in the Upper Respiratory Tract-the B Cell Side.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.70229}, pmid = {41578632}, issn = {1398-9995}, support = {10.55776/PAT3959823(OG)//Austrian Science Fund/ ; P32953andI4437(BB)//Austrian Science Fund/ ; P36664(KMS)//Austrian Science Fund/ ; 10.55776/KLP4891723(JED)//Austrian Science Fund/ ; Danube-ARCP03(BB)//Federal State of Lower Austria/ ; P04(HB)//Federal State of Lower Austria/ ; P10(TK)//Federal State of Lower Austria/ ; EXC22167-390884018(RAM)//Deutsche Forschungsgemeinschaft/ ; MA2273/16-1(CCU)//Deutsche Forschungsgemeinschaft/ ; J06/2024(CCU)//Junior Program of the Medical Section of the University of Lübeck/ ; }, abstract = {Allergic diseases are on the rise worldwide, driven by respiratory epithelial barrier dysfunction that promotes sensitization to inhalant allergens such as pollen, dust mites, pet dander, and fungal spores. These antigens trigger IgE-mediated immune responses that lead to diseases such as allergic rhinitis (AR) and asthma. B cells play a central role by producing allergen-specific IgE, presenting antigens, releasing cytokines, and forming memory B cells (MBCs). Their differentiation into IgE-secreting plasma cells (PCs) mainly relies on T cell help, germinal center (GC) reactions, and/or extrafollicular responses and class switch recombination (CSR), which makes them important therapeutic targets. The nasal mucosa, as the first point of contact for allergens, acts both as a barrier and as an immunological site. In AR, IL-13-driven goblet cell hyperplasia and overproduction of mucus compromise the integrity of the barrier. Although the nasal microbiome can influence the immune response, its role in atopy remains unclear. Local B cell activity, including extrafollicular IgE production and ectopic GCs, enhances mucosal immunity. Epithelial cells detect allergens via pattern recognition receptors (PRRs) and release alarmins (IL-25, IL-33, TSLP), which can trigger type 2 inflammation. Proteases from allergens such as house dust mites (HDM) disrupt epithelial junctions, while pollutants, smoke, microplastics, and allergen-derived metabolites further modulate immune activation. Allergens are transported to the lymph nodes by the passive flow to follicular dendritic cells (FDCs) or by active uptake by interferon regulatory factor (IRF) 4-dependent conventional type 2 DCs, which activate T follicular helper (TFH) cells to drive IgE responses. Advanced lymphoid organoids that mimic the microenvironment of GCs offer promising models for the study of allergic sensitization but require improved standardization.}, } @article {pmid41578559, year = {2026}, author = {Qin, X and Deng, J and Chen, B and Tan, X and Xie, X and Zhou, G and Hou, W and Wen, S and Lin, Y}, title = {Circulating metabolites mediating the effect of psoriatic arthritis on Crohn disease risk: A mediation Mendelian randomization study.}, journal = {Medicine}, volume = {105}, number = {4}, pages = {e47362}, doi = {10.1097/MD.0000000000047362}, pmid = {41578559}, issn = {1536-5964}, mesh = {Humans ; *Crohn Disease/genetics/blood/epidemiology ; Mendelian Randomization Analysis ; *Arthritis, Psoriatic/genetics/blood/epidemiology/complications ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Male ; Risk Factors ; Adult ; Female ; }, abstract = {Psoriatic arthritis (PsA) and Crohn disease (CD) are chronic immune-mediated illnesses that afflict a growing number of adults and children worldwide. Observational studies have revealed a link between PsA and CD, but the modifiable risk variables that mediate the causal effects remain unknown. We aim to look into the relationship between PsA and CD, and to see if circulating metabolites have a role in the pathophysiology of both disorders. By scanning the whole genome of a large number of people and detecting millions of genetic variation sites in the genome, we take advantage of the random assignment of genotypes in nature and use single nucleotide polymorphisms as instrumental variables to simulate the environment of randomized controlled trials, so as to infer the causal relationship between exposure factors and outcomes. Using summary statistics from genome-wide association studies of predominantly European ancestry, we used two-sample Mendelian randomization (MR) to estimate the effects of PsA on CD (1637 cases/212,242 controls; 1401 cases/461,532 controls), and two-step MR to assess the association with 1400 circulating metabolites. Genetic predisposition to PsA was associated with a higher risk of CD (pooled odds ratio, 1.00051; 95% confidence interval [CI], 1.00023-1.00078; P < .001). The statistical association between PsA and CD was mediated by the concentrations of homocitrulline, 5-hydroxyhexanoate, carnitine C14, gamma-glutamylthreonine, furaneol sulfate, and trans-urocanate, which accounted for 4.23% (95% CI, -0.68% to 9.15%, P = 4.58 × 10-2), 7.85% (95% CI, -1.74% to 17.44%, P = 9.91 × 10-3), 6.09% (95% CI, -1.70% to 13.88%, P = 3.09 × 10-2), 7.45% (95% CI, -1.21% to 16.11%, P = 1.31 × 10-3), 8.88% (95% CI, 0.23% to 17.54%, P = 8.39 × 10-3), and 3.96% (95% CI, -0.48% to 8.40%, P = 2.29 × 10-2) of the total effect, respectively. Our MR analysis identified significant PsA-CD associations mediated through specific metabolites, particularly the gut microbiome-derived furaneol sulfate (showing highest mediation), supporting gut-joint axis involvement. These findings establish a crucial theoretical framework for guiding clinical practice in the management of PsA and CD.}, } @article {pmid41578374, year = {2026}, author = {Wang, Z and Ma, T and He, J and Ge, Y and Liu, Q and Lan, X and Liu, L and Wan, F and Shen, W}, title = {Impact of zearalenone on quorum sensing signaling molecules and its association with the suppression of ruminal microbial fermentation in a RUSITEC system.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {15}, pmid = {41578374}, issn = {1674-9782}, support = {32302764//National Natural Science Foundation of China/ ; 2024JJ5179//Hunan Provincial Natural Science Foundation/ ; XJSLSW-2023001//Key laboratory for the feed and biology technique of Xinjiang Uygur Autonomous Region/ ; HARS-08//Hunan Herbivores Industry Technological System/ ; }, abstract = {BACKGROUND: Zearalenone (ZEN), a common mycotoxin in ruminant diets, could disturb the rumen ecosystem and impair rumen fermentation. Noticeably, ZEN has been shown to reduce the relative abundances of specific bacterial taxa that potentially possess quorum sensing (QS) functions, which are deemed essential for the microbial interactions and adaptations during rumen fermentation. Nonetheless, whether QS communications participate in the responses of rumen microbial fermentation to ZEN remains unknown. Therefore, the present trial was performed to explore the potential roles of QS during the alterations of rumen microbial fermentation by ZEN through a rumen simulation technique (RUSITEC) system, in a replicated 4 × 4 Latin square design.

RESULTS: ZEN significantly (P < 0.05) reduced QS signal autoinducer-2 (AI-2), and tended to (P = 0.051) downregulate QS signal C4-homoserine lactone (HSL). ZEN also significantly (P < 0.05) decreased total volatile fatty acid (TVFA), acetate, propionate, isobutyrate, isovalerate, organic matter disappearance (OMD), neutral detergent fiber disappearance (NDFD), and acid detergent fiber disappearance (ADFD) in different manners. The linear discriminant analysis effect size (LEfSe) analysis indicated significantly (P < 0.05) differential enrichments of a series of bacterial taxa such as Butyrivibrio_sp_X503, Rhizobium daejeonense, Hoylesella buccalis, Ezakiella coagulans, Enterococcus cecorum, Ruminococcus_sp_zg-924, Polystyrenella longa, and Methylacidimicrobium fagopyrum across different treatments. The phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) analysis suggested that QS were predicted to be significantly (P < 0.05) affected by ZEN. The metabolomics analysis detected considerable significantly (P < 0.05) differing metabolites and implied that ZEN challenge significantly (P < 0.05) influenced the indole alkaloid biosynthesis, biosynthesis of alkaloids derived from shikimate pathway, and sesquiterpenoid and triterpenoid biosynthesis. Significant (P < 0.05) interconnections of QS molecules with the differential rumen fermentation traits, differential bacterial taxa, and differential metabolites were exhibited by Spearman analysis.

CONCLUSIONS: ZEN negatively affected the QS signals of AI-2 and C4-HSL, which was found to correlate with the fluctuations in specific rumen fermentation characteristics, ruminal bacterial populations, and ruminal metabolisms. These interrelationships implied the potential involvement of QS in the reactions of rumen microbiota to ZEN contamination, and probably contributed to the inhibition of rumen fermentation.}, } @article {pmid41578371, year = {2026}, author = {Reynolds, J and Sosnowski, K and Carlson, C and McGuire, TD and Roman, W and Yoon, JY}, title = {Smartphone-based multispectral autofluorescence analysis of bacteria mixtures of staphylococci using convolutional neural network.}, journal = {Journal of biological engineering}, volume = {20}, number = {1}, pages = {15}, pmid = {41578371}, issn = {1754-1611}, support = {Partnerships to Advance Cancer Health Equity (PACHE) program/CA/NCI NIH HHS/United States ; One Health Initiative Pilot Grant//University of Arizona/ ; NC-1194//National Institute of Food and Agriculture/ ; Partnerships to Advance Cancer Health Equity (PACHE) program/CA/NCI NIH HHS/United States ; }, abstract = {UNLABELLED: Despite the numerous merits of bioreceptor-based biosensors for detecting bacteria, they often fail to identify complex bacterial mixtures, such as those encountered in microbiome analysis, especially when the bacterial mixtures belong to the same genus. Additionally, their procedure involves multiple steps of reagent rinsing and/or staining. This work demonstrates the proof-of-concept for smartphone-based multispectral autofluorescence analysis of bacterial mixtures belonging to the same genus: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus capitis, and Staphylococcus aureus, that does not require bioreceptors or staining processes. These staphylococci mixture models represent the skin infection model, where the goal is to identify the presence of pathogenic S. aureus (coagulase-positive) from other Staphylococcus spp. (coagulase-negative staphylococci or CoNS). We designed and tested a portable, inexpensive smartphone-based imaging platform using a smartphone microscope attachment with a 3D-printed housing, LEDs for sample excitation, and low-cost color films for filtering fluorescent emission. For each data point, the excitation light sources and emission filters were alternated by sliding the color films into place and pressing the LED buttons to acquire nine unique autofluorescence images. A convolutional neural network (CNN) model was developed for various bacterial mixtures of CoNS and CoNS + S. aureus. It demonstrated excellent performance in detecting S. aureus presence, with a sensitivity of 91%. However, a small number of false positives compromised the overall accuracy to 84%. Experiments were further replicated with the CoNS- and S. aureus-spiked human skin swab samples. While the sensitivity (for identifying S. aureus) remained satisfactory at 81%, the overall accuracy was compromised to 68% due to the substantial number of false positives. This could be attributed to the inherent limitations of the currently available smartphone-based microscope attachment, which makes focusing challenging, especially with skin swab samples. Overall, this work provides a proof-of-concept for identifying bacterial mixtures belonging to the same genus without using bioreceptors or laboratory equipment, toward low-cost, rapid assessment of complex bacterial mixture samples.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-025-00616-7.}, } @article {pmid41578188, year = {2026}, author = {Ding, X and Chai, Y and Zhang, Q and Lan, J and Liu, J and Zhou, N and Hou, R and Zhou, J and Lei, H}, title = {Faecal microbiome and serum metabolomics: potential biomarkers for type 2 diabetes.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04571-7}, pmid = {41578188}, issn = {1471-2180}, support = {Applied Basic Research project (01041217)//Other/ ; }, abstract = {BACKGROUND: Type 2 diabetes (T2D) presents clinical challenges due to its difficult early diagnosis and treatment insensitivity. Further, the relationship between gut microbiota and serum composition in T2D has not been fully characterized. This study aimed to determine the relationship between gut microbiome and serum metabolome in patients with T2D.

METHODS: We collected fecal and serum samples from 30 T2D patients and healthy controls (HCs). The fecal microbiome composition was analyzed using 16S rRNA sequencing, and serum metabolites were detected by UHPLC-MS/MS. Alpha and beta diversity indices (Chao1, Shannon, PCoA, etc.) were calculated to assess microbial diversity and community structure. Differential metabolites were integrated to identify potential biomarkers, and random forest modeling was used for predictive analysis to investigate and validate the importance of specific gut microbial genera.

RESULTS: The feces and blood of T2D patients demonstrated different characteristics of 20 differential microbiomes in the gut and 30 metabolite in the blood from HCs. Further, a significant correlation was observed between the gut microbiota and serum metabolomic profiles, reflecting the influence of the microbiota on metabolic activity. In addition, the states of T2D and HC groups were clearly distinguishable based on differences in gut microbes and metabolites, with the random forest model achieving excellent diagnostic performance (AUC values of 0.9764 and 0.9823, respectively).

CONCLUSIONS: Our study provides a comprehensive profile of changes in the microbiome and serum metabolomics, indicating their potential application as biomarkers for future diagnosis and treatment in T2D.}, } @article {pmid41578147, year = {2026}, author = {Thompson, B and Petrić Howe, N}, title = {Briefing Chat: The canny cow that can use tools, and how babies share their microbiomes.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-026-00235-2}, pmid = {41578147}, issn = {1476-4687}, } @article {pmid41577965, year = {2026}, author = {Ishihara, C and Sako, M and Tsutsumi, K and Fujii, N and Hashimoto, D and Sato, A and Ichiba, Y and Chikazawa, T and Kakizawa, Y and Nishinaga, E and Uchiyama, A}, title = {Correction: Involvement of propionate, citrulline, homoserine, and succinate in oral microbiome metabolite-driven periodontal disease progression.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {3251}, doi = {10.1038/s41598-026-36866-8}, pmid = {41577965}, issn = {2045-2322}, } @article {pmid41577755, year = {2026}, author = {Ilaria, F and Ekaterina, T and Raphael, T and Oussama, B and Georg, L and Luigimaria, B and Tanja, M}, title = {Five years of oxen grazing enhances soil carbon and structure in alpine vineyards.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35761-6}, pmid = {41577755}, issn = {2045-2322}, } @article {pmid41577717, year = {2026}, author = {Khodadad, CLM and Dixit, AR and Hummerick, ME and Spencer, LE and Spern, CJ and Torres, J and Monje, O and Richards, JT and Gooden, J and Curry, AB and Massa, GD and DuFour, N and Poulet, L and Romeyn, MW and Wheeler, RM}, title = {Evaluating microbial community profiles of Chile peppers grown on the International Space Station provides implications for fruiting crops.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-20440-9}, pmid = {41577717}, issn = {2045-2322}, abstract = {One of NASA's goals is growing edible crops in spaceflight to supplement the astronauts' diet with fresh, safe-to-eat vegetables. Growing plants in spaceflight presents challenges to achieve optimal plant growth and productivity. It is important to understand the optimal conditions for crops grown in spaceflight. The Advanced Plant Habitat (APH), an enclosed, environmentally controlled plant growth facility on the International Space Station (ISS) has been used to grow plants and monitors the environment. A technology demonstration mission on the ISS used the APH to grow chile peppers, Capsicum annuum, cv. NuMex Española Improved to maturity. Over 25 peppers were successfully harvested as a mix of red and green peppers at 109 and 137 days after initiation. Half of the fruit were consumed by the crew, and half were frozen at - 80 °C and returned with the science carrier (SC) to Kennedy Space Center, FL to determine microbial load and food safety. Bacterial and fungal counts, ranged from below detection limit to 111 CFU/gram fresh weight found on a single pepper only. Foodborne pathogens were not detected. Investigation of the communities using the V4 region of the 16S rRNA gene revealed taxonomic variations between the SC quadrants as well as between hardware components and plant tissues, indicating possible vertical or horizontal transfer of some bacteria. An investigation into the bacterial communities indicated 13 genera and 1 unidentified microbe as possible core microbiome components. In addition, bacteria such as Burkholderia and Sphingomonas previously identified from ISS water samples were present in the communities. This technology demonstration growing a long duration fruiting crop on the ISS provided verification of the pre-determined environmental conditions, contributed to the validation of the APHs' capability to support fruiting crops in space, and provided the crew a safe-to-eat addition to their pre-packaged diet. This technology demonstration may serve as a baseline for future space crop production systems or long duration spaceflight missions.}, } @article {pmid41577579, year = {2026}, author = {Tyagi, B and Toppo, L and Biradar, A}, title = {Comment on "Impact of oral butyrate on clinical and biochemical parameters in IBD: A randomized placebo-controlled study targeting gut microbiota".}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2025.12.027}, pmid = {41577579}, issn = {1878-3562}, } @article {pmid41577500, year = {2026}, author = {Gabriel, PE and Xylinas, E}, title = {The Future of Non-muscle-invasive Bladder Cancer: Towards a Molecular-Digital Paradigm for Personalized Management.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2026.01.005}, pmid = {41577500}, issn = {2405-4569}, abstract = {The management of non-muscle-invasive bladder cancer (NMIBC) is undergoing a major paradigm shift driven by molecular biomarkers, artificial intelligence (AI), and a better understanding of the tumor microenvironment and bladder microbiome. Traditional risk stratification based on stage and grade fails to capture the biological heterogeneity of NMIBC and its variable clinical behavior. Recent evidence highlights the prognostic and dynamic value of urinary and circulating tumor DNA for detecting aggressive disease, anticipating recurrence, and guiding treatment escalation. In parallel, AI-based models that integrate clinicopathological variables and computational histology significantly outperform current guideline-based risk calculators and thus allow refined patient stratification. Furthermore, emerging data demonstrate that immune infiltration patterns and microbiome composition influence response to intravesical therapies, particularly bacillus Calmette-Guérin. Together, these advances support a unified molecular-digital framework that integrates biomarkers, AI, and immunomicrobial profiling to personalize surveillance and treatment strategies. This evolving approach hold promise for optimizing bladder preservation and improving oncological outcomes in NMIBC. PATIENT SUMMARY: Combining tumor DNA tests, artificial intelligence tools, and analysis of the immune and microbial environment in the bladder may improve assessment of risk for patients with non-muscle-invasive bladder cancer. This approach could allow more personalized treatment and follow-up.}, } @article {pmid41577432, year = {2026}, author = {Shen, J and Tigabu, A and Mishra, SK and Urmi, U and Ozkan, J and Stapleton, F and Yasir, M and Willcox, M}, title = {Antimicrobial resistance surveillance: lessons learnt from large databases of antimicrobial resistance genes.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328620}, pmid = {41577432}, issn = {1468-2079}, abstract = {Ocular infections, caused by a variety of microbes, are likely to become more difficult to treat due to the global increase in antimicrobial resistance (AMR). Traditional assays for resistance only analyse a small proportion of the possible resistance capability of microbes. This review discusses the use of genomic datasets for predicting AMR and their current applications in investigating ocular infections. The use of whole genome sequencing coupled with several large databases on antimicrobial resistance genes (ARGs) can predict phenotypic resistance and multidrug resistance in bacteria. Use of this technology for viral and fungal infections is less advanced and would be a useful area for future research. Metagenomic analysis of the ocular surface microbiome for ARGs could be a sensitive and rapid method for tracking resistance in ocular infections, and monitoring commensal reservoirs of transferable ARGs. Applications of these newer technologies to ocular infections also have the potential to assess the long-term impact of topical antibiotics, disinfectants and preservative use on the ocular microbiome, as well as being used in epidemiological studies to study acquisition and transmission of ARGs.}, } @article {pmid41577126, year = {2026}, author = {Hu, J and Zheng, Y and Li, L}, title = {The untapped potential of metaproteomics in microbial systems ecology.}, journal = {Journal of proteomics}, volume = {}, number = {}, pages = {105604}, doi = {10.1016/j.jprot.2026.105604}, pmid = {41577126}, issn = {1876-7737}, abstract = {As a direct readout of protein presence and abundance in complex microbiomes, metaproteomics has become central to uncovering functionality across diverse microbial ecosystems. Recent collaborative efforts within the research community have driven methodological advances, computational innovations, and diverse applications. With rising confidence in the deepening development of metaproteomics, we highlight the Proteome-level Microbial Systems Ecology (ProMiSE) framework as a focus for the next phase, which provides the conceptual lens to interpret metaproteomics data with a bottom-up perspective that extends beyond functional profile and taxonomic composition to the quantitative assessment of system properties, processes, and dynamics. Building on existing metrics such as β-diversity and functional redundancy, future work can further develop quantitative approaches for resilience, exergy, and functional energy landscapes, thereby enabling a deeper systems-level understanding of microbiome dynamics and opening new avenues for the precise functional regulation of microbiomes. SIGNIFICANCE: This Perspective reviews the development of metaproteomics-particularly in the Journal of Proteomics-and envisions it as a transformative tool in microbial systems ecology, introducing the ProMiSE framework to integrate protein-resolved data with ecological theory and properties such as redundancy, resilience, and functional energy landscapes for the future of precise microbiome regulation.}, } @article {pmid41577072, year = {2026}, author = {Hiratsuka, D and Matsuo, M and Hirota, Y}, title = {The Reproductive Tract Microbiome and Female Fertility: Dysbiosis, Disease Links, and Emerging Therapeutic Strategies.}, journal = {Fertility and sterility}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.fertnstert.2026.01.010}, pmid = {41577072}, issn = {1556-5653}, abstract = {The reproductive tract microbiome plays a pivotal role in female fertility, with Lactobacillus-dominated communities maintaining a protective, low-pH environment. Dysbiosis-characterized by a reduction in Lactobacillus species and overgrowth of anaerobes-is associated with adverse outcomes. Chronic endometritis frequently involves diminished Lactobacillus species and colonization by pathogenic microbes such as Gardnerella and Escherichia, and antibiotic treatment may restore eubiosis and has been reported to improve implantation rates. Recurrent implantation failure is often linked to non- Lactobacillus-dominated endometrial microbiota, which can be partially normalized through combined antibiotic and probiotic interventions. In polycystic ovary syndrome, gut dysbiosis-marked by low microbial diversity, reduced short-chain fatty acid-producing bacteria, and increased lipopolysaccharide-producing Gram-negative species-correlates with both metabolic and reproductive dysfunction. Dietary fiber, probiotics, and metformin may help reestablish microbial balance. Patients with endometriosis and adenomyosis tend to harbor high-diversity reproductive tract microbiota with decreased Lactobacillus abundance, potentially exacerbating inflammatory pathways. During pregnancy, a Lactobacillus-rich vaginal microbiota is associated with lower risks of miscarriage and preterm birth, whereas bacterial vaginosis-like, high-diversity communities are linked to increased risks. Emerging therapies-including antibiotics, vaginal probiotics, and vaginal microbiota transplantation-aim to restore eubiosis and improve reproductive outcomes. Collectively, this review highlights the impact of dysbiosis on fertility and summarizes emerging therapeutic strategies to optimize reproductive success.}, } @article {pmid41576957, year = {2026}, author = {Shibl, AA and Denekew, TW and Ahmad, AR and Abdelrazig, S and Leonor, CE and Utenova, L and Zhang, G and AbdelBaqi, M and Malla, Y and Arshad, M and Arnoux, M and Drou, N and Abdulle, A and , and Ali, R and Amin, SA and Idaghdour, Y and Jha, AR}, title = {Integrative multi-omics analysis reveals oral microbiome-metabolome signatures of obesity.}, journal = {Cell reports}, volume = {}, number = {}, pages = {116819}, doi = {10.1016/j.celrep.2025.116819}, pmid = {41576957}, issn = {2211-1247}, abstract = {Obesity is a leading global health challenge and risk factor for cardiometabolic disorders, driven in part by industrialization and low-fiber, ultra-processed diets. While the gut microbiome has been implicated in obesity, the contribution of the oral microbiome-the body's second largest microbial ecosystem-remains underexplored. We analyze a prospective cohort of 628 Emirati adults, including multi-omics profiling of 97 obese individuals and 95 matched controls, generating the most comprehensive oral microbiome analysis to date. Obese participants show altered microbial diversity, composition, functions, and metabolites with enrichment of proinflammatory Streptococcus parasanguinis, Actinomyces oris, and lactate-producing Oribacterium sinus. Pathways for carbohydrate metabolism, histidine degradation, and obesogenic metabolites are upregulated, whereas B-vitamin and heme biosynthesis are depleted. Corresponding metabolites-including lactate, histidine derivatives, choline, uridine, and uracil-are elevated and correlate with obesity-linked cardiometabolic markers. These findings reveal mechanistic oral microbiome-metabolite shifts, highlighting oral microbiome-host interactions as novel targets for obesity prevention and intervention.}, } @article {pmid41576946, year = {2026}, author = {Lan, X and Liang, Q and He, J and Wu, J and Zhang, X and Li, F and Li, L and Zhao, G and Guo, R and Jia, H}, title = {Microbial single-cell omics in situ.}, journal = {Cell genomics}, volume = {}, number = {}, pages = {101128}, doi = {10.1016/j.xgen.2025.101128}, pmid = {41576946}, issn = {2666-979X}, abstract = {Metagenomics has enabled the understanding of the microbial composition and functional potential in various environments. Using laser-induced forward transfer (LIFT) technology, we report high-quality microbial single-cell genomes or transcriptomes in complex samples such as mouse gut, human saliva, and tumor sections. Bacterial cells in close proximity to each other or to host cells could be directly analyzed using this single-cell approach. Bacterial cells in mice or human samples could be fluorescently labeled for single-cell visualization before collection. The high-quality single-cell transcriptome results allow us to delineate cell-fate commitment in Bacillus sporulation and preliminary characterize gene expression from Bacteroides in a colorectal cancer sample. The method is scalable and precise and empowers insights about microbial populations and single-cell interactions with the host.}, } @article {pmid41576942, year = {2026}, author = {Masi, D and Watanabe, M and Clément, K}, title = {Gut microbiome and obesity care: Bridging dietary, surgical, and pharmacological interventions.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102573}, doi = {10.1016/j.xcrm.2025.102573}, pmid = {41576942}, issn = {2666-3791}, abstract = {In the mid-2000s, mouse studies suggested that the gut microbiome might influence energy harvest, fat storage, appetite, insulin sensitivity, and inflammation. Since then, our understanding of the gut microbiome's role in obesity has advanced significantly. Mechanistic studies identified microbial metabolites, such as short-chain fatty acids, bile acids, branched-chain amino acids, tryptophan catabolites, and imidazole propionate, as key modulators of metabolism, inflammation, and gut-brain communication. Metagenomic and multi-omics technologies now provide deeper insights into the intricate interactions between microbes, metabolites, and host factors, reshaping obesity research and reinforcing the need for phenotype stratification by recognizing microbiome-driven metabolic profiles. Integrating gut microbiome data into clinical strategies may enable targeted interventions for specific obesity subtypes, advancing prevention and personalized care. However, as new anti-obesity medications emerge, it is imperative to determine how microbiome-based therapies can complement them, considering efficacy, cost, and patient-specific variability.}, } @article {pmid41576933, year = {2026}, author = {Hernandez-Leyva, AJ and Berna, AZ and Bui, MH and Liu, Y and Rosen, AL and Lint, MA and Whiteside, SA and Jaeger, N and McDonough, RT and Joardar, N and Santiago-Borges, J and Tomera, CP and Luo, W and Odom John, AR and Kau, AL}, title = {The gut microbiota shapes the human and murine breath volatilome.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.12.013}, pmid = {41576933}, issn = {1932-7420}, abstract = {The gut microbiota is crucial to health, yet implementation of microbiota-based therapeutics is limited by the lack of rapid diagnostics. We hypothesize that breath contains gut microbe-derived volatile organic compounds (VOCs) reflecting microbiota composition and metabolism. In healthy children, we found that breath VOC composition (or volatilome), assessed by gas chromatography-mass spectrometry, correlates with gut microbiome composition and function. By capturing exhaled breath from human-stool-colonized and monocolonized gnotobiotic mice, we profiled breath VOCs and discovered that murine breath is also significantly influenced by the gut microbiome. VOCs from cultured gut microbes were identified in vivo in monocolonized gnotobiotic colonized mice. As a proof of principle, we demonstrated that exhaled breath predicts the abundance of a disease-associated bacterium, Eubacterium siraeum, in children with asthma. Altogether, our studies identify microbe-derived VOCs in breath, show that gut bacterial metabolism directly contributes to mammalian breath VOC profiles, and inform the development of non-invasive microbiome diagnostics.}, } @article {pmid41576821, year = {2026}, author = {Li, B and Zhang, M and Zhong, J and Qin, J and Cai, H and Sun, C and Yang, F and Wu, Y and Liu, S and Yang, H and Huang, F}, title = {Phosphorus Speciation and Mobility in the Dredged Sediment of an Urban Lake: The Role of Coupled Fe-S-P Dynamics and Microbial Succession.}, journal = {Water research}, volume = {293}, number = {}, pages = {125423}, doi = {10.1016/j.watres.2026.125423}, pmid = {41576821}, issn = {1879-2448}, abstract = {Sediment dredging is a widely used strategy to mitigate eutrophication and internal phosphorus (P) loading in urban lakes. However, a comprehensive understanding of its long-term effectiveness and the underlying mechanisms controlling internal P loading remains limited. Furthermore, the effects of dredging on sediment microbial community structure, functional diversity, and subsequent recovery processes have not been systematically investigated. To address this gap, a simulated dredging experiment was conducted on sediments from a shallow eutrophic urban lake (Xuanwu Lake, XWL). To comprehensively track the post-dredging dynamics of phosphorus and the sediment microbiome, we integrated high-resolution geochemical profiling using diffusive gradients in thin films and porewater samplers. We analyzed microbial community structure using 16S rRNA gene sequencing and metabolic functional diversity through community-level physiological profiling. We found that following an initial disturbance period, dredging effectively reduced the release flux of soluble reactive phosphorus (SRP) from sediments by an average of 27.4%. Concurrently, dredging significantly altered P speciation, which was characterized by a 29.4% decrease in mobile P and a 40.3% increase in the stable aluminum-bound P fraction. Importantly, dredging restructured seasonal P dynamics, making them primarily governed by the iron (Fe) cycle. This led to a paradoxical effect: enhanced P sequestration during cold and oxic seasons but a substantially intensified P-release during warm anoxic summers. This summer P-release rebound was driven by blooms of the iron-reducing bacterium Geobacter and was further exacerbated by the redeposition of P-rich suspended particulate matter. Our findings reveal that dredging is not merely a physical removal process but initiates a long-term Fe-S-P biogeochemical succession centered at the sediment-water interface, fundamentally regulated by microbial community dynamics. These findings challenge the conventional view of dredging as a one-time measure and highlight the need for season-specific monitoring and long-term management strategies.}, } @article {pmid41576626, year = {2026}, author = {Sickinger, C and Thiel, A and Bornhorst, J and Christa, G and Preisfeld, A}, title = {Nickel and cobalt disrupt the microbiome and metabolic function of the photosymbiotic sea slug Berghia stephanieae (Á. Valdés, 2005).}, journal = {Marine environmental research}, volume = {216}, number = {}, pages = {107845}, doi = {10.1016/j.marenvres.2026.107845}, pmid = {41576626}, issn = {1879-0291}, abstract = {The rapid global expansion of electromobility has increased demand for nickel and cobalt, which are key components in lithium-ion batteries. As a result, mining activities are intensifying, yet their ecological impact on marine ecosystems remains poorly understood. In this study, we examine the effects of nickel and cobalt on the microbiome composition and bacterial metabolic pathways of the marine photosymbiotic gastropod Berghia stephanieae. Preliminary toxicity tests showed concentration-dependent metal uptake, with behavioural stress responses such as lethargy, cessation of feeding, and shedding of cerata occurring at high concentrations (around 18 mg/L for nickel and cobalt). Microbiome analysis across three concentrations (1, 3, and 17 mg/L for nickel and cobalt) revealed significant changes in community composition and function. At 1 mg/L, the observed effects were concentration-dependent rather than metal-specific, as indicated by a decline in alpha diversity and a shift in community composition, characterised by a reduction in Mycoplasma sp. and an increase in Pseudofulvibacter and Endozoicomonas sp. At 3 mg/L, Shewanella spp. abundance increased and metal-specific effects emerged, with a strong downregulation of the metabolic pathways denitrification and lignin degradation for cobalt and an upregulation of sulfur oxidation for nickel. At 17 mg/L, many functional pathways were downregulated, aligning with observed host stress and pointing to a possible loss of functional redundancy. Overall, nickel and cobalt exposure led to distinct microbiome alterations, with intermediate levels eliciting the strongest metabolic response.}, } @article {pmid41576514, year = {2026}, author = {Hao, Y and Li, Y and Liu, F and Long, J and Yang, H}, title = {Metagenomic insights into the influence of goose farming on the gut microbiome and antibiotic resistome of workers.}, journal = {Poultry science}, volume = {105}, number = {4}, pages = {106487}, doi = {10.1016/j.psj.2026.106487}, pmid = {41576514}, issn = {1525-3171}, abstract = {Antimicrobial resistance (AMR) seriously threatens the health of humans and animals. Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) were enriched in the goose farms. However, the influence of goose farming exposure on the gut microbiota and ARGs of workers was unclear. In this study, metagenomic analysis was used to characterize gut microbiome structures, annotate bacterial taxa, and quantify the abundances of ARGs and MGEs in geese and human samples. Results showed that goose feces harbored more abundant ARGs and ARB than human feces. Significantly higher abundances of special ARGs (such as vanY, lsaE, AAC3-IId and ampC) were identified in workers compared to villagers. Compositions of gut bacteria were significantly different between workers and villagers, and some certain gut pathogens were abundant in the feces of workers, including Bacillus anthracis, Clostridium perfringens, and Escherichia coli O45:K1:H7. A total of 51 ARGs were pinpointed in the metagenome-assembled genomes (MAGs). Based on ARG-MGE associations and co-occurrence signals in MAGs, the potential for horizontal gene transfer (HGT) was inferred. With this transfer capacity and ubiquitous gut colonization, E. coli carrying 38 ARGs is proposed as a putative AMR indicator for the goose farm. This study demonstrates that goose farming had non-ignorable influences on the gut microbiome and antibiotic resistome of workers. More efforts should be made to control the ARGs and ARB in the goose farm.}, } @article {pmid41576417, year = {2026}, author = {Enríquez-Belenguer, A and Flores Ventura, E and Valls-Verdoy, A and Collado, MC}, title = {Evolution of the gut microbiome in infancy: recent advances.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, pmid = {41576417}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: The early-life gut microbiome is a dynamic ecosystem that alongside other niches, such as the oral and skin microbiomes, undergoes rapid assembly and genetic evolution from birth through to adulthood. Although it was originally considered to be a passive colonisation process, recent findings suggest that early microbial development is a co-evolving, host-modulated process influenced by multiple factors, including maternal microbiota, mode of delivery, human milk, feeding practices, environmental exposure, and genetics, highlighting the timeliness of this review.

RECENT FINDINGS: In recent years, high-resolution sequencing and longitudinal multiomics have enabled the detailed observation of the early stages of microbial adaptation, assembly, strain transmission, diversification, and horizontal gene transfer in the early stages of life. New data also reveal maternal-foetal microbial signalling via metabolites and extracellular vesicles, as well as the evolutionary role of human milk oligosaccharides, and the involvement of phages, plasmids, and mobile genetic elements in infant gut microbial evolution.

SUMMARY: This review provides a summary of advances during gestation, birth, breastfeeding and infancy. However, further research is required into microbial evolution, and predicting its clinical significance, as well as  the role of artificial intelligence tools. Understanding early microbial adaptation processes could transform nutrition, precision medicine, and paediatric care.}, } @article {pmid41576237, year = {2026}, author = {Savitz, BL and Duckworth, K and Slutsky, HL and Gutama, B and Mubang, R and Kitko, CL and Lineaweaver, W}, title = {Bidirectional Interactions: Microbiome and Immune System Function in Cutaneous Graft-Versus-Host Disease.}, journal = {Annals of plastic surgery}, volume = {96}, number = {2}, pages = {193-196}, doi = {10.1097/SAP.0000000000004450}, pmid = {41576237}, issn = {1536-3708}, mesh = {Humans ; *Graft vs Host Disease/immunology/microbiology/therapy ; *Microbiota/immunology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Skin Diseases/immunology/microbiology ; *Skin/microbiology/immunology ; Skin Transplantation ; Dysbiosis/immunology ; }, abstract = {Chronic graft-versus-host disease (cGVHD) of the skin represents a complex immunopathologic process triggered by donor-derived immune cells following allogeneic hematopoietic stem cell transplantation (HSCT). While traditionally understood through the lens of alloimmune activation and fibrotic remodeling, emerging evidence highlights the role of microbial dysbiosis-particularly in the skin microbiome-as both a contributor to and a consequence of disease progression. This review explores the evolving understanding of the microbiome-immune interface in cutaneous GVHD, focusing on how shifts in microbial composition, such as the loss of Staphylococcus epidermidis and the overgrowth of S. aureus, may impair barrier function, promote local immune activation, and potentiate systemic inflammation. Disruption of commensal-derived signals leads to reduced antimicrobial peptide production, diminished regulatory T cell activity, and proinflammatory T cell polarization, all of which contribute to immune-mediated skin damage. A self-reinforcing cycle of barrier dysfunction and microbial imbalance emerges, suggesting new avenues for intervention. We discuss microbiome-targeted therapies including donor-derived skin allografting as potential strategies to restore microbial equilibrium and mitigate inflammation. Additionally, we highlight the diagnostic potential of skin microbiome profiling as a biomarker for disease activity and treatment response. Understanding the bidirectional interactions between the microbiome and immune system may offer novel therapeutic and prognostic tools for managing cutaneous cGVHD.}, } @article {pmid41576101, year = {2026}, author = {Moran, MM and Li, J and Shen, Q and Drummond, SP and Milner, CM and Day, AJ and Naqib, A and Sumner, DR and Plaas, A}, title = {Evidence of an allostatic response by intestinal tissues following induction of joint inflammation.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0338053}, pmid = {41576101}, issn = {1932-6203}, mesh = {Animals ; Rats ; *Arthritis, Experimental/pathology/immunology/chemically induced ; Male ; Freund's Adjuvant ; *Inflammation/pathology ; Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism/pathology ; Ileum/pathology/metabolism/immunology ; Colon/pathology/metabolism/immunology ; Synovial Membrane/pathology/metabolism ; *Arthritis, Rheumatoid/pathology ; }, abstract = {Disrupted intestinal epithelial barrier function has been proposed to be integral to rheumatoid arthritis (RA) progression and pathogenesis. To further define the molecular pathways in synovial inflammation and the response of the intestinal tissues, we have used a rat model of mono-joint inflammatory arthritis, induced by intra-articular injection of Complete Freund's adjuvant (CFA). The predominant inflammatory response of a single injection of the adjuvant into the knee joint resulted in rapid and reproducible formation of a fibrotic myeloid-infiltrated synovial pannus. Our aim was to determine how intestinal tissues, including the proximal and distal ileum and distal colon, responded to inflammatory changes in the synovium in a temporally coordinated manner by comparing their transcriptomic landscapes using RNASeq analyses. We confirmed the timeline of joint inflammation by knee joint swelling measurement, increased synovial fluid levels of bikunin (a component of both the acute phase protein pre-alpha-inhibitor and inter-alpha-inhibitor) and demonstrated a self-correcting response of trabecular and cortical bone to the CFA challenge. Intestine-specific responses were monitored by 16S microbiome amplicon sequencing, histopathology for mucus layer integrity, and immune cell immunohistochemistry. We present data that shows the intestinal tissue displays an allostatic response to the acute joint inflammation and was region specific. The ileum primarily responded with increased mucus secretion and silencing of T-cell specific pathways, whereas the colon showed a transient upregulation of macrophages, with a broader suppression of immune related and metabolic pathway related transcripts. Interestingly, many neuropathways were activated early but then suppressed later in both the ileum and colon. There were only insignificant changes in the fecal microbiome composition in ileum or colon post-CFA administration. In summary, our data show for the first time a suppression of intestinal inflammatory and immune responses following the induction of joint inflammation and only minimal and transient changes in the microbiome. The results help clarify the molecular responses of intestinal tissues to inflammatory stresses that accompany the pathogenesis of inflammatory joint diseases.}, } @article {pmid41575990, year = {2026}, author = {Su, T and Lai, S and Chen, H}, title = {Intestinal decontamination with rifaximin attenuates LSEC dysfunction and liver fibrosis in mice.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0340664}, pmid = {41575990}, issn = {1932-6203}, mesh = {Animals ; *Rifaximin/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Liver Cirrhosis/drug therapy/pathology/microbiology ; Male ; Lipopolysaccharides/blood ; Mice, Inbred C57BL ; *Endothelial Cells/drug effects/metabolism/pathology ; Carbon Tetrachloride/toxicity ; Liver/pathology/drug effects ; Toll-Like Receptor 4/metabolism ; }, abstract = {BACKGROUND: The gut microbiome plays a pivotal role in the development and progression of liver disease. Liver sinusoidal endothelial cells (LSECs), as the first hepatic barrier exposed to blood from the portal circulation, may be influenced by gut-derived microbiota and their byproducts. This study aimed to investigate the interaction between gut microbiota and LSECs and to clarify how this interaction impacts the progression of liver cirrhosis.

METHODS: Liver cirrhosis was induced by carbon tetrachloride (CCl4) injection and bile duct ligation (BDL). CCl4 and BDL mice were administered rifaximin. The primary LSECs were isolated from mice and treated with LPS. 16S rRNA sequencing was conducted to examine changes in the gut microbiota of cirrhotic mice following rifaximin treatment.

RESULTS: Rifaximin attenuated liver fibrosis and LSEC dysfunction in CCl4 and BDL mice. Liver cirrhosis induced remarkable changes in the gut microbiome while rifaximin treatment could partially reverse these alterations. Serum lipopolysaccharides (LPS) level was elevated in cirrhotic mice, while reduced following rifaximin treatment. Furthermore, LPS treatment could induce LSEC dysfunction by inhibiting eNOS mRNA expression, which was attenuated by TLR4 inhibitor, indicating that TLR4 signaling was involved in LPS-induced LSEC dysfunction.

CONCLUSIONS: Intestinal microbiota dysbiosis allows more LPS to enter the portal circulation, which may in turn exacerbate LSEC dysfunction and liver fibrosis. Intestinal decontamination with rifaximin improves LSEC function and alleviates liver fibrosis, a process linked to the reconstruction of the gut microbiome and a reduction in gut-derived LPS.}, } @article {pmid41575985, year = {2026}, author = {Jin, M and Keku, T and McCoy, A and Brown, JA and Peterson, M and Hunter, J and Smith, S and Black-Grant, S and Yates, MS and Peery, AF and Bae-Jump, VL and Azcarate-Peril, MA and Engel, SM and Olshan, AF and Nichols, HB}, title = {Stool and vaginal microbiome profiles patterns among Black and White endometrial cancer survivors: A pilot study in North Carolina.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0336772}, pmid = {41575985}, issn = {1932-6203}, mesh = {Aged ; Female ; Humans ; Middle Aged ; Black or African American ; *Cancer Survivors ; *Endometrial Neoplasms/microbiology ; *Feces/microbiology ; Lactobacillus/isolation & purification/genetics ; *Microbiota ; North Carolina ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; *Vagina/microbiology ; White ; }, abstract = {BACKGROUND: Endometrial cancer is the most common gynecologic cancer in the US. Endometrial cancer survivors may experience changes in microbiome due to cancer treatment and other factors. The human microbiome plays a crucial role in maintaining the proper functioning of the body. A more diverse microbiome often indicates a healthier gut environment, while lower vaginal microbiome diversity, specifically a Lactobacillus-dominant vagitype, is associated with more favorable health outcomes. The objectives of this pilot study were to evaluate potential variation in stool and vaginal microbiome communities and to assess the feasibility and acceptability of self-sampling among endometrial cancer survivors.

METHODS: Endometrial cancer survivors (N = 50) enrolled in the Carolina Endometrial Cancer Study, a cohort of women diagnosed with endometrial cancer, were mailed Genotek vaginal swab and stool self-collection kits. Self-reported questionnaires assessed information on survivors' demographics, sexual and bowel function, and perspectives on the self-sampling processes. Tumor characteristics and cancer treatment information were assessed from medical records. Microbiota profiles were characterized by bacteria 16S rRNA amplicon sequencing.

RESULTS: Overall, 48 vaginal swabs and 47 stool samples were obtained. Alpha (Shannon p = 0.04) and beta (Bray-Curtis p = 0.004) diversity of vaginal microbiome samples varied by cancer treatment, with higher microbial diversity after chemotherapy or radiation compared to surgery alone. In the surgery only group, 63% of samples were Lactobacillus-dominant compared to 17% among the chemotherapy or radiation group. Stool microbiome diversity did not vary by cancer treatment status. No statistically significant differences in alpha or beta diversity were observed in either vaginal or stool microbiome communities across racial subgroups or by sexual or bowel function.

CONCLUSION: Self-collection of stool and vaginal microbiome samples is feasible and acceptable in cancer survivors. Our results suggest that radiation and chemotherapy for endometrial cancer may decrease the abundance of beneficial Lactobacillus and increase less favorable vaginal microbial diversity among endometrial cancer survivors.}, } @article {pmid41575877, year = {2026}, author = {Bernstein, CN and Nugent, Z and Panaccione, R and Marshall, DA and Kaplan, GG and Vanner, S and Dieleman, LA and Graff, LA and Otley, A and Jones, J and Buresi, M and Murthy, S and Borgaonkar, M and Bressler, B and Bitton, A and Croitoru, K and Sidani, S and Fernandes, A and Moayyedi, P}, title = {Patient-reported Symptoms Are Independent of Extent of Disease in Longstanding Ulcerative Colitis: Magic in Imagine.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000002329}, pmid = {41575877}, issn = {1539-2031}, abstract = {BACKGROUND: The Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects Strategy for Patient Oriented Research Network (IMAGINE) has conducted a 5-year multicenter prospective observational cohort study, Mind And Gut Interactions Cohort (MAGIC) in 14 centers across Canada from 2018 to 2022. Herein, we investigated the relationship between ulcerative colitis (UC) phenotypes, demographics and other relevant outcomes, and symptom reporting.

METHODS: At baseline, participants answered surveys assessing disease activity, medications and complementary therapies, lifestyle factors, psychological status, and comorbidities. UC phenotypes were classified by the Montreal Classification. Herein, we describe the association between phenotypes and demographics, medications used, comorbidities, and symptoms experienced in adults with UC. The Inflammatory Bowel Disease Symptom Inventory (IBDSI) was used to assess symptoms.

RESULTS: The maximal extent phenotypic distribution based on chart review was E1 (proctitis) n=261 (14.5%), E2 (left-sided colitis) n=671 (37.2%), and E3 (subtotal or pancolitis) n=794 (44.0%). More males had E3. Different phenotypes did not lead to differences in the use of complementary therapies. There was greater likelihood of primary sclerosing cholangitis but a lower likelihood of hypertension in E3. Among the 25 different symptoms queried in the IBDSI, there was no difference across phenotypes, except among persons with overall active IBDSI, there was more waking for urges for bowel movements in persons with E3.

CONCLUSIONS: Overall, there was no difference in symptom reporting based on extent of UC except for cohort with overall active IBDSI there were some differences in nocturnal waking based on disease extent.}, } @article {pmid41575856, year = {2026}, author = {Li, J and Li, Z and Bao, Q and Chen, Y and Zhang, M and Tian, R and Yang, X and Liu, Z and Yao, Y and Lin, Q and Zhang, Z and Li, L and Zhang, L}, title = {Polystyrene nanoplastics readily penetrate intestine and cause sex-specific effects mediated by bile acids and microbiome.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116859}, doi = {10.1016/j.celrep.2025.116859}, pmid = {41575856}, issn = {2211-1247}, abstract = {Orally ingested nanoplastics can enter the blood flow; however, their digestive tract fate is unclear. We found that ∼60% of ingested polystyrene nanoparticles (PSNPs) cross the intestine wall in 3 h, but most are captured by the liver and discharged via the biliary system. Nanoparticle-bound bile acids (BAs) and apical sodium-dependent bile acid transporter (ASBT) mediate this fast absorption of PSNPs. In the liver, PSNPs block CYP7A1 degradation by disrupting lysosome biogenesis, which promotes BA synthesis and increases colitis susceptibility of mice by reducing Lactobacillus and increasing Enterobacteriaceae. Significant sexual dimorphism is unexpectedly discovered after PSNP treatment, where male mice are more sensitive than females due to the higher ASBT expression on enterocytes in males. In summary, our results could guide usage of plastic and prompt design of efficient carriers for oral drug delivery as well as indicate that sex should not be ignored both in drug administration and disease.}, } @article {pmid41575760, year = {2026}, author = {Li, X and Han, Z and Sun, S and Wu, Y and Zhang, X and Yin, Y and Zhao, Z and Hai, J and Wang, B}, title = {Chiral Cascade-Targeted Nanoassembly Eradicates Intratumoral Bacteria via Ferroptosis to Potentiate STING-Driven Antitumor Immunity.}, journal = {ACS applied materials & interfaces}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsami.5c24093}, pmid = {41575760}, issn = {1944-8252}, abstract = {Intratumoral bacteria, particularly those residing intracellularly, are emerging as critical regulators of tumor progression and immunosuppression, yet their precise eradication and conversion of this process into an immunostimulatory signal remain a formidable challenge. Here, we report a chiral supramolecular nanoassembly, ZnO2@CDP/Fc-DA, designed for cascade targeting of tumor cells and intracellular bacteria via d-alanine-mediated chiral matching and metabolic labeling. This system acts as a "Trojan horse", disassembling in the acidic lysosomes of tumor cells to release H2O2 and ferrocene-derivatized d-alanine (Fc-DA). The sustained Fenton reaction induces bacterial ferroptosis, an immunogenic form of bacterial death, which triggers the release of microbial DNA. This bacterial DNA, synergizing with the concurrently released Zn[2+], robustly activates the cGAS-STING pathway, a cornerstone of innate immunity. Concurrently, the nanoassembly promotes immunogenic cell death (ICD) in tumor cells via ROS-mediated ferroptosis. The synergistic engagement of bacterial DNA-driven STING activation and tumor cell ICD reprograms the immunosuppressive tumor microenvironment, leading to dendritic cell maturation, cytotoxic T-cell infiltration, and profound inhibition of both primary and metastatic tumors. In contrast, the l-enantiomeric control (ZnO2@CDP/Fc-LA) showed an inferior efficacy. This work presents a chirality-guided strategy that harnesses intratumoral bacteria as an endogenous trigger for potent antitumor immunity, establishing bacterial ferroptosis as a powerful modality for microbiome-potentiated immunotherapy.}, } @article {pmid41575675, year = {2026}, author = {Kopalli, SR and Wankhede, N and Rahangdale, SR and Sammeta, S and Aglawe, M and Koppula, S and Taksande, B and Upaganlawar, A and Umekar, M and Kale, M}, title = {Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders.}, journal = {Biogerontology}, volume = {27}, number = {1}, pages = {42}, pmid = {41575675}, issn = {1573-6768}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Aging/physiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.}, } @article {pmid41575630, year = {2026}, author = {Weirauch, T and Yahav, D and Zahavi, I and Würstle, S and Vehreschild, MJGT}, title = {A review on antibiotic and non-antibiotic decolonization strategies of multidrug-resistant bacteria in the gastrointestinal tract.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {41575630}, issn = {1439-0973}, abstract = {The escalating global threat of antimicrobial resistance represents a critical challenge for contemporary medicine. Intestinal colonization by multidrug-resistant organisms (MDROs) is increasingly identified as a primary driver of hospital-acquired infections across various patient cohorts. While localized eradication via non-absorbable antibiotics was once viewed as a viable strategy, clinical evidence has failed to demonstrate its efficacy. Consequently, attention has shifted toward microbiome-modulating interventions, such as fecal microbiota transfer (FMT), probiotics, and live biotherapeutic products (LBPs), which have shown potential in preliminary studies. However, current evidence remains fragmented and lacks the support of large-scale randomized controlled trials (RCTs). This review critically assesses both traditional and novel decolonization methods and features a comprehensive summary of clinical studies to highlight existing research gaps. A notable limitation of this analysis is the absence of a formal methodological quality assessment for the included studies. Ultimately, definitive conclusions remain elusive, necessitating future large-scale, pathogen-specific RCTs to validate these emerging approaches.}, } @article {pmid41575614, year = {2026}, author = {Bhalla, S and Srivastava, R}, title = {Gut Microbiota and Mitochondrial Dysfunction in Autism: Clinical Correlations and Future Directions.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {392}, pmid = {41575614}, issn = {1559-1182}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mitochondria/metabolism/pathology ; Animals ; *Autistic Disorder/microbiology/metabolism ; *Autism Spectrum Disorder/microbiology/metabolism ; Dysbiosis ; Brain/metabolism ; }, abstract = {Autism spectrum disorder (ASD) is a multifactorial, neuro-psychiatric, and neurodevelopmental illness possessing impaired social, behavioral, and communicative presentations. Research suggested the important role of the gut-brain axis in ASD, especially related to gut dysbiosis and mitochondrial dysfunction. This review comprehensively summarizes the existing evidence of the association between gut microbiota, microbial metabolites, and mitochondrial dysfunction in ASD, comprising of clinical, experimental, and epidemiological data over the last decade. The focus was on the research that clarifies the gut-mitochondria crosstalk and role in ASD pathophysiology. ASD patients demonstrate a substantial shift in the variety of gut microbiota, such as a decrease in the number of beneficial microbes and the growth of pathogenic taxa. These changes affect the biosynthesis of major neuroactive metabolites executing immune modulation and neurotransmission. The review detects the microbial metabolites that regulate mitochondrial activity through mechanisms like vagus nerve, intestinal hormones, and immune signaling. The different mitochondrial signaling pathways were inhibited including AMPK, mTOR, and NF-κB. Preventive interventions that concentrate on modulation of the microbiome and mitochondria may present a prospective line of therapy. Nevertheless, uncovered gaps should be mentioned in future research, multi-omics studies, longitudinal studies, and the protocol to understand the components of gut-brain axis in ASD to develop personalized therapy.}, } @article {pmid41575584, year = {2026}, author = {Ma, Y and Xu, Q and Sun, F and Wang, X and Zhou, W and Yue, M and Gao, L and Li, W}, title = {Potassium-Solubilizing Bacteria Mediate Light-Potassium Synergy to Enable Native Pueraria lobata to Outcompete Invasive Mikania micrantha.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-026-02695-5}, pmid = {41575584}, issn = {1432-184X}, support = {2022A1515011169//National Natural Science Foundation of China-Guangdong Joint Fund/ ; 2023S017084//Guangdong Province Science and Technology Innovation Strategic Special Project/ ; 2022s037//the Maoming City Science and Technology Plan Project/ ; 32172430//National Natural Science Foundation of China/ ; }, abstract = {The invasive vine Mikania micrantha H. B. K. poses severe threats to biodiversity and ecosystem stability in tropical and subtropical regions, calling for sustainable ecological approaches. This study explores how the native legume Pueraria lobata var. thomsonii Benth displaces M. micrantha in the field, with a focus on the synergistic roles of light capture advantage and rhizosphere potassium (K) dynamics driven by specialized bacteria. In competitive ecotones, P. lobata demonstrated superior growth and photosynthetic performance relative to M. micrantha. Its main stem length was 1.31 times greater, while net photosynthetic rate, stomatal conductance, and chlorophyll content were 80%, 110.7%, and 21.4% higher, respectively. Soils associated with P. lobata contained significantly higher available K, correlated with enhanced enzyme activities, indicating a "microbe-enzyme-K" activation cascade. P. lobata specifically enriched efficient potassium‑solubilizing bacteria (KSB), such as Pseudomonas and Acinetobacter. Isolated KSB strains exhibited K‑solubilizing and plant‑growth‑promoting capacities and increased the competitive balance index of P. lobata in inoculation assays. Partial least‑squares discriminant analysis confirmed that KSB‑mediated K mobilization boosted stem elongation primarily by improving photosynthetic potassium use efficiency (PKUE), forming a reinforcing "light-K-microbe" loop that drives competitive displacement. This work establishes a "microbe‑mediated invasion suppression" framework, demonstrating how a native plant can couple superior light‑use efficiency with a specialized rhizosphere microbiome to outcompete an invasive species. We propose that managing potassium‑solubilizing microbiomes offers a sustainable strategy for ecological restoration in K‑limited ecosystems.}, } @article {pmid41575335, year = {2026}, author = {Chambers, LM and Chalif, J and Yao, M and Reizes, O and Rose, PG and Michener, CM and Vargas, R}, title = {Gram-positive targeting antibiotics are associated with progression and death in women with platinum-sensitive recurrent high grade epithelial ovarian cancer.}, journal = {Journal of gynecologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.3802/jgo.2026.37.e69}, pmid = {41575335}, issn = {2005-0399}, support = {5K12CA076917-22//K12 Grant/United States of America ; }, abstract = {OBJECTIVE: To evaluate oncologic outcomes in women with recurrent platinum-sensitive ovarian cancer (OC) receiving antibiotics (ABX) during platinum-based chemotherapy.

METHODS: A retrospective, single-institution cohort study was performed in women undergoing platinum chemotherapy for recurrent platinum-sensitive OC from 2009-2017. ABX for >48 hours, including anti-gram-positive antibiotics (G+ ABX), were recorded. The impact of ABX on time to second progression (PFS2), time to platinum resistance, and overall survival (OS) were assessed using univariate and multivariable Cox regression models.

RESULTS: Of 261 women with recurrent platinum-sensitive OC, 80 (30.7%) received ABX during platinum chemotherapy, and 20 (7.7%) received G+ ABX. On univariate analysis for PFS2, there was no difference for ABX versus none (13.1 vs. 12.3 months: hazard ratio [HR]=1.23, 95% confidence interval [CI]=0.93-1.62, p=0.15), but this was decreased for G+ ABX versus none (10.2 vs. 12.3 months: HR=1.71; 95% CI=1.05-2.77; p=0.03). There was no difference in OS for ABX versus none (30.8 vs. 33.5 months: HR=1.01; 95% CI=0.73-1.39; p=0.97), but G+ ABX were associated with decreased OS compared to no ABX (26.4 vs. 33.4 months: HR=2.13; 95% CI=1.28-3.57; p=0.004) and other ABX (26.4 vs. 37.9 months: HR=2.43; 95% CI=1.34-4.41; p=0.003), respectively. On multivariable analysis, no ABX were associated with improved PFS2 (HR=0.54; 95% CI=0.33-0.88; p=0.014) and OS (HR=0.49; 95% CI=0.29-0.81; p=0.006) versus G+ ABX.

CONCLUSION: This retrospective study of women with recurrent platinum-sensitive OC treatment with G+ ABX during platinum chemotherapy was associated with decreased PFS2 and OS.}, } @article {pmid41575305, year = {2026}, author = {Ibrahim, S and Ngyuen, J and Salgado, V and Chiu, K and Laws, MJ and Flaws, JA and Bashir, ST and Nowak, RA}, title = {The Gut Microbiome Influences Uterine Development in Mice.}, journal = {Reproduction (Cambridge, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/reprod/xaag003}, pmid = {41575305}, issn = {1741-7899}, abstract = {Diisononyl phthalate (DiNP), a plasticizer increasingly replacing DEHP, is an endocrine-disrupting chemical (EDC) linked to female reproductive harm. Ingestion is the most common route of DiNP exposure, making the gastrointestinal tract and gut microbiome a direct target for EDC exposure. This study examined the effects of acute DiNP exposure either in the absence or presence of a gut microbiome on uterine development. Female C57Bl/6 germ-free (-microbiome) 40-day-old mice were orally dosed, over 3 days, with either sterile phosphate buffer saline (PBS) (n = 8) to remain germ-free (-microbiome) or with colon contents (n = 10) to develop a gut-microbiome (+microbiome). This was followed by a 10-day period where half of the -microbiome and +microbiome mice were orally dosed with corn oil while half were orally dosed with 200 μg/kg/day of DiNP. The control group were specific pathogen-free (SPF) conventionally housed mice born with a microbiome. Mice were euthanized in diestrus at the end of the 10 days. Uteri were collected for histological analyses. Uterine development was significantly delayed in germ-free mice, regardless of later microbiome reintroduction or DiNP exposure. Key findings included reduced uterine diameter, stroma area, gland number, and thinner myometrial layers. Endometrial stromal cell proliferation was also lower in germ-free mice. DiNP exposure alone showed no significant effects. Estradiol levels and ovarian follicle counts were similar across groups, but germ-free mice had fewer, smaller litters in fertility tests. The study highlights that the gut microbiome critically influences postnatal uterine development, with its absence leading to persistent structural deficits. DiNP, at the tested dose, did not exacerbate these effects.}, } @article {pmid41575223, year = {2026}, author = {Han, N and Peng, X and Zhang, T and Qiang, Y and Li, X and Zhang, W}, title = {Hidden reservoir of highly adaptable multi-host plasmids that propagate antibiotic genes in healthy human populations.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrag004}, pmid = {41575223}, issn = {1751-7370}, abstract = {Plasmids are key vectors for disseminating antibiotic resistance genes, yet their diversity and dynamics in the healthy human gut microbiome remain largely unexplored. Using fecal metagenomes from two cohorts (n = 498 samples), we constructed a comprehensive atlas of the healthy human gut plasmidome. We observed a polarization: while 97.4% of 19 151 plasmid clusters exhibited low prevalence (<5%), we identified 17 plasmid clusters detected in >30% of individuals. Among these, plasmid pGut1 emerged as a paradigm of a stealth vector. Prevalent globally (>50% in independent cohorts), pGut1 possesses a minimal 4-kb conserved backbone ensuring stability and a hypervariable region acting as a "plug-and-play" module. We documented 40 distinct cargo inserts, including multiple antibiotic resistance genes like cfr(C), erm(B), and aphA, across individuals, within individuals over time, and even within single fecal samples, validated by single-cell and Nanopore sequencing. Screening 2.3 million bacterial genomes revealed pGut1 in 93 strains across 49 genera and 2 phyla, including pathogenic Clostridioides difficile and three distinct Salmonella enterica strains. This suggests potential repeated cross-species transmission events, equipping pathogens with new antibiotic resistance genes. Our study exposes a hidden reservoir of highly adaptable, multi-host plasmids like pGut1 silently propagating antibiotic resistance genes in healthy populations. These plasmids, pre-adapted for cross-boundary dissemination, may pose a threat for fueling multidrug-resistant pathogens.}, } @article {pmid41575217, year = {2026}, author = {Williams, CL and Williams, CE and King, SND and Shier, DM}, title = {Captivity drives multi-generational shifts in the gut microbiome that mirror changing animal fitness.}, journal = {mBio}, volume = {}, number = {}, pages = {e0351625}, doi = {10.1128/mbio.03516-25}, pmid = {41575217}, issn = {2150-7511}, abstract = {Gut microbiomes can dramatically affect host health and fitness, but can shift rapidly under changing environmental conditions. Understanding the interplay between microbiota, environmental pressures, and host responses is critical for predicting species' resilience, particularly in populations transitioning from the wild to human care for conservation breeding. Although captivity can profoundly alter microbial communities and host physiology, the dynamics of these transitions across generations remain poorly understood. We evaluated gut microbiota and fitness metrics in the endangered Pacific pocket mouse (Perognathus longimembris pacificus) during the establishment of a conservation breeding and reintroduction program, spanning five generations. Microbiome composition shifted gradually, stabilizing into a distinct captivity-associated state after two to three generations. These transitions paralleled changes in host weight and reproductive performance, suggesting coordinated host-microbiome adaptation. In addition, we identified microbial taxa correlated with successful reproduction, highlighting potential microbial markers of fitness. Our findings provide the first characterization of gut microbiota in Pacific pocket mice and demonstrate how captivity shapes host-microbiome systems across generations. More broadly, they underscore the importance of considering microbiome dynamics in conservation management and suggest that microbial responses to environmental change may require multiple generations to reach a new stable state.IMPORTANCEIn human-altered landscapes, animals face numerous threats to their survival, yet little is known about how rapid environmental change affects host-microbiome dynamics across generations. Microbial communities play critical roles in host nutrition, immunity, and overall fitness, and shifts in composition may alter an organism's ability to adapt. We examined the gut microbiota of the endangered Pacific pocket mouse during the transition from wild to captive environments and across four descendant generations. We found that the microbiome did not immediately shift with captivity but instead stabilized into a distinct, captivity-associated state only after several generations. This study provides the first characterization of gut microbiota in pocket mice and is the first to show, at this resolution, how a wildlife species' microbiome adapts to environmental change while tracking health and fitness across generations. Our findings highlight the need to incorporate microbiome dynamics into conservation breeding and management strategies.}, } @article {pmid41549262, year = {2026}, author = {Hahn, JW and Lim, JG and Lee, KJ and Moon, JS and Kim, TH and Son, Y and Yon, DK and Lee, YJ and Seo, Y and Park, J and Lee, S and Kim, D and Ko, JS}, title = {Clinical and microbial correlates of response to lifestyle intervention in pediatric metabolic dysfunction-associated steatotic liver disease.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {6}, pmid = {41549262}, issn = {1757-4749}, support = {RS-2023-00227939//National Research Foundation of Korea/ ; 2022R1F1A1071396//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Lifestyle modifications are fundamental in managing metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the effects of a 12-week lifestyle intervention on hepatic steatosis, liver function, and gut microbiota composition in pediatric MASLD patients, and to explore clinical and baseline microbial features associated with treatment response.

RESULTS: A total of 40 patients were recruited, and 31 were included after applying exclusion criteria. After 12 weeks, significant reductions were observed in body weight, waist circumference, liver enzymes, and triglycerides. MRI-measured hepatic steatosis decreased from 27.1% to 20.8% (p < 0.05). Greater reductions in hepatic fat were associated with higher daily step counts and a higher proportion of dietary protein intake. Baseline gut microbial composition differed between clinical responder groups. Clostridium sensu stricto 1 was enriched in participants with significant weight loss, Faecalibacterium in those with ALT or GGT improvement, and Lachnospiraceae_ND3007_group in those with MRI-PDFF reduction, with baseline microbial profiles discriminating responders with AUC ≥ 0.75.

CONCLUSIONS: A 12-week lifestyle intervention led to significant improvements in hepatic steatosis, metabolic parameters, and anthropometric measures in pediatric MASLD. Baseline gut microbial profiles differed between individuals with metabolic improvements, suggesting a potential association between pre-intervention microbiome composition and treatment response.

TRIAL REGISTRATION: The Clinical Research Information Service of the Korea Center for Disease Control and Prevention, Number: KCT0010340.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13099-026-00798-5.}, } @article {pmid41575215, year = {2026}, author = {Zang, W and Zhou, Z and Shen, Y and Zhang, B and Chen, X and Yue, W and Li, X and Cai, Y and Chen, J and Bian, J and Huang, L and Li, H and Dai, Y and Yang, H}, title = {Desaminotyrosine promotes tuft cell expansion and integrates intestinal type 2 immunity.}, journal = {mBio}, volume = {}, number = {}, pages = {e0328925}, doi = {10.1128/mbio.03289-25}, pmid = {41575215}, issn = {2150-7511}, abstract = {Intestinal microbiota are essential for maintaining the host's immune homeostasis, but the mechanism is not fully understood. While microbial metabolite desaminotyrosine (DAT) is recognized for its protective role in viral immunity, its potential involvement in anti-parasitic defense remains unexplored. Here, we demonstrate that DAT orchestrates tuft cell hyperplasia and subsequent type 2 immunity, establishing critical defense against helminth infection. Mechanistically, DAT-mediated intestinal epithelial remodeling requires histone deacetylase 3 (HDAC3), as pharmacological inhibition of this epigenetic regulator abrogates both tuft cell expansion and impairs type 2 immune responses. Collectively, our findings not only explore DAT novel effects in anti-parasitic defense but also reveal a pathway whereby the small molecule metabolites calibrate intestinal type 2 immunity.IMPORTANCEA small molecule metabolite DAT drives tuft cell hyperplasia and type 2 immunity in the small intestine. DAT-mediated tuft cell hyperplasia depends on HDAC3 and an intact microbiota; our findings reveal how small molecule metabolites fine-tune intestinal type 2 defenses against parasites.}, } @article {pmid41575201, year = {2026}, author = {Kleinhans, M and Lissen, A and Hewitson, L and Rijkers, GT}, title = {From fecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy: how far down the road are we?.}, journal = {Expert review of anticancer therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737140.2026.2621240}, pmid = {41575201}, issn = {1744-8328}, abstract = {INTRODUCTION: The outcome of immune checkpoint inhibition (ICI) therapy of cancer appears to be influenced by the gut microbiota composition of the patient. Microbiome-based therapy by fecal microbiota transplantation (FMT) appears to improve the outcome of ICI therapy. The ideal composition of the microbiota as well as treatment schedule are not yet established.

AREAS COVERED: The most recent published studies are reviewed, as well as the study designs of registered clinical trials which are ongoing. The effect of pretreatment of patients with antibiotics, aimed to improve engraftment of the transplant, is evaluated.

EXPERT OPINION: The optimal treatment schedule would be to start with FMT, followed by ICI, implying FMT should be given to ICI naive patients. Rather than donor derived FMT, defined consortia of microbiota could be preferred.}, } @article {pmid41575196, year = {2026}, author = {Asaduzzaman, M and Oláh, P and Yaseen, NJ and Taifi, A and Járay, T and Gulyás, G and Boldogkői, Z and Tombácz, D}, title = {Longitudinal long-read microbiome profiling in a canine model reveals how age, diet, and birth mode shape gut community dynamics.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0127925}, doi = {10.1128/msystems.01279-25}, pmid = {41575196}, issn = {2379-5077}, abstract = {The gut microbiome undergoes dynamic age-related changes shaped by diet and maternal factors. Here, we present a species-level, long-read 16S rRNA survey of the developing gut microbiome in a translational canine model, profiling 89 purebred Hungarian Pumis across early-life and reproductive stages. We collected 456 fecal samples longitudinally: 60 puppies followed from birth to 81 weeks, their mothers sampled during pregnancy and lactation, and adult controls from six kennels. We recorded detailed dietary metadata and reproductive status throughout the study. Age was the strongest determinant of alpha diversity, with a rapid increase during weaning and stabilization by 6 months of age. Beta diversity analyses revealed structured compositional transitions from early developmental phases to adulthood, including a shift toward more uniform, adult-like communities. Within-kennel variation was modest, consistent with shared environmental exposures. Mixed-effects models showed robust associations between specific taxa and age, diet, and kennel, while SparCC-inferred co-occurrence networks indicated increasing ecological complexity with age. We also demonstrated that the delivery mode-vaginal versus cesarean-impacted early-life microbiome composition: Lactobacillus spp. were significantly more abundant in cesarean-born puppies than in vaginally delivered littermates during the 8-10-week window. We also observed reproducible maternal microbiome shifts during pregnancy and lactation, with potential implications for vertical microbial transfer. Taken together, our results show that domestic dogs follow a reproducible, age-structured trajectory of microbial maturation that parallels human development, including delivery-mode effects and diet-responsive taxa.IMPORTANCEMicrobiome research is among the fastest-moving areas in biomedicine driven by major global efforts to understand how microbial communities shape human health and disease. Dogs provide an ideal translational model because their gut microbiota more closely resembles that of humans than that of other studied animals; moreover, breeds show high within-breed genetic homogeneity; diets can be tightly regulated; and longitudinal sampling across the lifespan is feasible. Mapping shifts driven by diet and maternal factors-from early-life events through later life, including senior stages-is essential to leverage microbial plasticity for prevention, with implications for inflammation, metabolic disease, and neurodegeneration. Here, we advance this goal by providing a longitudinal, high-resolution data set and demonstrating that full-length 16S rRNA sequencing is a powerful tool for resolving fine-scale patterns of gut colonization and maturation.}, } @article {pmid41575036, year = {2026}, author = {Boudaud, M and Arnone, D and Touly, N and Chassaing, B}, title = {[Intestinal microbiota biodiversity and the modern diet: consequences for human health].}, journal = {Medecine sciences : M/S}, volume = {42}, number = {1}, pages = {65-70}, doi = {10.1051/medsci/2025253}, pmid = {41575036}, issn = {1958-5381}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diet/adverse effects/trends ; *Biodiversity ; Dysbiosis/microbiology ; *Health ; }, abstract = {The advent of the modern diet - characterized by increased consumption of ultra-processed foods rich in saturated fats and simple sugars, but deficient in fiber and micronutrients - has profoundly altered the biodiversity of the intestinal microbiota. This dysbiosis disrupts the intricate metabolic, immune, and nutritional interactions between the host and its microbiota, leading to significant downstream impacts on human health. Dietary imbalances result in reduced production of beneficial microbial metabolites, increased intestinal permeability, chronic inflammation, and heightened risks of obesity, diabetes, and inflammatory diseases. Conversely, diversified diets rich in fiber, unsaturated fatty acids, and plant-based proteins support a resilient and diverse microbial ecosystem that enhances gut barrier function, immunity, and the synthesis of protective compounds. A deeper understanding of these complex host-microbiota-nutrition interactions can pave the way for preventive and therapeutic strategies targeting the microbiome to promote human health.}, } @article {pmid41575016, year = {2026}, author = {Hamza, MA and Un Nisa, N}, title = {Combining Robotics and Microbiome Science to Treat Unusual Post-Herpetic Neuralgias Resembling Complex Regional Pain Syndrome.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {26}, number = {2}, pages = {e70119}, doi = {10.1111/papr.70119}, pmid = {41575016}, issn = {1533-2500}, } @article {pmid41574983, year = {2026}, author = {Qian, S and Hou, J and Xiong, X and Duan, Q and Jiang, T and Zheng, Y and Quan, W and Xu, J and Chen, K and Qian, J and Gao, H and Xie, C}, title = {Exploring the Fecal Microbiome Dysbiosis and Its Plasma Metabolome Determinants in Advanced Parkinson's Disease With Motor Complications.}, journal = {CNS neuroscience & therapeutics}, volume = {32}, number = {1}, pages = {e70750}, pmid = {41574983}, issn = {1755-5949}, support = {82001363//Projects of the National Science Foundation of China/ ; 81600977//Projects of the National Science Foundation of China/ ; 82271469//Projects of the National Science Foundation of China/ ; LQ23H090007//the Projects of the Natural Science Foundation of Zhejiang Province/ ; Y19H090059//the Projects of the Natural Science Foundation of Zhejiang Province/ ; LZ23H090001//the Projects of the Natural Science Foundation of Zhejiang Province/ ; 2023R01002//Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang/ ; 2025C02111//the "Pioneer" and "Leading Goose" R&D Program of Zhejiang Province/ ; Y20220164//The Projects of the Wenzhou City Committee of Science and Technology/ ; 2024Y0194//The Projects of the Wenzhou City Committee of Science and Technology/ ; }, mesh = {Humans ; Male ; *Dysbiosis/microbiology/blood/metabolism ; Female ; *Parkinson Disease/complications/blood/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Aged ; Middle Aged ; *Metabolome/physiology ; *Feces/microbiology ; Metabolomics ; }, abstract = {BACKGROUND: Parkinson's disease with motor complications (PD-MC) lacks effective diagnostic and therapeutic strategies. The perturbations of the gut microbiota and plasma metabolites are closely associated with the etiopathogenesis of PD. However, whether fecal microbiome dysbiosis and changed plasma metabolites are involved in PD progression, particularly in the development of PD-MC, is still unclear.

METHODS: In this study, we performed an extensive multiomics analysis involving 108 PD patients for 16S rRNA gut microbiome profiling and 246 PD patients for plasma nontargeted metabolomics. Our findings revealed distinct gut microbiota and plasma metabolites associated with PD-MC. Utilizing these discriminative features, we developed a multivariate diagnostic model for PD-MC. The relationships between differential metabolites and microorganisms were evaluated using Spearman correlation analysis. Functional interpretation of the key metabolites was conducted through enrichment and pathway analysis, employing the KEGG and SMPDB databases.

RESULTS: PD-MC patients had distinct gut microbial signatures as compared with PD without motor complications (PD-NMC) individuals and were increased in fecal Lactobacillus, Limosilactobacillus, Bifidobacterium, and Ligilactobacillus genera along with depleted Agathobacter. Moreover, metabolomic analysis revealed the differences in plasma 3-deoxysappanchalcone (3-DSC), 1,3-Dimethyluracil (1,3-DTl), Leucine, and N-Acetylisoleucine (N-AIL), Dodec-6-enoic acid (D-6-E), N-butyl Oleate (N-BO), and 4-hydroxyundecanoic acid (4-HUA) in PD-MC compared to PD-NMC. Spearman correlation analysis showed that the fecal microbiota aberrations in PD-MC patients were linked to plasma metabolic changes, indicating the association between key microbial populations and metabolomic profiles in PD-MC.

CONCLUSIONS: This study underscores the value of employing integrated multiomics profiling of the fecal microbiome and plasma metabolome to enhance the mechanistic understanding of PD-MC and to identify potential diagnostic biomarkers.}, } @article {pmid41574946, year = {2026}, author = {Cho, M and Chu, J and No, CW and Kim, YW and Lee, J and Joung, H and Kwon, YJ and Shin, CH and Lee, J and Ha, JH}, title = {Lactiplantibacillus plantarum Q180 Supplementation Restores High-Fat Diet-Induced Gut Dysbiosis and Intestinal Barrier Dysfunction in Mice.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxag021}, pmid = {41574946}, issn = {1365-2672}, abstract = {AIMS: Gut microbiota dysbiosis and intestinal barrier disruption are key features of metabolic disorders associated with high-fat diet (HFD) consumption. While probiotics show promise in modulating these pathways, the role of Lactiplantibacillus plantarum Q180 (LPQ), formerly Lactobacillus plantarum Q180, in restoring gut microbial balance and intestinal barrier integrity remains unclear. In this study, we aimed to investigate whether LPQ supplementation alleviated high-fat diet (HFD)-induced gut dysbiosis, intestinal barrier dysfunction, and systemic endotoxemia in a mouse model.

METHODS AND RESULTS: Male C57BL/6 J mice received either a normal control diet or an HFD, with the latter administered with or without LPQ or resmetirom (positive control). Gut microbiota composition was assessed via 16S rRNA gene sequencing, and intestinal barrier function was assessed by fecal and serum endotoxin quantification and colonic expression of tight junction and mucin proteins. LPQ supplementation restored microbial balance, increasing short-chain fatty acid-producing genera (Lactobacillus, Bifidobacterium, Blautia, and Faecalibaculum) and reducing potentially pathogenic taxa. These microbial alterations were accompanied by decreased endotoxin levels, upregulation of epithelial tight junction genes (Zo-1, Ocln, and Claudin-1), and downregulation of mucin genes (Muc2 and Muc4). Positive correlations were noted between specific commensal bacteria and barrier-related gene expression, suggesting a microbiota-linked mechanism supporting epithelial integrity.

CONCLUSION: LPQ attenuated HFD-induced gut microbial imbalance and intestinal barrier dysfunction, accompanied by reduced systemic endotoxemia. These findings suggest that LPQ may serve as a microbiota-targeted intervention for gut dysbiosis-related metabolic disturbances. Further studies are warranted to validate its long-term and translational potential in humans.}, } @article {pmid41574913, year = {2026}, author = {Sawan, HM and Ledder, RG and McBain, AJ}, title = {Screening of Human and Environmental Microbiota-Derived Extracts Reveals Pathogen-Specific Anti-Virulence Activity.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxaf299}, pmid = {41574913}, issn = {1365-2672}, abstract = {AIMS: Targeting bacterial virulence is a promising alternative to traditional antibiotics. In this study, we aimed to identify microbiome-derived factors capable of suppressing virulence traits in pathogenic bacteria.

METHODS AND RESULTS: Eighty-two cell-free extracts (CFEs) applied at 10% (v/v), from human (n = 56) and soil (n = 26) bacterial isolates were screened for effects on planktonic growth, biofilm formation, and virulence using a Galleria mellonella infection model. Growth inhibition was rare, observed only for S. aureus exposed to a Bacillus flexus extract. Anti-biofilm activity was frequent against P. aeruginosa (65/82 CFEs, 79%), less so for S. aureus (20/82, 24%), and absent or reversed for E. coli. Eight CFEs improved larval survival in P. aeruginosa infections; one partly protected against S. aureus, while (47/82, 57%) increased mortality in E. coli-infected larvae. Thirty-eight of 65 anti-biofilm CFEs (58%) for P. aeruginosa tested positive (i.e. observed) in a violacein-based quorum-sensing inhibition assay. One extract (Streptococcus australis) also protected keratinocytes from P. aeruginosa-induced cell loss. Proteomic analysis of P. aeruginosa exposed to S. australis CFE indicated modulation of proteins associated with biofilm regulation and quorum-sensing pathways (e.g. the RsmA/CsrA family), consistent with anti-virulence activity.

CONCLUSIONS: Of 82 microbiome-derived CFEs, (65/82, 79%) partially inhibited P. aeruginosa biofilm formation, (20/82, 24%) affected S. aureus, and none inhibited E. coli biofilms. Ten % improved in vivo survival in P. aeruginosa infections, while (47/82, 57%) increased mortality in E. coli-infected larvae. Anti-virulence effects were pathogen-specific and occurred without measurable impacts on planktonic growth under the conditions tested.}, } @article {pmid41574888, year = {2026}, author = {Wang, L and Ni, Y and Gaynanova, I}, title = {Truncated Gaussian copula principal component analysis with application to pediatric acute lymphoblastic leukemia patients' gut microbiome.}, journal = {Statistical methods in medical research}, volume = {}, number = {}, pages = {9622802251412844}, doi = {10.1177/09622802251412844}, pmid = {41574888}, issn = {1477-0334}, abstract = {Increasing epidemiologic evidence suggests that the diversity and composition of the gut microbiome can predict infection risk in cancer patients. Infections remain a major cause of morbidity and mortality during chemotherapy. Analyzing microbiome data to identify associations with infection pathogenesis for proactive treatment has become a critical research focus. However, the high-dimensional nature of the data necessitates the use of dimension-reduction methods to facilitate inference and interpretation. Traditional dimension reduction methods, which assume Gaussianity, perform poorly with skewed and zero-inflated microbiome data. To address these challenges, we propose a semiparametric principal component analysis method based on a truncated latent Gaussian copula model that accommodates both skewness and zero inflation. Simulation studies demonstrate that the proposed method outperforms existing approaches by providing more accurate estimates of scores and loadings across various copula transformation settings. We apply our method, along with competing approaches, to gut microbiome data from pediatric patients with acute lymphoblastic leukemia. The principal scores derived from the proposed method reveal the strongest associations between pre-chemotherapy microbiome composition and adverse events during subsequent chemotherapy, offering valuable insights for improving patient outcomes.}, } @article {pmid41574450, year = {2026}, author = {Chen, S and Hoang, MH and Hu, D and He, Q and Gao, Y}, title = {Gut microbiota in early and established stages of rheumatoid arthritis: from pathogenesis to promising prevention and treatment.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2613484}, doi = {10.1080/07853890.2026.2613484}, pmid = {41574450}, issn = {1365-2060}, mesh = {Humans ; *Arthritis, Rheumatoid/microbiology/immunology/prevention & control/therapy ; *Gastrointestinal Microbiome/immunology/physiology ; Probiotics/therapeutic use ; Disease Progression ; Animals ; Antirheumatic Agents/therapeutic use ; }, abstract = {Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Before overt disease, genetically prone individuals may undergo a lengthy pre-clinical phase during which loss of tolerance triggers autoantibody emergence. The gut-joint axis was proposed decades ago, and mounting evidence now suggests that alterations in the gut microbiome may matter most in early, rather than established, RA.Results: By modulating intestinal permeability, mucosal and systemic immunity, genetic-risk pathways, molecular mimicry, and microbial metabolites, the gut microbiota plays a pivotal role in the onset and progression of RA. The window of opportunity for RA therapy may lie before joint inflammation becomes evident, and microbiota-targeted interventions are emerging. Probiotics, dietary interventions, and natural compounds hold promise as potential strategies for both RA prevention and adjunctive therapy after onset.Conclusions: This review highlights the gut microbiota not merely as a modulator of established RA, but - more critically - as a driver of early disease pathogenesis and a promising therapeutic target, thereby providing new insights for managing pre-clinical RA and refining treatment of established RA.}, } @article {pmid41574347, year = {2025}, author = {Du, H and Lin, Y and Qi, M and Qu, P and Xu, Z and Lin, R and Xie, C and Xiao, T and Dong, S and Wang, B and Ge, Y}, title = {Intercropping Amomum villosum enhances soil stratification, nutrient complementarity, and microbial communities in rubber plantations.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1720828}, pmid = {41574347}, issn = {1664-302X}, abstract = {Intercropping is widely promoted to sustain soil function, yet evidence for its application in rubber-based agroforestry, particularly with the shade-tolerant herb Amomum villosum, is limited. We evaluated whether A. villosum intercropping improves soil properties and reorganizes microbiomes across the vertical profile of mature rubber plantations. Soil samples were taken at 0-10, 10-20, and 20-30 cm depths in both intercropped and monoculture stands. Physical and chemical properties were quantified, and bacterial (16S rRNA V3-V4) and fungal (ITS2) communities were analyzed using high-throughput amplicon sequencing with depth-resolved data on diversity, composition, and functional inference (FAPROTAX, FUNGuild). Intercropping consistently improved soil structure and fertility, with the strongest effects at 0-10 cm. Total porosity (12%), organic matter (38.9%), alkali-hydrolyzable nitrogen (75.4%), and available phosphorus (131%) were markedly higher than in monoculture. Benefits extended to mid-depth with a 65.2% increase in alkali-hydrolyzable nitrogen. Microbial richness (bacteria and fungi) increased, and communities separated clearly by treatment and depth. Intercropped soils showed higher relative abundances of copiotrophic and particle-attached phyla (e.g., Proteobacteria, Planctomycetota), while Acidobacteriota and several Chloroflexi declined. Nitrospirota increased with depth. Fungal trophic structure shifted away from pathotrophs at 20-30 cm and toward symbiotrophs, particularly arbuscular mycorrhizal lineages, at subsurface layers. Functional predictions indicated greater potential for nitrogen transformations (e.g., nitrogen fixation, nitrification), greater C1/hydrocarbon utilization, and a reduced bacterial plant-pathogen signal under intercropping. Collectively, A. villosum intercropping reorganizes the soil environment and microbiome in mutually reinforcing ways-improving physical structure, enlarging near-term nitrogen supply, and favoring beneficial fungal guilds. These depth-resolved effects help explain the agronomic appeal of rubber-A. villosum systems and support their wider deployment in rubber plantations.}, } @article {pmid41574346, year = {2025}, author = {Kuizenga, M and Shankregowda, AM and Siriyappagouder, P and Delahaut, V and Calboli, FCF and Bervoets, L and Yadav, BS and Volckaert, FAM and De Boeck, G and Raeymaekers, JAM}, title = {Differential gut microbiome composition in three-spined stickleback populations with contrasting levels of mercury accumulation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1673354}, pmid = {41574346}, issn = {1664-302X}, abstract = {INTRODUCTION: Environmental micropollutants and other anthropogenic xenobiotics are potential drivers behind compositional shifts and functional dysregulation of gut microbial communities. Mercury and many of its compounds are highly toxic and ubiquitous environmental pollutants that pose a risk for aquatic biota and humans. Here we compared the gut microbial communities of natural three-spined stickleback (Gasterosteus aculeatus Linnaeus, 1758) populations in Flanders, Belgium, with contrasting muscle mercury concentrations. We hypothesized that exposure to a high mercury load selects for gut flora species with the capacity to tolerate or adapt to this stressor and, thus, leads to a change in the composition of the gut microbiota.

METHODS: The gut microbiota of 128 host individuals from four populations with low levels of accumulated mercury and four populations with high mercury levels were characterized using 16S rRNA amplicon sequencing. Gut microbial communities were compared across host muscle mercury content levels, host populations and sexes to consider the contribution of these factors in the observed differences in gut microbial diversity and composition.

RESULTS: Microbial community composition varied significantly between males and females, as well as between host populations with high and low muscle mercury content. While the abundance of 22 amplicon sequence variants (ASVs) was associated with the host's muscle mercury content, we detected no specific indicator species for high mercury.

CONCLUSION: Overall, our results suggest that local factors specific to a host population, potentially including mercury accumulation and sex-specific factors, differentiate the microbial communities inhabiting the gastrointestinal tracts of the three-spined stickleback.}, } @article {pmid41574344, year = {2025}, author = {Liu, J and Wang, H and Tang, Y and Bao, J and Tan, P and Peng, F}, title = {Soil nifH-harboring community assemblage varies across pecan cultivars.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1716240}, pmid = {41574344}, issn = {1664-302X}, abstract = {INTRODUCTION: This study focused on three pecan (Carya illinoinensis) cultivars ('Pawnee', 'Mahan', and 'Jinhua'), systematically assessing variations in soil nitrogenase activity, characteristics traits of nifH-harboring microbial communities across these cultivars.

METHODS: Using high-throughput sequencing technology, differences in the diversity, community composition, and network structure of nifH-harboring communities in the rhizosphere and bulk soils of pecan were examined across cultivars.

RESULTS: Both cultivar type and soil compartment had significant effects on nitrogenase activity (p < 0.01). Among the three cultivars, 'Mahan' exhibited the highest soil nitrogenase activity in both its rhizosphere and bulk soils relative to the other two cultivars. Notably, rhizosphere soils across all cultivars displayed significantly stronger soil nitrogenase activity than their bulk soil counterparts. 'Mahan' harbored significantly higher microbial α-diversity (Sobs, Shannon, and Chao indices) than other cultivars (p < 0.05). β-diversity analysis revealed marked community divergence among cultivars, with the most pronounced differences observed in bulk soils. Specifically, the bulk soil of 'Jinhua' harbored a distinct microbial signature, marked by significant enrichment of Cyanobacteria and depletion of Alphaproteobacteria. Linear discriminant analysis effect size (LEfSe) further identified Rhizobiales and Burkholderiales as distinct biomarkers for the rhizosphere and bulk soils of 'Jinhua', respectively (LDA score > 4.0, p < 0.05). Microbial co-occurrence network analysis showed that the bulk soil of 'Jinhua' harbored the most complex microbial interaction network, characterized by the highest number of edges, and average connectivity. In co-occurrence networks, Azohydromonas, Bradyrhizobium, Azoarcus, Rhodomicrobium were found as the keystone taxa in maintaining network stability.

DISCUSSION: This research elucidates the regulatory roles of pecan cultivars in shaping soil nitrogen fixation functions and microbial community assembly, providing valuable practical implications for precision microbiome management in pecan production.}, } @article {pmid41574341, year = {2025}, author = {Destras, G and Sabatier, M and Bal, A and Simon, B and Semanas, Q and Regue, H and Boyer, T and Ploin, D and Gillet, Y and Lina, B and Anani, H and Josset, L}, title = {Comparison between metatranscriptomics and viral metagenomics, 16S, and host transcriptomics for comprehensive profiling of the respiratory microbiome and host response.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1685035}, pmid = {41574341}, issn = {1664-302X}, abstract = {INTRODUCTION: Omics-based studies focusing on a single kingdom, such as bacterial 16S gene sequencing, viral metagenomics, and human mRNA sequencing, are commonly used to explore the microbiome and its association with host responses. But combining these approaches is often expensive and time-consuming. Metatranscriptomics provides a snapshot of the entire active microbiome through bulk RNA sequencing in a single test, yet its performance relative to kingdom-specific methods has not been systematically assessed.

METHODS: We compared metatranscriptomics with three kingdom-specific sequencing approaches in 20 nasopharyngeal aspirates from infants 7 months of age hospitalized for bronchiolitis at the Hospices Civils de Lyon.

RESULTS: Applying specific sequencing depth thresholds (≥1,000 bacterial reads, ≥100,000 human reads, and detection of an internal RNA control), metatranscriptomics showed high detection concordance and correlated abundance for RNA viruses and human coding genes. Metatranscriptomics also detected RNA from both eukaryotic and prokaryotic DNA viruses, suggesting potential for identifying transcriptional activity. For the bacteriome, 82% of genera exceeding 0.5% relative abundance were captured, revealing distinct transcriptional profiles at the species level. Metatranscriptomics reproduced multi-omics-derived host-microbiome endotypes and revealed stronger key microbial associations, particularly for transcriptionally active microorganisms.

DISCUSSION: These findings indicate that a single metatranscriptomics run can complement or replace kingdom-specific approaches for profiling RNA viruses and the host transcriptome, while also identifying transcriptionally active bacteria and DNA viruses. Low-abundance or latent microorganisms may still require targeted assays. Metatranscriptomics thus provides a cost- and time-efficient strategy for integrated microbiome research and holds promise for clinical applications in acute infections and cases of diagnostic uncertainty.}, } @article {pmid41574336, year = {2025}, author = {Shen, W and Yang, W and Qin, S and Liu, Y and Li, G and Zhang, X and Bao, M and Lu, Y and Sun, K and Ma, W and Li, H and Ismayil, A and Cao, A}, title = {Soil fertility and rhizosphere microbiome affecting hydroxysafflor yellow A accumulation in safflower.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1738669}, pmid = {41574336}, issn = {1664-302X}, abstract = {INTRODUCTION: Safflower (Carthamus tinctorius L.) is a prized medicinal species whose therapeutic value hinges on the abundance of bioactive metabolites. Accumulation of these metabolites are influenced by a range of environmental and edaphic factors, including soil physicochemical parameters, extracellular enzyme activities, composition and function of rhizosphere microbiome. However, how these factors individually and synergistically orchestrate the biosynthesis, transport, and ultimate storage of pharmaceutically active compounds within Safflower tissues remains unknown.

METHODS: Here, high-throughput amplicon sequencing coupled with comprehensive physiological profiling was employed to investigate soil characteristics, enzyme activities, and rhizosphere microbial communities of safflower across 36 soil samples collected at two distinct altitudes and two growth stages.

RESULTS: The effective component content was detected in 18 samples, and our results revealed that the safflower stigmas from the high- altitude site (YM) contained significantly elevated levels of hydroxysafflor yellow A (HSYA) compared to those from the lowland site (YF). Soils at the YM site exhibited markedly higher fertility, with available phosphorus, total nitrogen, and organic matter identified as key drivers of HSYA accumulation. Both sites showed high diversity and abundance in rhizosphere microbial communities, with Actinobacteria and Proteobacteria dominating the bacterial communities, and Ascomycota being the predominant fungal phylum.

DISCUSSION: Taken together, our findings show that soil properties, microbial communities, and climatic conditions work interactively to influence the buildup of bioactive compounds in safflower. These insights suggest that precise management of soil nutrients and the rhizosphere microbiome can improve medicinal safflower quality.}, } @article {pmid41574321, year = {2025}, author = {Torres, FN and Donda, ALV and Melo, DF}, title = {Scalp Apocrine Glands: The Neglected Component of the Hair Follicle Complex.}, journal = {Skin appendage disorders}, volume = {}, number = {}, pages = {}, pmid = {41574321}, issn = {2296-9195}, abstract = {BACKGROUND: In humans, apocrine glands are generally associated with chemical signaling and body odor. Their presence in the scalp is poorly documented, commonly being associated with benign and malignant tumors. If apocrine glands are consistently present in the normal scalp or become apparent only under pathological circumstances remains unclear. Moreover, their potential physiological role in relation to the hair follicle and microbiome modulation has yet to be fully elucidated.

SUMMARY: The role of scalp apocrine glands is often considered rudimentary and may be underestimated. However, the higher excretions of urea and potassium compared to eccrine glands suggest a potential role in the removal of metabolic waste products and electrolyte balance. Additionally, the openings of apocrine ducts drain into the hair follicle, mixing with follicular contents and sebum before reaching the skin's surface. This highlights a possible close interaction between the apocrine glands and microbiome. Furthermore, given the anatomical and functional association between follicular units and apocrine glands, it is likely that they participate in the pathogenesis of follicular occlusion diseases.

KEY MESSAGES: This article aimed to review existing research on scalp apocrine glands, clarifying this underexplored topic and highlighting them as a potentially relevant component of scalp physiology and pathology.}, } @article {pmid41574302, year = {2025}, author = {Mehrnia, N and Van Dyke, TE}, title = {Microbial dysbiosis and immune dysregulation in periodontitis and peri-implantitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1678163}, pmid = {41574302}, issn = {2235-2988}, mesh = {*Dysbiosis/immunology/microbiology ; *Peri-Implantitis/immunology/microbiology/pathology ; Humans ; *Periodontitis/immunology/microbiology/pathology ; Microbiota/immunology ; Inflammation/immunology ; Animals ; Cytokines/metabolism ; Adaptive Immunity ; Immunity, Innate ; Biofilms/growth & development ; }, abstract = {Periodontitis and peri-implantitis are chronic inflammatory diseases which are primarily driven by excessive and dysregulated immune responses. This would result in irreversible tissue destruction around teeth and implants. Although the microbiome serves as an initiator of inflammation and leads to microbial dysbiosis, persistent and unresolved inflammation is the primary driver of tissue and bone loss. These conditions result from a dynamic interplay between the host immune response and pathogenic biofilms. Microbial dysbiosis results from a shift from a eubiotic (symbiotic) oral microbiome to a dysbiotic microbial community. This is initiated by excessive inflammation and manipulates host immunity to promote chronic inflammation. Concurrently, immune dysregulation, including imbalances in innate and adaptive immune responses that result from a failure of resolution of inflammation pathways, exacerbates tissue destruction through the overproduction of pro-inflammatory cytokines and the activation of destructive pathways, such as neutrophil-mediated degradation and osteoclast activation. This review explores the mechanisms underlying microbial dysbiosis and immune dysregulation in periodontitis and peri-implantitis, emphasizing their contribution to inflammation, bone resorption, and disease progression.}, } @article {pmid41574121, year = {2026}, author = {Kramp, RD and Janecka, MJ and Tardent, N and Jokela, J and Kohl, KD and Stephenson, JF}, title = {Host Genetics and the Skin Microbiome Independently Predict Parasite Resistance.}, journal = {Ecology and evolution}, volume = {16}, number = {1}, pages = {e72923}, pmid = {41574121}, issn = {2045-7758}, abstract = {Host responses to parasite infection involve several interacting systems. Host genetics determine much of the response, but it is increasingly clear that the host-associated microbiome also plays a role. Host genetically determined systems and the microbiome can also interact; for example, the microbiome can modulate the immune response, and vice versa. However, it remains unclear how such interactions between the host immune system and the microbiome may influence the host's overall response to parasites. To investigate how host genetics and the microbiome interact to shape responses to parasites, we imposed truncation selection on Trinidadian guppies (Poecilia reticulata) for low and high resistance to the specialist ectoparasite Gyrodactylus turnbulli. After 3-6 generations of breeding without parasites, we sampled the skin-associated microbiome and infected fish from each line. We applied Dirichlet Multinomial Modeling (DMM) machine-learning to identify bacterial community types across lines and evaluated how selection line and community type explained variations in infection severity. Our findings showed that among females, the resistant line had significantly lower infection severity, while the susceptible line had higher infection severity. Among males, only the susceptible line experienced higher infection severity compared to the other lines. Line did not explain skin microbial diversity, structure or composition. Our DMM analysis revealed three distinct bacterial community types, independent of artificial selection lines, which explained just as much variation in infection load as selection line. Overall, we found that the microbiome and host genetics independently predict infection severity, highlighting the microbiome's active role in host-parasite interactions.}, } @article {pmid41574027, year = {2026}, author = {Lin, A and Xiong, M and Jiang, A and Chen, L and Huang, L and Li, K and Wong, HZH and Zhang, J and Liu, Z and Cheng, Q and Tang, B and Zhang, P and Luo, P}, title = {Tumor Immunotherapy and Microbiome: From Bench-to-Bedside Applications.}, journal = {MedComm}, volume = {7}, number = {2}, pages = {e70454}, pmid = {41574027}, issn = {2688-2663}, abstract = {Cancer immunotherapy has emerged as a transformative therapeutic strategy that harnesses the immune system to combat malignant tumors, overcoming critical limitations such as the nonspecific cytotoxicity of conventional chemotherapy and radiotherapy and drug resistance arising from target mutations in targeted therapies. Growing evidence demonstrates that the human microbiome plays a pivotal role in modulating immune responses and influencing the efficacy of immunotherapeutic interventions. Although the impact is increasingly recognized, the molecular mechanisms and translational potential of microbiome-based strategies remain incompletely explored. This review systematically elucidates how microorganisms from distinct anatomical sites (including bacteria, fungi, and viruses residing in the gut, oral cavity, skin, respiratory tract, and urogenital tract) and intratumoral microbes modulate the tumor immune microenvironment through metabolites, immune cell priming, and antigen mimicry. Furthermore, we discuss how specific microbial signatures predict responses to immune checkpoint inhibitors (ICIs) and CAR-T cell therapy, and highlight emerging interventional strategies, including fecal microbiome transplantation (FMT), probiotics, and engineered bacteria, that demonstrate synergistic effects with immunotherapy in preclinical and clinical settings. By integrating mechanistic insights with translational advances, this review provides a comprehensive scientific foundation for microbiome-based precision immunotherapy, aimed at improving patient survival outcomes and reducing treatment-related adverse events.}, } @article {pmid41574026, year = {2026}, author = {Hernández-Cacho, A and Ni, J and García-Gavilán, JF and Konstanti, P and Belzer, C and Vioque, J and Corella, D and Fitó, M and Vidal, J and Torres-Collado, L and Coltell, O and Babio, N and Hernando-Redondo, J and Moreno-Indias, I and Ruiz-Canela, M and Tinahones, FJ and Salas-Salvadó, J}, title = {The Gut Microbiota as a Mediator in the Relationship Between Dietary Patterns and Depression.}, journal = {MedComm}, volume = {7}, number = {2}, pages = {e70562}, pmid = {41574026}, issn = {2688-2663}, abstract = {The interplay between diet, gut microbiota, and depressive symptoms is increasingly recognized, but underlying mechanisms remain unclear. We investigated whether adherence to several dietary patterns relates to gut microbial signatures and whether these profiles are associated with depressive symptoms in an elderly Mediterranean cohort. In 644 participants, 16S ribosomal RNA gene sequencing and dietary intake from a food-frequency questionnaire were obtained at baseline and 1-year follow-up. Adherence scores were computed for the Mediterranean diet adherence score (MEDAS), energy-reduced MEDAS (erMEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthy Plant-Based Diet Index (HPDI), Unhealthy Plant-Based Diet Index (UPDI), and Western Diet Score (WESTDIET). Healthy patterns (erMEDAS, MEDAS, DASH, HPDI) were associated with 22, 28, 24, and 16 genera, of which 82%, 75%, 79%, and 88% showed a protective profile (more abundant with lower, or less abundant with higher, depressive symptoms). UPDI and WESTDIET were associated with 20 and 27 genera, but only 25% and 26% were protective. Mediation analyses indicated that gut microbiota mediated the associations of MEDAS (ACME = -0.066, p = 0.006) and erMEDAS (ACME = -0.029, p = 0.011) with depressive symptoms. This study is among the first to test whether diet shapes a microbiota signature that mediates the diet-depression relationship, adding mechanistic insight into diet-mental health research.}, } @article {pmid41573938, year = {2025}, author = {Holmes, ZA and Shyti, I and Hoffman, AL and Duncker, KE and Ma, HR and Zhou, Z and Lee, D and Maddamsetti, R and Kim, K and Şimşek, E and Hamrick, GS and Son, H and Villalobos, CA and Lu, J and Ha, Y and Shende, AR and Yao, Z and Liu, S and Shapiro, DM and Kholina, K and Davis, H and Baig, Y and Wu, F and Wang, S and Wang, X and Chatterjee, P and Lynch, M and Lopatkin, AJ and David, L and Chory, E and You, L}, title = {A foundation model for microbial growth dynamics.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.01.691707}, pmid = {41573938}, issn = {2692-8205}, abstract = {Microbial growth dynamics contain rich information about microbial populations, which support applications from antibiotic testing to microbiome engineering. However, the high dimensionality of growth data and the scarcity of large, task-specific datasets have limited generalizable modeling analysis across systems. Here, we develop a foundation model for microbial growth dynamics. It is a large-scale, self-supervised representation model trained on ∼370,000 experimental and simulated growth curves spanning diverse microbial species, environmental conditions, and community contexts. The model learns lower-dimensional latent embeddings that capture essential dynamical features of raw growth data and enable accurate reconstruction of these data. The concise representations enhance predictive performance in diverse downstream applications. Using these embedding, we achieve few-shot learning for antibiotic classification and concentration prediction, accurate forecasting of simulated and experimental communities, and inference of total abundance from relative-abundance data. By extracting transferable representations from heterogeneous datasets, our model provides a general framework for analyzing and predicting microbial community dynamics from limited measurements.}, } @article {pmid41573876, year = {2025}, author = {de Oliveira Andrade, F and Bouker, KB and Ozgul-Onal, M and Jin, L and Cruz, I and Helferich, W and Gao, A and Andrade, K and Verma, V and Staley, C and Foley, PL and Hilakivi-Clarke, L}, title = {Isoflavones impair response to anti-PD1 therapy in murine breast cancer models, irrespective of dietary fiber and fecal short chain fatty acid levels.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.05.692375}, pmid = {41573876}, issn = {2692-8205}, abstract = {BACKGROUND: Fermentable dietary fibers, also called microbiota-accessible carbohydrates (MAC), and the consequent increase in fecal short-chain fatty acids (SCFAs) are linked to improved responsiveness to immune checkpoint blockade (ICB) therapy in human and mouse studies. However, experimental diets high in MAC also often contain estrogenic isoflavones, which may counter fiber's beneficial effects by causing immunosuppression.

METHODS: We studied the effects of feeding female C57BL/6Tac mice low-MAC (AIN93G), low-MAC supplemented with isoflavone genistein, high-MAC (5V5M) or high-MAC isoflavone (high-MACi; 5058D) diet on their gut microbiome and response to anti-PD1 therapy against E0771 allografted triple negative breast cancer (TNBC) and 7,12-dimethylbenz[a]anthracene (DMBA)-initiated estrogen receptor α positive (ERα+) mammary tumors. We also determined whether blocking ERα with tamoxifen (TAM) impacted responsiveness to anti-PD1 therapy in mice fed different diets. The effect of diet and treatments on immune cell signaling pathways was investigated using NanoString PanCancer Immune Profiling Panel.

RESULTS: High-MAC and high-MACi diets increased fecal microbial alpha-diversity and the abundances of SCFA producing families Lachnospiraceae, and Oscillospiraceae as well as fecal SCFA levels, compared with low-MAC diet. E0771 tumors responded to anti-PD1 in mice fed high-MAC, while mice fed high-MACi did not respond. Low-MAC fed mice with single E0771 allograft also responded to anti-PD1, but genistein supplementation eliminated responsiveness. E0771 tumors in high-MAC fed mice contained elevated levels of exhausted CD8+ T cells, which were decreased after anti-PD1 therapy. Opposite effects were seen in mice fed high-MACi diet. Mice with DMBA-initiated ERα+ mammary tumors did not respond to anti-PD1. TAM converted TNBC and ERα+ tumors to become sensitive to anti-PD1 therapy in mice fed high-MACi or low-MAC diets, respectively. Genes in TH17 differentiation pathways were linked to TAM-induced improved anti-PD1 response both in TNBC and ERα+ mammary tumors.

CONCLUSIONS: Our results highlight the role of diet in impacting the effectiveness of ICB therapies. We found that increased SCFA levels alone are not predictive of response to anti-PD1, but if tumor expresses ERα or if diet contains ERα activating compounds, such as isoflavones, blocking ERα+ might convert unresponsive tumors responsive to anti-PD1. Word count : 339.

Dietary fiber is proposed to improve response to checkpoint inhibitor therapy against melanoma, but this has been challenged by a recent preclinical study in which different mouse tumor models were used. None of the studies have been done in breast cancer or preclinical breast cancer models.

WHAT THIS STUDY ADDS: Our study showed, using triple negative breast cancer (TNBC) and estrogen receptor positive (ER+) breast cancer models, that indeed high levels of microbiota accessible carbohydrates (MACs) in diet did not alone determine responsiveness to anti-PD1 therapy, but diet high in plant isoflavones/ hormones impaired anti-PD1 effectiveness, regardless of whether diet contained high fiber levels or not. We also found that the adverse effects of isoflavones were counteracted by tamoxifen, partial estrogen receptor antagonist.

Our findings could indicate that breast cancer patients, both those with TNBC and ER+ disease, should not consume diets high in isoflavones when treated with anti-PD1.}, } @article {pmid41573853, year = {2025}, author = {Bresette, N and Ericsson, AC and Woods, C and Lin, AL}, title = {MeLSI: Metric Learning for Statistical Inference in Microbiome Community Composition Analysis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.04.692328}, pmid = {41573853}, issn = {2692-8205}, abstract = {UNLABELLED: Microbiome beta diversity analysis relies on distance-based methods including PERMANOVA combined with fixed ecological distance metrics (Bray-Curtis, Euclidean, Jaccard, and UniFrac), which treat all microbial taxa uniformly regardless of their biological relevance to community differences. This "one-size-fits-all" approach may miss subtle but biologically meaningful patterns in complex microbiome data. We present MeLSI (Metric Learning for Statistical Inference), a novel machine learning framework that learns data-adaptive distance metrics optimized for detecting community composition differences in multivariate microbiome analyses. MeLSI employs an ensemble of weak learners using bootstrap sampling, feature subsampling, and gradient-based optimization to learn optimal feature weights, combined with rigorous permutation testing for statistical inference. The learned metrics can be used with PERMANOVA for hypothesis testing and with Principal Coordinates Analysis (PCoA) for ordination visualization. Comprehensive validation on synthetic benchmarks and real datasets shows that MeLSI maintains proper Type I error control while delivering competitive or superior F-statistics when signal structure aligns with CLR-based weighting and, crucially, supplies interpretable feature-weight profiles that clarify which taxa drive group separation. On the Atlas1006 dataset, MeLSI achieved stronger effect sizes than the best traditional methods, and even when performance was comparable, the learned feature weights provided biological insight that fixed metrics cannot supply. MeLSI therefore offers a statistically rigorous tool that augments beta diversity analysis with transparent, data-driven interpretability.

IMPORTANCE: Understanding which microbes differ between groups of interest could reveal therapeutic targets and diagnostic biomarkers. However, current analysis methods treat all microbes equally (similar to using the same ruler to measure everything, regardless of what matters most). This means subtle but clinically important differences may go undetected, especially when only a few key species drive disease while hundreds of "bystander" species add noise. MeLSI solves this by learning which microbes matter most for each specific comparison. In comparing male and female gut microbiomes, MeLSI identified specific bacterial families driving the differences, providing actionable biological insights that standard methods miss. This capability is particularly crucial for detecting early disease biomarkers, where differences are subtle and masked by biological variability. By telling researchers not just whether groups differ, but which specific microbes drive those differences, MeLSI accelerates the path from microbiome data to testable biological hypotheses and clinical applications.}, } @article {pmid41573687, year = {2026}, author = {Cui, Q and Wang, J and Huang, Y and Zhou, F and Wu, J and Song, F and Zhao, Q and Feng, R and Zhang, X}, title = {Isolation, identification, and plant growth-promoting mechanisms of strain BN5, with a focus on exogenously Trp-independent IAA biosynthesis, and its impact on cucumber cultivation.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100549}, pmid = {41573687}, issn = {2666-5174}, abstract = {The genus Niallia was recently separated as a taxonomic group from Bacillus based on conserved signature insertions and deletions in the genome. Unlike its role in bioremediation, its function in plant growth promotion has not attracted widespread attention. This study identifies Niallia taxi BN5, focusing on the role of tryptophan in IAA synthesis and regulation, as well as the effects of cucumber. The study employed pot and greenhouse experiments to evaluate the impacts of BN5 on cucumber growth, yield, and quality. Genome analysis explored the tryptophan-regulated IAA biosynthesis pathway, with transcriptome and qPCR examining expression of IAA-related, tryptophan synthesis, and motility genes. It also evaluated impacts on rhizosphere microbial communities and soil enzyme activities. BN5 significantly enhanced cucumber growth (height: +24.29 %, stem diameter: +11.23 %), yield (+17.55 %), and quality (vitamin C: +17.2 % soluble sugar: +37.41 %, all p < 0.05). It increased soil enzyme activities (urease by +52.12 %, dehydrogenase by +44.70 %, p < 0.05) and reshaped the microbial structure. Owing to its possession of a complete tryptophan synthase operon (trpE-D-G-C-F-B-A), strain BN5 is able to produce IAA at a concentration of 17.64 μg/mL via a tryptophan-dependent biosynthetic pathway, with no reliance on exogenous tryptophan. Exogenous tryptophan downregulated the trp cluster but upregulated motility genes (mcp and fliC, p < 0.05), indicating adaptive regulation of IAA precursors. This study clarifies the plant growth-promoting mechanisms of Niallia spp., focusing on tryptophan-mediated regulation of IAA biosynthesis that is independent of exogenous tryptophan. It lays a foundation for efficient microbial fertilizers, highlighting BN5's potential in sustainable agriculture.}, } @article {pmid41573337, year = {2026}, author = {Liu, J and Chen, Y and Wang, Y and Li, D and Xu, Z and Zhang, J and Qin, L and Han, B and Jing, Y and Cui, D and Zhu, Y and Xia, S and Jiang, C}, title = {Diversity of Gut Microbiota and Metabolites in Benign Prostatic Hyperplasia with Different Prostate Volumes.}, journal = {European urology open science}, volume = {84}, number = {}, pages = {40-49}, pmid = {41573337}, issn = {2666-1683}, abstract = {BACKGROUND AND OBJECTIVE: The gut microbiota, influenced by age and sex hormones, may correlate with the development and progression of benign prostatic hyperplasia (BPH). This study aims to characterize gut microbiota and metabolite profiles in BPH patients with varying prostate volumes.

METHODS: Fecal samples from BPH patients were analyzed using 16S rDNA sequencing and untargeted metabolomics. Microbial and metabolic differences were assessed via the Linear discriminant analysis Effect Size, KEGG pathway enrichment, and a mediation analysis.

KEY FINDINGS AND LIMITATIONS: We identified 26 differential amplicon sequence variants (ASVs) and 70 metabolites, with 18 microbes correlating significantly with clinical BPH indicators. The key pathways included unsaturated fatty acid and steroid hormone biosynthesis. Akkermansia (ASV549) may affect prostate volume through the regulation of intestinal amino acid metabolism and may negatively affect prostate-specific antigen levels by inhibiting heat shock protein (HSP) 90 (luminespib). Limitations include sample size and unmeasured confounders.

Gut microbiota and metabolite diversity are associated with prostate volume; further studies are warranted to elucidate the potential interventions via microbiome modulation or metabolic targeting for BPH management.

PATIENT SUMMARY: In this study, we identified the potential associations between gut and both prostate volume and benign prostatic hyperplasia symptoms. These findings suggest that dietary interventions or fecal microbiota transplantation may represent potential strategies for modulating prostate health in the future.}, } @article {pmid41573287, year = {2026}, author = {Kassaian, N and Ahangarzadeh, S and Vakili, B and Shoaei, P and Alibakhshi, A and Rostami, S and Gavanji, S and Arbabnia, S and Mohammadi, E}, title = {Assessment of Breastmilk Microbiome Focusing on Probiotics.}, journal = {Iranian journal of nursing and midwifery research}, volume = {31}, number = {1}, pages = {133-138}, pmid = {41573287}, issn = {1735-9066}, abstract = {BACKGROUND: Breastmilk is an important factor affecting the infant's gut microbiota and health. Both milk microbiome and the content of oligosaccharides play a role in this effect. The mother's lifestyle can affect the breast milk microbiome. In this study, we assessed the breast milk microbiome in healthy mothers in Iran and its relationship to the mother's lifestyle during lactation.

MATERIALS AND METHODS: In a cross-sectional study, from May 2022 to January 2023, 20 mother-neonates participated by donating their breastmilk samples and completing two questionnaires (food recall for nutritional status and DASS-21 for psychological status). Milk samples in aerobic and anaerobic conditions were cultured to isolate bacterial strains, and the probiotic strains were determined. Data entrees and analysis were done using SPSS-15, and the independent T-student or Mann-Whitney U test was used for statistical analysis.

RESULTS: Seven bacterial species were isolated, including Pedicoccus acidilactici, Lactobacillus fermentum (potential probiotics), Corynebacterium kroppenstedtii, Staphylococcus epidermidis, Rothia kristinae, Streptococcus rubneri, and Streptococcus parasanguinis. It was shown that the consumption of dairy products in the diet was related to probiotic strains in breast milk (p value = 0.03).

CONCLUSIONS: Among the microbiome isolated from breast milk, two probiotics, Pedicoccus acidilactici and Lactobacillus fermentum, were detected. In the mother's diet, dairy product intake during lactation can increase the probiotics in breast milk and give the infant more valuable content.}, } @article {pmid41573256, year = {2025}, author = {Manzano-Marín, A and Böhne, A and Monteiro, R and Marcussen, T and Struck, TH and Oomen, RA and , and , and , and Howard, C and Howe, K and Blaxter, M and McCarthy, S and Wood, JMD and Martin, F and Lazar, A and Haggerty, L and Bortoluzzi, C}, title = {ERGA-BGE reference genome of Hirudo verbana, a once neglected freshwater haematophagous European medicinal leech.}, journal = {Open research Europe}, volume = {5}, number = {}, pages = {395}, pmid = {41573256}, issn = {2732-5121}, abstract = {Hirudo verbana Carena, 1820, commonly known as the southern medicinal leech, is one of several European medicinal leeches, whose full diversity has just recently started to be uncovered. Historically, it has been widely used as a medicinal leech and for centuries it was treated erroneously under the specific name of Hirudo medicinalis L. 1758. Recent molecular and taxonomic analyses have revealed subspecific diversity within the morphospecies H. verbana. Hirudo verbana is a blood-feeding species sucking blood from amphibians, fish, and mammals. It occupies freshwater habitats, typically shallow ponds and lakes. Studies show that this leech species has a "naturally limited microbiome", suggesting it may serve as a powerful model system for the study of gut microbiota. We expect this chromosome-level assembly of H. verbana to serve as a high-quality genomic resource for this most famous leech genus and to serve as a foundation to the study of the diversification and biodiversity of European medicinal leeches, as well as their gut-associated symbionts. The genome of H. verbana was assembled into two haplotypes through a phased assembly approach; however, only the primary haplotype was designated as the reference genome for annotation and downstream analyses. The entirety of the primary haplotype was assembled into 14 contiguous chromosomal pseudomolecules, including the mitogenome. This chromosome-level assembly encompasses 0.18 Gb, composed of 277 contigs and 27 scaffolds, with contig and scaffold N50 values of 1.3 Mb and 13.4 Mb, respectively.}, } @article {pmid41573225, year = {2025}, author = {Calderon, RB and Gouli, S and Barphagha, I and Ham, JH}, title = {Growth promotion and stress tolerance of soybean plants driven by seed treatment with synthetic bacterial community of soybean-associated beneficial bacteria.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1729743}, pmid = {41573225}, issn = {1664-462X}, abstract = {INTRODUCTION: Beneficial microbes provide a sustainable approach to improving crop production and reducing risks from intensive farming. Microbial consortia, complementary traits, often outperform single strains in promoting plant health. This study aimed to develop an effective biological strategy to enhance soybean growth and health using beneficial bacterial consortia.

METHODS: Bacteria were isolated from the root endosphere and rhizosphere of field-grown soybean plants and screened for traits such as nutrient solubilization, hormone production, and pathogen suppression. Seven synthetic bacterial communities (SBCs), each comprising 5 to 20 SABB strains, were constructed to evaluate their potential in promoting soybean growth and health. Impact of SBC seed treatments on the structure of soybean microbiota was also investigated.

RESULTS: Two SBC sets, Set2 and Setm4, demonstrated superior performances in enhancing plant growth and resistance to the fungal pathogen Rhizoctonia solani when applied via seed treatment. Notably, seed treatment with Set2 or Setm4 also improved soybean resilience to abiotic stresses, including drought and waterlogging. Profiling of the root endosphere and rhizosphere microbiota revealed that SBC application through seed treatment significantly altered the composition of soybean-associated microbial community, including the enrichment of key symbiotic taxa, such as Bradyrhizobium elkanii, and increased microbial network complexity.

DISCUSSION: The beneficial effects of SBC through seed treatment are closely related to microbiome restructuring in soybean roots. This study provides valuable insights into the development of innovative and sustainable crop management strategies, highlighting the potential of SBC-based seed treatments to enhance growth and stress resilience in soybeans and other major crops.}, } @article {pmid41573214, year = {2025}, author = {Ren, Y and Yan, H and Ma, A}, title = {Plant genomic and microbial interplay in the rhizosphere under salt stress: a review.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1667328}, pmid = {41573214}, issn = {1664-462X}, abstract = {Soil salinization has been considered as a global problem in agriculture, which decreases crop productivity and threatens food security. Salt stress causes complex physiological damages in plants such as ionic imbalance, osmotic stress, and oxidative damage. However, plants have developed several genomic mechanisms to reduce these negative influences that are further supported by dynamic interactions with rhizosphere microbial communities. This review integrates current advances in understanding the interplay between plant genomes and the rhizosphere microbiome under salt stress. It highlights the role of plant-growth-promoting rhizobacteria (PGPR), arbuscular mycorrhizal fungi (AMF), and microbial volatiles in modulating gene expression and root architecture. Notably, PGPR such as Enterobacter sp. SA187 and Bacillus velezensis have been shown to upregulate key stress-related genes and increase antioxidant enzyme activities, which boost plant resilience under salinity. These microbes also influence stress signaling pathways such as SOS and ABA. Furthermore, this review also discusses the effect of root exudates on microbial communities, the application of synthetic microbial consortia, and genome-scale strategies such as transcriptomics, GWAS, and CRISPR. Our findings show that root exudation patterns shift significantly under salt stress, which enriches beneficial microbial taxa such as Sphingomonas and Streptomyces, while volatile compounds like benzenoids and ketones contribute to systemic stress responses. Understanding the synergistic plant-microbe interactions provides a foundation to engineer salt-resilient crops and for the advancement of sustainable agricultural practices in saline soils.}, } @article {pmid41573169, year = {2026}, author = {Nap, B and Weston, B and Brandt, A and Wodak, MF and Bergheim, I and Thiele, I}, title = {The nutrition toolbox permits in silico generation, analysis, and optimization of personalized diets through metabolic modelling.}, journal = {Bioinformatics advances}, volume = {6}, number = {1}, pages = {vbaf325}, pmid = {41573169}, issn = {2635-0041}, abstract = {MOTIVATION: Nutrition is an important factor in human health, used to alleviate or prevent symptoms of various diseases. However, the effects of nutrition on the gut microbiome and human metabolism are not well understood. Whole-body metabolic models (WBMs) have been applied to study relationships between regional diets and human/microbiome metabolism. This method requires diets to be defined at the metabolite level, rather than the food item level, which has gated the application of personalized diets to WBMs.

RESULTS: We developed the Nutrition Toolbox, which leverages open-source databases containing metabolite composition for over ten thousand food items to convert food items into their metabolic composition to create in silico diets. Additionally, when used with a previously published nutrition algorithm, minimal changes to a diet can be identified to achieve desirable shifts in human and microbiome metabolism. Taken together, we believe that the Nutrition Toolbox can help to understand the effects of nutrition on human metabolism and has the potential to contribute to personalized nutrition.

The Nutrition Toolbox is written in MATLAB. The code can be found at https://github.com/opencobra/cobratoolbox. A tutorial explaining the code is available in the COBRA toolbox and as view-only supplementary tutorial. Details on installing the COBRA toolbox are available at https://opencobra.github.io/cobratoolbox/stable/installation.html.}, } @article {pmid41572842, year = {2026}, author = {Ahmadi, P and Honardoost, M and Janzadeh, A and Taherkhani, S}, title = {Flavonoids and Their Influence on the Gut Microbiome: Implications for Cardiovascular Health.}, journal = {Nutrition bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1111/nbu.70039}, pmid = {41572842}, issn = {1467-3010}, abstract = {Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, necessitating effective preventive and therapeutic strategies. Flavonoids and polyphenols, which are abundant in colourful fruits and vegetables, have emerged as promising bioactive compounds for mitigating CVD. This study elucidates the mechanisms by which flavonoids exert cardioprotective effects through their antioxidant, prebiotic, and mitochondrial restorative properties. Flavonoids function as hydrogen donors, scavenging free radicals such as nitric oxide (NO[•]), superoxide anions (O[•]), and hydroxyl radicals (OH[•]), thereby reducing oxidative stress by decreasing inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) activity while enhancing endothelial nitric oxide synthase (eNOS) functionality to promote vasodilation and prevent hypertension. Additionally, flavonoids act as prebiotics, fostering the symbiotic gut microbiota (GM), including Bifidobacteria and Lactobacillus, which produce short-chain fatty acids (SCFAs) and suppress pathogenic trimethylamine-N-oxide (TMAO)-producing bacteria. This enhances gut epithelial barrier integrity, reduces inflammation mediated by lipopolysaccharide (LPS), and protects against heart failure, ischaemia, and atherosclerosis. Under ischemic and heart failure conditions, flavonoids inhibit apoptosis, necrosis, ferroptosis, and fibrosis by restoring hypoxia-damaged mitochondrial function and cardiac energy metabolism. Furthermore, flavonoids prevent arteriosclerosis by inhibiting low-density lipoprotein (LDL) oxidation, reducing cholesterol absorption, promoting bile salt-hydrolysing bacteria, and decreasing vascular cell adhesion molecule (VCAM)-1 expression on coronary vessels. Here, we aim to advance the understanding of flavonoid-mediated cardioprotection by considering their antioxidant, anti-inflammatory, and gut microbiome-modulating effects, offering novel insights into dietary interventions for CVD prevention and management. The findings underscore the potential of flavonoids as accessible, natural agents to address global health disparities in CVD burden.}, } @article {pmid41572827, year = {2026}, author = {Xu, B and Liu, P and Yan, N and Wang, T and Liu, L and Cheng, Y}, title = {Multi-omics insights into gut microbial dysbiosis and metabolic alterations in immune checkpoint inhibitor-induced thrombocytopenia.}, journal = {Immunotherapy}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/1750743X.2026.2618937}, pmid = {41572827}, issn = {1750-7448}, abstract = {BACKGROUND: Immune checkpoint inhibitors-induced thrombocytopenia (ICIs-TCP) is a rare immune-related adverse events (irAEs). The physiological changes underlying ICIs-TCP remain incompletely elucidated.

METHODS: We performed multi-omics analysis (gut microbiome, plasma metabolomics/proteomics) comparing microbial/metabolic alterations in cancer patients with (n = 8) and without ICIs-TCP (n = 8). Fecal metagenomic shotgun sequencing was performed to assess microbial composition and function, while plasma metabolomics and proteomics analyses identified systemic metabolic and protein expression changes associated with ICIs-TCP.

RESULTS: Patients with ICIs-TCP exhibited distinct gut microbiota profiles, with an increased abundance of Segatella, Prevotella, and Clostridium, alongside a depletion of Bacteroides and Roseburia. Functional analysis revealed significant downregulation of metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism. Plasma metabolomics identified reduced arginine levels and disruptions in key amino acid and energy metabolism pathways, suggesting systemic arginine depletion. Proteomic analysis further demonstrated down-regulation of folate hydrolase 1 (FOLH1), a key enzyme in glutamate metabolism, implicating metabolic dysregulation in TCP pathogenesis.

CONCLUSION: The depletion of arginine and associated metabolic disruptions are associated with ICIs-TCP and may represent a potential therapeutic target for mitigating TCP risk in patients receiving ICIs.}, } @article {pmid41572814, year = {2026}, author = {Fathima, N and Mascarenhas, R and Umar, D and Rekha, PD and Shetty, S and Amin, V}, title = {Impact of removing fixed orthodontic appliances on oral microbial dysbiosis: A longitudinal study and metagenomic sequencing analysis.}, journal = {Journal of orthodontics}, volume = {}, number = {}, pages = {14653125251408048}, doi = {10.1177/14653125251408048}, pmid = {41572814}, issn = {1465-3133}, abstract = {OBJECTIVE: To investigate the impact of appliance removal on oral microbial diversity, composition, and abundance using metagenomic sequencing. It aims to identify the core microbiome and assess changes between mid-treatment and 2 weeks after debonding to better understand the relationship between orthodontic therapy and oral health.

METHODS: This longitudinal cohort study recruited 26 patients undergoing fixed orthodontic treatment between January 2022 and June 2023. Saliva samples were collected at two predefined time points: mid-treatment (T0, defined as before appliance removal) and 2 weeks after debonding (T1). Microbial DNA was extracted and the V1-V3 hypervariable regions of the 16S rRNA gene were sequenced using Illumina NovaSeq. Bioinformatics analysis was performed using QIIME and the SILVA database to evaluate microbial diversity and composition at T0 and T1. Beta diversity metrics and statistical tests, including PERMANOVA and Wilcoxon signed-rank tests, were applied to identify significant differences (P < 0.05). Effect sizes with 95% confidence intervals (CIs) were reported.

RESULTS: The analysis revealed significant shifts in microbial diversity and composition between T0 and T1. A total of 189 species across 63 genera were identified, with Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria as dominant phyla. Genera such as Fusobacterium periodonticum (↑ 12.4%, 95% CI = 10.1-14.7) and Veillonella parvula (↑ 9.8%, 95% CI = 7.6-11.3) increased after debonding, while Prevotella melaninogenica (↓ 10.2%, 95% CI = 8.1-12.0) and Rothia dentocariosa (↓ 7.9%, 95% CI = 6.3-9.2) decreased. Beta diversity analysis confirmed a statistically significant microbial community shift (P < 0.05).

CONCLUSION: This study demonstrated significant microbial shifts between mid-treatment and 2 weeks after debonding, including increases in potentially pathogenic genera and alterations in the core microbiome. These findings indicate microbial changes persist for at least 2 weeks after appliance removal. Further research with pre-treatment baselines and extended follow-up is required to better define the long-term trajectory of these changes.}, } @article {pmid41572811, year = {2026}, author = {Jana, A and Mukhopadhyay, D and Sinha, S and Basak, A and Paramanik, B and Mondol, SA}, title = {Exploring the nano revolution: trends and risks in soil nanotechnology.}, journal = {Nanotoxicology}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/17435390.2026.2617638}, pmid = {41572811}, issn = {1743-5404}, abstract = {Technical advances have improved scientists' ability to think critically and turn theoretical ideas into actual research. Nanotechnology's potential allows it to spread in modern agriculture. Agricultural nanotechnology may improve food supply, security, sustainability and climate change. Nanoparticles' effects on the soil-plant system reveal their soil ecological hazards. Nano-enzymes promote the balance of ROS by acting as strong antioxidants, thereby enhancing the stress tolerance of plants. They activate antioxidant enzymes like SOD, CAT, and POD, stabilize cellular membranes, and protect photosynthetic machinery. Nanomaterials influence soil pollutants' fate, mobility and toxicity in remediation methods. Nanomaterials' performance and fate rely on soil interactions. Despite many potential benefits, its field applications are restricted. Current research lacks practical ways to assess risk and nanoparticle toxicity to plants, soil and soil microbiomes after release. Environmental safety and risk evaluation need understanding of the manufactured nanoparticle-soil interactions. Nanotechnologies in ecosystems raise health risks. Given the circumstances, nanoparticles in soil must be evaluated and security measures be taken.}, } @article {pmid41572742, year = {2026}, author = {Patil, S and Doshi, G}, title = {Gut Microbiota in the Hepato-Cardiorenal Axis: Microbial Metabolites, Inflammation, and Emerging Therapeutic Targets.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128413464251209115653}, pmid = {41572742}, issn = {1873-4286}, abstract = {INTRODUCTION: To sustain systemic homeostasis, the gut microbiota manages immunological, metabolic, and inflammatory processes. Multiorgan diseases, especially those impacting the liver, kidney, and cardiovascular system through the hepato-cardiorenal axis, have been strongly associated with dysbiosis.

METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, with the focus on articles till 2025. Eligible sources included clinical trials, systematic reviews, and peer-reviewed academic publications that discussed metabolites, gut microbiota, and treatment approaches for diseases of the liver, kidney, and heart. A qualitative synthesis of the data indicated important mechanisms and potential treatments.

RESULTS: SCFAs have anti-inflammatory and intestinal barrier integrity-enhancing qualities, whereas uremic toxins and TMAO promote oxidative stress, fibrosis, and vascular dysfunction. Hepatic steatosis, insulin resistance, and systemic inflammation are all affected by the dysbiosis-induced bile acid imbalance. Microbiotatargeted therapies include fecal microbiota transplantation, fiber- or polyphenol-rich diets, probiotics, prebiotics, synbiotics, and pharmacological modification of bile acid or TMAO pathways, which have potential but need more comprehensive validation.

DISCUSSION: The findings show that, among other factors, gut metabolites-such as uremic toxins, bile acids, TMAO, and SCFAs - are key players in mediating inflammation and metabolic dysregulation across the hepato-cardiorenal axis. However, the lack of consistent treatment protocols and differences in microbiome composition limit the practical application of preclinical research that has clearly demonstrated the existence of mechanistic links. Future research should focus on long-term clinical outcomes, biomarker identification, and precise microbiome modifications to establish causation and improve therapy effectiveness.

CONCLUSION: The gut microbiota significantly influences the hepato-cardiorenal axis through metabolitemediated signalling. While therapeutic modulation shows promise, precision medicine approaches and highquality randomized trials are essential to tackle multi-organ metabolic and inflammatory diseases.}, } @article {pmid41572689, year = {2026}, author = {Ibrahim, HA and Mohamad, WMW and Mohamad, N and Kassim, NK and Ismail, TNNT and Ab Rahman, WSW and Yudin, ZM and Das, S and Zin, SRM}, title = {Insight into Molecular Mechanisms and Pathways Related to the Association of Periodontal Disease and Type 2 Diabetes Mellitus.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303415067251124044844}, pmid = {41572689}, issn = {2212-3873}, abstract = {INTRODUCTION: Periodontal disease is a condition that damages the supporting tissues, potentially resulting in tooth extraction, while type 2 diabetes is a condition that involves insulin resistance, leading to hyperglycaemia and systemic inflammation.

METHODS: A broad literature search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and ProQuest. Search terms included combinations of keywords related to periodontal disease, type 2 diabetes, bone metabolism, genetics/epigenetics, inflammation, and oxidative stress, refined using Boolean operators. Titles and abstracts were screened, and eligible full-text articles were reviewed for relevant data.

RESULTS: This review found that periodontal disease, a major cause of tooth loss in adults, is strongly influenced by the bidirectional relationship with type 2 diabetes. Hyperglycaemia in poorly controlled diabetes exacerbates periodontal inflammation by enhancing the formation of advanced glycation end-products, triggering pro-inflammatory pathways such as the activation of Nuclear Factor kappa-light-chain-enhancer of activated B cells and cytokine release (e.g., Tumour Necrosis Factor-α, Interleukin [IL]-6, IL-18). Concurrent dysbiosis of the oral microbiome disrupts immunoregulation, while an imbalance in the receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) system promotes osteoclastogenesis, collectively leading to accelerated tissue destruction, impaired healing, and an increased risk of complications.

CONCLUSION: This review clarifies the molecular mechanisms of the triad axis of oral microbiota- inflammatory factors-bone metabolism markers in the bidirectional association between periodontal disease and type 2 diabetes. Understanding the underlying mechanisms of this bidirectional relationship can provide valuable information for researchers to identify potential targets for effective management strategies for periodontal disease in patients with type 2 diabetes.}, } @article {pmid41572685, year = {2026}, author = {Chen, H and Liu, H and Zeng, Y and Yang, Y}, title = {Preliminary Study on Laboratory Indicators and Gut Microbiota Differences between Genders with Gastrointestinal Inflammation.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303394944251031095347}, pmid = {41572685}, issn = {2212-3873}, abstract = {INTRODUCTION: The human gastrointestinal tract is home to a vast array of microorganisms, and the imbalance of these microorganisms is closely linked to various diseases. The composition of gut microbiota in individuals is influenced by many factors, among which gender differences are often overlooked and lack targeted treatment plans in clinical practice. Based on this, we conducted this study aimed at exploring the pathogenesis of gastrointestinal inflammation and the importance of gender specificity, providing new ideas and targets for the diagnosis and treatment of gastrointestinal inflammation stratified by gender.

METHODS: We collected fecal samples from 89 patients with gastrointestinal inflammation (40 males and 49 females) for DNA extraction, DNA library construction, sequencing, and clinical data analysis.

RESULTS: In laboratory indicators, male patients had significantly lower mean LDH levels than females (P < 0.05), whereas median GGT, HB, M, and E values were significantly higher (P < 0.05). Additionally, significant differences in microbial α diversity at the species level were observed between the two groups (all P < 0.05). In the prediction analysis of microbial population function, the mean values of heterologous biodegradation and metabolism, signal transduction, cell activity, metabolism of other amino acids, and bacterial infectious disease pathways in the female patient group were higher than those in the male patient group (all P<0.05), and the mean values of nucleotide metabolism, replication and repair, and transcription and translation were lower than those in the male patient group (all P<0.05).

DISCUSSION: Gender differences affect gastrointestinal inflammation progression, with male and female patients showing distinct gut microbiota and laboratory indicators. Males have lower LDH but higher GGT, HB, M, and E, linked to hormonal effects. The gut microbiome composition differs by gender, with males having a higher prevalence of Prevotella and altered metabolic pathways. Females show higher activity in xenobiotic degradation and infection-related functions. Diet, exercise, and clinical interventions, such as FMT, can modulate the microbiota, but gender-specific responses exist.

CONCLUSION: Analysis revealed significant sex-based differences in gastrointestinal disease patients, including variations in laboratory indicators (LDH, GGT, HB, M, E), gut microbiome composition and diversity, and predicted microbial functional profiles. This provides insights for precise medical treatment of gastrointestinal inflammation stratified by gender.}, } @article {pmid41572438, year = {2026}, author = {Maes, M and Almulla, AF and Vasupanrajit, A and Jirakran, K and Tunvirachaisakul, C and Maes, A and Chancham, P and Klomkliew, P and Payungporn, S and Zhang, Y}, title = {Functional Shotgun Metagenomic Insights into Gut Microbial Pathway and Enzyme Disruptions Linking Metabolism, Affect, Cognition, and Suicidal Ideation in Major Depressive Disorder.}, journal = {Acta neuropsychiatrica}, volume = {}, number = {}, pages = {1-47}, doi = {10.1017/neu.2026.10056}, pmid = {41572438}, issn = {1601-5215}, abstract = {BACKGROUND: Major depression (MDD) is linked to neuro-immune, metabolic, and oxidative stress (NIMETOX) pathways. The gut microbiome may contribute to these pathways via leaky gut and immune-metabolic processes.

AIMS: To identify gut microbial alterations in MDD and to quantify functional pathways and enzyme gene families and integrate these with the clinical phenome and immune-metabolic biomarkers of MDD.

METHODS: Shotgun metagenomics with taxonomic profiling was performed in MDD versus controls using MetaPhlAn v4.0.6, and functional profiling was conducted using HUMAnN v3.9, aligning microbial reads to species-specific pangenomes (Bowtie2 v2.5.4) followed by alignment to the UniRef90 v201901 protein database (DIAMOND v2.1.9).

RESULTS: Gut microbiome diversity, both species richness and evenness, is quite similar between MDD and controls. The top enriched taxa in the multivariate discriminant profile of MDD reflect gut dysbiosis associated with leaky gut and NIMETOX mechanisms, i.e., Ruminococcus gnavus, Veillonella rogosaem and Anaerobutyricum hallii. The top four protective taxa enriched in controls indicate an anti-inflammatory ecosystem and microbiome resilience, i.e., Vescimonas coprocola, Coprococcus, Faecalibacterium prausnitzii, and Faecalibacterium parasitized. Pathway analysis indicates loss of barrier protection, antioxidants and short-chain fatty acids, and activation of NIMETOX pathways. The differential abundance of gene families suggests that there are metabolic distinctions between both groups, indicating aberrations in purine, sugar, and protein metabolism. The gene and pathway scores explain a larger part of the variance in suicidal ideation, recurrence of illness, neurocognitive impairments, immune functions, and atherogenicity.

CONCLUSION: The gut microbiome changes might contribute to activated peripheral NIMETOX pathways in MDD.}, } @article {pmid41572422, year = {2026}, author = {Ahmad, HH and Peck, B and Terry, D}, title = {Probiotics and developmental progression in healthy preschool-aged children: a double-blind, placebo-controlled trial.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/1028415X.2026.2617360}, pmid = {41572422}, issn = {1476-8305}, abstract = {BACKGROUND: The gut-brain axis is well known to have a bilateral relationship. Recent research has shown the positive influence of probiotic supplementation on mental flexibility and stress scores among healthy elderly population. However, no similar research has been conducted for young children.

AIM: To investigate the influence of probiotic supplementation on the developmental progress of healthy children.

METHODS: A prospective, randomised, double-blind, placebo-controlled trial was conducted among 105 healthy children, who received either probiotic or placebo supplementation over a six-month period. Of those, 51 were allocated to the probiotic group and 54 to the placebo group. Pre - and post-developmental assessments were conducted using the ASQ-3 and ASQ:SE-2 questionnaires.

RESULTS: Per-protocol analysis showed that children in both the probiotic and placebo groups demonstrated significant improvements in 3 of the 6 ASQ-3 developmental domains. However, baseline analysis by age group revealed significant differences in 3 of the 6 ASQ-3 domains, with children older than 44 months showing better developmental scores. Moreover, increasing age and higher consumption of fruits and vegetables were identified as significant confounders associated with developmental progress.

CONCLUSION: This first-of-its-kind study conducted among healthy preschoolers concludes that probiotic supplementation did not significantly influence developmental progress. However, the study was underpowered for its primary outcome. Future large-scale studies involving diverse populations are recommended.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12622000153718..}, } @article {pmid41572381, year = {2026}, author = {Choi, Y and Kang, A and Seo, E and Lee, DJ and Park, J and Kim, Y and Yu, K and Yun, CH and Jang, KB and Kim, WK and Shim, K and Kang, D and Kim, Y}, title = {Combination of bacteriophage-probiotics alleviates intestinal barrier dysfunction by regulating gut microbiome in a chick model of multidrug-resistant Salmonella infection.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {14}, pmid = {41572381}, issn = {1674-9782}, support = {NRF-2021R1A2C3011051//National Research Foundation of Korea/ ; RS-2023-00218476//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics. In this study, we evaluated a combination of lytic Salmonella-infecting bacteriophages (SLAM_phiST45 and SLAM_phiST56) and a probiotic bacterium Limosilactobacillus reuteri (SLAM_LAR11) in a chick model challenged with Salmonella enterica serovar Typhimurium infection.

RESULTS: Co-administration with two-phage cocktail and a probiotic showed markedly reduced Salmonella colonization in the gut and systemic organs of chicks, comparable to the effect of phage-only treatment. In contrast with phage-only treatment, the combined therapy significantly improved the rate of body-weight change from the day of infection to necropsy (P < 0.0001) and alleviated infection-associated splenomegaly (P = 0.028) and hepatomegaly (P = 0.011). In the ileum, the villus height-to-crypt depth ratio (VH/CD) increased significantly (P = 0.044). In the colon, expression of tight-junction genes OCLN (P = 0.014), TJP1 (P < 0.0001), and MUC2 (P = 0.011) was elevated, whereas the pro-inflammatory cytokine IL6 was reduced (P = 0.018). These improvements were accompanied, in the cecum, by trends toward decreases in Escherichia-Shigella (P = 0.09) and Clostridium (P = 0.16) and a trend toward an increase in Blautia (P = 0.11); additionally, in the ileum, Lactobacillus (P = 0.037) and Blautia (P = 0.016) increased significantly, yielding a more balanced microbiota than with phage-only treatment. Consistently, levels of functional metabolites, including acetic acid (LDA = 3.32) and lactic acid (LDA = 5.29), were increased.

CONCLUSION: Taken together, these findings demonstrate that phage-probiotic co-administration not only enhances the clearance of multidrug-resistant Salmonella more effectively than phage treatment alone but also promotes intestinal health, highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.}, } @article {pmid41572341, year = {2026}, author = {Ornelas, MAS and Ortiz Sanjuán, JM and Leonard, FC and Correia-Gomes, C and Estellé, J and O'Neill, L and Manzanilla, EG}, title = {Cross-sectional study characterizing the porcine faecal microbiome in commercial farms.}, journal = {Porcine health management}, volume = {12}, number = {1}, pages = {1}, pmid = {41572341}, issn = {2055-5660}, support = {2020EN510//International Coordination of Research on Infectious Animal Diseases (ICRAD)/ ; }, } @article {pmid41572302, year = {2026}, author = {Einarsson, GG and Das, S and Silversides, JA and Fundano, N and Lonsdale, E and McMullan, R and McAuley, DF and Irwin, NJ and McCoy, CP and Wylie, MP and Sherrard, LJ}, title = {Biofilm communities above and below the cuff of endotracheal tubes are spatially homogenous.}, journal = {Respiratory research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12931-025-03485-2}, pmid = {41572302}, issn = {1465-993X}, support = {NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; NICHS 2020_C05//Northern Ireland Chest Heart and Stroke/ ; }, } @article {pmid41572173, year = {2026}, author = {Kim, H and Siddiqui, NY and Karstens, L and Ma, L}, title = {A negative binomial latent factor model for paired microbiome sequencing data.}, journal = {BMC bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12859-025-06362-3}, pmid = {41572173}, issn = {1471-2105}, support = {R03-AG060082/AG/NIA NIH HHS/United States ; R01-GM135440/GM/NIGMS NIH HHS/United States ; EEC-2133504//National Science Foundation/ ; }, abstract = {BACKGROUND: Microbiome sequencing data are often collected from several body sites and exhibit dependencies. Our objective is to develop a model that enables joint analysis of data from different sites by capturing the underlying cross-site dependencies. The proposed model incorporates (i) latent factors shared across sites to explain common subject effects and to serve as the source of correlation between the sites and (ii) mixtures of latent factors to allow heterogeneity among the subjects in cross-site associations.

RESULTS: Our simulation studies demonstrate that stronger associations between two sites lead to greater efficiency loss in regression analysis when such dependence is ignored in modeling. In a case study involving samples collected from a study on the female urogenital microbiome with aging, our model leads to the detection of covariate associations of the vaginal and urine microbiomes that are otherwise not statistically significant under a similar regression model applied to the two sites separately.

CONCLUSIONS: We propose a latent factor model for microbiome sequencing data collected from multiple sites. It captures the presumptive underlying cross-site associations without compromising estimation accuracy or inference efficiency in the absence of such associations. In addition, our proposed model improves predictive performance by enabling the prediction of microbial abundance at one site based on observations from another. We also provide an extended framework that allows for clustering of subjects (samples) and cluster-specific levels of paired association. Under this extended framework, clusters can be classified according to their association strengths.}, } @article {pmid41572156, year = {2026}, author = {Zhang, S and Shi, H and Liu, B and Ge, Z and Zhang, N and Liu, Q and Duan, Z and Chang, Q}, title = {Influences of transcutaneous neuromodulation on fecal microbiota and short chain fatty acids in patients with functional constipation.}, journal = {BMC gastroenterology}, volume = {26}, number = {1}, pages = {51}, pmid = {41572156}, issn = {1471-230X}, support = {2015F11GH098//Dalian municipal science and technology plan project/ ; }, mesh = {Humans ; *Constipation/therapy/microbiology/metabolism/blood ; *Fatty Acids, Volatile/metabolism ; Male ; Female ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Feces/microbiology/chemistry ; Adult ; *Transcutaneous Electric Nerve Stimulation ; Serotonin/blood ; }, abstract = {OBJECTIVES: Transcutaneous neuromodulation (TN) has been reported effective for functional constipation (FC). The underlying mechanism remains unclear. In this study, we aimed to investigate the gut microbiota (GM) and short chain fatty acids (SCFAs) metabolism changed in FC patients due to TN treatment. The correlation between GM and 5-HT was evaluated.

METHODS: Fourteen FC patients were recruited, and the FC related symptoms were evaluated by questionnaires before and after 4-week TN treatment. Blood and fecal samples were collected to assess the fecal microbiome and SCFAs.

RESULTS: The richness and diversity of fecal microbiota were both found to be increased in FC patients before TN treatment. Fecal metabolomic differences between FC patients and healthy controls were observed at baseline, including elevated branched-chain SCFAs (isobutyric, isovaleric, and valeric acids) in FC. TN treatment did not significantly alter SCFA levels but improved constipation symptoms and increased plasma 5-HT. The correlation of Blautia-serotonin and 5-HT was observed in FC patients (r = 0.574, P = 0.035) and disappeared after TN treatment (r = 0.160, P = 0.584).

CONCLUSION: TN treatment significantly improved the symptoms of FC patients and increased their plasma 5-HT expression levels. The correlation between 5-HT and Blautia-serotonin (which changed after TN treatment) indicated that the 5-HT changes caused by TN treatment might have a potential interaction with the dynamic changes of the intestinal microbiota.}, } @article {pmid41571971, year = {2026}, author = {Wang, H and Dean, LE and Li, X and Fitzjerrells, RL and Wang, K and Mangalam, AK and Marek, RF and Kennedy, CL and Ridlon, MM and Spiegelhoff, A and Stietz, KPK and Lehmler, HJ}, title = {The influence of an environmentally relevant polychlorinated biphenyl mixture on the intestinal microbiota in post-weaning mouse dams.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {41571971}, issn = {1614-7499}, abstract = {Polychlorinated biphenyls (PCBs) are environmental pollutants linked to neurological impairments by mechanisms involving the gut microbiome. This study examines the effects of maternal exposure to a PCB mixture on the gut microbiome of post-weaning mouse dams. Female C57BL/6 J mice were exposed daily to PCBs at different doses (0, 0.1, 1, or 6 mg/kg body weight/day) before mating, and throughout gestation and lactation. Post-weaning intestinal contents from dams were analyzed to assess microbiome abundance and quantify PCBs and their metabolites. PCB exposure affected the composition of microbial taxa, though not significantly. However, topic modeling analysis identified a distinct microbial community that was significantly more prevalent in the control group compared to post-weaning mouse dams exposed to the MARBLES mixture at medium and high doses. Complex PCBs and metabolite mixtures were detected in the intestinal contents. Certain PCBs and their metabolites were associated with changes in bacterial abundance, as determined by network analysis. These findings show that individual PCBs and their metabolites can affect gut microbial communities, potentially contributing to neurological impairments in mice exposed to PCBs during gestation and lactation.}, } @article {pmid41571898, year = {2026}, author = {Guedes, MS and Yildiz, D}, title = {Sex matters: mechanistic insights into sex-driven patterns of autoimmunity and implications for pharmacotherapy.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41571898}, issn = {1432-1912}, abstract = {Autoimmune diseases (AiDs) affect up to 10% of the global population and exhibit striking differences between sexes. These disparities encompass prevalence, incidence, age at onset, disease severity and how patients respond to treatment. This review provides a comprehensive overview of the key biological mechanisms underlying sex-biased autoimmunity across multiple levels, including the immunomodulatory roles of sex hormones, sex-specific innate and adaptive immune responses, X-chromosome gene dosage and escape from inactivation as well as epigenetic regulation of immune pathways. In addition, we address how environmental and lifestyle factors, such as smoking, infections and the gut microbiome interact with sex-specific biology to shape autoimmune risk. Finally, we consider the pharmacological implications of sex differences, including variability in drug efficacy, safety and immune-related adverse events, further highlighting current gaps in sex-stratified clinical research. Recognizing sex as a fundamental biological variable is essential for advancing the understanding of AiDs and for the development of more effective, tailored therapeutic strategies.}, } @article {pmid41571815, year = {2026}, author = {Chen, E}, title = {What your breath says about the bacteria in your gut.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {41571815}, issn = {1476-4687}, } @article {pmid41571673, year = {2026}, author = {Bautista, J and Lamas-Maceiras, M and Hidalgo-Tinoco, C and Guerra-Guerrero, A and Betancourt-Velarde, A and López-Cortés, A}, title = {Gut microbiome-driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00883-8}, pmid = {41571673}, issn = {2055-5008}, abstract = {Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide and is increasingly recognized as the outcome of complex host-microbe interactions. Beyond established genetic and environmental drivers, the gut microbiome has emerged as a causal and mechanistic contributor to CRC initiation, progression, and therapy response. This review synthesizes current molecular, ecological, and translational evidence to explain how gut microbial communities reprogram immune, metabolic, neural, and endocrine networks within the tumor microenvironment. CRC-associated dysbiosis is characterized by enrichment of pathobionts such as Fusobacterium nucleatum, pks[+] Escherichia coli, and enterotoxigenic Bacteroides fragilis, and by loss of protective, short-chain-fatty-acid-producing commensals. These microbes promote carcinogenesis through genotoxin-induced DNA damage, epithelial barrier disruption, metabolic rewiring, and chronic inflammation that collectively sustain immune suppression and tumor growth. Defined mutational signatures from bacterial metabolites, including colibactin, cytolethal distending toxin, and indolimines, now directly link microbial exposures to human cancer genomes. By integrating these findings, this review conceptualizes CRC as a biofilm-structured, microbiome-driven ecosystem disease, where polymicrobial consortia coordinate barrier breakdown, immune evasion, and metabolic cooperation. Finally, we highlight emerging microbiota-targeted strategies, including dietary modulation, pre- and probiotics, postbiotics, bacteriophage therapy, engineered live biotherapeutics, and fecal microbiota transplantation, that translate these insights into precision prevention and therapy. Through this integrative framework, the review aims to reposition the microbiome from a correlative feature to a tractable determinant of CRC pathogenesis and treatment response.}, } @article {pmid41571653, year = {2026}, author = {Yuan, Y and DeMott, MS and Byrne, SR and Flores, K and Poyet, M and Groussin, M and Berdy, B and Bahunde, JR and Girard, C and Lehtimäki, J and Mabulla, AZP and Mwikarago, IE and Nartey, YA and Nguyen, LTT and Onyekwere, CA and Roberts, LR and Shapiro, BJ and Vatanen, T and Comstock, LE and Alm, EJ and Dedon, PC}, title = {Phosphorothioate DNA modification by BREX type 4 systems in the human gut microbiome.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68412-5}, pmid = {41571653}, issn = {2041-1723}, support = {R01AI093771//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; T32-ES007020//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, abstract = {Among dozens of microbial DNA modifications regulating gene expression and host defense, phosphorothioation (PT) is the only known backbone modification, with sulfur inserted at a non-bridging oxygen by dnd and ssp gene families. Here we explored the distribution of PT genes in 13,663 human gut microbiome genomes, finding that 6.3% possessed dnd or ssp genes predominantly in Bacillota, Bacteroidota, and Pseudomonadota. This analysis revealed several previously undescribed PT synthesis systems, including type 4 Bacteriophage Exclusion (BREX) type 4 brx genes, which we genetically validated in Bacteroides salyersiae. Mass spectrometric analysis of DNA from 226 gut microbiome isolates possessing dnd, ssp, and brx genes revealed 8 PT dinucleotide settings confirmed in 10 consensus sequences by PT-specific DNA sequencing. Genomic analysis showed PT enrichment in rRNA genes and depletion at gene boundaries. These results illustrate the power of the microbiome for discovering prokaryotic epigenetics and the widespread distribution of oxidation-sensitive PTs in gut microbes.}, } @article {pmid41571627, year = {2026}, author = {Ta, LP and Corrigan, S and Abeysekera, H and Horniblow, RD}, title = {Extremely oxygen-sensitive next-generation probiotics: can current microcomposite formulations ensure effective colonic delivery?.}, journal = {Microsystems & nanoengineering}, volume = {12}, number = {1}, pages = {37}, pmid = {41571627}, issn = {2055-7434}, abstract = {This narrative review evaluates the suitability of conventional biopolymer-based microencapsulation strategies, originally developed for facultative and aerotolerant probiotics, for the protection and delivery of extremely oxygen-sensitive (EOS) next-generation probiotics (NGPs). With increasing interest in NGPs, there is a pressing need to establish whether conventional formulation approaches can be effectively translated for these highly oxygen-sensitive bioactives. We reviewed commonly used microencapsulation materials and techniques, assessing their suitability and potential to preserve EOS bacterial viability. Hydrated pectin- and gellan-based microcomposite systems, particularly when combined with xanthan gum or other polymers, exhibited the strongest oxygen-protection performance. In contrast, alginate alone demonstrated inconsistent barrier properties, though its performance improved when blended or coated with chitosan. Dehydrated microcomposite systems did not yield additional viability benefits compared to their hydrated counterparts. Importantly, none of the studies explicitly quantified oxygen exposure parameters or established threshold levels required for effective protection of EOS strains. Despite some microcomposite systems demonstrating potential for EOS colonic delivery, our findings highlight a critical gap in formulation science for these sensitive bioactives and underscore the need for the development of bespoke, tailored delivery systems that advance beyond conventional approaches designed for facultative or aerotolerant strains. Addressing these gaps will support the advancement of microencapsulation technologies, improve biotherapeutic NGP formulation, and ultimately facilitate the translation of exploratory clinical findings into rationally designed, accessible, and effective microbiome-based interventions.}, } @article {pmid41571367, year = {2026}, author = {Lin, Y and Jiang, Z and Yu, Z and Huang, T and Gui, W and Wang, Z and Li, F and Xiao, P and Li, C and Liu, E}, title = {Honokiol attenuates diabetes by enriching Akkermansia muciniphila andregulating tryptophan metabolism in mice.}, journal = {Chinese journal of natural medicines}, volume = {24}, number = {1}, pages = {59-72}, doi = {10.1016/S1875-5364(26)61077-1}, pmid = {41571367}, issn = {1875-5364}, mesh = {Animals ; *Lignans/administration & dosage/pharmacology ; *Tryptophan/metabolism ; Gastrointestinal Microbiome/drug effects ; Mice ; *Biphenyl Compounds/administration & dosage/pharmacology ; Male ; Mice, Inbred C57BL ; *Hypoglycemic Agents/administration & dosage ; Glucagon-Like Peptide 1/metabolism ; *Akkermansia/drug effects ; Receptors, Aryl Hydrocarbon/metabolism ; *Diabetes Mellitus, Experimental/drug therapy/metabolism/microbiology ; Humans ; *Diabetes Mellitus/drug therapy/metabolism/microbiology ; Fecal Microbiota Transplantation ; Allyl Compounds ; Phenols ; }, abstract = {Diabetes mellitus (DM) is a chronic disease influenced by gut microbiome disturbances. Honokiol (HON), a low oral bioavailability compound from Magnolia officinalis bark, has demonstrated potential as a treatment for DM. This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM. After 8 weeks of intervention through fecal microbiota transplantation (FMT) or antibiotic treatment, HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner. Specifically, HON administration significantly increased Akkermansia muciniphila (AKK) abundance and modulated tryptophan (TRP) metabolism, as evidenced by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and untargeted/targeted metabolomics analysis. Notably, research revealed that AKK metabolized TRP into tryptamine (TA) and other metabolites in vitro. Both AKK and TA activated the aryl hydrocarbon receptor (AHR) pathway, increasing circulating glucagon-like peptide-1 (GLP-1) levels and ameliorating diabetes-related symptoms in DM mice. These findings indicate that HON's hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA, potentially enhancing HON's clinical applications.}, } @article {pmid41571088, year = {2026}, author = {Dantas, LO and Candeiro, GTM and Pereira, ACB and Pereira, ACC and Mita, D and Zajac, N and Attin, T and Schwendener, S and Karygianni, L and Pinheiro, ET}, title = {Metatranscriptomic Insights into Bacterial Activity, Virulence, and Antimicrobial Resistance in the Root Canal Microbiome of Acute Apical Abscesses.}, journal = {Journal of endodontics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.joen.2026.01.002}, pmid = {41571088}, issn = {1878-3554}, abstract = {INTRODUCTION: This study employed metatranscriptomics to investigate the endodontic microbiome and resistome in acute apical abscesses (AAA) and asymptomatic apical periodontitis (AAP).

METHODS: Root canal samples were collected from 20 patients, including 10 cases of AAA and 10 cases of AAP. RNA sequencing was conducted using the NovaSeq 6000 system (Illumina). Taxonomic analysis utilized the expanded Human Oral Microbiome Database (eHOMD) database, while functional annotation was executed using the DIAMOND and EGGNOG databases. Resistome analysis was conducted with the Comprehensive Antibiotic Resistance Database (CARD) and BacMet - Antibacterial Biocide and Metal Resistance Database. Differential expression analysis was carried out using DESeq2 from the DESeq2 R package (P<0.05).

RESULTS: Taxonomic analysis showed more Gram-negative species in AAA samples (P<0.05), particularly from the Bacteroidota phylum. In functional analysis, Tannerella forsythia and Streptococcus anginosus group (SAG) showed the highest transcriptional activity in AAA. T. forsythia displayed high expression of Rag/SusD proteins, suggesting a potential virulence mechanism. The main protein family found in both conditions was the adenosine triphosphate-binding cassette (ABC) transporter. Transcripts possibly involved in resistance against various antibiotics (cephalosporins, fluoroquinolones, lincosamides, macrolides, tetracyclines), metals (silver, chromium, zinc), and disinfectants (phenolic compounds, acids, and bases) were identified.

CONCLUSIONS: T. forsythia and SAG demonstrated high activity within the root canal microbiome in cases of AAA, suggesting their involvement in the pathogenicity of the community associated with acute infections. The ABC transporter may play a significant role in antimicrobial resistance through an antibiotic efflux mechanism and contribute to tolerance against disinfectants and antiseptics.}, } @article {pmid41571080, year = {2026}, author = {Yan, L and Wang, H and Shi, J and Tan, H and Liu, Q}, title = {Bibliometric analysis of neuroinflammation in Alzheimer's Disease: Insights from APP/PS1 mouse model research in the past two decades.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2026.01.020}, pmid = {41571080}, issn = {1873-7544}, abstract = {BACKGROUND: The APP/PS1 transgenic mouse is a foundational model in Alzheimer's disease (AD) research, particularly for investigating the pivotal role of neuroinflammation in disease pathogenesis. Although substantial experimental work has explored inflammatory mechanisms in AD, the field still lacks a comprehensive overview of how research hotspots have evolved, which key scientific questions remain unresolved, and how global research efforts align with existing mechanistic gaps. Therefore, this investigation systematically evaluated scholarly trends, geographic contributions, institutional productivity, and thematic evolution to synthesize actionable insights that will guide subsequent experimental designs.

METHODS: Bibliometric analysis was conducted on peer-reviewed articles indexed in the Web of Science Core Collection (2005-2024). Analytical tools, including VOSviewer, CiteSpace, and Bibliometrix, were employed to quantify research output, collaborative networks, citation metrics, and keyword co-occurrence patterns.

RESULTS: Annual publication numbers exhibited exponential growth post-2015, reflecting an intensified focus on neuroinflammatory mechanisms in AD. China and the United States contributed 83.4 % of total publications, with the University of Barcelona as the most productive institution. High-impact journals such as Nature, Nature Neuroscience, and Brain Behavior Immunity. The analysis identified key scientific issues and evolving research fronts, with current hot topics focusing on oxidative stress, activated microglia releasing inflammatory cytokines, and abnormal autophagy-lysosome pathways.

CONCLUSION: The APP/PS1 mice have a significantly enhanced mechanistic understanding of neuroimmune interactions in AD pathogenesis. Future research should explore microglia-mediated neuroinflammation and brain-gut microbiome interactions to uncover novel diagnostic and therapeutic strategies for AD. This study offers an evidence-based framework to guide researchers using APP/PS1 mice model.}, } @article {pmid41570877, year = {2026}, author = {Wang, Y and Wang, X and Gan, B and Jia, T and Xu, T and Xu, H}, title = {Ferroptosis and Hepatic Fibrosis induced by Cooperative Exposure to Polylactic Acid Nanoplastics and Copper: Emphasis on Gut Microbiota Dysbiosis.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {127698}, doi = {10.1016/j.envpol.2026.127698}, pmid = {41570877}, issn = {1873-6424}, abstract = {Co-exposure to polylactic acid nanoplastics (PLA-NPs) and copper (Cu) in the environment poses a health risk, yet their combined toxic effects remain poorly understood. This study investigated the synergistic hepatotoxicity and underlying mechanisms, focusing on the gut-liver axis, in a mouse model of subacute exposure. Results demonstrated that co-exposure caused significant synergistic effects, including exacerbated changes in body weight (BW), increased hepatic index ratio, and severe liver injury marked by elevated Aspartate Aminotransferase/Alanine Aminotransferase/Alkaline Phosphatase (AST/ALT/AKP) activities and histopathological damage. Crucially, co-exposure synergistically induced hepatic ferroptosis (evidenced by dysregulated Glutathione (GSH), Malondialdehyde (MDA), and iron homeostasis), disrupted lipid metabolism, and promoted oxidative stress. These hepatic injuries were indeced by intestinal barrier damage and gut microbiota dysbiosis, characterized by reduced beneficial Lactobacillus murinus. The fecal microbiota transplantation (FMT) experiment definitively confirmed the causal role of gut microbiota, as transferring microbiota from donor mice to healthy recipients recapitulated the key hepatointestinal injuries. This study demonstrates that co-exposure to PLA-NPs and Cu induces synergistic hepatotoxicity primarily mediated through gut microbiota disruption and gut-liver axis dysfunction, leading to hepatic ferroptosis and fibrosis. These findings highlight the critical role of the gut microbiome in modulating the synergistic toxicity of environmental contaminants and provide new insights into the health risks of mixed pollutant exposure.}, } @article {pmid41570819, year = {2026}, author = {Xie, QY and Hamilton, JK and Danska, JS}, title = {Gut microbiota and metabolic disease risk in youth.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102571}, doi = {10.1016/j.xcrm.2025.102571}, pmid = {41570819}, issn = {2666-3791}, abstract = {The rapidly increasing global incidence of youth-onset diabetes is a critical public health concern. Earlier type 2 diabetes (T2D) onset in children and young people is characterized by faster progression and higher risk for complications. An area of expanding research is understanding how obesogenic environments modify the composition and function of the gut microbiota and, in turn, modulate host immune response as well as metabolism. The association between obesity and altered gut microbiota is complicated by hormonal changes during puberty and chronic inflammation that potentiates insulin resistance in multiple responsive tissues. This review examines the risk factors and mechanisms underlying T2D pathogenesis in children and young people and current evidence connecting gut microbiota to stages of disease progression and treatment opportunities. The potential for early intervention through modifications of the gut microbiota opens avenues to alleviate metabolic complications in critical developmental period and blunt the risk for early T2D onset.}, } @article {pmid41570686, year = {2026}, author = {Jiao, P and Xu, Y and Zhao, X and Zhang, Q and Zheng, R and Zhang, L and Huang, Y and Bai, B and Liu, S and Xue, Y and Hao, L}, title = {Comparative yak and Simmental rumen microbiome-metabolome across lactation stages: Implications for milk nutritional superiority.}, journal = {Food chemistry}, volume = {505}, number = {}, pages = {148068}, doi = {10.1016/j.foodchem.2026.148068}, pmid = {41570686}, issn = {1873-7072}, abstract = {Both yaks and Simmental are dual-purpose highland varieties, but the mechanisms behind the differences in their milk production are not yet fully understood. This study compared milk composition, rumen microbial communities, and metabolomes across a range of lactation stages for both breeds. Yak milk yields were lower and it had higher levels of fat, protein, long-chain and polyunsaturated fatty acids, key amino acids, and essential minerals than Simmental milk. The microbial community of yak rumen exhibited unique characteristics, with the Family_XIII_AD3011_group persistently enriched and positively correlated with rumen fermentation parameters and milk quality, and the content of glutamate and glutamine in yak rumen was higher than in Simmental and positively correlated with milk quality. Therefore, key microorganisms and metabolites in yak rumen are crucial factors for high-yield dairy production, providing new insights to enhance milk production in ruminant dairy cattle.}, } @article {pmid41570523, year = {2026}, author = {Alizadeh, M and Oladokun, S and Fazel, F and Fletcher, C and Blake, K and Sharif, S and Rodriguez-Lecompte, JC}, title = {Modulation of gut immunity and microbiota by Bacteroides thetaiotaomicron confers dose-dependent protection against necrotic enteritis in broiler chickens.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106480}, doi = {10.1016/j.psj.2026.106480}, pmid = {41570523}, issn = {1525-3171}, abstract = {Necrotic enteritis (NE), caused by Clostridium perfringens, remains a major challenge in broiler chicken production. Probiotics represent a promising alternative strategy to mitigate NE by modulating intestinal immunity and microbiota composition. This study evaluated the effects of oral administration of the commensal bacterium Bacteroides thetaiotaomicron on immune responses, microbial profiles, and lesion development in broiler chickens challenged with C. perfringens. One-day-old male broilers (n = 120) were assigned to four groups and received either a low (1 × 10[7] CFU) or high (5 × 10[7] CFU) dose of B. thetaiotaomicron on days 1, 7, 14, and 21 post-hatch. Birds were subsequently challenged to induce NE. Ileal and cecal tonsil tissues were collected for gene expression analysis, and cecal contents were analyzed by 16S rRNA gene sequencing. High-dose B. thetaiotaomicron significantly reduced intestinal lesion scores compared with the positive control, whereas the low dose was ineffective. High-dose supplementation enhanced intestinal immune signaling, with increased expression of TLR2 and TLR4, primarily in the ileum. This was associated with increased expression of pro-inflammatory cytokines (IFN-γ and IL-1β) during the early post-challenge phase and sustained upregulation of regulatory cytokines (IL-10 and IL-2). The epithelial defense-associated cytokine IL-22 was upregulated in both the ileum and cecal tonsils, while TGF-β showed transient induction in the ileum. Markers of epithelial barrier integrity were improved, as evidenced by increased occludin expression, whereas ZO-1 expression remained unchanged. Microbiome profiling revealed that high-dose supplementation enriched beneficial taxa such as Lactobacillus while reducing the abundance of the pathogenic species Enterococcus cecorum. These findings highlight the potential of B. thetaiotaomicron as a probiotic strategy to enhance intestinal immunity and resilience against necrotic enteritis in broiler chickens.}, } @article {pmid41570295, year = {2026}, author = {Ma, J and Jiang, G and Hong, L and Luo, L}, title = {Global clinical trial landscape of microbiome modulator therapy in sepsis: gut microbiota interventions and challenges.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000004472}, pmid = {41570295}, issn = {1743-9159}, } @article {pmid41570114, year = {2026}, author = {Zhao, Y and Lee, TF and Zhou, B and Wang, C and Schmidt, AM and Liu, M and Li, H and Hu, J}, title = {Joint Modeling of Longitudinal Biomarker and Survival Outcomes with the Presence of Competing Risk in the Nested Case-Control Studies with Application to the TEDDY Microbiome Dataset.}, journal = {Bioinformatics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/bioinformatics/btag038}, pmid = {41570114}, issn = {1367-4811}, abstract = {MOTIVATION: Large-scale prospective cohort studies collect longitudinal biospecimens alongside time-to-event outcomes to investigate biomarker dynamics in relation to disease risk. The nested case-control (NCC) design provides a cost-effective alternative to full cohort biomarker studies while preserving statistical efficiency. Despite advances in joint modeling for longitudinal and time-to-event outcomes, few approaches address the unique challenges posed by NCC sampling, non-normally distributed biomarkers, and competing survival outcomes.

RESULTS: Motivated by the TEDDY study, we propose "JM-NCC", a joint modeling framework designed for NCC studies with competing events. It integrates a generalized linear mixed-effects model for potentially non-normally distributed biomarkers with a cause-specific hazard model for competing risks. Two estimation methods are developed. fJM-NCC leverages NCC sub-cohort longitudinal biomarker data and full cohort survival and clinical metadata, while wJM-NCC uses only NCC sub-cohort data. Both simulation studies and an application to TEDDY microbiome dataset demonstrate the robustness and efficiency of the proposed methods.

AVAILABILITY: Software is available at https://github.com/Zhaoyn-oss/JMNCC and archived on Zenodo at https://zenodo.org/records/18199759 (DOI: 10.5281/zenodo.18199759).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid41570019, year = {2026}, author = {Murdoch, B and Kleinschmit, AJ and Santibáñez-López, CE and Graham, MR}, title = {Microbiota discovered in scorpion venom.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0328427}, pmid = {41570019}, issn = {1932-6203}, mesh = {*Scorpion Venoms ; Animals ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Scorpions/microbiology ; Phylogeny ; *Bacteria/genetics/classification/isolation & purification ; }, abstract = {With low nutrient availability and presence of numerous antimicrobial peptides, animal venoms have been traditionally considered to be harsh sterile environments that lack bacteria. Contrary to this assumption, recent studies of animal venom and venom-producing tissues have revealed the presence of diverse microbial communities, warranting further studies of potential microbiota in other venomous animals. In this study we used 16S rRNA amplicon sequencing to elucidate whether scorpion venom contained bacteria, to characterize the bacterial communities, and determine if venom microbiomes differed across geologically complex geographic locations. Our study compares the venom microbiome of two scorpion species, sampled from sites in the Mojave and Great Basin deserts, Paruoctonus becki (family of Vaejovidae) and Anuroctonus phaiodactylus (family of Anuroctonidae), and represents the first assessment of microbial diversity ever conducted using the venom secretion itself, rather than the venom-producing organ and its surrounding tissues.}, } @article {pmid41569851, year = {2026}, author = {Kabil, AK and Cait, A and Reynolds, LA and Chopra, S and Bilenky, M and Moksa, M and Li, Y and Cait, J and Hernaez, DC and Scott, RW and Fogarty, E and Finlay, BB and Mohn, WW and Hirst, M and Hughes, MR and McNagny, KM}, title = {Early-life microbiota skews long-term gene expression and chromatin states of bone marrow hematopoietic precursors.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116871}, doi = {10.1016/j.celrep.2025.116871}, pmid = {41569851}, issn = {2211-1247}, abstract = {Early life is a critical window during which the gut microbiota sculpts immunity and long-term susceptibility to allergic disease. Using neonatal antibiotic administration and bone marrow transplantation assays, we show that depletion of short-chain fatty acid (SCFA)-producing bacteria alters gene expression in hematopoietic stem and progenitor cells (HSPCs) and imprints a persistent, transplantable atopic immune phenotype. Bone marrow transplants from exposed mice generate recipients with elevated serum immunoglobulin E (IgE), downstream increased IgE bound to basophils, and exacerbated allergic lung inflammation following papain challenge. Depletion of SCFA-producing bacteria also impairs recovery from chemotherapy-induced myelosuppression and increases DNA damage in long-term HSPCs in an antibiotic-specific manner. Histone 3 lysine 27 (H3K27) chromatin immunoprecipitation sequencing (ChIP-seq) analyses further reveal differential histone acetylation in HSPCs, consistent with an SCFA-mediated epigenetic regulatory mechanism. Collectively, these findings establish a link between gut microbiota composition, hematopoiesis, and long-term immune function, offering a mechanistic explanation for microbiota-driven susceptibility to atopic disease and hematopoietic dysfunction.}, } @article {pmid41569365, year = {2026}, author = {Duarte, M and Mansilha, C and Melo, A and Sobral, D and Ferreira, R and Gomes, JP and Rebelo, H and Veber, A and Puskar, L and Schade, U and Jordao, L}, title = {Detection of polycyclic aromatic hydrocarbons, microplastic presence and characterization of microbial communities in the soil of touristic zones at Alqueva's edges (Alentejo, Portugal).}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {41569365}, issn = {1614-7499}, abstract = {Environmental pollution is a growing concern. Here, we assessed the occurrence of two groups of persistent organic pollutants (POPs-polycyclic aromatic hydrocarbons (PAHs) and microplastics (MPs)) and bacterial populations in the topsoil of three tourist spots located at the Alqueva's edges during 1 year, once per season. Soil chemical analysis revealed low content of total organic carbon, pH close to neutrality, and nitrogen and phosphorus levels consistent with acquisition of these nutrients only by atmospheric deposition. PAH's concentrations were in the range of ng/kg, being significantly below the "reference values" for contaminated soils. Nevertheless, potentially carcinogenic PAHs, detected at all locations, raise ecotoxicological concerns. Polyamide, polyester, polystyrene, and styrene acrylonitrile resin MPs were found. Six bacterial phyla constitute the core microbiome in the three locations and include genera of bacteria reported as plastic degraders, such as Bacillus, Exiguobacterium, Paenibacillus, and Pseudomonas. The presence of POPs, even at low levels, in the soil at the edges of a water reservoir should be monitored. The identification of bacteria reported as plastic degraders in the soil, and previously in the water, is promising, and their ability to spontaneously ensure the detoxification of the ecosystem should be further investigated.}, } @article {pmid41569044, year = {2026}, author = {Chitre, S and Gharaibeh, RZ and Newsome, RC and Jiang, J and Brock, A and Schmittgen, TD and Jobin, C}, title = {Campylobacter jejuni infection impacts host-derived miRNAs targeting bacterial and host genes.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0318425}, doi = {10.1128/spectrum.03184-25}, pmid = {41569044}, issn = {2165-0497}, abstract = {UNLABELLED: The intestinal microbiota has been shown to influence host-derived microRNAs (miRNAs), small regulatory RNAs involved in host-pathogen interactions. However, the specific role of individual bacterial species in modulating host extracellular vesicles (EV)-derived miRNA profiles remains unclear. We compared stool miRNA profiles from three groups: (i) Germ-free (GF) mice, (ii) mice colonized with a consortium of 13 bacteria (C13), and (iii) mice colonized with C13 and Campylobacter jejuni 81-176 (C13 + C. jejuni). miRNA profiling revealed unique differential expression of 8 miRNAs in C13 vs GF, 38 in C13 + C. jejuni vs C13, and 159 in C13 + C. jejuni vs GF (Padj < 0.05), indicating a substantial shift in host miRNA landscape following C. jejuni exposure. Notably, C13 + C. jejuni mice showed increased expression of miRNAs predicted to target bacterial virulence genes, suggesting a potential host response mechanism aimed at regulating microbial activity. Integration with spatial transcriptomics of the mouse colon revealed that specific EV-derived miRNAs, including mmu-miR-155-5p, mmu-miR-122-5p, mmu-miR-21a-5p, mmu-let-7i-5p, and mmu-miR-142a-3p target epithelial genes involved in immune regulation, inflammation, and barrier function. C. jejuni exposure selectively enriched these host miRNAs, suggesting a mechanism by which EVs modulate epithelial transcriptional responses and potentially influence microbial gene expression. In conclusion, C. jejuni infection modified host EV-derived miRNA expression profile that may have a potential to bind to the bacterial gene targets.

IMPORTANCE: Host-derived microRNAs (miRNAs) are known to regulate bacterial gene expression and maintain gut homeostasis. However, how these miRNAs survive harsh gut conditions to remain functional is not fully understood. This study tested whether extracellular vesicles (EV) carry microRNAs in the gut and whether infection with the enteric pathogen Campylobacter jejuni alters the microRNA profile packaged in these vesicles. We utilized fecal samples from mice, either maintained germ-free (absence of microbiota) or, C13 (defined 13 bacterial consortium), and C13 + C. jejuni to analyze the EV-derived miRNA pattern across the groups. Our results revealed distinct sets of miRNAs in each group and suggested possible interactions between these miRNAs and gene transcripts from both the host and bacteria. These findings provide new insights into how C. jejuni infection may change communication between the host and its microbiome, potentially affecting gut health and disease.}, } @article {pmid41569026, year = {2026}, author = {Hazra, L and Biswas, S and Saha, KK and Chatterjee, S and Dutta, S and Mandal, S}, title = {Endophytic Drought-Tolerant Bacterial Community Dynamics Across Contrasting Agroclimatic Zones.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovag013}, pmid = {41569026}, issn = {1472-765X}, abstract = {Rice (Oryza sativa) sustains more than half of the global population but is particularly vulnerable to water limitation in rainfed upland and lowland ecosystems. Endophytic microbiomes represent a sustainable strategy for improving drought resilience, yet their diversity and functional potential in traditional rice landraces remain underexplored. This study investigated endophytic bacterial communities associated with indigenous upland and lowland cultivars of West Bengal, India, using 16S rRNA amplicon sequencing, predictive functional profiling, culture-based screening, and biochemical validation. Distinct microbial assemblages revealed for diverse agro-ecosystems, with upland cultivars enriched in stress-adapted taxa such as Proteobacteria, Actinobacteria, and Firmicutes. PICRUSt2 predictions indicated higher representation of KEGG pathways associated with osmolyte biosynthesis, antioxidant defence and compatible solute metabolism in upland microbiomes. Culture isolates, notably Enterobacter sp. KNR1 and Klebsiella sp. GBR1, exhibited strong tolerance to PEG-induced osmotic stress, producing elevated proline, glycine betaine, EPS, and IAA, alongside efficient root colonization in susceptible rice. Collectively, these findings establish indigenous upland rice as a reservoir of functionally resilient endophytes and provide a foundation for developing microbial consortia to enhance rice performance under water-limited conditions.}, } @article {pmid41568957, year = {2026}, author = {George, SD and Amerson-Brown, MH and Sousa, LGV and Rinehart, AH and Tamhane, A and Riegler, AN and Leal, SM and Lammons, JW and Elnaggar, JH and Graves, KJ and Łaniewski, P and Herbst-Kralovetz, MM and Taylor, CM and Cerca, N and Muzny, CA}, title = {Spatial organization of Gardnerella species, Prevotella bivia, and Fannyhessea vaginae in the bacterial vaginosis biofilm.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0063025}, doi = {10.1128/iai.00630-25}, pmid = {41568957}, issn = {1098-5522}, abstract = {Key bacterial vaginosis (BV)-associated bacteria implicated in biofilm formation include Gardnerella species, Prevotella bivia, and Fannyhessea vaginae. We investigated their spatial organization in the BV biofilm over time from longitudinal vaginal specimens obtained from women with incident BV (iBV) using peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH). Heterosexual women with optimal vaginal microbiota self-collected vaginal specimens twice daily for 60 days or until iBV development (Nugent score 7-10 on ≥4 consecutive specimens). Women who developed iBV were matched to healthy controls by age, race, and contraceptive method. Gardnerella spp., P. bivia, and F. vaginae were quantified using PNA-FISH 2 days pre-iBV, the day of iBV, and 2 days post-iBV across five optical layers (z, z + 2, z + 4, z + 6, and z + 8 μm). Total counts of all three bacterial species were significantly higher on the day of iBV compared to 2 days pre-iBV (P = 0.011) and remained elevated 2 days post-iBV. Across most layers and time points, pooled mean Gardnerella spp. counts were significantly higher than F. vaginae counts (P ≤ 0.022-0.0003). On the day of iBV and 2 days post-iBV, pooled mean counts of Gardnerella spp. and F. vaginae progressively increased across most biofilm layers (P ≤ 0.043-0.0012). Controls had significantly lower counts of Gardnerella spp. and F. vaginae. P. bivia had low counts in all specimens. During the critical time period surrounding iBV, Gardnerella spp. are abundant throughout the developing biofilm and facilitate F. vaginae incorporation at later time points and higher biofilm layers. Additional research, including other Prevotella spp., is needed.IMPORTANCEBacterial vaginosis (BV) is the most common vaginal infection in reproductive-age women worldwide with a global prevalence of 30%. Recurrence rates can be up to 60% within 1 year of treatment. While BV is characterized as a polymicrobial biofilm infection, the exact etiology remains unknown. The BV biofilm may persist after antibiotic treatment, possibly due to incomplete eradication by current antimicrobial therapies, contributing to recurrent infection. Data are limited in evaluating the spatial formation of the BV biofilm around the time of incident BV. Providing a better understanding of this critical time period in incident BV pathogenesis is necessary to inform the development of prevention methods aimed at inhibiting biofilm formation and improving long-term treatment outcomes.}, } @article {pmid41568748, year = {2026}, author = {Wang, Y and Qiu, J and Wang, C and Yang, R and Guo, F and Li, T and Li, S and Yang, L and Ding, W}, title = {Sustainable Strategy of Natural trans-Anethole in Controlling Bacterial Wilt: Virulence Suppression and Beneficial Microbiome Enrichment.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13627}, pmid = {41568748}, issn = {1520-5118}, abstract = {Plant-derived terpenoids are essential secondary metabolites exhibiting broad-spectrum antibacterial properties. However, the bioactivities of terpenoids against Ralstonia solanacearum remain unexplored. Herein, the bioactivities of 30 terpenoids against R. solanacearum were assessed, and trans-anethole (TAN) was identified as a potent antibacterial agent with a minimum inhibitory concentration and minimum bactericidal concentration of 50 and 75 mg/L, respectively. TAN was low-toxic to silkworms, earthworms, seeds, and E. coli. Furthermore, TAN (>25 mg/L) significantly impeded the R. solanacearum growth, blocked ATP and exopolysaccharide (EPS) synthesis, caused DNA damage and cell rupture, and affected swimming motility and biofilm formation, and suppressed expressions of related genes. Compared with thiodiazole copper, and ethylicin, 100 mg/L TAN had a significantly greater control efficiency in both greenhouse and field tests. Importantly, TAN enhanced the abundance of the beneficial bacteria Bacillus and Sphingomonas. These findings highlight TAN as a potential bacterial wilt control agent.}, } @article {pmid41568738, year = {2026}, author = {Warren, A and Wynia, Z and Corr, PG and Devin, MF and Celikkol, Z and Gordon, L and Farah, M and Karam, M and Villarreal, D and Jackson, SA and Frame, LA}, title = {The microbiota-gut-brain axis in mild cognitive impairment and Alzheimer's disease: a scoping review of human studies.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {22}, number = {1}, pages = {e71023}, pmid = {41568738}, issn = {1552-5279}, support = {//TMCity/ ; }, mesh = {Humans ; *Cognitive Dysfunction/microbiology ; *Alzheimer Disease/microbiology ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Probiotics/therapeutic use ; *Brain ; }, abstract = {Alzheimer's disease (AD) is projected to become the highest-burden neurological disorder globally. Mounting evidence implicates the gut microbiome in AD pathogenesis. This scoping review of gut microbiomes in mild cognitive impairment (MCI) and AD included dietary and probiotic interventions. We included original research and systematic reviews/meta-analyses. Animal and non-English studies were excluded. We searched PubMed, Scopus, and Cochrane Library through February 2023. Using Arksey and O'Malley's framework and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-Extension for Scoping Reviews (ScR) checklist, we screened 4751 articles, with 58 meeting predefined inclusion criteria. Our results demonstrated that gut dysbiosis was frequently reported in MCI and AD, including increased Pseudomonadota and Actinomycetota in AD and reduced diversity in some cases. Probiotic and dietary interventions showed promise in modulating cognition and microbiota, inconsistently. Emerging evidence links dysbiosis to cognitive decline; however, methodological heterogeneity and limited follow-up impede causal inference. Research should prioritize standardized protocols, functional microbiome analysis, and longitudinal human studies to clarify therapeutic potential. HIGHLIGHTS: Gut dysbiosis is a common feature of MCI and AD, with phylum-level microbial shifts frequently observed. Pseudomonadota and Actinomycetota are enriched in AD across multiple human studies. Beneficial genera like Faecalibacterium and Roseburia are consistently reduced in MCI and AD in a small number of studies. Probiotic and dietary interventions are promising to modulate the microbiota-cognition axis. More longitudinal human studies are needed to assess causal microbiome relationships.}, } @article {pmid41568432, year = {2026}, author = {Harford, TJ and Singh, KD and Pardhi, TR and Desnoyer, R and Ravi, T and Jara, ZP and Zalavadia, A and Stenson, K and Naga Prasad, SV and Karnik, SS}, title = {Microbial Metabolite 4EPS Inhibits AT1R to Reduce Blood Pressure and Aortic Aneurysm Outcome.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1161/HYPERTENSIONAHA.125.25364}, pmid = {41568432}, issn = {1524-4563}, abstract = {BACKGROUND: Plasma accumulation of the gut microbial metabolite 4-ethylphenylsulfate (4EPS), derived from dietary amino acid, tyrosine, has been associated with cardiovascular, renal, metabolic, and neurological disorders. AngII (angiotensin II) infusion increases circulating 4EPS in mice, suggesting a potential mechanistic role. We hypothesized that 4EPS modulates AngII-regulated pathophysiology and disease progression by directly inhibiting AT1R (angiotensin II type 1 receptor).

METHODS: This hypothesis was tested by combining AT1R pharmacology, cell signaling assays, ex vivo vascular studies, an AngII-induced aortic aneurysm growth model, and plasma proteomics analysis.

RESULTS: in vitro, 4EPS reduced the binding of both AngII and the antagonist candesartan to AT1R and suppressed AngII-induced calcium signaling. Ex vivo, 4EPS attenuated AngII-mediated vasoconstriction. In vivo, high-fat diet-fed ApoE-null mice coinfused with AngII and 4EPS showed significant blunting of blood pressure elevation and a marked reduction in aortic aneurysm-related mortality compared with mice infused with AngII alone. Analysis of aortic remodeling revealed increased elastin preservation and decreased thickening of the intimal and medial layers in 4EPS-treated animals. Plasma proteomics indicated alterations in actin-cytoskeletal signaling pathways consistent with reduced activation of ERK (extracellular-regulated kinase) 1/2, filamin-A, and proteins involved in vascular smooth muscle cell motility.

CONCLUSIONS: These findings identify 4EPS as a benign, endogenous AT1R antagonist that diminishes AngII-mediated hemodynamic and vascular pathology. By suppressing cytoskeletal signaling associated with vascular remodeling, 4EPS provides significant protection against hypertension and aortic aneurysm progression in mice, revealing a previously unrecognized protective role for a gut microbial metabolite in modulating renin-angiotensin system activity.}, } @article {pmid41568344, year = {2025}, author = {Doshier, J and Anderson, B and Yang, F and Stewart, SD and Calapa, KA and Cooper, R and Wilson-Robles, H and Embree, M and Khanna, C}, title = {Pilot study evaluating tolerability and changes in fecal microbiota associated with novel probiotic administration to dogs with diarrhea.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1720932}, pmid = {41568344}, issn = {2297-1769}, abstract = {BACKGROUND: Diarrhea is one of the most common reasons for visiting canine veterinary clinics or emergency centers. Common treatment approaches include dietary modification, antibiotics, and/or probiotics, which are frequently initiated empirically. Antibiotics can have detrimental long-term effects on the gut microbiome and contribute to antimicrobial resistance, prompting a need for alternative therapies. Probiotics are a promising option; however, their strain-specific effects on the canine gut microbiome have been insufficiently characterized in vivo, particularly in dogs with diarrhea.

HYPOTHESIS/OBJECTIVES: This study aimed to evaluate tolerability and changes in fecal microbiota in dogs with diarrhea during the administration of a novel, advanced microbiome-derived probiotic (AMP) consisting of live Peptacetobacter hiranonis, Megamonas funiformis, and Enterococcus faecium, strains of which were all originally isolated from the feces of a healthy dog.

ANIMALS: This single-arm, prospective observational pilot study consisted of 11 client-owned adult dogs of various breeds presenting for chronic diarrhea (>5 days) with a Purina Fecal Score (PFS) between 4 and 7.

METHODS: Tolerability of the AMP was assessed through serial clinical examinations and comparison of PFS to baseline. Dogs were classified as responders if their PFS improved to <4 by day 7, and as non-responders otherwise. Fecal samples collected at baseline, day 7, and day 56 of AMP administration underwent Illumina amplicon next-generation sequencing (NGS) of 16S rRNA gene fragments (V4 region) to assess the fecal microbiome composition and diversity in each patient.

RESULTS: No adverse events were noted in any dogs receiving the AMP. Clinical improvement in diarrhea was noted in eight of 11 dogs after administration of the AMP. Increases in fecal microbiome alpha-diversity were observed after 1 week of AMP administration for six out of seven long-term participants.

This pilot study indicates that the AMP was well tolerated in dogs with diarrhea, with dogs maintaining or improving clinical appearance during administration. These preliminary findings justify larger controlled studies to evaluate AMP efficacy and to explore associations between treatment, fecal microbiome changes, and clinical response.

CLINICAL TRIAL REGISTRATION: Identifier: VCT23005615.}, } @article {pmid41568321, year = {2026}, author = {Yahyapour, A and Najafi, A and Ahmadi, A and Salarizadeh, N}, title = {Immunoprotective and neuroprotective properties of gut microbiome in psoriasis.}, journal = {Journal of translational autoimmunity}, volume = {12}, number = {}, pages = {100348}, pmid = {41568321}, issn = {2589-9090}, abstract = {Psoriasis impacts nearly 100 million people globally and is associated with neuropsychiatric comorbidities such as depression and anxiety. With gut microbiome dysbiosis serving as a primary pathophysiological factor, the gut-brain-skin axis provides a crucial framework for understanding this relationship. This review evaluates the mechanisms of the gut-brain-skin axis in psoriasis pathophysiology and assesses the therapeutic potential of microbiome-based treatments, combining preclinical, clinical, and multi-omics data. Patients with psoriasis show specific gut dysbiosis patterns, including reduced microbial diversity, lower SCFA-producing bacteria (especially Faecalibacterium and Akkermansia), and increased pro-inflammatory bacteria. This microbial imbalance damages intestinal barrier integrity, triggers systemic inflammation, activates cutaneous Th17 pathways, and induces neuroinflammation through blood-brain barrier disruption. Axis communication occurs through immune-inflammatory mechanisms mediated by SCFAs and neuroendocrine pathways involving microbially-derived neurotransmitters (GABA, serotonin, dopamine). Metagenomic research indicates functional deficiencies in neurotransmitter and SCFA synthesis pathways are more significant than taxonomic alterations. Machine learning models can utilize these functional features to identify patients at risk for neuropsychiatric comorbidities and predict treatment response. Recent randomized controlled trials demonstrate that targeted interventions (probiotics, prebiotics, postbiotics, fecal microbiota transplantation) significantly improve Psoriasis Area and Severity Index scores, inflammatory markers, and microbiota composition. The evidence supports a shift toward integrated microbiome strategies, emphasizing functional approaches including mitochondrial therapies, psychobiotics, precision nutrition, and multi-omics-guided therapies.}, } @article {pmid41568320, year = {2025}, author = {Perry, S and Pillarisetti, L and Gelfman, T and Agrawal, DK}, title = {Gut-Brain Axis in Inflammatory Bowel Disease: Pathogenesis and Therapeutics.}, journal = {Archives of internal medicine research}, volume = {8}, number = {4}, pages = {339-345}, pmid = {41568320}, issn = {2688-5654}, support = {R25 AI179582/AI/NIAID NIH HHS/United States ; }, abstract = {Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract driven by complex interactions between genetic susceptibility, environmental triggers, microbial dysbiosis, and immune dysregulation. The gut microbiome, composed primarily of Firmicutes and Bacteroidetes, plays a crucial role in maintaining intestinal barrier integrity, immune balance, and neuroimmune signaling. Disruption of this microbial ecosystem is characterized by loss of beneficial short chain fatty acid producing bacteria and expansion of pathogenic species which promotes mucosal inflammation, cytokine release, and neuroimmune signaling that can disrupt mental health through the gut-brain axis. Emerging evidence links microbial metabolites, vagal tone, and the hypothalamic-pituitary-adrenal axis in a feedback loop that perpetuates inflammation and alters mood regulation. Current therapeutic approaches include diet modification, osteopathic manipulative treatments, fecal microbiota transplantation and phage therapy. This article focuses on understanding mechanisms linking dysbiosis, immune activation, and neuroinflammation to guide future interventions. A holistic model addressing the gut-brain axis holds the greatest promise for improving outcomes and personalizing care for IBD.}, } @article {pmid41568235, year = {2026}, author = {Sun, M and Zang, D and Chen, J}, title = {Redefining microbial clearance and ecological recovery in periodontal microbiome studies.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2616968}, pmid = {41568235}, issn = {2000-2297}, } @article {pmid41568050, year = {2025}, author = {Yang, J and Yuan, N and Guo, T and Feng, Y and Guo, S and Zhou, D and Lin, P and Wang, A and Jin, Y}, title = {Comparative study of milk microbiota and metabolome in long-lived dairy cows with different persistent production capacities.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1725031}, pmid = {41568050}, issn = {1664-302X}, abstract = {Improving dairy cow lifespan is essential for sustainable livestock production. The milk microbiome and metabolome are closely associated with mammary gland health and influence the persistent productivity of dairy cows. However, the characteristics of the milk microbiome and metabolome underlying persistent productivity remain unknown. In this study, 16S rRNA sequencing and untargeted metabolomics were applied to evaluate the milk microbiome and milk metabolome composition of long-lived, high-yielding cows (LH) and long-lived, low-yielding cows (LL). The results showed that no significant differences were observed in the α- and β-diversity of milk microbiota between the two groups (p > 0.05). However, the community assembly processes differed significantly. The LH group exhibited significantly higher levels of homogeneous selection, drift (and others) (p < 0.05). In contrast, dispersal limitation, homogeneous dispersal, and heterogeneous selection were significantly lower (p < 0.05). In addition, in the milk of LH cows, UCG-005, Prevotellaceae UCG-003, Ruminococcus, unclassified f Oscillospiraceae, norank f Fodinicurvataceae, and unclassified f Ruminococcaceae were significantly enriched (LDA > 2, p < 0.05). The bacterial functions of protein digestion and absorption and N-glycan biosynthesis were significantly enriched in the LH group, while thyroid hormone synthesis and pathogenic Escherichia coli infection were significantly enriched in the LL group (LDA > 2, p < 0.05). Additionally, the milk of LH cows exhibited elevated levels of omega-3 polyunsaturated fatty acids (PUFAs), including PE (20:5/0:0), LPC (20:5 (5Z, 8Z, 11Z, 14Z, 17Z)/0:0), LPE (0:0/20:5 (5Z, 8Z, 11Z, 14Z, 17Z)), and PE (22:5/0:0) (LDA > 2, p < 0.05). Milk PE (18:3/0:0) showed a significant positive correlation with milk Prevotellaceae UCG-003 and UCG-005 (|r| > 0.50, p < 0.05). These bacterial genera were significantly negatively correlated with the predicted microbial function pathogenic E. coli infection (|r| > 0.50, p < 0.05). The accumulation of omega-3 PUFAs in milk may help maintain the homeostasis of mammary microbial environment and promote mammary health. These results provide novel insights into the microbial and metabolic signatures underlying persistent productivity, offering potential targets for nutritional and microbial interventions to enhance dairy cow longevity.}, } @article {pmid41568046, year = {2025}, author = {Pîrvu, AS and Biţă, A and Scorei, IR and Gheonea, DI and Mogoşanu, GD}, title = {Boron symbiotaxis: a new concept in host-microbiome communication.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1719918}, pmid = {41568046}, issn = {1664-302X}, abstract = {Boron (B) participates in biological systems through reversible complexation with diols and phosphate esters, enabling it to stabilize labile furanosyl intermediates and to modulate the chemical landscape in which QS signals operate. Dietary B appears to enter two functional pools: plasma-accessible boron (PAB), composed of freely diffusible B(OH)3/B(OH)4 [-], and microbiota-accessible boron complexes (MABCs), formed in situ with polyols, chlorogenic acids, and fructans/inulins. MABCs persist at the mucus-epithelium interface, creating local reservoirs that can influence the persistence, diffusion, and recognition of AI-2-related molecules. Here we propose a structured, testable framework-"boron symbiotaxis"-to describe how B may stabilize 4,5-dihydroxypentane-2,3-dione (DPD)-derived intermediates (and, in defined lineages, form the furanosyl borate diester AI-2B), localize chemical potential via MABCs at the mucosal surface, and orient microbial behavior toward particular community states. This framework does not assume that enhanced AI-2 signaling is inherently beneficial; QS coherence can also support opportunistic growth or virulence, depending on ecological context. We therefore outline experimental approaches-including speciation-resolved [11]B-NMR, targeted LC-MS for AI-2/AI-2B, and bacterial reporter strains with defined AI-2 receptors-to discriminate beneficial from adverse outcomes. Altogether, we highlight B as a chemically plausible modulator of QS architectures in the gut, propose falsifiable predictions linking diet → B speciation → AI-2 dynamics → host phenotypes, and identify scenarios in which B-driven stabilization or localization could be either advantageous or detrimental.}, } @article {pmid41568044, year = {2025}, author = {Kan, Y and Ma, XY and Wang, YL and Sun, B and Wang, S}, title = {A comprehensive comparison of web-based tools for amplicon-metagenomic analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1711000}, pmid = {41568044}, issn = {1664-302X}, abstract = {Amplicon sequencing provides a suitable approach for microbiome profiling, supported by a variety of R-based and web-based tools. In this review, we systematically evaluated eight freely accessible web-based tools suitable for users without scripting experience, comparing their performance across modules including alpha and beta diversity, taxonomic composition, differential comparison, network and correlation analysis, functional profiling, machine learning, tree-plot and user experience. While all tools exhibit limited data filtering and normalization options, performance varied considerably across modules. Mian and MicrobiomeAnalyst 2.0 excelled in alpha diversity analysis and taxonomic composition analysis, METAGENassist outperformed others in beta diversity, and MicrobiomeAnalyst 2.0 achieved the highest score in differential comparison and functional analysis. Namco and Mian outperform in network analysis and correlation analysis, respectively. Machine-learning functions were comparable across animalcules, MicrobiomeAnalyst 2.0 and METAGENassist, with the best treeplot visualization in animalcules and MicrobiomeAnalyst 2.0. And, user experience was highest for animalcules and Mian. Overall, MicrobiomeAnalyst 2.0 achieving the highest overall performance, followed by Mian and Namco. Several limitations among evaluated tools include inconsistent accessibility, diverse input data formats, restricted feature sets, and incomplete retention of key information in exported figures. Future development should integrate preprocessing, interactive visualization and figure export, alongside advanced statistical methods, multi-omics integration and meta-analytical capabilities, to enhance flexibility, reproducibility and interpretability. This comprehensive assessment provides a practical reference for researchers in selecting the most suitable web-based tools for specific microbiome analysis tasks, highlighting the importance of both module-specific performance and overall tool capabilities.}, } @article {pmid41568043, year = {2025}, author = {Li, P and Peng, H and Huang, Z and Sun, Z and Li, Y and Wu, S and Lin, L and Zhang, S and Li, H and Cao, Y}, title = {Integrated metabolomics and gut microbiota to reveal the anti-tumor mechanism of Jinfu'an decoction in tumor-bearing mice.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1643268}, pmid = {41568043}, issn = {1664-302X}, abstract = {INTRODUCTION: Jinfu'an Decoction (JFAD), a traditional Chinese medicine, is used to treat lung cancer and has shown significant anti-tumor effects in clinical and experimental studies. This study integrates metabolomics and gut microbiota analysis to elucidate JFAD's anti-tumor mechanisms.

METHODS: A suspension of A549-luc cells, approximately 1 × 10[6] in number, was injected subcutaneously into the right axilla of mice to establish a tumor-bearing nude mouse model. Mice were randomly assigned to four groups: model group (MG), low-dose JFAD (JFAD-L), medium-dose JFAD (JFAD-M), and high-dose JFAD (JFAD-H), receiving treatments via gavage for 21 days. Additionally, three nude mice formed the normal group (NG), receiving no treatment. Changes in gut microbiota and serum metabolites were assessed using 16S rRNA gene sequencing and UHPLC-QE-MS non-targeted metabolomics.

RESULTS: JFAD may help restore the balance of intestinal flora in mice with lung cancer to a more normalized state. Our findings indicate that JFAD increases the abundance of Bacteroidia and decreases the presence of Firmicutes and Clostridia, thereby altering intestinal bacterial composition. Primary metabolic pathways associated with significant differences include nicotinate and nicotinamide metabolism, glycine, serine and threonine metabolism, and pyrimidine metabolism. A key differential metabolite identified was succinic acid, part of the central carbon metabolism pathway in cancer. Succinic acid showed a negative correlation with gut microbiota families Tannerellaceae and Campylobacterota. In the MG group, essential amino acid levels were markedly diminished but were significantly elevated after JFAD-M intervention. KEGG pathway analysis identified these amino acids as being linked to the PI3K/AKT and mTOR signaling pathways.

DISCUSSION: JFAD regulates the homeostasis of intestinal flora and influences amino acid and succinic acid metabolism through various pathways. These mechanisms could serve as potential targets for JFAD in inhibiting lung cancer invasion and metastasis.}, } @article {pmid41568034, year = {2025}, author = {Yu, F and Song, J and Qi, L and Liu, J and Yang, Y and Li, W and Li, L and Ma, ZS}, title = {Gene and function diversity-area relationships in the inflammatory bowel disease fecal and mucosal microbiome.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1660973}, pmid = {41568034}, issn = {1664-302X}, abstract = {The diversity-area relationship (DAR), an extension of the classic species-area relationship (SAR), provides a powerful framework for understanding how biodiversity scales across space. In this study, we applied DAR and its metagenomic counterpart (m-DAR) to investigate the spatial scaling of metagenomic genes (MGs) and metagenomic functional gene clusters (MFGCs) of seven functional databases in the gut microbiomes of individuals with inflammatory bowel disease (IBD) and healthy cohorts. Using shotgun sequencing data from 42 mucosal and 22 fecal samples from both healthy and IBD cohorts, we modeled how this MGs and MFGCs accrues with area (samples), estimating diversity scaling parameters (z), pair-wise diversity overlap (PDO), and maximal accrual diversity (MAD), which reflects the total potential diversity. We found that mucosal communities exhibited greater dissimilarity (less pair-wise diversity overlap) between individuals than fecal cowmmunities at the levels of gene richness and evenness (q = 1, 2), whereas fecal communities showed a stronger influence from dominant, abundant genes (q = 2, 3). Furthermore, healthy gut microbiomes showed greater similarity than those of IBD at the level of gene richness (q = 0), but showed greater dissimilarity at the level of abundant genes and dominant genes. Healthy gut microbiomes generally demonstrated a higher potential total diversity compared to those from IBD patients. Notably, fecal samples captured a broader range of microbial diversity than mucosal samples. Additionally, mucosal communities showed greater dissimilarity than fecal communities in almost all the MFGCs of the seven databases except ARDB, which showed the same trend as MGs. We also identified that specific functional clusters related to antibiotic resistance, such as genes for chloramphenicol and vancomycin resistance, displayed distinct scaling behaviors, suggesting their potential role in IBD pathogenesis. These findings demonstrate that the gut microbiome in IBD is not merely less diverse but is fundamentally restructured in its spatial architecture. The application of DAR provides a novel, quantitative insight to diagnose and understand this dysbiosis, moving beyond simple diversity metrics to capture the spatial diversity scaling of microbial genes and functions.}, } @article {pmid41568032, year = {2025}, author = {Wang, M and Sun, Y and Gong, W}, title = {Machine learning models diagnose oral squamous cell carcinoma based on cross-cohort oral microbial signatures.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1692186}, pmid = {41568032}, issn = {1664-302X}, abstract = {INTRODUCTION: The saliva microbiome of oral squamous cell carcinoma (OSCC) patients has been gradually unveiled, but there is a lack of cross-cohort studies, and there is no non-invasive diagnostic model across cohorts for OSCC.

METHODS: This study aimed to investigate the differences in saliva microbial composition between OSCC patients and healthy individuals using cross-cohort saliva microbiome data, comprising 354 healthy individuals and 311 OSCC patients (total n=665).

RESULTS: We found significant differences in saliva microbial composition between OSCC patients and healthy people. Seven microorganisms were significantly reduced and seven were significantly increased in OSCC patients, serving as potential biomarkers. Machine learning models, including Random Forest, Extra Trees, Gradient Boosting, and XGBoost, were constructed to diagnose OSCC using saliva microorganisms. These models achieved area under the curve (AUC) values ranging from 63.1% to 96.9% at both genus and species levels in a rigorous leave-one-cohort-out cross-validation.

DISCUSSION: Our study provides a robust non-invasive diagnostic model for OSCC and demonstrates that high diagnostic accuracy is achievable at both genus and species levels, suggesting that taxonomic resolution is not the primary limiting factor. Instead, the choice of model construction methods is crucial. Therefore, greater attention should be paid to the selection of model methods in clinical applications.}, } @article {pmid41568030, year = {2025}, author = {Van den Abbeele, P and Vu, LD and Poppe, J and van Hengel, IAJ and Baudot, A and Zhang, Y and Chen, Z and Yan, J}, title = {Yeast protein modulates metabolites derived from the human gut microbiota of older male adults ex vivo to strengthen gut barrier function and reduce inflammation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1697734}, pmid = {41568030}, issn = {1664-302X}, abstract = {INTRODUCTION: The rising global demand for protein is accelerating interest in sustainable alternatives with health benefits. While glycans are well-known for supporting gut health, the role of dietary proteins in promoting healthy aging via microbiome modulation is less understood. Yeast protein (YP) represents a sustainable, non-animal, hypoallergenic option.

METHODS: Using the clinically predictive ex vivo SIFR[®] technology (Systemic Intestinal Fermentation Research), we examined how YP influences the microbiome of older human adults (50-65 years, n = 6), comparing its effects to whey protein isolate (WPI) and soy protein isolate (SPI).

RESULTS: At a dose equivalent to 40 g/day, all protein sources supported gut barrier integrity and reduced inflammation, reflected by decreased pro-inflammatory markers and increased IL-10. These benefits were linked to higher short-chain fatty acid (SCFA) production, mainly from Bacillota and Bacteroidota, including microbial markers associated with healthy aging. YP and SPI specifically restored butyrate-producing microbes and increased microbial diversity, which is linked to longevity. Untargeted metabolomics revealed numerous beneficial amino acid-derived metabolites, including indoles and polyamines, known to act through gut-organ axes to extend health span. Despite similar overall profiles, product-specific differences emerged: YP most strongly reinforced barrier integrity, produced the lowest gas levels (suggesting superior tolerability), and yielded the lowest trimethylamine N-oxide, a compound linked to increased mortality in older adults.

DISCUSSION: Collectively, these findings highlight the potential of YP as a sustainable protein source that modulates the microbiome and metabolome, reduces inflammation, and reinforces gut barrier function, which are key mechanisms for preserving health span and mitigating age-related decline.}, } @article {pmid41567836, year = {2026}, author = {Yang, J and Park, JS and Oh, SO and Oh, SY and Hur, JS}, title = {Fungal Microbiome Within Lichen as a Potential Bioindicator of Climate Change: Insights from Transplant Field Study.}, journal = {Mycobiology}, volume = {54}, number = {1}, pages = {146-160}, pmid = {41567836}, issn = {1229-8093}, abstract = {Global warming is a major driver of ecological change, yet its impacts on bioindicators such as lichens remain unclear. Lichens, formed by symbiotic associations between fungi and photosynthetic partners, are widely used to assess environmental conditions. However, studies relying on traditional physiological measures, including chlorophyll content and photosynthetic activity, have reported inconsistent responses to climate change. We hypothesized that short-term exposure of lichens to elevated temperatures would not alter these conventional physiological traits but might instead lead to changes in their associated microbiomes. Using a field transplant experiment, we exposed lichens to higher temperature environments and assessed both physiological and microbiome responses. Chlorophyll content and tissue damage showed no significant differences between control and warmed conditions. In contrast, high-throughput sequencing of 16S and ITS regions revealed pronounced shifts in microbial communities. Fungal assemblages exhibited marked declines in alpha diversity, co-occurrence network complexity, and stability of the core microbiome. By comparison, bacterial communities demonstrated greater resilience. Notably, the black yeast Cutaneotrichosporon debeurmannianum became dominant in high-temperature environments. Our findings show that while traditional physiological traits of lichens remain stable under short-term warming, their fungal microbiomes are highly sensitive to thermal stress. We identify fungal community structure-particularly the presence of C. debeurmannianum-as a promising indicator of climate change. These results highlight the importance of considering microbial symbionts when evaluating the ecological responses of lichens to global warming.}, } @article {pmid41567684, year = {2025}, author = {Lanas, A and Alvarez-Mercado, AI}, title = {Editorial: Improving the gut microbiome: applications of fecal transplantation in disease, volume II.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1758943}, doi = {10.3389/fmed.2025.1758943}, pmid = {41567684}, issn = {2296-858X}, } @article {pmid41567608, year = {2025}, author = {Kayashima, A and Fukuhara, S and Miyamoto, K and Iwasaki, E and Kato, M and Sujino, T}, title = {Correction: Biliary stents reshape the bile microbiome in the absence of cholangitis.}, journal = {Endoscopy international open}, volume = {13}, number = {}, pages = {a27723924}, doi = {10.1055/a-2772-3924}, pmid = {41567608}, issn = {2364-3722}, abstract = {[This corrects the article DOI: 10.1055/a-2733-3468.].}, } @article {pmid41567559, year = {2026}, author = {Mu, Y and Li, D and Deng, X and Lei, Y and Wang, Y and Wu, K and Jiang, L and Zhang, H and Zhao, C and Huang, Y and Yu, S and Liu, X and Zhang, C}, title = {Effects of region and ripening on the physicochemical properties, microbiome, metabolome, and volatilome of Chinese dry-cured ham.}, journal = {Food chemistry: X}, volume = {33}, number = {}, pages = {103502}, pmid = {41567559}, issn = {2590-1575}, abstract = {Long-term ripened dry-cured ham is popular across China, but the mechanisms by which production region and ripening time regulate its quality remain incompletely understood. Therefore, the temporal dynamics of multi-dimensional characteristics of Zhejiang Jinhua, Yunnan Xuanwei, and Guizhou Panxian hams were explored. Results showed decreased moisture and fat but increased pH, NaCl, protein, and amino acid nitrogen with prolonged ripening. Bacterial α-diversity and fungal β-diversity were closely related to ripening and region, respectively, while the relative abundance of dominant genera (Staphylococcus, Kocuria, Aspergillus, and Debaryomyces) varied by both factors. GC-TOF-MS and GC-IMS detected 76 non-volatile metabolites (predominantly amino acids and their derivatives) and 84 volatile compounds (mainly alcohols and aldehydes), highlighting the crucial role of region in shaping the metabolic profile. Moreover, correlation analysis and functional prediction confirmed the indispensable contribution of bacteria to quality formation. These results provide scientific support for the high-quality development of the dry-cured ham industry.}, } @article {pmid41567401, year = {2025}, author = {Gahlot, KD}, title = {Microbial strategies for drought stress mitigation- a sustainable frontier in plant resilience.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1740879}, pmid = {41567401}, issn = {1664-462X}, abstract = {Drought stress is a major constraint on global agriculture, exacerbated by climate change and increasing water scarcity. Conventional strategies such as breeding and genetic engineering have improved drought tolerance in crops, yet their scalability and adaptability remain limited. Microbial interventions, particularly those involving beneficial plant-associated microorganisms, offer a sustainable and complementary approach to enhance plant resilience under water-deficit conditions. This opinion article explores microbial strategies for drought mitigation, emphasizing the role of Rhizobium strains, digested distillery spent wash, and multi-omics technologies. Recent studies demonstrate that developed Rhizobium strains significantly improve soil fertility, nodulation, and nitrogen fixation in legumes, contributing to higher yields and better soil health in drought-prone regions. Similarly, the application of digested distillery spent wash in chickpea (Cicer arietinum) enhances nutrient uptake, photosynthetic activity, and drought tolerance. Advances in genomics, transcriptomics, proteomics, and metabolomics have revealed complex plant-microbe interactions, identifying microbial metabolites and signaling pathways that activate drought-responsive genes and osmo-protective mechanisms. Despite these promising findings, challenges persist in translating laboratory results to field conditions due to soil heterogeneity and microbial competition. Precision microbiome engineering, informed by multi-omics data, and the development of tailored microbial consortia represent a transformative frontier for sustainable agriculture. By integrating ecological complexity with technological innovation, microbial strategies can reduce chemical inputs, promote regenerative practices, and build resilient agroecosystems. This article advocates elevating microbes from supporting roles to central players in addressing drought stress and ensuring global food security.}, } @article {pmid41567168, year = {2026}, author = {Arshad, MT and Ali, MKM and Awlqadr, FH and Maqsood, S and Ikram, A and Hossain, MS and Abdullahi, MA and Rashed, MM}, title = {Mitigation of Metabolic Diseases Through Personalized Nutrition: A Critical In-Depth Review.}, journal = {Food science & nutrition}, volume = {14}, number = {1}, pages = {e71387}, pmid = {41567168}, issn = {2048-7177}, abstract = {Obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM) represent major global health and economic concerns. Traditional dietary recommendations frequently overlook individual heterogeneity in metabolic health. Personalized nutrition will provide a more focused approach to preventing chronic diseases by tailoring dietary recommendations according to lifestyle, metabolic, and genetic factors. This review examines the role of personalized nutrition in preventing metabolic diseases, with a focus on key components of nutrient-gene interactions, including nutrigenomics, nutrigenetics, the gut microbiome, and biomarker-based therapies. The main aim of this article is to investigate how variation within the microbiome and among genes impacts nutrient metabolism and make a case for successful evidence of individualized dietary intervention for obesity, diabetes, and cardiovascular disease. Future advancements in artificial intelligence, and genetic testing may make personalized nutrition more accessible, but there are questions about the price, feasibility, and ethics of its widespread use. The scope for personalized nutrition is wide and has strong potential to impact preventative health. An independent assessment calls for sustained scientific research, equitable accessibility, and ethical considerations that can make public health policies clinically relevant.}, } @article {pmid41567085, year = {2026}, author = {Jackson, CM and Collado, MC and Dallas, DC and Insel, RA and Macpherson, AJ and Palmer, DJ and Seppo, AE and Verhasselt, V and Järvinen, KM}, title = {An Old Story Back: Human Milk Antibodies' Protective Roles Against Allergy Development.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.70218}, pmid = {41567085}, issn = {1398-9995}, support = {639226//H2020-ERC/ ; //Horizon Europe Program/ ; //European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI-HDHL)/ ; PCI2021-122059-2A//Programación Conjunta Internacional/ ; PID2022-139475OB-I00//Spanish Ministry of Science and Innovation/ ; R01HD109193/GF/NIH HHS/United States ; R01HD097367/GF/NIH HHS/United States ; R01HD106140/GF/NIH HHS/United States ; //Family Larsson Rosenquist Foundation/ ; //Stan Perron Charitable Foundation Fellowship/ ; U19AI175113//National Institute of Allergy and Infectious Diseases of the National Institutes of Health/ ; U01AI173032//National Institute of Allergy and Infectious Diseases of the National Institutes of Health/ ; }, abstract = {Human milk is a rich source of immunomodulatory factors that influence the development of the infant immune system, including susceptibility to allergic diseases. Among these components, milk antibodies have been extensively studied for their role in protecting against infections; however, their potential contribution to allergy prevention may be equally important. The mechanisms of protection include allergen exclusion, enhanced and targeted antigen presentation, immune modulation via shaping of the infant gut microbiome, and direct regulation of gut immune responses. This review summarizes current evidence on the secretion of human milk antibodies, highlights what is known and what remains unclear about their role in allergy prevention and outlines the need for further research to develop antibody-based strategies for early allergy prevention.}, } @article {pmid41566746, year = {2026}, author = {Navarro, A and Rodea, GE and de la Cruz-Montoya, AH and Díaz-Velásquez, CE and Vaca-Paniagua, F and Navarro-Cid Del Prado, A and Tirado-Gómez, LL and Vilchis-Reyes, A and García de la Torre, G and Cruz-Licea, V and Eslava-Campos, C and Castelán-Sánchez, HG}, title = {Gut Microbiota Composition in Adolescents From Mexico City, Associations With Nutritional and Socioeconomic Factors: Results From a Pilot Study.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {2}, pages = {e70386}, pmid = {41566746}, issn = {1613-4133}, support = {//Programa de Innovación Tecnológica (PAPIIT)/ ; }, mesh = {Humans ; Adolescent ; *Gastrointestinal Microbiome/physiology ; Mexico ; Male ; Female ; Child ; Pilot Projects ; Diet ; Socioeconomic Factors ; Feces/microbiology ; Body Mass Index ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics ; Nutritional Status ; }, abstract = {The gut microbiota is a key determinant of metabolic health in adolescence, a critical period for the onset of obesity. Understanding its associations with body mass index (BMI), diet, and socioeconomic status (SES) helps identify early determinants of metabolic risk. We analyzed stool samples from 95 Mexican adolescents (11-15 years) using 16S rRNA V3-V4 sequencing. The main phyla were Bacteroidetes, Firmicutes, and Proteobacteria, with. At the genus level Azobacteroides Candidatus, Parabacteroides, Bacteroides, and Prevotella being the most abundant. Overweight and obese adolescents showed lower diversity and more Bacteroidetes, while normal-weight peers had more Firmicutes and beneficial taxa. Lactobacillus was enriched in normal-weight individuals, while Parabacteroides and Prevotella were more abundant in adolescents with low SES. A diet high in sugar-sweetened beverages and low in whole grains was associated with a predominance of Bacteroides and lower diversity. Low SES was also associated with potential pathogens, including Escherichia and Salmonella, and gastrointestinal symptoms. In particular, Vibrio and Salmonella were inversely associated with cholesterol and triglycerides, while Clostridiodes was positively correlated with triglycerides. Diet and SES influenced the adolescent gut microbiome, by shaping diversity, potentially pathogenic taxa, and their associations with metabolic health indicators.}, } @article {pmid41566434, year = {2026}, author = {Xu, L and Lv, X and Lu, X and Zhang, X and Liu, J and Meng, Y and Wu, D}, title = {Microbial and metabolic responses of maize silage to leaf blight: implications for fermentation and protein stability.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08142-4}, pmid = {41566434}, issn = {1471-2229}, support = {202301AU070035//Yunnan Fundamental Research Projects/ ; 2023//Xingzhao Talent Support Program/ ; 2025//Yunnan "Colorful Clouds Postdoctoral Program" Innovation Project/ ; 202301BA070001-120//Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities' Association/ ; }, abstract = {Foliar fungal diseases lead to a significant reduction in dry matter of plants, thereby negatively affecting silage fermentation kinetics. This study investigated the effects of leaf blight on ensiling kinetics, microbial succession, and nitrogen metabolism in whole-crop maize, and further examined whether inoculation with Lactiplantibacillus plantarum HT1 could mitigate disease-induced proteolysis through remodeling of the metabolic pathways. Three treatments were established: (i) healthy maize silage (CON), (ii) maize silage affected by leaf blight (DCON), and (iii) maize silage affected by leaf blight and inoculated with L. plantarum HT1 (HT1, 1 × 10[5] cfu/g FM based on the fresh weight basis). Samples of 300 g fresh material were packed into polyethylene vacuum bags (300 × 400 × 0.2 mm) and vacuum-sealed to establish anaerobic conditions for 60 days of ensiling. Before ensiling, DCON had significantly lower crude protein content (7.06% vs. 8.91% DM, P = 0.001) compared with CON. In addition, the WSC content markedly decreased by leaf blight (88.7 vs. 119 g/kg DM, P = 0.016). LAB abundance was significantly lower (3.22 vs. 4.22 log CFU/g FM, P = 0.022), whereas mold counts sharply increased (4.25 vs. 3.22 log CFU/g FM, P = 0.001) in DCON than in CON. The DCON showed elevated pH, significantly reduced lactic acid content, and markedly increased butyric acid content compared with those of the CON (P < 0.05). DCON had the highest NH3-N content (17.2 g/kg TN), exceeding those of CON (12.3 g/kg TN) and HT1 (10.3 g/kg TN, P = 0.005). Aminopeptidase and carboxypeptidase activities increased to 46.4 and 167 U·h[- 1]·g FM[- 1], respectively, which were much higher than those of the CON (27.4 and 140 U·h[- 1]·g FM[- 1]). Microbiome β-diversity separated DCON from CON and HT1, with enrichment of putative proteolytic taxa. Metabolomics indicated upregulated amino acid degradation (branched chain and glutamate pathways) and disrupted nitrogen homeostasis in the DCON treatment. Leaf blight created an early high-pH window that amplified proteolysis and nitrogen loss through coordinated shifts in substrates, microbiota, and amino acid catabolism. Inoculation with L. plantarum HT1 caused rapid acidification, curtailed proteolysis, and rewired metabolic and community networks toward a healthy state, achieving coordinated restoration of fermentation quality and protein preservation in disease-challenged maize.}, } @article {pmid41566339, year = {2026}, author = {Fernández-Trapote, E and Cobo-Díaz, JF and Oliveira, M and Puente, A and Berdejo, D and Puente, H and Cordero-García, R and López, M and Prieto, M and Argüello, H and Alvarez-Ordóñez, A}, title = {Microbiome and resistome successions in pig carcasses and fresh pork meat throughout slaughtering, processing and shelf-life.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02288-3}, pmid = {41566339}, issn = {2049-2618}, support = {FPU21/03421//Ministerio de Ciencia, Innovación y Universidades, Spain/ ; PRE2021-098910//Ministerio de Ciencia, Innovación y Universidades, Spain/ ; CNS2022-136066//Ministerio de Ciencia, Innovación y Universidades, Spain/ ; No 818368//European Commission under the European Union´s Horizon 2020/ ; PID2020-118813GB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; }, abstract = {BACKGROUND: Slaughterhouses and meat cutting plants represent potential hotspots for the spread and transfer of spoilage and pathogenic, including antimicrobial resistant, bacteria to meat and meat products. Here, we characterise the progression of the microbiome and resistome of two pork cuts (loin and sirloin) at different stages of processing, from the slaughter line to the end of shelf-life. To this end, we analysed samples from facility surfaces, carcasses, and meat cuts using whole metagenome sequencing.

RESULTS: The taxonomic and antimicrobial resistance gene (ARG) profiles of carcasses and meat cuts were significantly influenced by the point of sampling and the processing room. The facility surfaces were found to be the main source of some abundant genera, such as Anoxybacillus, Acinetobacter, Pseudomonas, and Brochothrix, in carcasses and meat cuts. A total of 1,291 metagenome-assembled genomes were reconstructed, corresponding to the most prevalent species identified in the taxonomic analysis at the read level. A reduction in bacterial and ARGs richness and diversity was observed for carcasses and meat cuts along the production chain, which suggests that processing procedures are effective in reducing bacterial and ARGs loads. Nonetheless, an increase in the ARGs load was observed at two sampling points: the carcass after evisceration and the sirloin at the end of its shelf-life (in this case linked to the increase of a single gene, tet(L)). The ARGs most frequently detected were those associated with resistance to tetracyclines, aminoglycosides, and lincosamides. Acinetobacter (in processing environments and carcass/meat samples) and Staphylococcus (in carcasses and meat) were identified as the main genera associated with the ARGs found.

CONCLUSIONS: Overall, our results provide the most detailed metagenomics-based perspective on the microbial successions of pig carcasses and fresh meat cuts during slaughtering, processing, and commercialisation. The observations made suggest that selection pressures imposed by processing steps and contact with facility surfaces contribute to shaping the microbiome and resistome of the two pork products throughout their production line and shelf-life. Video Abstract.}, } @article {pmid41566333, year = {2026}, author = {Liu, W and Sha, X and Zhao, N and Liu, B and Yang, G and Jia, L and Sui, G}, title = {Multi-omics reveals an association of the gut butyrate-IDO1-tryptophan axis with Yinchenhaotang plus Zexietang-ameliorated NASH in a microbiota-dependent manner.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {44}, pmid = {41566333}, issn = {1749-8546}, support = {82374423//National Natural Science Foundation of China/ ; 82474221//National Natural Science Foundation of China/ ; 2024-MSLH-290//Liaoning Province Science and Technology Plan Joint Program (Natural Science Foundation - Surface Project/ ; LJ222410162041//the Education fund item of Liaoning province/ ; }, abstract = {BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a complex metabolic disorder with limited effective treatments, and its pathogenesis involves intricate crosstalk between gut microbiota, metabolism, and host signaling. Yinchenhaotang plus Zexietang (YCHZX), a traditional Chinese medicine (TCM) formulation, exhibits therapeutic potential in NASH, but its underlying mechanism-especially its interactions with the gut microbiota and metabolic networks-remains unclear.

METHODS: A NASH mouse model was established via a high-fat/high-fructose/high-cholesterol diet. Mice were treated with YCHZX or its individual components (YCH, ZX). Serum biochemistry and liver histopathology were used to evaluate systemic therapeutic effects. Integrated multi-omics analyses (16S rRNA microbiome, serum metabolomics, colon transcriptomics) combined with immunofluorescence, immunohistochemistry, RT‒qPCR and ELISA were employed to explore regulatory networks. Complementarily, the effects of sodium butyrate and indolelactic acid (ILA) were investigated using an LPS-stimulated Caco-2 cell model. Antibiotic-mediated gut microbiota ablation was performed to verify microbiota dependency.

RESULTS: YCHZX outperformed YCH and ZX in improving TC, LDL-C and hepatic pathology. Integrated multi-omics analysis demonstrated that the efficacy of YCHZX was associated with a distinct restructuring of the gut microbiota, specifically enriching butyrate-producing genera such as Lachnospiraceae_NK4A136_group. Concomitantly, YCHZX intervention suppressed colonic indoleamine 2,3-dioxygenase 1 (IDO1) and significantly elevated serum levels of ILA, a shift validated in vitro by the direct inhibitory effect of sodium butyrate on IDO1. The elevated ILA was shown to strengthen the gut barrier by upregulating occludin expression in LPS-stimulated Caco-2 cells via an aryl hydrocarbon receptor (AhR)-dependent mechanism. Further, YCHZX activated the AhR, upregulating tight-junction proteins (occludin) to reduce lipopolysaccharide (LPS) translocation, and inhibiting hepatic LPS/TLR4 signaling, TG accumulation, and IL-1β inflammation. All these effects of YCHZX were diminished by antibiotic-induced gut microbiota depletion.

CONCLUSION: Our findings demonstrate that YCHZX alleviates NASH in a gut microbiota-dependent manner. We propose a mechanism whereby YCHZX enriches butyrate-producing bacteria, which is associated with the suppression of colonic IDO1 and a shift in tryptophan metabolism toward ILA production. The increased ILA, in turn, contributes to the activation of the AhR, thereby restoring gut barrier integrity and mitigating liver inflammation.}, } @article {pmid41566206, year = {2026}, author = {Aliyat, FZ and Ibijbijen, J and El Mderssa, M and Hijri, M and Ahmed, B}, title = {Argan fruit microbiomes: influence of biogeographic and soil driven environmental factors.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08168-8}, pmid = {41566206}, issn = {1471-2229}, support = {AS-77//OCP Group/ ; Seed Grant - 151STPR07-4//Université Mohammed VI Polytechnique/ ; }, } @article {pmid41565962, year = {2026}, author = {Simms, C}, title = {Sending babies to nursery completely reshapes their microbiomes.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {41565962}, issn = {1476-4687}, } @article {pmid41565819, year = {2026}, author = {Ricci, L and Heidrich, V and Punčochář, M and Armanini, F and Ciciani, M and Nabinejad, A and Fazaeli, F and Piperni, E and Servais, C and Pinto, F and Valles-Colomer, M and Asnicar, F and Segata, N}, title = {Baby-to-baby strain transmission shapes the developing gut microbiome.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {41565819}, issn = {1476-4687}, abstract = {The early infant microbiome is largely primed by microbial transmission from the mother between birth and the first few weeks of life[1-3], but how interpersonal transmission further shapes the developing microbiome in the first year remains unexplored. Here we report a metagenomic survey to model microbiome transmission in the nursery setting among babies attending the first year, their educators and their families (n = 134 individuals). We performed dense longitudinal microbiome sampling (n = 1,013 faecal samples) during the first year of nursery and tracked microbial strain transmission within and between nursery groups across 3 different facilities. We detected extensive baby-to-baby microbiome transmission within nursery groups even after only 1 month of nursery attendance, with nursery-acquired strains accounting for a proportion of the infant gut microbiome comparable to that from family by the end of the first term. Baby-to-baby transmission continued to grow over the nursery year, in an increasingly intricate transmission network with single strains spreading in some classes, and with multiple baby-acquisition and species-transmissibility patterns. Having siblings was associated with higher microbiome diversity and reduced strain acquisition from nursery peers, while antibiotic treatment was the condition that most accounted for the increased influx of strains. This study shows that microbiome transmission between babies is extensive during the first year of nursery, and points to social interactions in infancy as crucial drivers of infant microbiome development.}, } @article {pmid41565754, year = {2026}, author = {Solís-Marín, FA and Vergara-Ovando, C and Rojas-Oropeza, M and Calderón-Gutiérrez, F and Medina-Tanco, G and Cabirol, N}, title = {Asterinides sp. an endemic stygobitic seastar from an anchialine cave and its interactions among prokaryotic communities.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36065-5}, pmid = {41565754}, issn = {2045-2322}, support = {PAPIIT-IN207021//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; PAPIIT-IN207021//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; Posgraduate grant//Universidad Nacional Autónoma de México/ ; }, abstract = {Anchialine caves house a vast variety of organisms that support complex ecological relationships among themselves and their environment. The following study was made in the anchialine karst cave El Aerolito, found on Cozumel Island, Quintana Roo, Mexico. It explores the relationship between wall microbial mats and the diet of Asterinides sp., an endemic stygobitic seastar. Wall microbial mats inside the cave were sampled and the stomach microbiome of Asterinides sp. was obtained through regurgitation. Asterinides sp. sampling was made through the Catcher Collection Chamber (CCC), an innovative technology for the exploration of these ecosystems. The obtained results suggest that microbial mats are part of the diet of Asterinides sp. The following results highlight the potential relevance of the microbial communities inside the trophic chain present in El Aerolito. Additionally, the methodology presented here provides a useful framework for future ecological research in El Aerolito cave.}, } @article {pmid41565726, year = {2026}, author = {Moreno-León, A and Majó, N and Lavín, JL}, title = {Exploring the chicken respiratory microbiome: a comprehensive meta-analysis of factors shaping chicken respiratory microbiota.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-33989-2}, pmid = {41565726}, issn = {2045-2322}, support = {PID2020-114060RR-C33//Agencia Estatal de Investigación/ ; }, } @article {pmid41565669, year = {2026}, author = {Schneeberger, PHH and Dommann, J and Rahman, N and Hürlimann, E and Sayasone, S and Ali, S and Coulibaly, JT and Keiser, J}, title = {Profound taxonomic and functional gut microbiota alterations associated with trichuriasis: cross-country and country-specific patterns.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00911-1}, pmid = {41565669}, issn = {2055-5008}, support = {101019223/ERC_/European Research Council/International ; }, abstract = {The human gut microbiota is vital for immune function, metabolism, and resistance to pathogens. Soil-transmitted helminths like Trichuris trichiura can disrupt this microbial community, but the extent and functional significance of these disruptions across diverse regions remain unclear. We investigated the impact of T. trichiura infection on gut microbiota composition and function in three endemic regions-Côte d'Ivoire, Laos, and Tanzania-using standardized, high-resolution metagenomic profiling. Our findings reveal consistent depletion of key short-chain fatty acid (SCFA) producers, including Blautia sp. MSJ 9 and Holdemanella biformis, and enrichment of mucin-degrading genera such as Ruminococcus and Bacteroides. These changes coincided with increased microbial utilization of host-derived carbohydrates and destabilization of microbial networks, notably with the emergence of Segatella copri in infected individuals. Although taxa-level responses varied by region, similar trends in SCFA depletion and mucin degradation were observed across sites, pointing to a potentially shared metabolic response to infection. These alterations suggest compromised gut barrier function and immune modulation, potentially promoting parasite persistence. Our results underscore the potential of microbiome-based strategies, such as targeted probiotics or dietary interventions, to support helminth control by restoring microbial balance and improving host resilience.}, } @article {pmid41565496, year = {2026}, author = {Hassert, M and Harty, JT}, title = {The endemic dilemma: why whole sporozoite malaria vaccine efficacy falls in the field.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2025.12.003}, pmid = {41565496}, issn = {1471-5007}, abstract = {Whole sporozoite vaccines (WSVs) are the most effective malaria vaccines developed to date. However, their durable efficacy declines sharply when moving from homologous CHMI studies to field trials in endemic regions. We argue this reduced efficacy reflects the complex context of vaccine deployment rather than a single cause. The antigen mismatch hypothesis postulates that limited genetic diversity in current vaccines fails to capture the diversity of field parasites, reducing immune recognition. The host-context hypothesis describes how genetics, infection history, microbiome, and nutrition influence vaccine outcomes. We propose that the future of malaria vaccines will depend on integrating parasite genomics, systems immunology, and the development of animal models which more accurately depict the context of individuals living in malaria endemic regions.}, } @article {pmid41564849, year = {2026}, author = {Terry, CE and Halle-Smith, JM and Merali, N and Marudanayagam, R and Chatzizacharias, N and Dasari, BVM and Bartlett, DC and Raza, SS and Frampton, AE and Sutcliffe, RP and Roberts, KJ}, title = {Colonization of bile with gammaproteobacteria is associated with reduced survival after surgery for pancreatic cancer in patients receiving gemcitabine-based adjuvant chemotherapy.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {52}, number = {3}, pages = {111396}, doi = {10.1016/j.ejso.2026.111396}, pmid = {41564849}, issn = {1532-2157}, abstract = {BACKGROUND: Evidence suggests that the biliary microbiome influences the progression of pancreatic ductal adenocarcinoma (PDAC) in patients undergoing adjuvant chemotherapy. Specifically, Gammaproteobacteria (GPB) has been shown to have the potential to develop mutations which can metabolise gemcitabine into an inactive form. This study hypothesised that GPB influences survival in patients with PDAC undergoing adjuvant gemcitabine-based chemotherapy following surgery.

METHODS: This was a retrospective study of patients undergoing pancreatoduodenectomy from 2010 to 2020. Associations between patient and tumour characteristics, survival data, and results of intraoperative bile cultures (GPB + or GPB-) were investigated. Analysis of patients matched by chemotherapy regimen and numbers of cycles of adjuvant therapy was also performed. Survival was analysed using Kaplan-Meier curves and Cox regression analysis.

RESULTS: Analysis of 313 patients revealed that adjuvant gemcitabine-based therapy improved overall survival (OS). Patients who receive gemcitabine-based chemotherapy with a GPB + biliary culture had a shorter OS compared to those who were GPB-, and a median survival of 17.9 vs 26.2 months, P = 0.002. After matching for key chemotherapy variables, survival was greater in the GPB- group 26.8 vs 19.8 months, P = 0.016. This association was not seen among patients who received no adjuvant therapy or non-gemcitabine based therapy.

CONCLUSION: Patients receiving gemcitabine-based chemotherapy after surgery are likely to have reduction in OS if they have a biliary culture positive for GPB.}, } @article {pmid41564716, year = {2026}, author = {Limo, L and Donovan, J and Frisbee, S and Gomaa, N}, title = {The exposome and the human oral microbiome through the one health lens.}, journal = {Archives of oral biology}, volume = {183}, number = {}, pages = {106504}, doi = {10.1016/j.archoralbio.2026.106504}, pmid = {41564716}, issn = {1879-1506}, abstract = {OBJECTIVES: To map and synthesise current evidence on how lifelong biological, environmental, and social exposures, collectively conceptualised as the exposome, interact with the human oral microbiome to influence oral disease development and progression within a One Health framework.

DESIGN: A scoping review was conducted to identify peer-reviewed studies published in English that examined the relationships between the exposome and the human oral microbiome. The review followed the Arksey and O'Malley framework, applying its five-stage methodological approach. Comprehensive searches were performed in MEDLINE, Embase, PsycInfo, Scopus, Web of Science, and CINAHL. Study quality was assessed using the Joanna Briggs Institute (JBI) tools, and results were reported in accordance with PRISMA-ScR guidelines.

RESULTS: A total of twenty-nine studies were included in this review. These showed that health status, non-communicable diseases, medication use, and psychosocial factors influence the biodiversity, abundance, and function of the human oral microbiome. Other studies suggested that animal interactions and physical and chemical exposures can alter host-microbiome interactions, as well as microbial community dynamics within the oral cavity. While the studies reviewed used reliable methods and standardized protocols, they were of moderate quality due to small sample sizes, potential reverse causality, and limited control for confounding and multiple testing.

CONCLUSION: This review highlights the complexity of the human oral microbiome and its interactions with the various components of the exposome, emphasizing the focus on disease impact and health behaviours, while noting a gap in research on non-bacterial communities, interaction mechanisms, and long-term effects on dysbiosis.}, } @article {pmid41564597, year = {2026}, author = {Rogozarski, J and Steiner-Gager, GM and Preindl, K and Wicik, Z and Eyileten, C and Skos, C and Gerner, C and Dizdarevic, A and Postula, M and Meier-Menches, SM and Siller-Matula, JM}, title = {Plasma metabolomic profiling of patients with acute coronary syndrome treated with potent platelet inhibitors.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {195}, number = {}, pages = {119013}, doi = {10.1016/j.biopha.2026.119013}, pmid = {41564597}, issn = {1950-6007}, abstract = {Ticagrelor and prasugrel are key antiplatelet agents used in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Beyond their antiplatelet effects, both drugs exhibit pleiotropic actions that may contribute to side effects. Notably, ticagrelor has been associated with dyspnea in clinical trials. This study aimed to identify metabolomic markers linked to the effects of ticagrelor and prasugrel using targeted metabolomics. Plasma samples from 207 ACS patients treated with either prasugrel (n = 106) or ticagrelor (n = 101) were analyzed for up to 631 metabolites. Several metabolites differed significantly between the groups (p < 0.05). The most notable changes were found in DHEAS (p = 0.0004, FC = -1.66) and 3-Met-His (p = 0.0024, FC = 1.75). After adjusting for risk factors, lysoPC a C17:0, 3-Met-His, and DHEAS remained significantly altered. Subgroup analysis revealed that diabetic patients had distinct metabolic profiles, including elevated TMAO and choline and reduced GUDCA levels, compared to non-diabetics. Additional changes were observed in hexoses, Met-SO, and TCDCA. The findings support a novel hypothesis that ticagrelor-induced dyspnea may be linked to low DHEAS levels. Reduced methionine and Met-SO levels could suggest lower oxidative stress. Moreover, diabetic patients showed a gut microbiome-related metabolic shift associated with a more ischemic profile.}, } @article {pmid41564594, year = {2026}, author = {Hussein, AA and Klugman, Y and Carlson, J and Bhat, TA and Jing, Z and Gomez, EC and Singh, PK and Wang, J and Jacobi, J and Smith, G and Goodrich, D and Guru, KA}, title = {Does the urinary microbiome reflect the bladder-cancer-associated microbiome? Characterizing the microbiome in urine and cancer tissue in bladder cancer.}, journal = {Urologic oncology}, volume = {44}, number = {4}, pages = {110978}, doi = {10.1016/j.urolonc.2025.12.014}, pmid = {41564594}, issn = {1873-2496}, abstract = {INTRODUCTION: We sought to characterize the microbiome in bladder cancer tissue samples and to compare it with the microbiome in simultaneously collected urine.

METHODS: Bladder cancer tissue and transurethral urine specimens were collected simultaneously from consecutive patients with bladder cancer at the time of transurethral resection of bladder tumor (TURBT) or radical cystectomy (RC). Samples were analyzed using 16S rRNA sequencing. Urinary and tissue microbiome were compared. Overlaps among bladder cancer tissue and respective urine samples were described. Microbiome was further described in terms of alpha (diversity within a sample measured by Observed, Chao1, Shannon, and Simpson indices), beta diversities (diversity among different samples measured by Bray Curtis Diversity index) and differential abundance of bacteria at the genus level.

RESULTS: Twenty-one patients were included in the study (15 males and 6 females). Transurethral urine samples were available for all but 3 patients, where voided samples were used. Nineteen patients had high grade urothelial carcinoma and 2 had low grade. Looking at the overlapping genera among the urine and tissue samples, only Pseudomonas, Staphylococcus, Acinetobacter, Corynebacterium, Escherichia-Shigella, Anaerococcus, Streptococcus, and Prevotella were present in >75% of both urine and tissue samples. Comparing tissue and urine specimens, there was no significant difference across all alpha diversity indices, while Bray Curtis for beta diversity showed significant dissimilarity (p<0.0001). There was significantly higher abundance of Moraxella, Herbaspirillum, Clostridium sensu stricto 8, Cellulomonas, Pleomorphomonas, Conchiformibius, Prevotella_9, Lachnospiraceae, Marmoricola, Pseudoglutamicbacter, Helicobacter, Jeotgalicoccus, Roseburia, Granulicatella, Lachnoclostridium, Odoribacter, Dermabacter, Akkermansia, Abiotrophia, and Reinbacterium in the urine samples. On the other hand, there was significantly higher abundance of Conexibacter, Cnuella, Mobilitalea, Fulvimonas, Pedomicrobium, Pectobacterium, Weissella, Selenomonas, Tannerella, Aliterella, Xanthobacter, Sporosarcina, Gordonia, Bosea, Pantoea, SM1A02, Vibrio, Pediococcus, Lacticaseibacillus and Blastococcus in the tissue specimens.

CONCLUSION: In this cohort, bladder-cancer tissue associated microbiome exhibited a distinct microbial signature when compared to urine. These results suggest that the urinary microbiome may not provide an accurate representation of the bladder-cancer associated microbiome. Validation in larger, standardized cohorts with contamination control is warranted.}, } @article {pmid41563958, year = {2026}, author = {Ying, JP and Zou, YF and Jiang, T and Chang, JL}, title = {Bacterial-archaeal co-occurrence in honey bee gut microbiomes across host species and management regimes.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0339926}, pmid = {41563958}, issn = {1932-6203}, mesh = {Animals ; Bees/microbiology ; *Gastrointestinal Microbiome/genetics ; *Archaea/genetics/classification/isolation & purification ; RNA, Ribosomal, 16S/genetics ; *Bacteria/genetics/classification/isolation & purification ; }, abstract = {Honeybees are key pollinators, and their overwintering period represents a critical bottleneck for colony survival. We investigated how host species and husbandry practices influence the composition of gut bacterial and archaeal communities of overwintering honeybees, as well as the potential functional consequences for energy metabolism and resilience. Using 16S rRNA amplicon sequencing combined with marker-gene functional inference, we observed that wild Apis cerana (wAc) harbors the most diverse gut microbiome across both bacterial and archaeal domains. Notably, wAc exhibited a significant enrichment of methanogenic archaea (e.g., Methanocorpusculaceae and Methanosarcinaceae), a pattern potentially consistent with bacterial-archaeal metabolic coupling that may improve fermentation thermodynamics and energy extraction under winter resource limitation. In contrast, the gut communities of managed Apis cerana (mAc) and Apis mellifera (Am) were dominated by Lactobacillus, and mAc exhibited a relative increase in predicted carbohydrate metabolism and replication/repair pathways based on marker-gene inference. Most archaeal sequences from Am and mAc remained unclassified, underscoring gaps in primer coverage and reference databases. Because each experimental group in this study was represented by a single pooled sample, the analyses are descriptive and hypothesis-generating rather than definitive; functional inferences should be treated as provisional and validated in future work. Overall, the results generate testable hypotheses that dietary diversification, reduced antibiotic exposure, and targeted microbial interventions might help support overwintering resilience, but targeted validation is required before making management recommendations.}, } @article {pmid41563580, year = {2026}, author = {Kozák, M and Majoros, L and Panyiczki, Z and Bagoly, Z and Hodossy-Takács, R and Dobos, LV and Várkonyi, I}, title = {Severe vitamin K deficiency-associated coagulopathy triggered by Clostridioides difficile infection and antibiotic-associated dysbiosis: A case report and literature review.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {41563580}, issn = {1439-0973}, abstract = {PURPOSE: Clostridioides difficile infection (CDI) represents a major healthcare associated infection with potentially life-threatening complications. While gastrointestinal and systemic manifestations are well recognized, severe micronutrient deficiencies, particularly vitamin K deficiency are rarely described. We aimed to report a unique case of CDI-and antibiotic-associated dysbiosis and malabsorption leading to profound vitamin K deficiency and coagulopathy, thereby highlighting the clinical intersection between infection, microbiome disruption, and hemostasis.

METHODS: We report the clinical course, diagnostic work-up, and therapeutic management of an elderly female patient with CDI complicated by life-threatening coagulopathy. In addition, a narrative review of published case reports of antibiotic-associated vitamin K deficiency was performed to contextualize our findings.

RESULTS: The patient developed extensive subcutaneous hematomas with a severely deranged coagulation profile (PT > 100 s, INR > 8, markedly reduced activities of vitamin K-dependent factors). Normal liver function and preserved platelet count excluded disseminated intravascular coagulation and hepatic failure. The findings were consistent with severe vitamin K deficiency secondary to antibiotic-induced dysbiosis, malnutrition, and persistent diarrhea. High-dose intravenous vitamin K supplementation resulted in rapid normalization of coagulation parameters within 24 h, with subsequent clinical stabilization and resolution of bleeding manifestations.

CONCLUSION: This case illustrates a rare but clinically significant complication of CDI: profound vitamin K deficiency-associated coagulopathy. Clinicians should maintain a high index of suspicion for vitamin K deficiency in elderly, malnourished, and antibiotic-exposed patients with CDI who present with unexplained coagulopathy or bleeding.}, } @article {pmid41563247, year = {2026}, author = {Borges, LP and Athesh, K and Santana, LAM and Guimaraes, AG and Moura, PHM and Silva, DMRR and Silva, EED and Gopalsamy, RG}, title = {Harnessing the immunological potential of the gut microbiome: a frontier in autoimmune disease management.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {97}, number = {4}, pages = {e20250953}, doi = {10.1590/0001-3765202520250953}, pmid = {41563247}, issn = {1678-2690}, } @article {pmid41563098, year = {2026}, author = {Vera, J and Vaz Ferreira, C and Moraes, M and Riera, N}, title = {Tracing the early bacterial settlers in preterm and very-low birth-weight infants: first report of microbiota dynamics in South American neonates.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0057025}, doi = {10.1128/iai.00570-25}, pmid = {41563098}, issn = {1098-5522}, abstract = {Mortality in very-low birth-weight (VLBW) infants accounts for up to 50%-70% of the neonatal mortality and up to 25%-30% of infant mortality. Despite the global increase in survival rates, this population remains at heightened risk for developing long-term neurodevelopmental delays, chronic lung disease, malnutrition, and visual and hearing disabilities. The gut microbial composition of VLBW differs from full-term infants and is typically dominated by pathobionts. In this study, we characterized the bacterial composition of the VLBW infant microbiota born at Pereira Rossell Children's Hospital (academic, tertiary referral center) in Montevideo, Uruguay by sequencing the full-length 16S rRNA gene using Oxford Nanopore Technologies. We describe a high predominance of Klebsiella pneumoniae and Escherichia coli in these infants. By sequencing stool samples from two time points, we show that the microbial community diversity increases over time with a higher relative abundance of Bacteroides and Veillonella. Moreover, we describe the effect on the microbial composition of long antibiotic exposure. Different species of the Klebsiella genus, along with Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Veillonella parvula were observed at a higher relative abundance in patients with more than 5 days of antibiotic treatment. Taken together, our findings shed light on the development and establishment of microbial communities in early-life microbial communities in South America. Our results point to postnatal antibiotics as a major factor orchestrating this process. The integration of microbial community health considerations into preterm clinical care is crucial for improving long-term infant development.}, } @article {pmid41563063, year = {2026}, author = {Zhu, K and Zhang, Y and Zhang, F and Ji, Q and Su, Q and Wu, Z and Chen, X and He, T and Wang, Z and Hou, S and Gui, L}, title = {Integrated metabolome and microbiome analysis deciphers the effects of resveratrol and β-hydroxy-β-methylbutyric acid on jejunal function under different protein levels in Tibetan sheep.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0284325}, doi = {10.1128/spectrum.02843-25}, pmid = {41563063}, issn = {2165-0497}, abstract = {Research has demonstrated that resveratrol (RES) and β-hydroxy-β-methylbutyric acid (HMB) promote gastrointestinal health by altering the intestinal microbiome. The present study aimed to evaluate the impacts of RES and HMB on the bacterial community composition and metabolomic profiles of the jejunum in Tibetan sheep. A total of 120 male Tibetan lambs, with an average initial body weight of 16.87 ± 0.31 kg, were randomly assigned to four experimental groups according to a 2×2 factorial design. The experimental diets contained 11.19% protein diet, or 12.69% protein diet supplemented with RES/HMB (H-RES-HMB and L-RES-HMB, respectively), and 11.19% protein diet, or 12.69% protein diet without supplemented with RES/HMB (LCP and HCP, respectively). The findings indicated a significant increase in jejunal digestive enzyme activities (α-amylase and chymotrypsin), antioxidant capacity (catalase, glutathione peroxidase, and superoxide dismutase), and immune responses (including immunoglobulins A, G, and M) in the H-RES-HMB group, in contrast to a notable decrease in markers of oxidative stress and pro-inflammatory cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor alpha) (P < 0.05). Morphological assessments revealed a significant reduction in crypt depth within the H-RES-HMB group (P < 0.05). Among the short-chain fatty acids, butyric acid concentration was significantly elevated in the H-RES-HMB group (P < 0.05). Additionally, mRNA expression levels of barrier-associated genes, including OCLN, Muc-2, and ZO-1 in the jejunum, were significantly enhanced in the H-RES-HMB group. Microbial community analysis demonstrated that the inclusion of RES and HMB in the 14% protein diet resulted in an increase in the relative abundance of Firmicutes, Bacillus, and Methanobrevibacter, while simultaneously reducing the abundance of Proteobacteria, Escherichia, and Shigella. Notably, the increased abundance of these beneficial bacteria was positively correlated with butyric acid concentrations. Furthermore, metabolomic analysis indicated higher levels of L-Arginine and His-Lys in the H-RES-HMB group, which also showed a positive correlation with butyric acid concentration, whereas isovaleric acid, D-xylose, and diacetyl concentrations were lower in this group. In conclusion, the findings suggest that a 14% protein diet is more effective in enhancing jejunal morphology and barrier function. Supplementation with RES and HMB in this diet resulted in elevated concentrations of volatile fatty acids, particularly butyric acid, by modulating microbial community composition (notably Firmicutes, Bacillus, and Methanobrevibacter) and metabolite profiles (including Gamma-aminobutyric acid, Succinate, L-Arginine, and His-Lys). A synergistic effect was found between the crude protein level (14%) and dietary RES/HMB on villus phenotype, digestive enzyme capacity, and antioxidant activity.IMPORTANCETo thrive in harsh, high-altitude environments, Tibetan sheep require efficient nutrient absorption. Our study shows that a diet with optimal protein (12.69%) supplemented with natural additives-resveratrol and β-hydroxy-β-methylbutyric acid-significantly enhances gut health. This dietary regimen strengthened the intestinal barrier, suppressed harmful inflammation, and boosted local immunity. Furthermore, it enriched the gut microbiome with beneficial butyric acid-producing bacteria, a key nutrient for intestinal cells. This research establishes a practical nutritional strategy to improve intestinal function and overall resilience in Tibetan sheep, supporting sustainable livestock production in challenging plateau regions.}, } @article {pmid41563007, year = {2026}, author = {Fijarczyk, A and Goessen, R and Morency, MJ and Gagné, P and Laganière, J and Wehenkel, C and Hernández-Velasco, J and Porth, I and Isabel, N and Martineau, C}, title = {Aspen-associated soil microbiomes reveal different strategies for nitrogen acquisition across ecosystems in Mexico and Canada.}, journal = {FEMS microbiology ecology}, volume = {102}, number = {2}, pages = {}, doi = {10.1093/femsec/fiaf130}, pmid = {41563007}, issn = {1574-6941}, support = {2018-265002//Fonds de recherche du Québec - Nature et technologies/ ; }, mesh = {*Soil Microbiology ; *Populus/microbiology/genetics ; *Microbiota ; *Nitrogen/metabolism ; Mexico ; Canada ; Bacteria/classification/genetics/metabolism/isolation & purification ; *Ecosystem ; Soil/chemistry ; Fungi/genetics/classification ; Mycorrhizae/genetics ; Rhizosphere ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 18S/genetics ; }, abstract = {Plant species shape soil microbiome composition through species-specific interactions. However, it is less clear how these interactions vary across populations that diverged a long time ago. In this study, we explore the influence of host genetic composition and edaphic factors on the soil microbiome of Populus tremuloides, one of North America's most widespread tree species. Using 16S, 18S rRNA gene, and ITS2 region metabarcoding on soils from natural stands and potting mix, rhizosphere, and root samples from a greenhouse common garden, we examined prokaryotic and fungal communities in two aspen genetic groups. The Eastern Canada group represents boreal and cold temperate ecoregions, and the one from Northwestern Mexico represents warm temperate ecoregion. Variation in microbial community structure correlated with soil properties but results from common gardens indicated that the host genetic makeup may also play a role. The ecoregions showed functional divergence: warm temperate sites hosted a higher abundance and diversity of nitrogen-fixing bacteria, while boreal stands exhibited stronger associations with ectomycorrhizal fungi. Our findings highlight how local adaptations to climate and soil conditions in aspen extend to their microbial partners, emphasizing the potential role of host-microbe interactions in shaping tree resilience and susceptibility to future climate changes.}, } @article {pmid41562992, year = {2026}, author = {Trunz, J and Schmandt, C and Hertig-Godeschalk, A and Glisic, M and Stoyanov, J and Perret, C}, title = {Probiotic and Prebiotic Supplementation for Gastrointestinal Discomfort in Chronic Spinal Cord Injury (PRO-GIDSCI): A Randomized Controlled Crossover Trial Protocol.}, journal = {Methods and protocols}, volume = {9}, number = {1}, pages = {}, pmid = {41562992}, issn = {2409-9279}, support = {10003400/SNSF_/Swiss National Science Foundation/Switzerland ; }, abstract = {BACKGROUND: Gastrointestinal discomfort affects up to 70% of individuals with spinal cord injury (SCI), largely due to gut dysbiosis caused by altered transit time and reduced gastrointestinal motility from autonomic disruption. Emerging evidence links prebiotics and probiotics to improved microbiome balance and reduced inflammation, yet data in SCI remain limited.

METHODS: Individuals aged ≥ 18 years, with a chronic SCI (≥1 year) experiencing significant gastrointestinal symptoms, will be invited to participate in this single-center randomized controlled crossover trial. Persons currently taking antibiotics, who have relevant eating or digestive disorders, or who have undergone a recent diet change will be excluded from the study. Participants will be randomized (1:1) into two groups. The first group will take a probiotic (Biotics-G, Burgerstein AG, Rapperswil-Jona, Switzerland) supplement for eight weeks, then after a four-week washout period, they will take a prebiotic (Oat Bran, Naturaplan, manufactured by Swissmill, Zurich, Switzerland) supplement for another eight weeks. The second group will receive the supplements in reverse order. The primary outcome is the Gastrointestinal Quality of Life Index, a questionnaire to assess quality of life related to gastrointestinal disorders. Secondary outcomes consist of gastrointestinal transit time, inflammatory blood markers, and gut microbiome composition.

ETHICS: The study will be conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee for Northwest/Central Switzerland (EKNZ, ID: 2025-00238, 24.02.2025, Version 2.0). The study is registered at ClinicalTrials.gov (ID: NCT06870331, 02.04.2025). Written informed consent will be obtained from all participants involved in the study.}, } @article {pmid41562912, year = {2026}, author = {George, MY and Gamal, NK and Safwat, K and Mamdouh, M and AbdElFatah, A and Atallah, A and Cerchione, C}, title = {From Glucose Transport to Microbial Modulation: The Impact of Sodium Glucose Co-Transporter-2 Inhibitors on the Gut Microbiota.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {41562912}, issn = {2076-3271}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use ; *Glucose/metabolism ; Diabetes Mellitus, Type 2/drug therapy/metabolism/microbiology ; Animals ; Hypoglycemic Agents/pharmacology/therapeutic use ; }, abstract = {Background: Sodium glucose co-transporter-2 (SGLT-2) inhibitors are antihyperglycemic drugs used in type 2 diabetes mellitus management, and they have associated cardiovascular and renal advantages beyond their glucose-lowering effects, with maintained proof linking gut microbiota modulation to their multiple therapeutic benefits. Aim: This review aims to deliver an overview of the current knowledge regarding the relationship between SGLT-2 inhibitors and the gut microbiota and how this interplay impacts the gut-organ axes such as the lung, heart, brain, liver, and hematological system. Methodology: A literature review was performed in Web of Science, PubMed, and Google Scholar to discover studies that assessed the effects of SGLT-2 inhibitors on gut microbiota composition, microbial metabolites, and associated systemic consequences. Results: SGLT-2 inhibitors modulate gut microbiota and its driven metabolites, strengthening the barrier integrity and alleviating endotoxemia, inflammation, and oxidative stress, resulting in beneficial outcomes across the different gut-organ axes. Conclusion: Gut microbiota modulation is an emerging approach in mediating the multifaceted beneficial impacts of SGLT-2 inhibitors, revealing that their effectiveness goes beyond glycemic control. Future research should concentrate on the microbial taxa and metabolites that mediate these impacts and testing combination approaches that target SGLT-2 pathways and gut microbiota to enhance preservation of different organs.}, } @article {pmid41562852, year = {2026}, author = {Sather, B and Larson, J and Hutt Vater, K and Westrum, J and McDermott, TR and Bothner, B}, title = {Beyond Repression: ArsR Functions as a Global Activator of Metabolic and Redox Responses in Escherichia coli.}, journal = {Proteomes}, volume = {14}, number = {1}, pages = {}, pmid = {41562852}, issn = {2227-7382}, support = {DE-SC0020246//Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U.S. Department of Energy/ ; R24GM137786//IDeA National Resource for Quantitative Proteomics at University of Arkansas School for Medical Science through their National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: The arsenic-responsive repressor, ArsR, has long been understood as a canonical regulator of the arsRBC operon, which confers resistance to arsenic stress. However, recent studies suggest a broader regulatory scope for ArsR. Here, we investigated the proteomic landscape of Escherichia coli strains with and without ArsR to elucidate ArsR as an activator in both non-stressing and arsenic-stressing conditions.

METHODS: Using mass-spectrometry-based shotgun proteomics and statistical analyses, we characterized the differential abundance of proteins across AW3110 (ΔarsRBC), AW3110 complemented with arsR, and wild-type K-12 strains under control and arsenite-stressed conditions.

RESULTS: Our study shows that ArsR influences proteomic networks beyond the ars operon, integrating metabolic and redox responses crucial for cellular adaptation and survival. This suggests that ArsR has a significant role in gut microbiome metabolomic profiles in response to arsenite. Proteins involved in alanine, lactaldehyde, arginine, thioredoxin, and proline pathways were significantly elevated in strains where ArsR was detected, both with and without arsenite. We identified proteins exhibiting an "ArsR-dependent" activation pattern, highlighting ArsR's potential role in redox balance and energy metabolism.

CONCLUSIONS: These findings challenge the classical view of ArsR as a repressor and position it as a pleiotropic regulator, including broad activation.}, } @article {pmid41562844, year = {2025}, author = {Semenova, N and Garashchenko, N and Nikitina, O and Kolesnikov, S and Belkova, N and Klimenko, E and Smurova, N and Novikova, E and Madaeva, I and Kolesnikova, L}, title = {Sleep Disorders in Climacteric Women: Glutathione, Glutathione S-Transferase P1 and Gut Microbiome Interrelation.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {33}, number = {1}, pages = {}, pmid = {41562844}, issn = {1873-149X}, abstract = {Background: Menopause, a critical period during a woman's life, is characterized by various changes, including disturbances in their oxidative balance and circadian rhythm. Currently, the gut microbiome is suggested as an important participant in these processes. Methods: This study involved 96 menopausal women. Their sleep quality was assessed using three questionnaires: the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). The GSH and GSTP1 contents in the serum were measured by means of immunoassay methods, while the composition of the gut microbiome was determined via molecular genetic methods. Results: E. coli, K. oxytoca, S. aureus, Enterobacter spp., Shigella spp., Streptococcus spp., Prevotella spp., and M. stadmanae were found to correlate with the GSH content in different sleep groups, while the presence of K. oxytoca, S. aureus, Enterococcus spp., K. pneumoniae, and M. stadmanae is also important for the GSH level in several of these groups. F. prausnitzii, S. aureus, P. micra, Acinetobacter spp., and E. rectale are associated with GSTP1 concentration in various sleep groups, while the presence of F. nucleatum and P. micra is also relevant for the GSTP1 content in some of these groups. Conclusions: Thus, in menopausal women, the composition and structure of the gut microbiota are associated with sleep disorders. GSH and GSTP1 are associated with some gut microbiome markers in menopausal women, but these relationships differ in different sleep disorders.}, } @article {pmid41562773, year = {2026}, author = {De Rosa, M and Canepari, S and Tranfo, G and Giampaoli, O and Patriarca, A and Smolinska, A and Marini, F and Massimi, L and Sciubba, F and Spagnoli, M}, title = {Urinary Metabolomics as a Window into Occupational Exposure: The Case of Foundry Workers.}, journal = {Journal of xenobiotics}, volume = {16}, number = {1}, pages = {}, pmid = {41562773}, issn = {2039-4713}, support = {GRANT BRIC 2022 ID 052//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {Foundries represent complex exposure scenarios where metals, particulate matter, and combustion by-products coexist, posing potential cumulative biological effects. Urinary metabolic profiles from 64 foundry workers and 78 residents living in surrounding areas were investigated using multivariate statistical modeling. Differences in urinary metabolite patterns were observed between the two groups, including lower levels of several amino acids (e.g., valine, alanine, tyrosine, and tryptophan) and tricarboxylic acid intermediates (e.g., citrate and succinate), together with higher levels of selected branched-chain amino acid catabolites (e.g., 3-hydroxyisobutyrate and erythro-2,3-dihydroxybutyrate) in workers. Variations in gut microbiota-related metabolites, such as phenylacetylglycine and p-cresol sulphate, were also detected. Based on these metabolic patterns, potential molecular mechanisms related to energy metabolism, oxidative stress and host-microbiome interaction are discussed as interpretative hypotheses. The comparison between workers and residents was interpreted, taking into account differences in demographic and lifestyle characteristics between groups. Overall, the results indicate that occupational exposure in foundries is associated with measurable differences in urinary metabolic profiles, demonstrating that the applied NMR-based metabolomic strategy is capable of capturing early biological effects and supporting its potential as a non-invasive and holistic biomonitoring tool for evaluating the health impact of complex occupational exposures.}, } @article {pmid41562704, year = {2026}, author = {Kašubová, I and Hornáková, A and Kotúľová, L and Rokos, T and Kolková, Z and Kapinová, A and Pribulová, T and Kozubík, E and Kalman, M and Biringer, K and Kúdela, E and Holubeková, V}, title = {Epigenetic Regulation and Gene Expression Profiles in Cervical Swabs: Toward Non-Invasive Biomarkers of Cervical Lesion Progression.}, journal = {Epigenomes}, volume = {10}, number = {1}, pages = {}, pmid = {41562704}, issn = {2075-4655}, support = {09I03-03-V04-00228//Recovery and Resilience Plan of the Slovak Republic./ ; }, abstract = {Background/Objectives: Cervical cancer is a common malignancy in women worldwide, closely associated with persistent human papillomavirus (HPV) infection. Epigenetic mechanisms, particularly promoter methylation, may contribute to tumour progression. This pilot study aimed to analyse the promoter methylation patterns and gene expression of selected genes (DNMT, BCL2, CDH1, CD8A, MUC1, ALCAM). The goal was to identify associations between promoter hypermethylation, gene expression, and HPV infection in cervical swab specimens obtained from patients with low-grade squamous intraepithelial lesions (SILs), high-grade SILs, or squamous cell carcinomas. Methods: A total of 81 cervical swab samples from Slovak participants were included in the study. DNA methylation and gene expression profiling was performed using real-time PCR (qPCR) and pyrosequencing. Results: BCL2 expression was significantly reduced across all lesion grades. CD8A expression was slightly elevated in low- and high-grade SILs, particularly in HPV-positive samples. MUC1 showed variability with lesion grade. No statistically significant differences in DNA methylation were observed across groups stratified by HPV status, community state type, and lesion grade. Conclusions: Our findings suggest that BCL2 downregulation and gene activity variability influenced by the vaginal microbiome may play a role in cervical lesion progression. These results highlight potential non-invasive biomarkers for monitoring cervical lesions.}, } @article {pmid41562645, year = {2026}, author = {Wang, J and Duan, H and Zhang, W and Li, H and Yang, Z and Zhang, C and Zhang, S and Guo, J and Ge, J and Wang, F and Gao, M}, title = {Lysinibacillus macroides 38352 isolated from traditional Chinese fermented foods: a dual effect on ochratoxin A detoxification and immune suppression alleviation.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0236325}, doi = {10.1128/spectrum.02363-25}, pmid = {41562645}, issn = {2165-0497}, abstract = {UNLABELLED: Ochratoxin A (OTA), a nephrotoxic, immunosuppressive, and potentially carcinogenic mycotoxin produced by Aspergillus and Penicillium species, poses a persistent threat to global food safety and livestock health. Although current biological detoxification strategies can degrade OTA, they often overlook its detrimental impact on vaccine efficacy, and safe probiotic candidates with dual functions of detoxification and immune restoration remain scarce. In this study, we isolated 3 OTA-degrading bacterial strains from 28 types of traditional Chinese fermented foods. Among them, Lysinibacillus macroides 38352 exhibited the highest degradation efficiency, removing 51.4% of 2.5 µg/mL OTA within 72 h at 37°C, with further increases observed over time. Mechanistic analysis revealed that the degradation was mediated not by cell surface adsorption but by secreted metabolites generated through active cellular metabolism. The strain also demonstrated excellent probiotic properties, including tolerance to pH 2-12 and 0.2% bile salts, sensitivity to 15 antibiotics (indicating no resistance), and no pathogenicity in mice. Notably, oral administration of L. macroides 38352 significantly reversed OTA-induced immunosuppression, enhancing vaccine-induced specific IgG, neutralizing antibody titers, and cytokine levels (interleukin [IL]-1β, IL-4, IL-12, IL-17, and interferon gamma), while also reducing inflammatory damage and improving growth performance in OTA-exposed broilers. Our study demonstrates that L. macroides 38352 is a dual-function probiotic capable of both OTA biodegradation and immune restoration. These findings provide a mechanistically distinct microbe-based strategy that couples mycotoxin detoxification with host immune restoration, advancing microbiome-informed interventions for sustainable livestock production and food safety.

IMPORTANCE: Ochratoxin A (OTA) is a widespread food and feed contaminant known for its toxic, carcinogenic, and immune-disrupting effects, which pose serious challenges to animal health and food security. However, existing detoxification approaches rarely address the immune damage caused by OTA, and safe microbial solutions with both detoxifying and immune-supporting capabilities remain limited. This study introduces Lysinibacillus macroides 38352, a newly identified probiotic from traditional Chinese fermented food, as a dual-function candidate that not only degrades OTA efficiently through secreted metabolites but also helps repair immune function suppressed by OTA exposure. The strain shows excellent safety features and effectively improves vaccine responses and overall health in poultry. These findings highlight a novel microbe-based strategy that integrates mycotoxin detoxification with immune restoration, advancing the development of functional probiotics for microbiome-driven interventions in sustainable animal production and food safety.}, } @article {pmid41562624, year = {2026}, author = {Fletcher, JR and Malik, A and Driggers, J and Hunter, RC}, title = {Cross-feeding interactions between Fusobacterium nucleatum and the glycan forager Segatella oris.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0092225}, doi = {10.1128/msystems.00922-25}, pmid = {41562624}, issn = {2379-5077}, abstract = {Fusobacterium nucleatum is a common member of the oral microbiota frequently associated with extra-oral infections and diverse polymicrobial environments, including chronic airway diseases and colorectal tumors. Yet, its interactions with co-colonizing microbiota remain poorly defined. Here, we investigate cross-feeding interspecies dynamics between F. nucleatum and Segatella oris, a glycan-foraging anaerobe enriched in the airways, oral cavity, and gastrointestinal tumors. Using broth cultures, cell-free supernatants, and co-culture on primary human airway epithelial cells, we identify microbe-microbe and microbe-host interactions that shape nutrient acquisition, biofilm formation, gene expression, and host responses. While mucin or S. oris supernatants modestly enhanced F. nucleatum growth, both conditions triggered transcriptional remodeling, including induction of the nan operon for sialic acid catabolism, suggesting reliance on glycan degradation by S. oris. Conversely, S. oris exhibited differential expression of multiple polysaccharide utilization loci (PULs) when exposed to F. nucleatum or its metabolites. Biofilm formation by F. nucleatum was strongly inhibited by S. oris and its supernatants, indicative of metabolic regulation. Dual and triple RNA-seq revealed that epithelial responses were predominately shaped by F. nucleatum, with enrichment of inflammatory and cancer-associated pathways; however, co-colonization with S. oris modulated the expression of genes linked to the unfolded protein response and apoptosis, among others. These findings demonstrate that glycan-mediated cross-feeding and microbial interactions shape the physiology and pathogenic potential of F. nucleatum in mucosal environments. This work underscores the importance of modeling polymicrobial communities under host-relevant conditions to better understand pathobiont behavior at the epithelial interface.IMPORTANCEFusobacterium nucleatum is increasingly recognized as a pathobiont in mucosal diseases, including colorectal cancers and chronic airway infections, yet its functional interactions with co-colonizing microbiota remain poorly understood. Here, we demonstrate that F. nucleatum engages in bidirectional interactions with Segatella oris, a glycan-foraging anaerobe also enriched in mucin-rich environments. Through nutrient cross-feeding and transcriptional modulation, these interactions shape bacterial behavior and the host epithelial response. Notably, glycan degradation by S. oris enables F. nucleatum access to sialic acids, while F. nucleatum suppresses the expression of multiple polysaccharide utilization loci in S. oris, revealing a reciprocal ecological influence. Co-colonization of the airway epithelial surface also modulates gene expression linked to inflammation and cancer. These findings advance our understanding of polymicrobial dynamics at mucosal interfaces and highlight the importance of incorporating microbe-microbe-host interactions into reductionist models of infection and disease.}, } @article {pmid41562609, year = {2026}, author = {Dalmasso, M and Morvan-Bertrand, A and Goux, D and Elie, N and Sesboüé, A and Meuriot, F and Chagnot, C and Schlusselhuber, M and Desmasures, N and Launay, F and Noiraud-Romy, N and Prud'homme, M-P and Crétenet, M}, title = {Plant species, metabolites, and environmental factors shape the phyllosphere microbiota of grazed grasslands.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0128925}, doi = {10.1128/aem.01289-25}, pmid = {41562609}, issn = {1098-5336}, abstract = {The phyllosphere of permanent grasslands is a reservoir of microbial diversity, yet its composition and the factors influencing its fluctuations are still poorly understood. The aim of this study was to identify the factors driving the structure of the phyllosphere microbiota. Three plant species of two adjacent grasslands, one of the two receiving nitrogen (N) fertilization, were selected: two fructan-accumulating grasses (perennial ryegrass, Lolium perenne and Yorkshire fog, Holcus lanatus) and a non-fructan species (white clover, Trifolium repens). Samples were collected at three periods-two in summer and autumn-and the weather parameters were recorded. Bacterial enumerations and metabarcoding analysis of the plant microbiota were performed. Carbon and N) contents of the leaves and stomatal conductance regulation were assessed. The composition of leaf microbiota was determined mainly by the plant host species-T. repens grouping separately from the other plant species-, the period of the year (early summer versus late summer and autumn), and, to a lesser extent, fertilization. Methylobacterium was particularly dominant in T. repens. A significant effect of pinitol and fructans levels on the composition of the phyllosphere microbiota was observed in T. repens and in the Poaceae species, respectively. The daily temperature range, the rainfall amount, the daily average radiation, and evapotranspiration were significant drivers of the phyllosphere microbiota composition. This study provides insights into plant and environmental factors that shape grassland phyllosphere microbiota.IMPORTANCEThe phyllosphere is estimated to cover more than 10[8] km[2] over the globe, and grasslands cover about 30%-40% of the world land area. Grasslands host a vast microbial reservoir, characterized by both the abundance and diversity of microorganisms. Evidence of connections between phyllosphere and raw milk microbiota exists. The significance of our research is in highlighting grasslands as potential reservoirs of beneficial microorganisms for plants and dairy-derived products. The phyllosphere microbiota should be considered when evaluating the ecosystem services of grasslands as it contributes to supporting services by enhancing biodiversity and to provisioning services through microorganisms that can benefit agriculture and the food industry.}, } @article {pmid41562358, year = {2026}, author = {Huang, J and Liu, M and Zhang, H and Sun, G and Furey, A and Rahman, P and Zhai, G}, title = {Altered gut microbiota and host pathways in obesity-related knee osteoarthritis.}, journal = {Clinical and experimental rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.55563/clinexprheumatol/ksopba}, pmid = {41562358}, issn = {0392-856X}, abstract = {OBJECTIVES: To investigate gut microbial alteration and their functional consequences in obesity (OB)-related knee osteoarthritis (OA) by integrating microbiome with metabolomic, proteomic, and dietary data.

METHODS: Fecal and fasting plasma samples were collected from 91 knee OA patients and 12 OA-free controls, classified into four subgroups based on OB and OA status: 66 OB+OA+, 25 OB-OA+, 5 OB+OA-, and 7 OB-OA-. 16S rRNA gene sequencing was performed to profile gut microbiota. MaAsLin2 modelling was applied, and dietary intake was incorporated into the models. Plasma metabolomics (n=630 metabolites) and proteomics (n=5,416 proteins) were integrated with microbial signatures to assess functional associations.

RESULTS: OB+OA+ patients exhibited significantly lower a- and β-diversity than OB-OA+ (p<0.05). Seventeen microbial taxa were identified to be significantly associated with OB+OA+ (all p<7.65×10-5 after correcting tests for 654 ASVs), and 16 of them remained significant after adjustment for age, sex, antibiotic use, and dietary intake. PICRUSt2-based predictive analysis on these taxa suggested that bile acid biosynthesis was upregulated in OB+OA+ group. These taxa were correlated with 376 metabolites (p<0.05) with enrichment in fatty acid biosynthesis, linoleic/arachidonic acid metabolism, and propanoate metabolism pathways. They were also associated with 146 proteins (p<0.001) with enrichment in PI3K-Akt signalling, ECM-receptor interaction, and lipid/atherosclerosis pathways.

CONCLUSIONS: OB+OA+ patients exhibited significant gut microbial dysbiosis associated with systemic metabolic and proteomic alterations relevant to OA pathophysiology. The microbiome-metabolome-proteome axis may provide mechanistic insights into worsened OA outcomes in OB individuals and could inform microbiome-targeted interventions.}, } @article {pmid41562342, year = {2026}, author = {Winkler, M and Seel, W and Kornblum, C and Simon, MC and Reimann, J}, title = {The MicroIBioM study: the gut microbiome in inclusion body myositis.}, journal = {Clinical and experimental rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.55563/clinexprheumatol/1b8sv1}, pmid = {41562342}, issn = {0392-856X}, abstract = {OBJECTIVES: Inclusion body myositis (IBM) is a disorder with features of both inflammation and degeneration yet without effective treatment. Influences of the gut microbiome on degenerative as well as inflammatory disorders and immune treatments are known. We sought to investigate whether the gut microbiome might influence the development or recalcitrance of IBM.

METHODS: We appealed to IBM patients and their unaffected spouses/cohabitants for stool samples and data on clinical symptoms, gathering questionnaire data (modified Gastrointestinal Symptom Rating Scale (mGSRS), IBM Functional Rating Scale (IBMFRS) and Bristol Stool Scale) and stool samples for 16S rRNA V3V4 metagenomic analysis from 21 IBM and 20 control probands. Bioinformatic analyses used QIIME2 and MicrobiomeAnalyst software packages. LEfSe and Random Forest analysis aimed to identify group specific biomarkers. PICRUSt was used to perform pathway analysis.

RESULTS: No overall differences of alpha and beta diversity were found between IBM and control group. No impact of immune treatments was found, but a reduction in alpha diversity was identified comparing older (≥ 72 years) IBM and control probands. Increased abundances of some genera, in particular Bacteroides, were detected in the IBM group. Bacteroides, Clostridium CAG 352, and Eggerthella were identified as IBM biomarkers at genus level. Gastrointestinal symptoms (mGSRS) correlated with disease severity (IBMFRS).

CONCLUSIONS: General differences of gut microbiome seem unlikely to play a role in the genesis of IBM. Whether the late occurring or the more specific differences detected are part of the disease course needs to be addressed by investigations of further biosamples.}, } @article {pmid41562240, year = {2026}, author = {Vishnoi, V and Hoedt, EC and Watson, M and Gramlick, M and Zhao, M and Lott, N and Carroll, R and Pockney, P and Smith, SR and Keely, S}, title = {Dynamic 16S rRNA Sequencing of the Abdominal Wall Surgical Site Highlights Potential Pathways of Incisional Surgical Site Infection in Colorectal Surgery.}, journal = {ANZ journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1111/ans.70499}, pmid = {41562240}, issn = {1445-2197}, support = {//AVANT Doctor-in-Training Grant/ ; //Australian NSW Health Round 5 Early-Mid Career Grant/ ; }, abstract = {INTRODUCTION: Understanding the microbial changes within the surgical site may enhance our understanding of the origin and subsequent role of microbes in the causation of incisional surgical site infections (SSIs). In this study we used 16S rRNA sequencing to establish the dynamic microbiota of the surgical site in patients undergoing bowel resection.

METHODS: The surgical site of patients undergoing bowel resection was sampled at four different time points: on initial incision of the surgical site prior to peritoneal breach; on completion of the operation following fascial closure; from the lumen of the resected segment of bowel; and from the superficial skin of the surgical site in the follow-up period. DNA was extracted and used for 16S rRNA amplicon gene sequencing to establish the dynamic microbiota changes that occur within the surgical site.

RESULTS: A total of 250 samples were collected from 50 patients. The native subcutaneous abdominal plane is a low biodiversity Gram positive aerobic community, which following resection of the bowel, reflects a high biodiversity obligate anaerobic community, suggestive of contamination from the GI lumen. The follow-up sampling shows resilience of skin commensals, depletion of the most abundant luminal microbes with emergence of Enterobacteriaceae and Staphylococaceae. These two families thrive to colonise the follow up wound in all patients, highlighting potential pathways of infection in colorectal surgery.

CONCLUSIONS: Whilst this study does not demonstrate causality, it does add to the body of literature in deciphering the poorly understood pathogenesis of SSIs in colorectal patients. This study should be used as a platform to perform further multiomics-based investigations to try and underpin the exact mechanisms behind SSIs in this form of surgery, thus allowing us to improve preventative strategies in the future.}, } @article {pmid41562094, year = {2025}, author = {Tang, K and Zhang, Y and Meneses, C and Rogerio, LA and Willen, L and Iniguez, E and Kamhawi, S and Valenzuela, JG and Oliveira, F and Cecilio, P}, title = {Phlebotomus duboscqi gut microbiota dynamics in the context of Leishmania infection.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1717935}, pmid = {41562094}, issn = {1664-3224}, mesh = {*Gastrointestinal Microbiome ; Animals ; *Phlebotomus/microbiology/parasitology ; RNA, Ribosomal, 16S/genetics ; Metagenomics/methods ; *Leishmaniasis/parasitology ; *Insect Vectors/microbiology/parasitology ; Bacteria/genetics/classification ; }, abstract = {INTRODUCTION: The manipulation of the gut microbiota of disease vectors has emerged as a new approach to use in the integrated control of vector-borne diseases. For this purpose, a deep knowledge of their gut microbial communities is essential. To our knowledge, to date, no study has documented the gut microbiome dynamics of Phlebotomus duboscqi sand flies over the entire time-period required for the maturation of a Leishmania infection. Here, we address this limitation.

METHODS: P. duboscqi midguts were dissected both before and at different days after L. major infection and subjected to genomic DNA extraction followed by amplification of the V3-V4 hypervariable regions of the 16S rRNA, sequencing, and metagenomics analysis.

RESULTS: We observed a decrease in the number of Amplicon Sequence Variants (ASVs) early after infection, at D2, and late after infection, at D12. More so Sphingomonas, Ochrobactrum, and Serratia emerged as the most prevalent genera in relative terms, before, early after, and late after infection, respectively. These results translated into a separation between the 3 groups in the context of a beta diversity analysis, with statistical relevance. Importantly, we were able to establish Corynebacterium spp. and Enterococcus spp. as potential markers of non-infected and infected sand flies, respectively, as well as Streptococcus spp., Sphingomonas spp., Ralstonia spp., and Abiotrophia spp. as potential specific markers of late infections (ANCOM-BC analysis).

DISCUSSION: Overall, we show that the composition of the gut microbiota of P. duboscqi sand flies changes significantly over the course of an infection with L. major parasites.}, } @article {pmid41562083, year = {2025}, author = {Liu, J and Hong, W and Sun, Z and Zhang, S and Xue, C and Dong, N}, title = {The gut-lung axis: effects and mechanisms of gut microbiota on pulmonary diseases.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1693964}, pmid = {41562083}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Lung/immunology/metabolism/microbiology ; Dysbiosis/immunology ; *Lung Diseases/microbiology/immunology/metabolism/therapy/etiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {The proposal of the gut-lung axis has profoundly reshaped our understanding of the mechanisms underlying respiratory diseases. As a crucial component of this axis, the gut microbiota plays a central role in pulmonary immune regulation through inter-organ communication mediated by metabolic products. However, a systematic integration of mechanisms explaining how gut microbes achieve precise cross-organ immune regulation remains elusive. Existing research predominantly focuses on descriptive observations, such as the association between early-life microbiota dysbiosis and an increased risk of asthma and chronic obstructive pulmonary disease (COPD), as well as the frequent occurrence of acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), often accompanied by gut microbiome disruption. This paper focuses on three key gut microbial metabolites-short-chain fatty acids (SCFAs), tryptophan metabolites, and polyamines (PAs)-to examine their roles in immune regulation, maintenance of barrier function, and modulation of metabolic signaling networks. Based on the latest experimental and clinical evidence, this study systematically elucidates how dysbiosis of the gut microbiota, a key component of the gut-lung axis, crosses physiological barriers to exacerbate pulmonary inflammation. Regarding intervention strategies, probiotics, fecal microbiota transplantation (FMT), and CRISPR-Cas systems have demonstrated significant therapeutic potential in restoring gut microbial balance. Finally, this paper outlines future research directions, emphasizing the need to further explore non-invasive microbial sampling techniques, molecular interaction mechanisms of the gut-lung axis, and personalized microbiome-based diagnostic and therapeutic strategies to provide new insights for the prevention and treatment of respiratory diseases involving gut microbiota.}, } @article {pmid41562078, year = {2025}, author = {Pillai, AA and Pasya, SKR and Kansal, G and Jaikrishnan, A and Chauhan, A and Das, A and Manojbhai, KP and Prabu, VD and Nashatizadeh, MM}, title = {The gut microbiota-brain-CAR T cell axis: a systematic review of gut microbiome modulation and its impact on neurological complications and treatment responses in CAR T cell therapy.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1703146}, pmid = {41562078}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy, Adoptive/adverse effects/methods ; *Brain/immunology ; *Neurotoxicity Syndromes/etiology/immunology ; *Receptors, Chimeric Antigen/immunology ; }, abstract = {BACKGROUND: CAR T-cell therapy represents a substantial advance for relapsed/refractory hematologic cancers, but toxicities still limit its benefits. A particular concern is immune effector cell-associated neurotoxicity syndrome (ICANS), whose mechanisms remain only partly resolved. In parallel, work across immunology and neurogastroenterology shows that gut microbial communities can shape systemic inflammation and show correlations with brain function. Together, these strands suggest-without yet proving-that microbiome features could bear on both CAR T efficacy and ICANS risk.

OBJECTIVES: We examined human clinical evidence at three touchpoints: how CAR T and the gut microbiota interact; how gut profiles relate to brain function; and which signals accompany CAR T-related neurotoxicity. The aim was to locate areas of overlap, not to claim a single causal chain.

METHODS: Following PRISMA, PubMed, Scopus, and Embase were searched from 2015 to 11 April 2025. We included randomized trials, prospective cohorts, and retrospective series reporting gut microbial composition, inflammatory or neurobiological markers, CAR T outcomes, or ICANS. Study quality was appraised with the Newcastle-Ottawa Scale and certainty graded with GRADE.

RESULTS: Twenty-five studies were included (four CAR T-gut, eleven gut-brain, ten CAR T-neuro). Recurrent signals were (i) reduced microbial diversity, (ii) loss of short-chain fatty-acid producers, and (iii) prior antibiotic exposure-each linked to poorer clinical outcomes and higher or more severe ICANS. Candidate markers (e.g., C-reactive protein, interleukin-6, neurofilament light chain) and imaging findings, including PET abnormalities, were reported but remain exploratory and variably measured. Included studies are small and methodologically varied, and results should be interpreted with caution.

CONCLUSION: Taken together, the data support a convergence model: the gut microbiota may correlate with both treatment efficacy and neurotoxicity in CAR T recipients. The signal is consistent yet preliminary. Microbiome interventions such as probiotics and FMT are investigational and not yet recommended for CAR T recipients. Prospective, mechanism-rich studies-ideally pairing longitudinal stool profiling with inflammatory panels and neuroimaging-are needed before clinical translation.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024548645.}, } @article {pmid41562055, year = {2025}, author = {Zhao, Y and Tong, Z and Liu, L and Yang, R and Chen, Z and Wang, Z}, title = {Influence of stage-specific and location-related intratumoral microbiota on prognosis and metabolic reprogramming in non-small cell lung cancer.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1675448}, pmid = {41562055}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/microbiology/pathology/metabolism/immunology/mortality ; *Lung Neoplasms/microbiology/pathology/metabolism/immunology/mortality ; Prognosis ; Animals ; Tumor Microenvironment/immunology ; Female ; Mice ; Male ; Middle Aged ; Neoplasm Staging ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Aged ; *Bacteroides ; Cell Proliferation ; Cell Line, Tumor ; Metabolic Reprogramming ; }, abstract = {INTRODUCTION: Mounting evidence links intratumoral microbiota to tumor progression and immune regulation, but stage-specific and location-related microbial characteristics in NSCLC remain insufficiently explored.

METHODS: Tumor and adjacent non-tumor tissues from 21 NSCLC patients were analyzed using 16S rRNA gene sequencing to profile the intratumoral microbiota. Functional pathway analysis, in vitro co-culture experiments (A549/HCC827 cells), and in vivo mouse models were employed to validate microbial functions.

RESULTS: Microbial composition exhibited significant heterogeneity by tumor stage (early vs. advanced) and anatomical location (upper vs. lower lobes). Bacteroides was identified as a key genus enriched in early-stage tumors and correlated with improved prognosis. Functional analysis revealed enrichment of tumor-associated microbiota in metabolic and biosynthetic pathways (e.g., carbon metabolism, amino acid biosynthesis). Further experiments demonstrated that Bacteroides significantly suppressed NSCLC cell proliferation, inhibited migration, and promoted apoptosis, with anti-tumor effects mediated by remodeling the tumor immune microenvironment.

DISCUSSION: These findings elucidate intricate associations between intratumoral microbiota, immune cell infiltration, and patient prognosis, highlighting Bacteroides as a potential prognostic biomarker and therapeutic target for NSCLC.}, } @article {pmid41561899, year = {2026}, author = {Labbancz, J and Birnbaum, A and Dhingra, A}, title = {Long-read metagenomic dataset from domestic rabbit manure and domestic rabbit manure-derived vermicompost.}, journal = {Data in brief}, volume = {64}, number = {}, pages = {112425}, pmid = {41561899}, issn = {2352-3409}, abstract = {This dataset describes samples collected from two Domestic Rabbit manure sources and three Domestic Rabbit manure-derived vermicompost bins. Three samples were taken from each and total DNA was isolated. Nanopore sequencing was used to collect data from all isolated DNA samples. After length and quality filtering, 181.5 gigabases (Gb) of sequencing data was collected across 15 samples. Streptomyces, Bradyrhizobium, Mesorhizobium, and Microbacterium were in the top 5 genera for all vermicompost samples, but two vermicompost samples had very high proportions of Escherichia and Mycobacterium. Vermicomposting can enable the development of beneficial microbial communities, but often lacking a thermophilic phase, may also allow for the growth of potentially pathogenic microbes. The vermicomposts described by this dataset contains both beneficial and potentially harmful microbial communities and may be used to support comparisons between composts and vermicomposts of different backgrounds for safety and utility.}, } @article {pmid41561480, year = {2026}, author = {Martin, EM and Morales, MJ and Li, NY and Stoehr, MC and Kern, MJ and Winters, MF and Smith, CJ}, title = {Effects of combined prenatal exposure to air pollution and maternal stress on immune and dopaminergic gene expression in the gut-brain axis.}, journal = {Brain, behavior, & immunity - health}, volume = {51}, number = {}, pages = {101165}, pmid = {41561480}, issn = {2666-3546}, abstract = {Air pollution and maternal stress during pregnancy are both risk factors for neurodevelopmental disorders and often converge on the same communities. Epidemiological and animal studies suggest that maternal psychosocial stress may worsen the effects of air pollutants on neurodevelopmental outcomes. Previous work utilizing a mouse model of combined prenatal exposure to diesel exhaust particles (DEP) and maternal stress (MS) has found numerous sex-specific effects of DEP/MS exposure on neuroimmune outcomes, dopamine receptors, the gut-brain axis, and social behavior. However, it is unclear how broadly the immune landscape is shifted in the brain and intestinal epithelium following DEP/MS. Here, we analyzed immune gene expression in 5 brain regions important for social behavior and in 3 regions of the intestinal epithelium in both male and female offspring at ∼postnatal day 50, following either DEP/MS or control exposure. We found several interesting overall patterns. First, changes in expression of immune genes such as CD11b and Tlr4 were concentrated in the nucleus accumbens and hippocampus. Tlr4 and Il-17ra mRNA also increased in the jejunum and colon following DEP/MS, but only in females. Second, in the nucleus accumbens, catecholamine-O-methyltransferase (Comt) and dopamine transporter 1 (Slc6a3) gene expression were increased following DEP/MS, indicating increased dopamine degradation at and reuptake from the synapse, respectively. Additionally, dopamine D2 receptor (Drd2) mRNA was decreased following DEP/MS in males. Finally, we observed numerous sex differences in immune gene expression regardless of treatment in both the brain and gut. Together, these findings suggest the nucleus accumbens is a key site for neuroimmune and dopaminergic changes following DEP/MS exposure and indicate female-specific changes in intestinal immunity in young adulthood following these prenatal exposures.}, } @article {pmid41561435, year = {2026}, author = {Ladeveze, S and Tarquis, L and Cioci, G and Guieysse, D and Durand, J and Fauré, R and Li, A and Esque, J and Vivier, M and Malbert, Y and Laville, E and Potocki-Veronese, G}, title = {Dual-Activity Mannosyltransferase Phosphorylases in Family 130 of Glycoside Hydrolases.}, journal = {ACS catalysis}, volume = {16}, number = {2}, pages = {1211-1223}, pmid = {41561435}, issn = {2155-5435}, abstract = {We discovered that certain mannoside-active enzymes from family GH130 possess both glycoside phosphorylase (GP) and weak glycosyltransferase (GT) activities. This dual activity was observed only in glycoside phosphorylases acting on β-(1,2)- and β-(1,3)-mannosides, being absent in β-(1,4)-mannoside phosphorylases. We provide several three-dimensional (3D) structures of β-(1,2)-mannosyltransferase phosphorylases Uhgb_MS (identified from the human gut microbiome (subfamily GH130_4)) and Teth514_1788 (from Thermoanaerobacter sp. X514 (subfamily GH130_6)) and analyzed GT/GP partitioning among enzymes acting on d-mannosides. Structural analysis and mutagenesis of Uhgb_MS allowed us to show that loop L2 folding, as well as nucleotide and phosphate binding residues (P206, N211, R242) at the location of the common structural phosphate of αMan1P and GDP-Man, is an important structural element of bifunctionality in GH130.}, } @article {pmid41561310, year = {2026}, author = {Tulloch, S and Estarellas, M and Adams, DC and Bonacolta, A and Pagone, V and Fernández-Guiberteau, D and Amat, F and Montori, A and Carbonell, F and Obon, E and Alonso, M and Santmartín, M and Xarles, J and Marsol, R and Guinart, D and Solórzano, S and Talavera, A and Burriel-Carranza, B and Bosch, E and Del Campo, J and Carranza, S}, title = {Comparative skin microbiome analyses reveal differences between wild populations and captive groups of the Montseny brook newt (Calotriton arnoldi).}, journal = {ISME communications}, volume = {6}, number = {1}, pages = {ycaf245}, pmid = {41561310}, issn = {2730-6151}, abstract = {The Montseny brook newt, Calotriton arnoldi, is a Critically Endangered amphibian species endemic to the Montseny Massif in Catalonia, Northeastern Spain. Due to population declines and threats to its natural habitat, an ex-situ breeding program was initiated in 2007. A key goal of the program is to ensure the survival of captive-bred individuals after reintroduction, which in amphibians heavily relies on the specimens' microbiome being capable of protecting them from environmental microorganisms, especially considering the global Chytridiomycosis pandemic caused by the fungi Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). This study aims to characterize the skin microbiome of wild and captive C. arnoldi specimens and identify differences in their composition, contributing to future research on the microbiome's impact in captive-bred individuals upon reintroduction. Up to 5996 ASVs (Amplicon Sequence Variants) were identified from 138 samples from 21 and 61 wild and captive-bred individuals, respectively. Results indicate that wild populations from different subspecies have significantly different skin microbiome composition, as do wild and captive-bred groups from the same subspecies. Additionally, dissimilarities in skin microbiome variability were only found within each subspecies, between wild and captive-bred groups. In terms of composition, certain bacteria were identified as potential markers for both wild and captive environments. Enhancing skin microbiome variability might improve the survival prospects of reintroduced specimens. Thus, exposing captive specimens to a more natural environment while in captivity or a soft-release procedure could potentially mitigate the absence of exposure to other bacteria and potential pathogens from their native environment.}, } @article {pmid41561308, year = {2026}, author = {Mei, Z and He, C and Balcazar, JL and Fu, Y and Dou, Q and Liu, Y and Dercon, G and Jiang, X and Elsner, M and Wang, F}, title = {Antibiotic-degrading bacteria shape resistome dynamics and horizontal gene transfer potential in soils with contrasting properties.}, journal = {ISME communications}, volume = {6}, number = {1}, pages = {ycaf246}, pmid = {41561308}, issn = {2730-6151}, abstract = {Soils act as both reservoirs and filters of antimicrobial resistance genes (ARGs); however, the ecological and genetic traits of antibiotic-degrading bacteria (ADB) and their interactions with nondegrading bacteria (NADB) across soil types remain poorly understood. In particular, the role of ADB in ARG dynamics and their potential contribution to horizontal gene transfer (HGT) are still underexplored. Here, we applied [13]C-DNA stable isotope probing (DNA-SIP) combined with metagenomic sequencing to resolve active ADB from NADB in two contrasting soils: Ultisol and Mollisol. ADB harbored significantly more abundant and diverse chromosomal ARGs - especially multidrug and tetracycline resistance genes - often co-localized with mobile genetic elements (MGEs) and degradation genes, suggesting robust and regulated resistance strategies. In contrast, NADB relied more on plasmid-borne ARGs, reflecting flexible but potentially transient adaptation. Soil properties shaped both resistome composition and host taxa. Mollisol enriched enzymatic degraders such as Lysobacter and Nocardioides, while Ultisol favored stress-tolerant Burkholderia, which carried up to 34 ARGs and exhibited membrane-associated resistance. Notably, 89 ARGs or MGEs were found co-localized with degradation genes on assembled contigs, highlighting a strong potential for HGT. In addition, 24 high-potential ARG hosts were identified, including Ralstonia pickettii and Saccharomonospora viridis. These findings reveal that antibiotic degradation is embedded within complex, soil-specific resistome networks. This work enhances our understanding of ARG ecology and supports targeted mitigation strategies based on soil microbiome characteristics.}, } @article {pmid41561306, year = {2026}, author = {Tugui, CG and Cordesius, F and van Holthe, W and van Loosdrecht, MCM and Pabst, M}, title = {Wastewater metaproteomics: tracking microbial and human protein biomarkers.}, journal = {ISME communications}, volume = {6}, number = {1}, pages = {ycaf243}, pmid = {41561306}, issn = {2730-6151}, abstract = {Wastewater-based surveillance has become a powerful tool for monitoring the spread of pathogens, antibiotic resistance genes, and measuring population-level exposure to pharmaceuticals and chemicals. While surveillance methods commonly target small molecules, DNA, or RNA, wastewater also contains a vast spectrum of proteins. However, despite recent advances in environmental proteomics, large-scale monitoring of protein biomarkers in wastewater is still far from routine. Analyzing raw wastewater presents a challenge due to its heterogeneous mixture of organic and inorganic substances, microorganisms, cellular debris, and various chemical pollutants. To overcome these obstacles, we developed a wastewater metaproteomics approach including efficient protein extraction and an optimized data-processing pipeline. The pipeline utilizes de novo sequencing to customize large public sequence databases to enable comprehensive metaproteomic coverage. Using this approach, we analyzed wastewater samples collected over approximately three months from two urban locations. This revealed a core microbiome comprising a broad spectrum of microbes, gut bacteria and potential opportunistic pathogens. Additionally, we identified nearly 200 human proteins, including promising population-level health indicators, such as immunoglobulins, uromodulin, and cancer-associated proteins.}, } @article {pmid41561239, year = {2025}, author = {Yuan, Y and Tang, Y and Sun, Y}, title = {Integrating the Data From Microbiome and Metabolome Genome-Wide Association Studies to Uncover Gene-Microbe-Metabolite Interactions in Allergic Diseases.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99600}, pmid = {41561239}, issn = {2168-8184}, abstract = {Background Host genetics, gut microbiota, and metabolites have each been independently linked to allergic diseases such as asthma, allergic rhinitis, and eczema. However, the complex interactions between these three components remain poorly understood, largely due to a reliance on single-omics analyses. Integrating multi-omics data is essential for uncovering the underlying mechanisms of allergic disease pathogenesis. Methodology We performed a systematic, integrative analysis of large-scale public data from gut microbiome genome-wide association studies (GWAS) and blood metabolome-GWAS. We retrieved data from studies with cohorts of over 400 subjects. Overlapping genetic loci were identified by cross-referencing significant associations (p<1×10[-6] for gene-microbe and p<1×10[-5] for gene-metabolite) to define gene-microbe-metabolite trios. These trios were then cross-referenced with relevant databases (e.g., GWAS Catalog, gutMDisorder, and Human Metabolome Database (HMDB)) to establish their potential link to allergic diseases. Results Our integrative approach identified 12 distinct gene-gut microbiota-blood metabolite trios associated with allergic diseases. Established patterns were confirmed, including the ABO gene's influence on Bifidobacterium bifidum, which is known to impact immune regulation. Novel associations were also uncovered, including structural genes (e.g., LAMA2, PTPRT) potentially facilitating microbiota attachment and modulating metabolites such as octadecanedioate and genes involved in neurotransmitter signaling (e.g., SYN3, PDE1A), suggesting potential neuro-immune mechanisms. Conclusions By integrating microbiome-GWAS and metabolome-GWAS data, we have generated a valuable resource of candidate pathways underlying allergic disease pathogenesis. The identified trios provide specific, testable hypotheses for future validation studies and potential targets for biomarker discovery. This work underscores the power of multi-omics integration in allergy research and provides a clear roadmap for investigating complex gene-environment interactions.}, } @article {pmid41561167, year = {2025}, author = {Wang, R and Hu, L and Tu, Y and Zhai, Z and Niu, K and Guo, X and Cai, L and Liu, J}, title = {Policosanol alleviates chronic stress-induced growth impairment via gut microbiota-metabolite interactions: insights from 16S rRNA sequencing and LC-MS metabolomics.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1685003}, pmid = {41561167}, issn = {2296-861X}, abstract = {BACKGROUND/OBJECTIVES: Policosanol, a bioactive compound derived from rice bran wax, has demonstrated potential for alleviating stress, yet its underlying mechanisms remain elusive. This study aimed to elucidate its role in mitigating chronic stress-induced growth impairment and to explore its interactions with the gut microbiota and metabolomics.

METHODS: Male rats were subjected to a 4-week chronic restraint stress protocol with or without policosanol supplementation (2 mg/kg/day). Systemic responses were evaluated by measuring growth parameters (including weight gain and muscle mass), serum biomarkers [cortisol and catecholamines (CA)], 16S rRNA sequencing (for cecal microbiota analysis), and LC-MS metabolomics (for cecal metabolite profiling).

RESULTS: Stress induced a significant reduction in weight gain (-11.0%, p < 0.05) and a marked elevation of serum cortisol (+86.2%) and CA (+88.3%, both p < 0.05). Policosanol treatment restored weight gain to 85.5% of control levels (p < 0.05) and reduced cortisol and catecholamine levels by 29.5% and 26.8%, respectively (both p < 0.05). Stress-induced alterations in gut microbiota included a 4.1-fold increase in p_Verrucomicrobiota and a 3.8-fold increase in g_Akkermansia, along with metabolite changes such as a 4.2-fold elevation in Proscillaridin and a 65% decrease in Phenylacetylglutamine (PAGln) (both p < 0.05). Policosanol supplementation normalized gut microbiota composition (p_Verrucomicrobiota decreased by 36%, p < 0.05) and restored metabolite levels (PAGln increased by 80%, p < 0.01). Negative correlations were observed between g_Akkermansia abundance and weight gain (p < 0.01), while PAGln positively correlated with growth (p < 0.05) and negatively correlated with GSH-Px (p < 0.001), cortisol (p < 0.001), and CA (p < 0.001). Moreover, the g_Bacteroides-PAGln axis exhibited a strong interaction (p < 0.001).

CONCLUSION: Policosanol mitigates stress-induced growth impairment by modulating gut microbiota (e.g., reducing p_Verrucomicrobiota and g_Akkermansia abundances) and restoring metabolite levels (e.g., increasing PAGln). The coregulation of the gut microbiota and metabolome was highlighted by a strong correlation between g_Bacteroides and Phenylacetylglutamine (PAGln), suggesting a potential functional interaction that may contribute to the anti-stress effects of policosanol, though causality remains to be established.}, } @article {pmid41561096, year = {2025}, author = {Wan, L and Huang, C and Kong, W and Li, M and Lu, C}, title = {The analysis of gut microbiota characteristics in children with global developmental delay.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1606453}, pmid = {41561096}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Female ; Feces/microbiology ; Male ; *Developmental Disabilities/microbiology ; Child, Preschool ; *Bacteria/classification/genetics/isolation & purification ; High-Throughput Nucleotide Sequencing ; Child ; DNA, Bacterial/genetics ; Infant ; Biodiversity ; China ; }, abstract = {OBJECTIVE: To explore the composition and functional changes of gut microbiota in children with Global Developmental Delay(GDD),and to explore the role of gut microbiota in the pathogenesis of GDD using high-throughput sequencing.

METHODS: A prospective study was conducted to select 26 children diagnosed with GDD at Longgang District Maternal and Child HealthCare Hospital of Shenzhen City from January 2024 to December 2024 as the disease group(GDD), and 59 healthy children of the same age were selected as the healthy group(HC).General information of the children was collected through a questionnaire survey, and fecal samples from all participants were collected. Total DNA was extracted and amplified, and high-throughput sequencing of the 16S rRNA gene was performed for biological analysis of the sequencing results.

RESULTS: The alpha diversity analysis revealed a significant reduction in microbial diversity in the GDD group (Chao1 index, P = 0.007), while the beta diversity showed significant segregation between groups (R² = 0.067, P = 0.001);At the phylum level, the relative abundance of Actinobacteria was significantly increased (P < 0.01), while the abundance of Bacteroidetes was significantly decreased (P < 0.05) in the GDD group;At the genus level, the abundance of Bifidobacterium, Fusicatenibacter, and Erysipelatoclostridium were significantly increased in the GDD group (all P < 0.001), while the abundance of Faecalibacterium, Phascolarctobacterium, and Alistipes were significantly reduced (all P < 0.001);Functional prediction based on 16S rRNA data suggested potential differences in microbial metabolic pathways, including mRNA surveillance, proteasome, and atrazine degradation, in the GDD group. These findings hypothesize a functional shift in the gut microbiome associated with GDD, which requires validation by direct metagenomic or metabolomic methods.

CONCLUSION: Children with GDD have significant differences in gut microbiota composition and diversity compared to HC,and the abundance and abnormal metabolic pathway may be closely related to the neuroinflammatory process, suggesting that intestinal microecological regulation may become a new intervention target for GDD.}, } @article {pmid41561086, year = {2025}, author = {Zhang, MY and Chen, SY and Lin, YH and Yuan, XX}, title = {Gut microbiota modulation in gastrointestinal disorders: current evidence and therapeutic perspectives.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1740322}, pmid = {41561086}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Gastrointestinal Diseases/therapy/microbiology ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Tract/microbiology ; Phage Therapy ; Dysbiosis/therapy ; }, abstract = {Gut microbiome medicine is a promising field in functional medicine, offering personalized treatment strategies for gastrointestinal disorders. Advanced metagenomic and metabolomic technologies have revealed the gut microbiome's systemic influence, extending to distant organs like the brain and lungs. While small molecules and genes facilitate these effects, the gut microbiota's greatest abundance and activity are concentrated in the gastrointestinal tract, particularly in the distal regions. The balance of microbial communities in the small and large intestines is crucial for gastrointestinal health. However, the dominance of pathogenic bacteria can disrupt this balance, leading to tissue damage and contributing to gastrointestinal disorders. Emerging interventions, such as probiotics, fecal microbiota transplantation, and dietary enrichment with short-chain fatty acids, show potential in restoring microbial balance, enhancing immune function, and potentially protecting against carcinogenesis. Current evidence from clinical trials and animal models supports the therapeutic role of gut microbiome modulation in reversing gastrointestinal disorders. However, variability in study outcomes highlights the need for further research to standardize these approaches for clinical practice. This review underscores the gut microbiome's pivotal role in gastrointestinal health and the therapeutic promise of functional medicine in addressing these disorders. This review also explores emerging interventions, such as phage therapy and engineered microbes, and provides comparative analyses of microbiota signatures and therapeutic approaches across different gastrointestinal disorders.}, } @article {pmid41561025, year = {2025}, author = {Haller, R and Hazia, O and Feldbacher, N and Traub, J and Madl, T and Habisch, H and Horvath, A and Stadlbauer, V}, title = {Nitrogen recycling by the gut microbiome in sarcopenia.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1698437}, pmid = {41561025}, issn = {1664-302X}, abstract = {INTRODUCTION: Sarcopenia, which is defined as loss of skeletal muscle mass and strength, affects up to 70% of patients with liver cirrhosis. Since hibernating animals maintain muscle mass through microbial nitrogen recycling, urease-producing bacteria may have a protective role in humans. We hypothesized that altered microbial urease abundance contributes to differences in nitrogen recycling potential between patients with and without sarcopenia, with sex-specific effects.

METHODS: Stool samples from 152 patients with (n = 101) and without sarcopenia (n = 51) were analyzed. Functional profiles were predicted from 16S rRNA gene amplicon sequencing data using Tax4Fun2, and predicted abundances of urease subunit alpha were extracted. A systematic literature search identified 120 urease-producing taxa, of which 35 were represented in sequencing data.

RESULTS: Sarcopenia is associated with a lower predicted abundance of urease subunit alpha in patients with cirrhosis (n = 96; p = 0.045, r = 0.20; median = 0.0002 vs. 0.0004), irrespective of sex, and in women (n = 49, p = 0.037, r = 0.30, median = 0.0002 vs. 0.0004), irrespective of cirrhosis. Urease subunit alpha abundance increases with the use of proton pump inhibitors (PPIs) in the entire patient cohort (p = 0.0028, r = 0.24, median = 0.0003 vs. 0.0002), patients with cirrhosis (p = 0.033, r = 0.22, median = 0.0004 vs. 0.0002), and men (n = 103, p = 0.0005, r = 0.34, median = 0.0002 vs. 0.0001). Beta-blockers are associated with higher urease subunit alpha abundance in the entire patient cohort (p = 0.018, r = 0.19, median = 0.0003 vs. 0.0002) and women (p = 0.031, r = 0.31, median = 0.0004 vs. 0.0002). The overall abundance of potentially urease-producing taxa was comparable between the groups.

DISCUSSION: The increased urease subunit alpha abundance in patients with liver cirrhosis and women without sarcopenia, and the influence of medication on abundance, point towards potential additional effects of beta-blockers in sarcopenia.}, } @article {pmid41561022, year = {2025}, author = {Scott, DA and Lamont, GJ and Tan, J and Patel, AP and Guffey, JT and Thomas, SC and Xu, F and Diamond, G and Saxena, D}, title = {Identification of cannabinoid-sensitive and -resistant oral bacteria.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1709243}, pmid = {41561022}, issn = {1664-302X}, abstract = {Marijuana, an emerging risk factor for periodontitis, contains multiple potent antibacterials, particularly the phytocannabinoids. Microbial dysbiosis is a hallmark of this destructive oral disease. We examined a panel of oral bacteria for susceptibility to the major cannabinoid, cannabidiol (CBD), portended by an initial in vivo microbiome analysis of marijuana users and non-users with periodontitis. Multiple oral bacteria were found to be sensitive to physiologically relevant CBD doses-Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, several strains of Porphyromonas gingivalis, Streptococcus mutans, Streptococcus gordonii and Tannerella forsythia. Other oral bacteria, however, were resistant to even superphysiological CBD concentrations-Campylobacter gracilis, Corynebacterium durum, Haemophilus parainfluenzae, several oral Treponema species and Veillonella parvula. Enrichment of phytocannabinoid resistant bacterial pathobionts may help explain increased periodontitis prevalence in cannabis users who, like tobacco smokers, may have distinct therapeutic and preventive needs. To this end, a library of membrane permeabilizing peptoids (N-substituted glycine oligomers), based on an endogenous mammalian antimicrobial peptide, cathelicidin, was screened for activity against Treponema denticola. This spirochete was sensitive to a sub-set of stable and inexpensive antimicrobial peptoids that, presumably due to peptoid-induced outer membrane instability, also rendered CBD toxic to normally resistant spirochetes. The tobacco-stable, cannabinoid-labile pathobiont, P. gingivalis, was also sensitive to specific antimicrobial peptoids. Electron micrographs clearly suggest altered ultrastructure in both CBD-treated P. gingivalis and peptoid-exposed T. denticola. In summary, cannabis use may promote specific oral bacteria while suppressing others. The associated dysbiosis may help explain marijuana-exacerbated periodontitis. While more comprehensive studies of cannabis-induced microbial fluxes are warranted, adjunctive antimicrobial agents, such as cathelicidin-mimicking peptoids, that target cannabis-promoted pathobionts may also be worth exploring for therapeutic potential.}, } @article {pmid41560867, year = {2026}, author = {Zhang, M and Xiao, D and He, T and Guo, L and Yang, X}, title = {Role of the intestinal microbiota in sepsis-associated encephalopathy.}, journal = {Burns & trauma}, volume = {14}, number = {}, pages = {tkaf070}, pmid = {41560867}, issn = {2321-3868}, abstract = {Sepsis-associated encephalopathy (SAE) is a secondary cerebral dysfunction of the central nervous system (CNS) caused by sepsis and is associated with high mortality rate and poor prognosis. It significantly affects the quality of life of survivors. The pathological mechanisms associated with SAE include dysfunction of the blood-brain barrier (BBB), activation of glial cells, ischemic injury, leukocyte transmigration, and disturbances in neurotransmitters. The mechanisms of SAE interact with and contribute to its development. Numerous studies have demonstrated that the intestinal microbiota affects not only the health of the gut but also that of other organs. Throughout the progression of SAE, alterations in the gut microbiome composition lead to the production of toxic substances that damage the intestinal barrier and enter the bloodstream. This damage negatively affects BBB permeability and initiates a cascade of neuroinflammatory responses that result in neuronal injury. Conversely, specific microbiome-derived derivatives play exhibit a neuroprotective role in regulating brain function. Therefore, gut-brain crosstalk may be a crucial factor in brain dysfunction. This paper reviews the relationship between the intestinal microbiota and SAE, aiming to explore the role of the intestinal microbiota in SAE and potential therapeutic targets.}, } @article {pmid41560864, year = {2025}, author = {Jaleta, M and Junker, V and Hölzel, C and Zentek, J and Amon, T and Nübel, U and Kabelitz, T}, title = {Antimicrobial resistance genes in weaned pigs: quantitative abundance and group dynamics assessed by qPCR.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1709227}, pmid = {41560864}, issn = {2297-1769}, abstract = {Antibiotic resistance genes (ARGs) linked with the selection of resistant bacteria in intensive commercial livestock production require regular surveillance. This study quantified ARG abundances in weaner pigs, with emphasis on inter-individual variation and temporal trends of ARG dynamics over 8 weeks in a flat-deck housing system. Fecal samples from 103 individual pigs and 53 pooled pen-floor collections were analyzed. Broad-spectrum ARG profiling of pooled DNA from both sample types was performed using high-throughput qPCR (SmartChip), while standard qPCR quantified eight ARGs (aadA1, bla TEM, dfrA12, erm(B), lnu(F), qnrS, sul2, and tet(A)) and the 16S rRNA gene in all samples. Among the quantified ARGs, erm(B) and aadA1 were the most abundant, while qnrS was least frequently detected. Substantial inter-individual variation was observed for most ARGs, despite pigs living together under the same management conditions. Pooled pen-floor feces exhibited significantly higher ARG loads than individual fecal samples, suggesting that resistome profiles at the pen-floor level cannot be accurately inferred from fresh feces of individual animals. Temporal analysis revealed that 16S rRNA gene copies increased during the later period, while tet(A) and sul2 decreased, suggesting age-related effects. These findings reveal pronounced intra-cohort variability in ARG abundance among weaner pigs and underscore the impact of weaning-associated factors on resistome composition. Future investigations should examine the contribution of gut microbiome dynamics and evaluate dietary interventions aimed at stabilizing ARG profiles and mitigating the resistance development of microbial resistance.}, } @article {pmid41560593, year = {2026}, author = {Reddy, N and Lau, K and Naman, J and Lu, K and McGillivary, E and Salmasi, A and Liss, M and Stewart, T}, title = {Killing cancer takes guts: lessons learned from the manipulation of gut microbiome and immunotherapy for the future of urothelial carcinoma.}, journal = {Oncoimmunology}, volume = {15}, number = {1}, pages = {2611458}, pmid = {41560593}, issn = {2162-402X}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; *Carcinoma, Transitional Cell/therapy/immunology/microbiology ; *Urinary Bladder Neoplasms/therapy/immunology/microbiology ; }, abstract = {Urothelial carcinoma (UC) remains a common cancer with significant morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have helped revolutionize the treatment of UC, and there is growing evidence suggesting the crucial role of the gut microbiome in immune system function influences immunotherapy outcomes in this disease. Herein, we review the preclinical basis for how manipulation of the gut microbiome may alter the efficacy of immunotherapy for patients with cancer, highlight interventions optimizing gut microbiome diversity currently in use, review recent and ongoing clinical trials supporting the role of the gut microbiome in improving immunotherapy outcomes, and discuss clinical implications to improve outcomes for UC patients with immunotherapy in the real world. There is growing evidence that suggests that specific gut microbiome compositions significantly modulate the host immune system and response to ICIs. Early studies have shown that certain microbial taxa enhance antitumor immunity by influencing T cell priming, dendritic cell activation, and cytokine production. Fecal microbiota transplantation (FMT), probiotic supplementation, and dietary modulation have emerged as promising methods to alter microbiomes to improve immunotherapy outcomes. Taxa from positive immunotherapy responders across a variety of cancers demonstrate beneficial effects when transplanted into both treatment-naive or prior nonresponders. Increasing evidence suggests that the gut microbiome plays a crucial role in cancer care, particularly when patients are treated with immunotherapy. Future studies are needed to better understand the underlying mechanisms. While some studies are currently underway to explore gut manipulation for patients with UC, more studies are needed to investigate the potential to convert nonresponders into responders through microbiome manipulation.}, } @article {pmid41560310, year = {2026}, author = {Westheim, AJF and Dubois, LJ and Prades-Sagarra, E and Chan, J and van der Wiel, AMA and Lieuwes, NG and Biemans, R and Cong, Y and Houben, T and Meesters, DM and Yaromina, A and van Dijk, M and van Bergenhenegouwen, J and van Helvoort, A and Langen, RCJ and Penders, J and Shiri-Sverdlov, R and Theys, J}, title = {The Effect of Dietary Fiber Compositions on the Therapeutic Outcome of Combined Radio- and Immunotherapy in a Preclinical Cancer Model.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {2}, pages = {e70370}, pmid = {41560310}, issn = {1613-4133}, support = {16485 NutrI2FIT: Strengthening Immune Fi//NWO/ ; }, mesh = {Animals ; Female ; *Dietary Fiber/pharmacology/administration & dosage ; Mice, Inbred BALB C ; Gastrointestinal Microbiome/drug effects ; *Immunotherapy/methods ; Mice ; *Colonic Neoplasms/therapy ; Disease Models, Animal ; Combined Modality Therapy ; Fatty Acids, Volatile/analysis/metabolism ; Cell Line, Tumor ; }, abstract = {Several studies demonstrated curative responses of combined radio-immunotherapy, although not standard-of-care for most cancers. Increased fiber intake has been associated with improved radiotherapy and immunotherapy outcomes, but fiber compositions' impact remains unclear. This study aimed to explore whether dietary fiber composition influences the therapeutic outcome of combined radio-immunotherapy in a preclinical cancer model. A syngeneic mouse model of colon cancer (CT26) (female BALB/cOla Hsd) was used. Mice were randomized into three groups (n = 12) of iso-caloric diets with different fiber compositions. Five instances of local radiotherapy on tumors, combined with injections of anti-PD-L1, were administered over 5 and 10 days. Diets' impact was assessed on progression-free survival, SCFA levels in fecal and cecal samples, gut microbiome composition, and immunological profile. Progression-free survival was different between compositions, as well as their gut microbiota community structure, at all measured time-points. Therapeutic outcome (cure) was negatively associated with the relative abundance of Bacteroides and positively with Atopobiaceae Family. There was no association with SCFA levels. Cured mice displayed smaller spleens containing increased proportions of CD8+ T-cells and decreased proportions of myeloid-derived suppressor cells. Our data suggest that fiber composition may influence therapeutic outcome of combined radio-immunotherapy treatment in vivo.}, } @article {pmid41560008, year = {2026}, author = {Zhang, Y and Li, Q}, title = {Mendelian randomization study of the role of TD CD4+ T cells in the association between Streptococcus thermophilus and esophageal cancer.}, journal = {Medicine}, volume = {105}, number = {3}, pages = {e47174}, pmid = {41560008}, issn = {1536-5964}, mesh = {Humans ; *Esophageal Neoplasms/immunology/microbiology/genetics ; *Streptococcus thermophilus/immunology ; Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/immunology ; *CD4-Positive T-Lymphocytes/immunology ; Genome-Wide Association Study ; }, abstract = {Esophageal cancer (EC) remains a major global health burden, and emerging research highlights the potential influence of the gut microbiome on its pathogenesis. However, the causal relationship between specific microbial taxa and EC, as well as the immunological mechanisms mediating these effects, remains unclear. A 2-sample Mendelian randomization analysis was performed using data from 619 EC cases and 314,193 controls in the FinnGen R10 cohort, together with genome-wide association summary statistics of 412 gut microbiota taxa and 731 immune phenotypes obtained from the National Human Genome Research Institute-European Bioinformatics Institute Genome-Wide Association Studies Catalog. The analysis aimed to determine causal links between the gut microbiome and EC, and to explore immune cell-mediated pathways through mediation analysis. The results revealed a significant protective association between Streptococcus thermophilus and EC risk (odds ratio = 0.586, 95% confidence interval = 0.402-0.855, P = .006). Mediation analysis indicated that terminally differentiated CD4+ T cells partially mediated this relationship, accounting for approximately 6% of the total effect. This study identifies Streptococcus thermophilus as a potentially protective gut commensal that may reduce EC risk through immune modulation. The findings provide novel insights into microbiome-immune-cancer interactions and suggest possible preventive or therapeutic targets for EC.}, } @article {pmid41559841, year = {2026}, author = {Galgano, S and Faruk, MU and Eising, I and Houdijk, JGM and Khattak, F}, title = {Dietary muramidase leads to the downregulation of peptidoglycan biosynthesis and to caecal microbial modulation in laying hens.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {7}, pmid = {41559841}, issn = {2524-4671}, abstract = {BACKGROUND: In-feed muramidase enzyme has been linked to numerous advantages in several animal species. In the past years, muramidase has been shown to be effective in hydrolyzing peptidoglycan fragments, especially at small-intestine level in broilers, and to improve digestibility and performance. Moreover, previous studies also showed a possible anti-inflammatory effect of some secondary metabolites derived from the hydrolysis of peptidoglycan. Although a major effort has been carried out to unravel the in vivo mechanism of action of muramidase, there is currently little information on its metabolic interactions in laying hens, especially considering the fundamental differences with broilers in terms of microbiota and host genetics. Therefore, we conducted a 20-week study, testing five different levels of inclusion of muramidase, from 0 mg/kg to 600 mg/kg. We analyzed dry matter and nitrogen digestibility, apparent metabolizable energy, body weight gain, caecal microbiota and microbiome.

RESULTS: The intervention with muramidase (Balancius[®], DSM Nutritional Products Ltd., Basel, Switzerland) led to a drop in α-diversity (Shannon index; P < 0.05) and to microbial composition changes, with a decrease in Lactobacillus and an increase in Collinsella, amongst others (Q < 0.05), at all the muramidase concentrations compared to 0 mg/kg. In parallel, we found that muramidase led to an increased protein digestibility as revealed by the increased nitrogen retention, together with a dose-dependent amelioration of body weight, dry matter digestibility and metabolizable energy (P < 0.05). At functional gene level, we observed a net decrease in the microbial potential to metabolize amino acids, likely as a direct consequence of the lower amino acid availability at caecal level, as linked to the increased nitrogen retention. Moreover, muramidase also led to a decreased microbial functional potential to synthesize peptidoglycan.

CONCLUSION: This study is the first to investigate the effects of dietary muramidase supplementation on nutrient digestibility and metagenomics in laying hens. Our findings align perfectly with the previous studies in broilers, especially in terms of increased protein digestibility. Moreover, for the first time, a direct correlation between the observed phenotype and both microbiota and microbiome has allowed us to gain further insights into the mechanism of action of muramidase in laying hens.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00506-9.}, } @article {pmid41559836, year = {2026}, author = {Canavera, G and Vaccari, F and Del Zozzo, F and Poni, S and Gatti, M and Puglisi, E and Frioni, T}, title = {Cover crop-based under-row dry mulching enhances phyllosphere and rhizosphere microbial biodiversity in a non-irrigated vineyard.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00854-2}, pmid = {41559836}, issn = {2524-6372}, abstract = {BACKGROUND: In viticulture, temporary cover crops and organic mulching are sustainable practices that enhance biodiversity, improve soil fertility, and strengthen grapevine health/resilience, particularly in Mediterranean regions. However, their impact on microbial communities associated with grapevines in non-irrigated vineyards remains largely unexplored. Inter-row soil management included a cereal-based cover crop (CC), a mixed cereals, legumes and brassicas cover crop (MC), and a control with alternating soil tillage and spontaneous grass (GT). In spring, cover crops were terminated to form a dry mulch under the vine rows.

RESULTS: At veraison, under-row dry mulching significantly maintained higher soil water availability and reduced soil temperature by approximately 2.5 °C compared to the GT treatment. CC, in particular, enhanced grapevine physiological performances. These different soil conditions positively shaped the rhizosphere microbiome by maintaining higher microbial richness and promoting nutrient-cycling microorganisms (e.g., Bradyrhizobium sp., Nitrospira japonica) in both CC and MC. In contrast, the GT treatment selectively favored drought-tolerant plant growth-promoting rhizobacteria (PGPR) taxa such as Bacillus zanthoxyli, Gaiella occulta, Roseiflexus sp., Pseudarthrobacter sp., and Paenibacillus sp. In the phyllosphere, the abundance of Erysiphe necator, the powdery mildew agent, was lower in CC and MC, which also showed a higher presence of Aureobasidium pullulans, a species reported in the literature as a potential biocontrol agent.

CONCLUSIONS: Our results suggest that under-row dry mulching, by modifying soil conditions, can have a positive effect on grapevine microbial richness and biodiversity during the dry summer period, serving as an indicator of improved vineyard agroecosystem health and sustainability.}, } @article {pmid41559821, year = {2026}, author = {Zini, A and Müller, J and Fink, P and Forchhammer, K}, title = {Cultivation in a Natural Microbial Community Enhances the Industrial Performance of a Genetically Engineered Cyanobacterium for Bioplastic Production.}, journal = {Microbial biotechnology}, volume = {19}, number = {1}, pages = {e70302}, pmid = {41559821}, issn = {1751-7915}, support = {031B1399B//Bundesministerium für Bildung und Forschung/ ; }, mesh = {*Hydroxybutyrates/metabolism ; *Synechocystis/genetics/metabolism/growth & development ; *Microbiota ; *Microbial Consortia ; Genetic Engineering ; Metabolic Engineering ; Photobioreactors/microbiology ; *Cyanobacteria/genetics/metabolism/growth & development ; Industrial Microbiology ; }, abstract = {Large-scale production of polyhydroxybutyrate (PHB), a biodegradable bioplastic, using genetically engineered cyanobacteria offers a sustainable alternative to petrochemical-derived plastics. However, monoculture-based phototrophic systems face major limitations, such as poor resilience in large-scale reactors, hindering industrial upscaling. To address these challenges, we replaced the native cyanobacterium of a natural microbial consortium with a genetically engineered Synechocystis strain optimised for PHB production, establishing what we define a hybrid photosynthetic microbiome. This new community preserved the ecological structure and stability of the original microbiome while gaining synthetic production capacity. Compared to the axenic strain, the hybrid system exhibited enhanced robustness under abiotic stress, including light and temperature fluctuations, and improved tolerance to operational instability. These features made it suitable for upscaling and application in non-sterile environments. The hybrid microbiome sustained PHB production in scaled photobioreactors, reaching up to 32% PHB per cell dry weight (CDW) equal to ~230 mg L[-1] under fully photoautotrophic conditions. Production was also achieved under dark conditions with acetate supplementation, highlighting the system's metabolic flexibility. This work demonstrates the successful integration of an engineered phototroph into a stable native microbiome, positioning hybrid communities as powerful platform for industrial biotechnology.}, } @article {pmid41542591, year = {2026}, author = {Han, G and Yunker, R and Hasan, MH and Bruce, A and Baldaro, K and Pacia, J and Jarjour, NN and Beura, LK and Vaishnava, S}, title = {A host-adapted commensal fungus from pet store mice drives type 2 immunity and cross-kingdom protection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41542591}, issn = {2692-8205}, support = {K22 AI177360/AI/NIAID NIH HHS/United States ; P20 GM109035/GM/NIGMS NIH HHS/United States ; R01 DK113265/DK/NIDDK NIH HHS/United States ; S10 OD023461/OD/NIH HHS/United States ; }, abstract = {Naturalized, wilded, wildling, and dirty/pet store mouse models represent a spectrum of approaches designed to make laboratory mice more immunologically and physiologically similar to wild or human contexts by increasing their exposure to naturally occurring microbes and pathogens. In this study, we screened the gut mycobiome of pet store mice, and identified Kazachstania pintolopesii as a dominant fungus in pet store mice across various geographical locations. K. pintolopesii strains isolated from mice in geographically distinct pet stores stably colonize the gastrointestinal tract of laboratory mice, independent of gut bacterial composition, maintaining high fungal burdens for extended periods. K. pintolopesii rapidly became the dominant fungus in the mouse gut in conventional, antibiotic, and germ-free settings, outcompeting other non-murine fungal strains. Pet store-derived K. pintolopesii exhibited unique immunological properties distinct from typical anti-fungal responses. Unlike C. albicans colonization, K. pintolopesii did not induce circulating neutrophil expansion or Th17 cell populations in the gut mucosa. When administered systemically, K. pintolopesii-infected mice showed 100% survival with minimal fungal burden in kidneys, contrasting sharply with lethal C. albicans infections. Adaptive immune deficiency (Rag1 knockout mice) did not affect K. pintolopesii colonization or host response, indicating that B and T cell-mediated immunity does not restrain this fungus. K. pintolopesii colonization provided no cross-protection against systemic candidiasis further establishing lack of immune activation. These findings demonstrate that K. pintolopesii establishes a benign host-fungal relationship through neutrophil-independent mechanisms, avoiding classical anti-fungal immune activation while maintaining stable gut colonization. Instead, it selectively induces strong type 2 mucosal immune responses, increasing tuft and goblet cell counts and stimulating Th2 and group 2 innate lymphoid cell (ILC2) populations. This immune profile confers notable protection against intestinal nematode infection, demonstrated by reduced Heligmosomoides polygyrus egg counts. Altogether, K. pintolopesii serves as an exemplary model for commensal mycobiota, revealing distinct mechanisms for host tolerance and immune modulation.}, } @article {pmid41444592, year = {2025}, author = {Yan, B and Zhang, K and Ma, ZD and Qin, C}, title = {Comparison of gastric mucosa microbiota in metabolically healthy and unhealthy obesity.}, journal = {Diabetology & metabolic syndrome}, volume = {18}, number = {1}, pages = {30}, pmid = {41444592}, issn = {1758-5996}, support = {2024302006//Science and Technology Development Program of Jinan Municipal Health Commission/ ; }, abstract = {BACKGROUND: Previous studies have established a strong link between intestinal microbiota and metabolism. However, no research has examined the relationship between the gastric microbiome and metabolism status. This study characterizes the gastric microbiome in patients with metabolically healthy obesity (MHO) and compares it with that of patients with metabolically unhealthy obesity (MUO).

METHODS: Gastric microbiota composition was analyzed using deep sequencing of the 5-region (5R) 16 S ribosomal RNA (16 S rRNA) gene.

RESULTS: The gastric microbiota profiles of MHO differed significantly from those of MUO. PICRUSt functional inference revealed distinct microbial metabolic pathways between the groups. PICRUSt analysis identified 30 differentially regulated pathways, with arginine, proline, tryptophan, and phenylalanine metabolism upregulated in MUO. By contrast, DNA repair and recombination proteins, ribosomes, amino acid-related enzymes, and ribosome biogenesis (KEGG Level 3) were upregulated in MHO.

CONCLUSION: This study reveals significant differences in the gastric microbiome between MHO and MUO, highlighting the intricate relationship between microbiota composition and metabolic health. These findings suggest potential microbiome-based therapeutic targets for metabolic disorders.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-025-02075-y.}, } @article {pmid41559963, year = {2020}, author = {Barducci, L and Norton, JC and Sarker, S and Mohammed, S and Jones, R and Valdastri, P and Terry, BS}, title = {Fundamentals of the gut for capsule engineers.}, journal = {Progress in biomedical engineering (Bristol, England)}, volume = {2}, number = {4}, pages = {}, doi = {10.1088/2516-1091/abab4c}, pmid = {41559963}, issn = {2516-1091}, abstract = {The gastrointestinal (GI) tract is a complex environment comprised of the mouth, esophagus, stomach, small and large intestines, rectum and anus, which all cooperate to form the complete working GI system. Access to the GI using endoscopy has been augmented over the past several decades by swallowable diagnostic electromechanical devices, such as pill cameras. Research continues today and into the foreseeable future on new and more capable miniature devices for the purposes of systemic drug delivery, therapy, tissue biopsy, microbiome sampling, and a host of other novel ground-breaking applications. The purpose of this review is to provide engineers in this field a comprehensive reference manual of the GI environment and its complex physical, biological, and chemical characteristics so they can more quickly understand the constraints and challenges associated with developing devices for the GI space. To accomplish this, the work reviews and summarizes a broad spectrum of literature covering the main anatomical and physiological properties of the GI tract that are pertinent to successful development and operation of an electromechanical device. Each organ in the GI is discussed in this context, including the main mechanisms of digestion, chemical and mechanical processes that could impact devices, and GI motor behavior and resultant forces that may be experienced by objects as they move through the environment of the gut.}, } @article {pmid41559789, year = {2026}, author = {Bartsch, M and Hemmelrath, L and Kerlikowsky, F and Bruns, A and Burhop, M and Nebl, J and Greupner, T and Strowig, T and Lesker, TR and Amend, L and Vital, M and Berkemeyer, S and Hahn, A and Müller, M}, title = {Gut microbiome mediates the association between dietary quality and metabolic risk in a heterogeneous adult population.}, journal = {Nutrition & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12986-026-01077-5}, pmid = {41559789}, issn = {1743-7075}, abstract = {BACKGROUND: Diet is a determinant of metabolic health, partly through its effects on the gut microbiome, which influences nutrient metabolism, inflammation, and energy balance. We investigated the mediating role of gut microbiome features in the association between dietary quality and metabolic risk.

METHODS: In this cross-sectional study, we included 269 adults aged 25-76 years with heterogeneous metabolic profiles, BMI ranging from 17.5 to 47.6 kg/m², and fasting glucose levels between 5.6 and 6.9 mmol/L. Dietary quality was assessed using the Healthy Eating Index (HEI-MON), the Planetary Health Diet Index (PHEI-MON), and the alternate Mediterranean Diet Score (aMED), derived from food-frequency questionnaires and three-day food records. Metabolic risk was quantified using a continuous metabolic syndrome score (cMetS) incorporating waist circumference, mean arterial pressure, HDL cholesterol, triglycerides, and fasting glucose. Microbiome composition (16 S rRNA gene sequencing) and predicted SCFA pathways were analyzed using adjusted multiple linear regression, PERMANOVA, and differential abundance analysis. Mediation analyses examined microbial features as potential mediators of the association between diet and metabolic risk.

RESULTS: Higher HEI-MON, PHEI-MON, and aMED were associated with lower cMetS (q < 0.01). Christensenellaceae R7 group and Ruminococcaceae NK4A214 group were enriched with higher dietary quality and lower cMetS (q < 0.1), whereas Lachnoclostridium were associated with lower diet quality and higher cMetS (q < 0.1). The Enterotype Dysbiosis Score (EDS) correlated inversely with dietary quality (PHEI-MON q = 0.04) and positively with cMetS (q = 0.04). Butyrate-synthesis pathways were more abundant in individuals with higher dietary quality (q < 0.05) and inversely associated with cMetS (q < 0.05). Mediation analysis indicated that the Ruminococcaceae NK4A214 group, the Christensenellaceae R7 group, and Lachnoclostridium accounted for up to 16% of the association between diet and metabolic risk.

CONCLUSION: Better dietary quality is associated with lower metabolic risk and positive gut microbiome signatures across taxonomic, functional, and stability-related aspects. Certain taxa statistically mediated these associations, highlighting gut microbiome features that may contribute to observed links between dietary patterns and metabolic health.}, } @article {pmid41559776, year = {2026}, author = {Hu, LZ and Wang, ZJ and Yao, K and Yang, KF and Xu, R and Zhan, XY and Zhou, MS and Jia, H}, title = {Microbial metabolic profiling reshapes NF-κB-mediated immune metabolic network: a new mechanism for CRC development.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-025-07672-z}, pmid = {41559776}, issn = {1479-5876}, support = {No. 82204685//National Natural Science Foundation of China/ ; No. LJKMZ20221795//Department of Education of Liaoning Province/ ; }, } @article {pmid41559696, year = {2026}, author = {Silva, JMM and Azevedo, JLLC and Bezerra, KG and Guilarde, AO and Souza, LCS and Guimarães, RF and Leite, P and Júnior, HM and Gardinassi, LG and Romão, PRT and Fonseca, SG}, title = {Resilient gut microbiome is linked to immune control in HIV-1 infection.}, journal = {Biology direct}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13062-025-00720-0}, pmid = {41559696}, issn = {1745-6150}, support = {2014-50890/5//Institute of Investigation in Immunology- iii-INCT-CNPq/ ; }, } @article {pmid41559539, year = {2026}, author = {Jiang, H and Zeng, W and Huang, J and Pei, Y and Wang, Y and Zhu, P and Yang, F and Zhang, X and Fang, H and Qiu, T and Peng, A and Wang, J}, title = {Gut microbiota composition and functionality are associated with prolactin-secreting pituitary adenoma and serum lipid levels.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04592-2}, pmid = {41559539}, issn = {1471-2180}, support = {82172603//National Natural Science Foundation of China/ ; }, } @article {pmid41559043, year = {2026}, author = {Lin, Y and Li, S and Xu, X and Hu, X and Li, Y and Liang, S and Meng, J and Li, H and Li, Z and Xiong, D and Chen, H and Lai, J and Bao, Y and Liu, Z and Chu, J and Chen, X and Zhang, X and Liu, X and Lee, SY and An, S}, title = {Intermittent fasting inhibits Tp53-driven glioma through gut microbiota-mediated methionine-m[6]A regulation.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68512-2}, pmid = {41559043}, issn = {2041-1723}, abstract = {Intermittent fasting (IF) has emerged as a potential cancer treatment modality, although its tumor-suppressive effects are limited. Glioblastoma (GBM) can be classified into CDKN2A subtype and TP53 subtype. Here, we discover that the efficacy of IF is correlated with tumor subtypes of GBM. IF significantly inhibite GBM progression in mice with the Tp53 GBM model, whereas its inhibitory effect is not significant in the Cdkn2a GBM model. Multi-omics sequencing is performed in the IF-responsive Tp53 GBM mouse model, delineating a comprehensive molecular profiling of IF that including the spatial transcriptome, spatial metabolome, single-cell transcriptome, single-cell RNA methylation, metabolome, and microbiome. Through systematic biological analysis and rescue experiments conducted in IF-responsive Tp53 GBM mice model, we demonstrate that the efficacy of IF is primarily mediated by alterations in the gut microbiota, which subsequently modulate the production of the microbial metabolite methionine sulfoxide. Methionine sulfoxide, by regulating m[6]A modification, inhibits the TGF-β signaling pathway, resulting in suppressing GBM progression. This study proposes a genotype-based hypothesis for the therapeutic effects of IF on tumors, and elucidates the potential RNA modification-related molecular mechanisms underlying the effective suppression of GBM by IF.}, } @article {pmid41559005, year = {2026}, author = {Li, F and Jiao, X and Sun, A and Zheng, Y and Shen, JP and He, JZ and Hu, HW}, title = {Phyllosphere Keystone Beneficial Specialists Enhance Yield in Nutrient Deficiency-Resistant Sorghum Cultivars.}, journal = {Plant, cell & environment}, volume = {}, number = {}, pages = {}, doi = {10.1111/pce.70402}, pmid = {41559005}, issn = {1365-3040}, support = {FT230100158//Australian Research Council/ ; DP240101821//Australian Research Council/ ; 202204041101001//International Cooperation and Exchanges of Shanxi province/ ; 42307168//National Natural Science Foundation of China/ ; }, abstract = {The phyllosphere, the aboveground interface between plant leaves and their microbial residents, plays a vital yet underappreciated role in crop productivity. While root- and soil-associated microbiomes are well-studied, the ecological assembly and yield-related effects of host-mediated phyllosphere microbial communities remain largely understudied, particularly under field conditions. This study investigates the phyllosphere microbiomes of sorghum cultivars resistant and susceptible to nutrient deficiency, focusing on how host genotype mediates microbial community assembly, keystone enrichment, and yield outcomes. The β-diversity of phyllosphere microbiomes differs significantly between resistant and susceptible cultivars, with resistant lines also showing more modular co-occurrence networks enriched in keystone taxa. These cultivars supported a higher abundance of keystone beneficial specialists (KBS), predominantly affiliated with Bacteroidia and Bacilli, and their abundance was positively correlated with yield. In contrast, susceptible cultivars exhibited lower and more taxonomically dispersed KBS, with a negative correlation between KBS and yield. Structural equation modeling suggested that while soil properties consistently promoted yield across cultivars, the impact of KBS on yield was genotype-dependent. These findings reveal a host-driven microbial mechanism linking phyllosphere composition to yield performance and highlight KBS as potential targets for microbiome-informed breeding or foliar microbial applications to improve crop productivity in sustainable systems.}, } @article {pmid41558879, year = {2026}, author = {Chen, Q and Liu, X and Jiang, ZH}, title = {Bile acids as gatekeepers: Orchestrating gut-liver axis for metabolic and immune balance.}, journal = {Hepatobiliary & pancreatic diseases international : HBPD INT}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hbpd.2026.01.001}, pmid = {41558879}, issn = {1499-3872}, abstract = {Bile acids (BAs) represent the terminal products of cholesterol catabolism and are integral to a wide range of physiological processes. The maintenance of BAs homeostasis is essential for human health, with disruptions being implicated in various liver and intestinal disorders. The gut-liver axis, a bidirectional communication network connecting multiple organ systems, plays a crucial role in preserving both metabolic and immune homeostasis. Recent evidence suggests that BAs are key modulators within this axis, influencing intestinal barrier function, immune responses, and the composition of the gut microbiome. This review synthesizes recent advances in our understanding of BAs, including their origins, circulation within the gut-liver axis, and diverse roles in physiology, thereby highlighting the critical functional significance of this BAs-mediated network.}, } @article {pmid41558673, year = {2026}, author = {Al-Andoli, M and Schoch, S and Markovic, A and Mühlematter, C and Beaugrand, M and Jenni, OG and Liamlahi, R and Walser, JC and Nielsen, D and Kurth, S}, title = {Stool Dynamics and the Developing Gut Microbiome During Infancy.}, journal = {Journal of biological rhythms}, volume = {}, number = {}, pages = {7487304251407313}, doi = {10.1177/07487304251407313}, pmid = {41558673}, issn = {1552-4531}, abstract = {The infant gut microbiome is a dynamic ecosystem, and it is key to early development, immune maturation, and overall health. Recent insights reveal that the gut microbiota undergoes changes across the 24-h day, raising the possibility that it may act as a "zeitgeber," supporting the host's sleep-wake organization. Despite its importance, timing factors influencing microbiome composition are poorly understood, limiting its use as a health indicator. This study investigates the relationship between stool dynamics (defecation interval, time of sampling), sleep pressure (interval since last sleep), meal timing, and gut microbial composition. Stool samples from 198 healthy infants, aged 3 to 31 months, were analyzed to assess microbial diversity, richness evenness, and abundance. Our findings reveal that longer intervals between bowel movements are associated with increased microbial diversity, evenness, and richness. Stool timing is associated with shifts in microbial composition, especially in younger infants, indicating diurnal microbial fluctuations to become more stable as infants mature. Longer periods of wakefulness were associated with increased microbial diversity in early infancy, although this effect appeared to diminish with age. Feeding schedules had limited effects on the gut microbiome. Longer fasting before sampling showed no significant associations with most microbial parameters, except for a positive association with microbial richness. At the phylum level, results indicate that infant gut microbial composition is influenced by behavior and physiology. Longer intervals between bowel movements were associated with shifts in bacterial abundance, with Proteobacteria decreasing and Actinobacteria increasing. In addition, later stool sampling times revealed higher Actinobacteria levels, and longer fasting was associated with reduced Bacteroidetes. Sleep pressure showed a trend effect with Firmicutes displaying a slight decrease in infants who had been awake longer. Our findings underscore the importance of time-based factors on infant gut microbiome composition.}, } @article {pmid41558536, year = {2026}, author = {Kasuma, N and Fitri, H and Wulandari, RW and Ernesto, G and Juwita, DR and Effendi, MDS and Wirza, TR}, title = {Salivary Microbiome Differences in Stunted and Healthy Children: A Metagenomic Analysis.}, journal = {European journal of dentistry}, volume = {}, number = {}, pages = {}, doi = {10.1055/s-0045-1814094}, pmid = {41558536}, issn = {1305-7456}, abstract = {This study aimed to compare the composition and diversity of the salivary microbiome in stunted and nonstunted children using 16S rRNA gene sequencing to explore the relationship between nutritional status and oral microbiota.A total of 20 saliva samples were collected from children aged 6 to 10 years, comprising two groups: stunted (n = 10) and healthy controls (n = 10). Deoxyribonucleic acid was extracted, and the V3-V4 region of the 16S rRNA gene was amplified and sequenced. Bioinformatics analysis included taxonomic assignment, calculation of relative abundance, α diversity (using Shannon and Simpson indices), β diversity (UniFrac-based principal coordinate analysis and permutational multivariate analysis of variance [PERMANOVA]), and differential abundance testing using the Mann-Whitney U test.The dominant phyla in both groups were Proteobacteria, Firmicutes, and Bacteroidota, with Proteobacteria being more prevalent in the stunted group. At the genus level, Neisseria and Veillonella were more abundant in stunted children. Notably, Veillonella was significantly elevated in the stunted group (28.6%) compared with controls (14.9%, p = 0.0376). Alpha diversity indices revealed a higher diversity trend in the stunted group, although this difference was not statistically significant (Shannon, p = 0.130; Simpson, p = 0.762). Beta diversity analysis revealed no considerable clustering between groups (PERMANOVA p > 0.05), indicating moderate interindividual variability but no clear group separation.Children with stunted growth demonstrated distinct microbial signatures in their salivary microbiota, particularly in the increased abundance of Proteobacteria and Veillonella, suggesting a potential link between chronic undernutrition and oral microbial dysbiosis. These findings underscore the need for additional studies to investigate the impact of nutritional status on oral and systemic health through the microbiome axis.}, } @article {pmid41558386, year = {2026}, author = {Yinhang, W and Jing, Z and Zhanbo, Q and Jiang, L and Qing, Z and Qi, Z and Yin, J and Jianwen, S and Wei, W and Shuwen, H}, title = {Establishment of threshold of human gut microbes and risk assessment system for colorectal cancer.}, journal = {Computers in biology and medicine}, volume = {203}, number = {}, pages = {111484}, doi = {10.1016/j.compbiomed.2026.111484}, pmid = {41558386}, issn = {1879-0534}, abstract = {BACKGROUND: Being involved in the occurrence of colorectal cancer (CRC), gut microbes are potential targets for early diagnosis of CRC. Defining the threshold of these characteristic bacteria could provide a basis for the clinical application of microorganisms as novel tumor markers for CRC.

OBJECTIVE: To sort out and define the threshold of related bacteria and the ecological characteristics of gut bacteria.

METHODS: A total of 8021 fecal samples from healthy people and 497 from CRC patients in the public database were collected to analyse the reference range. CRC-related bacteria and gut microbial characteristics were screened by literature review and analysed. CRC related bacteria and 5-95 % medians of gut microbial characteristics in healthy populations were used as reference value. 16S rRNA Miseq sequencing (175 CRC patients and 175 healthy people) and PacBio sequencing (200 CRC patients and 200 healthy people) were used to detect stool DNA sequence. The community composition of gut microbiota between CRC and healthy subjects was plotted; the species differences were analysed by Lefse analysis. R studio software was used to analyse CRC-related bacteria and gut microbial characteristics.

RESULTS: A total of 218 CRC-associated bacteria and 15 gut microbial characteristics, such as enterotypes and Firmicutes/Bacteroidetes ratio, were reviewed and analysed. A 5-95 % threshold for these 218 CRC-associated bacteria and 15 gut microbiome signatures was developed to provide criteria for the normal range of gut bacteria. The CRC evaluation intelligent system software was developed and it could quickly calculate the value of 218 CRC related bacteria and 15 gut microbial characteristics using sequencing data, and assess whether they are within the threshold. And this software has the function of predicting CRC risk. The accuracy of CRC risk assessment ranged from 89.14 % to 91.50 %.

CONCLUSION: We established, for the first time, quantitative thresholds for CRC-associated bacteria and have driven advances in microbial risk prediction for CRC.}, } @article {pmid41558353, year = {2026}, author = {Wang, L and Liang, Z and Liang, J and Ge, L and Zou, L and Fan, Y and Xu, Q and Zhang, Y and Lv, B and Zhao, K and Wu, Y and Li, P}, title = {Multi-omics reveals taxonomic and functional adaptations of soil microbiota to Bt toxin exposure.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141175}, doi = {10.1016/j.jhazmat.2026.141175}, pmid = {41558353}, issn = {1873-3336}, abstract = {Bt toxins released from transgenic Bt plants exhibit biocidal activity and are considered exogenous environmental hazards in soil ecosystems. Here, we employed an integrated multi-omics approach to systematically characterize the taxonomic and functional regulatory mechanisms and adaptive strategies of soil microorganisms in response to Bt toxin exposure across a gradient of concentrations. Our findings demonstrate that different application amounts of Bt toxins significantly influenced both toxin persistence in soil and the soil nutrition multifunctionality (SNM) index. Notably, none of the tested Bt toxin concentrations exerted adverse effects on the diversity or complexity of soil microbial communities. Correlation analysis revealed that SNM was significantly positively associated with bacterial α-diversity (Sobs and Shannon indices) and microbial network edge numbers, but showed no such association with fungal communities, indicating distinct response patterns between soil bacteria and fungi to Bt toxin exposure. Divergent responses were also observed in the taxonomic and functional diversity of microbial communities under Bt toxin addition. Comparative transcriptomic analysis between Bt500_100 and Bt0_100 samples revealed that microorganisms downregulated energy metabolism pathways while upregulating genes associated with cell motility and environmental adaptation. These results collectively indicate that soil microorganisms employ adaptive metabolic strategies to mitigate nutrient limitation induced by the declining bioavailability of Bt toxin in soil environments.}, } @article {pmid41558335, year = {2026}, author = {Duell, EB and Loecke, TD and Hansen, PM and Koziol, L and Ramos, RJ and Sikes, BA and Bever, JD and McKenna, TP}, title = {Functional consequences of land-use history: Plant community and soil microbiome mediation of nutrient loss, soil aggregate stability, and soil erosion.}, journal = {The Science of the total environment}, volume = {1014}, number = {}, pages = {181311}, doi = {10.1016/j.scitotenv.2025.181311}, pmid = {41558335}, issn = {1879-1026}, abstract = {Alterations in land-use practices pose serious threats to biodiversity and ecosystem functioning, affecting ecosystem services such as soil stability and nutrient cycling. Conversely, the collective interactions between plants, soils, and associated soil microbiomes play a critical role in the maintenance of various ecosystem services. We found evidence of the degradation of soil microbiomes with land-use, as microbial composition, measured by amplicon sequencing targeting bacteria (16S), fungi (ITS), and AM fungi (LSU), differed between unplowed prairies, post-agricultural grasslands, and annual agricultural fields across Kansas (p = 0.003, 0.001, and 0.01, respectively). We then tested functional impacts on soil ecosystem services of the soil microbiome differences by conducting a greenhouse experiment that manipulated full-factorial combinations of soil microbiome composition of land-use history and plant assemblage. Specifically, we examined soil detachment, water-stable macroaggregates, and nitrate leaching through the soil profile, as well as plant and AM fungal biomass. Soil microbiomes, plant composition, and their interactions had strong influences on every metric of ecosystem function. Notably, native plant communities were more sensitive to degradation of the microbiome. Furthermore, living soil microbiomes, regardless of land-use history, reduced soil detachment, promoted formation of water-stable macroaggregates, and facilitated greater nitrate retention, highlighting the importance of soil microbiomes for many physical and biogeochemical processes. Moreover, the realized functional benefits of microbiome composition depended on the plant community. These results highlight the complexities of plant-soil-microbial interactions in the context of land-use histories, displaying the importance of intact microbiomes, especially AM fungi, in mitigating environmental consequences of agricultural intensification.}, } @article {pmid41558287, year = {2026}, author = {Yan, S and Chen, S and Shen, T and Zeng, S and Wang, J and Zhang, Z and Li, B and Zhou, H and Long, Y and Zhang, D}, title = {Association between environmental exposure, gut microbiome and risk of gestational diabetes mellitus in Guangzhou, China.}, journal = {Ecotoxicology and environmental safety}, volume = {310}, number = {}, pages = {119747}, doi = {10.1016/j.ecoenv.2026.119747}, pmid = {41558287}, issn = {1090-2414}, abstract = {Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication. Both environmental changes and gut dysbiosis have been associated with increased risk of GDM. While environmental exposures may influence gut microbiome, the exact mechanisms linking these factors to GDM risk remain poorly understood. The study aimed to investigate the relationships between environmental exposures, gut microbiome and GDM risk. A population-based cohort study was conducted in Guangzhou, China from January 2017 to September 2017, enrolling 260 women with GDM and 508 normal pregnancies. Ambient pollution and meteorological exposures during different pregnancy windows were estimated for each participant. We identified the changes in gut microbiome characteristics related to environmental exposures. Temperature exposure during the preconception period was most strongly associated with alterations in the gut microbiome observed during the second trimester, particularly in women who developed GDM. Multivariate logistic regression and interaction analyses showed potential relationships between temperature exposure, gut microbiome and GDM risk. These findings contribute to the understanding of the relationship between environmental exposures, gut microbiome and GDM, providing insights into public health strategies to shield pregnant women from the detrimental effects of environmental exposures.}, } @article {pmid41558030, year = {2026}, author = {Fan, C and Hayase, T and Chang, CC and Glover, IK and Flores, II and McDaniel, LK and Ortega, MR and Sanchez, CA and El-Himri, RK and Brown, AN and Karmouch, JL and Jamal, MA and Ahmed, SS and Halsey, TM and Jin, Y and Tsai, WB and Prasad, R and Enkhbayar, A and Mohammed, A and Schmiester, M and Damania, AV and Ajami, NJ and Wargo, JA and Peterson, CB and Rondon, G and Al-Juhaishi, T and Alousi, AM and Molldrem, JJ and Champlin, RE and Shpall, EJ and Martens, E and Arias, CA and Jenq, RR and Hayase, E}, title = {Fecal carbohydrate-degrading bacteria are associated with reduced incidence of lower gastrointestinal GVHD.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2025016780}, pmid = {41558030}, issn = {2473-9537}, abstract = {Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of allo-HSCT patient stool (n = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate degrading functionality of these bacteria, we investigated gene abundances for Carbohydrate-Active enZyme (CAZyme) and found that Parabacteroides merdae, Parabacteroides distasonis and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop LGI-GVHD compared to those who did. The specific gene abundances of xylosidase, which contribute to the degradation of xylose-containing polysaccharides, were significantly associated with reduced risk of LGI-GVHD. Together, these findings show the importance of carbohydrate degrading functionality of putative beneficial bacteria in mediating risk of LGI-GVHD.}, } @article {pmid41557647, year = {2026}, author = {Alvendal, C and Hasselrot, T and Balduck, M and Edfeldt, G and Schuppe-Koistinen, I and Brauner, A and Altman, D and Broliden, K and Bohm-Starke, N}, title = {Vaginal chlorhexidine gluconate versus fluconazole for recurrent vulvovaginal candidiasis: A randomized noninferiority trial.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0340862}, pmid = {41557647}, issn = {1932-6203}, mesh = {Female ; Humans ; *Candidiasis, Vulvovaginal/drug therapy/microbiology ; *Chlorhexidine/analogs & derivatives/administration & dosage/therapeutic use/adverse effects ; *Fluconazole/administration & dosage/therapeutic use/adverse effects ; Adult ; *Antifungal Agents/therapeutic use/administration & dosage ; Candida albicans/drug effects ; Vagina/microbiology/drug effects ; Recurrence ; Young Adult ; Administration, Intravaginal ; Microbiota/drug effects ; Treatment Outcome ; Biofilms/drug effects ; }, abstract = {BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is a common condition characterized by frequent relapses, often without a clearly identifiable cause. Fluconazole (FLZ) is the standard treatment but concerns about emerging resistance and drug interaction highlight the need for alternative therapies. Chlorhexidine gluconate (CHG), known for its antifungal and biofilm-disrupting properties, has been proposed as a potential alternative.

OBJECTIVE: To evaluate the efficacy, tolerability, and microbiome impact of a vaginal CHG formulation compared to oral FLZ in the treatment of RVVC caused by Candida albicans.

METHODS: An open label randomized non-inferiority trial was conducted to compare vaginal CHG and FLZ treatments. Primary outcome was negative cultures for C. albicans. Resistance profiles and changes in the vaginal microbiome composition were also assessed.

RESULTS: The study was terminated early due to local irritation associated with CHG and the study design was transitioned into a pilot study. CHG treatment showed comparable efficacy to FLZ in clearing C. albicans infections and preventing recurrences, although the sample size was limited. All 11 participants in the FLZ group cleared the infection after one week treatment, compared to 9 out 11 in the CHG group. No harmful changes to the vaginal microbiome were observed in the CGH or FLZ group. FLZ promoted a shift toward Lactobacillus crispatus dominance, unlike CHG. Notably, 16% of C. albicans isolates exhibited reduced susceptibility or resistance to FLZ.

CONCLUSION: Due to the limited number of participants, we cannot conclusively determine whether CHG is non-inferior to FLZ in terms of efficacy for clearing acute C. albicans infections or preventing recurrences. While the current CHG formulation caused local irritation and is not suitable for clinical use, its antifungal and biofilm-inhibiting properties remain promising. Further development of less irritative CHG formulations may offer a valuable alternative for RVVC treatment, particularly in the context of rising FLZ resistance.}, } @article {pmid41556698, year = {2026}, author = {Cao, F and Liu, A and Tong, J and Guo, C and Zhang, H and Pang, Y and Tang, K and Yu, Q and Guo, J}, title = {Integrative multi-omics analysis reveals gut-skin axis mechanisms and novel therapeutic target GALE in atopic dermatitis.}, journal = {mSystems}, volume = {11}, number = {1}, pages = {e0140325}, pmid = {41556698}, issn = {2379-5077}, support = {82074443//National Natural Science Foundation of China/ ; WXLH202403001//Sichuan Provincial central of Traditional Chinese Medicine/ ; 24ZYZYTS0310//Central and Local Goverments Lead the Project/ ; }, mesh = {Humans ; *Dermatitis, Atopic/genetics/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome ; Molecular Docking Simulation ; *Skin/metabolism/pathology ; Molecular Dynamics Simulation ; Female ; Male ; Methotrexate/pharmacology ; Adult ; Multiomics ; }, abstract = {UNLABELLED: The gut-skin axis represents a critical but poorly understood pathway in atopic dermatitis (AD) pathogenesis. This study aimed to establish causal relationships between gut microbiota and AD risk while identifying key molecular bridges and therapeutic targets. We integrated multiple analytical approaches, including single-cell RNA sequencing analysis of skin biopsies from five AD patients and four healthy controls, intercellular communication network analysis, pseudotime trajectory inference, reverse drug prediction, molecular docking, and molecular dynamics simulations. Analysis revealed increased keratinocyte heterogeneity and enhanced immune cell communication in atopic dermatitis (AD) samples. Intersection analysis between gut microbial metabolite-associated genes and skin pathology-related genes identified seven key bridging genes (AKR1C2, GALE, GGH, NR4A1, PLA2G4B, TYMS). Functional annotation indicated that these genes are primarily involved in vitamin precursor metabolism, suggesting that the Eubacterium eligens group influences AD pathogenesis mainly through vitamin precursor-mediated pathways that regulate systemic immune responses. Pseudotime trajectory analysis demonstrated dynamic temporal gene expression patterns during disease progression. Molecular docking revealed an unexpectedly high-affinity binding between methotrexate and GALE (binding energy = -10.4 kcal/mol), which exceeded its binding affinity for the classical target TYMS (-7.5 kcal/mol). Molecular dynamics simulations further confirmed the stable binding conformation of the protein-ligand complexes. This study provides mechanistic insights into how the Eubacterium eligens group influences atopic dermatitis through vitamin precursor-mediated systemic immune modulation and identifies GALE as a novel therapeutic target. The findings provide mechanistic insights into the gut-skin axis and support developing precision medicine approaches integrating microbiome interventions with targeted pharmacotherapy for AD management.

IMPORTANCE: Genetic-level evidence of gut microbiota causality in atopic dermatitis: this study established a causal relationship between specific gut microbiota and the risk of atopic dermatitis at the genetic level, providing strong genetic evidence for the "gut-skin axis" theory. GALE is identified as a novel therapeutic target with redefined methotrexate mechanism: molecular docking study unexpectedly found that GALE binding affinity of MTX was significantly higher than that of its classical target TYMS, suggesting that GALE may be an important but previously unrecognized target of MTX in the treatment of AD. Multi-omics integration framework reveals increased keratinocyte heterogeneity: integrating single-cell RNA sequencing and computational pharmacology provided a cellular and molecular basis for understanding the characteristics of chronicity and recurrence of the disease.}, } @article {pmid41556662, year = {2026}, author = {Zhang, N and Atoni, E and Nyaruaba, R and Kibaba, P and Shadrack, K and Wang, F and Agwanda, B and Zheng, Z and Dai, J and Yuan, Z and Xia, H}, title = {Host and geography shape microbial communities in Kenyan mosquitoes: insights from metatranscriptomics.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0142725}, doi = {10.1128/msystems.01427-25}, pmid = {41556662}, issn = {2379-5077}, abstract = {Mosquitoes harbor diverse microbial communities that influence their potential to transmit pathogens. However, the ecological drivers shaping these microbiomes, particularly in under-sampled regions like Africa, remain poorly resolved. We conducted a large-scale metatranscriptomic survey of 3,940 Aedes and Culex mosquitoes from diverse ecological zones across Kenya. Our analyses revealed that viruses dominated the overall transcriptome, while bacteria exhibited the greatest taxonomic richness. Geographic location emerged as the primary driver of microbial community structure, whereas host genus identity shaped virome diversity at local or city-level scales. Culex mosquitoes harbored higher viral richness, particularly in coastal regions, while Aedes supported more diverse bacterial assemblages. Microbial co-occurrence networks exhibited distinct topologies across hosts: Culex networks featured cross-domain interactions and viral keystone taxa, whereas Aedes networks were more cohesive and robust, centered on bacterial hubs. We identified 102 distinct viruses from 24 families, including 31 putative novel RNA viruses. Segment-resolved phylogenies revealed cryptic clades within Bunyavirales, Picornavirales, and other lineages. Collectively, our findings highlight the scale-dependent influences of geography and host identity on mosquito microbiomes in East Africa and demonstrate the utility of metatranscriptomics in uncovering hidden microbial diversity and ecological interactions. These insights provide a foundation for ecologically informed arthropod vector surveillance and microbiome-based intervention strategies.IMPORTANCEMosquitoes are more than just flying syringes; they are complex ecosystems hosting a variety of microbes. Understanding what shapes this microbial world inside mosquitoes is key to developing new control strategies. Our study of nearly 4,000 mosquitoes from Kenya reveals that where a mosquito lives matters most for its overall microbial makeup, but its genus dictates which viruses it carries. We discovered that different mosquito types have distinct microbial social networks: one type has a fragile network centered on viruses, while the other has a resilient network built around bacteria. This means that strategies to disrupt disease transmission by targeting mosquito microbes may need to be tailored to a specific mosquito genus. Our work provides a map of these microbial ecosystems, highlighting potential new viruses and offering insights for future public health surveillance and interventions.}, } @article {pmid41556651, year = {2026}, author = {Nguyen, VTT and König, S and Formes, H and Al Taleb, Z and Steinert, F and Bufe, B and Eggert, S and Stegmüller, S and Schermer, Y and Richling, E and Kins, S and Reinhardt, C and Endres, K}, title = {Monocolonization with Bacteroides thetaiotaomicron exerts region-specific effects on Alzheimer's disease-related traits in the murine brain.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0074425}, doi = {10.1128/spectrum.00744-25}, pmid = {41556651}, issn = {2165-0497}, abstract = {UNLABELLED: Bacteroides thetaiotaomicron (B. theta) dominates the gut microbiome of most mammals. This strictly anaerobic gut symbiont colonizes the mucus layer of host intestinal epithelial cells in both healthy and diseased conditions. Reduced neuronal and vagal afferent innervation observed in germ-free mice was found to be normalized by colonization with B. theta. In addition to deficits in gut innervation, germ-free mice have been reported to have reduced neuronal number and neurotransmitter levels in the brain. Here, we investigated the hallmarks of Alzheimer's disease (AD) in the brain of germ-free mice compared to mice mono-colonized with B. theta. We analyzed the number of mature neurons, neurotransmitter transporters, amyloid precursor protein processing, and inflammatory status in three brain regions: the hippocampus, prefrontal cortex (PFC), and cerebellum. The hippocampus and the PFC are regions thought to be highly susceptible to pathogenesis, whereas the cerebellum is thought to be only mildly affected. Interestingly, secretion of neuroprotective sAPPα decreased in hippocampus and remained unchanged in PFC, while levels were increased in the cerebellum in response to bacterial colonization. In addition, the number of presynaptic boutons increased in the hippocampus but remained unaffected in the cerebellum.

IMPORTANCE: The gut microbiome has been reported to not only contribute to diseases of the gastrointestinal tract but also to interfere with and potentially even initiate diseases of other organ systems, such as the brain. Interference with the gut microbiome has been shown to elicit cognitive changes, for example, in rodent models of AD. Colonization with the common gut microbe B. theta not only affected the brain per se in our study but also showed specific brain region-dependent effects related to AD. This implies that evaluating the impact the microbiome might have on brain disorders needs a much more detailed investigation in the future with spatial and also potentially time resolution.}, } @article {pmid41556507, year = {2026}, author = {Cheng, S and Tang, X and Huang, X and Li, Y and Huang, S and He, D and Moreno-Jiménez, E and Xu, J and Rillig, MC and Dai, Z and Delgado-Baquerizo, M}, title = {Stressor Combinations Shift Soil Microbial Communities From Rare to Unknown Taxa and Alter Genomic Strategies.}, journal = {Global change biology}, volume = {32}, number = {1}, pages = {e70704}, doi = {10.1111/gcb.70704}, pmid = {41556507}, issn = {1365-2486}, support = {41721001//National Natural Science Foundation of China/ ; 2019YFC1803704//National Key Research and Development Program of China/ ; +226-2024-00029//The Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Soil Microbiology ; *Microbiota ; Metagenomics ; *Metagenome ; *Stress, Physiological ; Biodiversity ; *Climate Change ; Ecosystem ; Bacteria/genetics/classification ; }, abstract = {Soil microorganisms constitute the largest portion of Earth's biodiversity. However, soil microorganisms are also highly sensitive to on-going global change, and the influence of an increasing number of stressors on common, rare, and unknown taxa across large environmental gradients remains virtually unknown. Here, we combined a large-scale spatial field survey across multiple different ecosystems and found that the diversity and abundance of soil rare taxa were significantly reduced under high environmental stressor number (i.e., a high number of stressors passing a 75% stressor threshold). Strikingly, the abundance of unknown soil taxa and unknown genes increased with increasing environmental stress number. We further identified the metagenome-assembled genomes (MAGs) that were considered as relatively common taxa using metagenomics. Compared to 9% of negative responders, 32% of common MAGs were resistant or positively responsive to multiple stress, displaying a reduced potential for cellular processes and an enhanced potential for environmental, genetic, and metabolic processes. Our study suggests that as stress increases, we would have less rare, but more unknown microorganisms and unique genomes of resistant common taxa, suggesting major changes in the soil microbiome in a world subjected to multiple global change stressors.}, } @article {pmid41556455, year = {2026}, author = {Zhang, H and Yan, X and Hou, Y and Ou, C and Luo, S and Liu, C and Li, Z and Zhang, G and Chen, T}, title = {Polyphenols Nonmonotonically Modulate the Inulin-Driven Gut Microbial Network In Vivo.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13003}, pmid = {41556455}, issn = {1520-5118}, abstract = {The interaction between dietary fiber and polyphenols in modulating gut microbiota is complex and not fully understood. This study investigated how the polyphenol structure (complex tannic acid vs simple ferulic acid) and dosage (20-320 mg/kg) modulated the gut microbiota and metabolic profile shaped by a high-dose inulin diet. Our results showed that all treatments were well-tolerated with no observed adverse health outcomes. While polyphenol addition did not cause large-scale shifts in overall microbiota composition, it fundamentally restructured the underlying microbial network. Each polyphenol established a distinct hub species, with Oscillospira for tannic acid and Allobaculum for ferulic acid. This restructuring was accompanied by nonmonotonic dose-response changes in short-chain fatty acid production, an effect attributed to a shifting balance between the polyphenols' trophic and antimicrobial activities. Our findings demonstrate that in a high-fiber context, polyphenols act as subtle modulators, rather than primary drivers, whose structure and dose critically shape the microbiome function.}, } @article {pmid41556347, year = {2026}, author = {}, title = {Correction to: HLRMDB: a comprehensive database of the human microbiome with metagenomic assembly, taxonomic classification, and functional annotation by analysis of long-read and hybrid sequencing data.}, journal = {Nucleic acids research}, volume = {54}, number = {2}, pages = {}, doi = {10.1093/nar/gkag014}, pmid = {41556347}, issn = {1362-4962}, } @article {pmid41556141, year = {2026}, author = {Dellisanti, W and Zhang, Q and Bollati, E and Seveso, D and Ferrier-Pagès, C and Younis, C and Camp, EF and Kühl, M}, title = {Interactive effects of warming and iron supplementation on O2 dynamics, trace metal content, and microbial diversity within different compartments of two Mediterranean corals.}, journal = {Biology open}, volume = {15}, number = {1}, pages = {}, doi = {10.1242/bio.062357}, pmid = {41556141}, issn = {2046-6390}, support = {101062810//European Union/ ; GBMF9206//Gordon and Betty Moore Foundation/ ; 202207940005//China Scholarship Council/ ; //European Union, Gordon and Betty Moore Foundation/ ; }, mesh = {*Anthozoa/metabolism/microbiology/physiology ; Animals ; *Iron/metabolism ; *Oxygen/metabolism ; *Microbiota ; *Trace Elements/metabolism/analysis ; *Global Warming ; Mediterranean Sea ; Symbiosis ; Temperature ; Biodiversity ; }, abstract = {Mediterranean corals living in coastal habitats are subjected to natural fluctuations in temperature and nutrient availability, including substantial iron (Fe) inputs via terrestrial runoff (up to 14.5 nM). While Fe is essential for coral and symbiont metabolism, the assimilation rate, physiological thresholds, and spatial allocation of Fe within coral compartments, and its interactive effects with warming, remain poorly understood. Here, we provide the first characterization of oxygen (O2) dynamics, trace metal content, and microbial community composition in two Mediterranean corals, Cladocora caespitosa and Eunicella singularis, exposed to chronic warming (18-24°C) and Fe(III) supplementation (20 nM day-1). We show that although these corals are not Fe-limited, increased temperature enhanced the Fe uptake in the algal symbionts of C. caespitosa. In C. caespitosa, Fe supplementation reduced the O2 availability within the gastrovascular cavity (GVC) and altered the composition and diversity of GVC microbial communities. In E. singularis, interactive effects of Fe and warming reduced GVC O2 availability within the GVC, and warming increased metal content, while the microbiome resembled the surrounding seawater. These intraspecific differences in the sensitivity of the coral holobiont to warming and Fe supplementation could have important implications for the resilience of Mediterranean corals to ongoing climate stress, underscoring the importance of considering coral compartments in ecophysiological research.}, } @article {pmid41556096, year = {2026}, author = {Aguirre Morgado, NP and Pereira Suárez, AL and Chabay, P and Peña Rodríguez, M and Amarillo, ME and Mangiaterra, T and Bueno Urquiza, L and Rubio Sánchez, AX and Vega Magaña, N}, title = {Tonsillar Microbial Signature of Fusobacterium nucleatum Associated With Epstein-Barr Virus Latency.}, journal = {Journal of medical virology}, volume = {98}, number = {1}, pages = {e70808}, doi = {10.1002/jmv.70808}, pmid = {41556096}, issn = {1096-9071}, support = {//PROINPEP/ ; //PROSNII/ ; //PROAC/ ; }, mesh = {Humans ; *Fusobacterium nucleatum/genetics/isolation & purification/classification ; *Palatine Tonsil/microbiology/virology/pathology ; *Herpesvirus 4, Human/physiology ; Male ; Female ; Child ; *Virus Latency ; *Epstein-Barr Virus Infections/virology/microbiology ; Child, Preschool ; *Microbiota ; *Fusobacterium Infections/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Epstein-Barr virus (EBV) acquired in childhood is asymptomatic, with the tonsils as the entry site to infect B lymphocytes and establish latency. Little is known about whether the microbiota influences EBV persistent infection. We aimed to characterize the tonsil microbiome with different EBV latency types. A cohort of 60 children with tonsillar hyperplasia were included. EBV latency types (0/I/II/III) and lytic phase were determined by immunohistochemistry. 16S NGS of lymphoid tonsillar tissue was carried out with the Illumina platform. Bioinformatic analysis was carried out with QIIME2 2023.2 software and the R studio packages Phyloseq and DESeq 2. Absolute quantification of Fusobacterium nucleatum and its subspecies was conducted using qPCR. A minor α-diversity was observed in the latency III group (p < 0.0014). Therefore, the reference employed for differential abundance analysis was the latency III group. Latency III group was characterized by Fusobacterium when compared with non-infected (LFC = 43.81, p = 2.03E-10), latency 0 (LFC = 23.20, p = 2.16E-05); latency I (LFC = 23.21, p = 1.36E-07), and latency II (LFC = 38.03, p = 7.36E-19). In contrast, Prevotella histicola was decreased (LFC = -26.06, p = 0.0004). Latency group III with lytic phase was characterized by Fusobacterium (LFC = 26.74, p = 5.30E-05). Fusobacterium nucleatum subspecies vicentii had a higher copy number within latency group III (p = 0.020). We found that a microbiome signature in lymphoid tonsillar tissue is related to EBV infection, where Fusobacterium nucleatum subspecies could play a crucial role in latency III and the lytic phase of EBV. This study provides the first evidence that the tonsil microbiome varies with EBV stages, a finding relevant to EBV-associated diseases.}, } @article {pmid41555920, year = {2025}, author = {Furlan, É and Polizel, GHG and Fernandes, AC and Prati, BCT and Pombo, GDV and Ramírez-Zamudio, GD and Fukumasu, H and Santana, MHA}, title = {The influence of prenatal nutrition on ruminal microbiome of beef cattle.}, journal = {Frontiers in genetics}, volume = {16}, number = {}, pages = {1708543}, pmid = {41555920}, issn = {1664-8021}, abstract = {INTRODUCTION: Maternal nutrition is recognized for inducing long-lasting effects on offspring performance during postnatal life. However, little is known about its potential role in modulating the ruminal microbiota during fetal development, as rumen colonization has traditionally been assumed to occur only at birth. This study aimed to evaluate the long-term effects of maternal nutrition during gestation on the offspring's ruminal microbiota in postnatal life.

METHODS: The experimental design comprised 28 Nellore bulls, offspring of a single sire and born to primiparous heifers. Dams were assigned to two groups and received either mineral supplementation (Control; n = 14; 0.3 g/kg BW) or protein-energy supplementation (Supplemented; n = 14; 5 g/kg BW) throughout gestation, from conception to calving. Calves from both groups were managed identically from birth to slaughter. At the finishing phase, ruminal fluid samples were collected from 10 bulls per treatment. The V4 region of the 16S rRNA gene was sequenced, and amplicon sequence variants (ASVs) were identified using DADA2 and phyloseq for microbial diversity and taxonomic analysis. Pathway over-representation analysis was also conducted using MicrobiomeProfiler.

RESULTS AND DISCUSSION: Maternal nutrition resulted in modest yet significant alterations in the ruminal microbial communities of the offspring. The Supplemented group exhibited higher relative abundance of Fibrobacter and Prevotellaceae UCG-003, with reduced abundance of Xylanibacter. Pathway analysis revealed enrichment of starch and sucrose metabolism, along with modulation of amino acid biosynthesis and nitrogen metabolism, suggesting potential improvements in microbial protein synthesis and nitrogen utilization. In conclusion, maternal nutrition during gestation has long-term effects on the offspring's ruminal microbiota, influencing specific bacterial taxa and metabolic pathways linked to carbohydrate metabolism and nutrient utilization.}, } @article {pmid41555705, year = {2026}, author = {Fontaine, F and Turjeman, S and Haib, M and Collado, MC and Callens, K and Koren, O}, title = {Programming the Infant Gut: How Maternal and Early Life Nutrition Shape the Infant Microbiome and Long-term Health-A Narrative Review.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {2}, pages = {e70385}, pmid = {41555705}, issn = {1613-4133}, support = {//Spanish Ministry of Science and Innovation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Female ; Infant ; *Maternal Nutritional Physiological Phenomena ; Pregnancy ; *Infant Nutritional Physiological Phenomena ; Breast Feeding ; Infant, Newborn ; Diet ; }, abstract = {Childhood malnutrition, including undernutrition, obesity, and micronutrient deficiencies, remains a major global health burden. Emerging evidence points to the gut microbiome as a critical mediator linking maternal, prenatal, and early-life nutrition to long-term offspring health outcomes. From conception and through the first years of life, maternal diet, metabolic state, and environmental exposures shape offspring microbial colonization and maturation. Breastfeeding and consumption of fiber-rich and fermented foods (maternal and post-weaning) support beneficial microbiota, while high-fat, high-sugar diets, xenobiotics, and artificial additives may promote dysbiosis. The composition and diversity of the infant microbiome influence immune, metabolic, and neurodevelopmental processes and may also contribute to the intergenerational transmission of malnutrition. While commercial formulas increasingly include "biotics" to mimic human milk, exclusive breastfeeding remains the gold standard. Complementary feeding practices, including timing and diet quality, are known to modulate microbial maturation. Diet-based interventions in pregnancy show promise in improving microbiome function and preventing disease in offspring. Because the microbiome is highly plastic in the first years of life, this window offers unique opportunities for preventive strategies targeting maternal and child nutrition. Integrating microbiome science into public health and dietary guidelines could enhance current approaches to breaking the cycle of malnutrition and promoting lifelong health.}, } @article {pmid41555509, year = {2026}, author = {Kim, JY}, title = {Gut Microbiota, Probiotics, and Aging: Molecular Mechanisms and Implications for Healthy Aging.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2511046}, doi = {10.4014/jmb.2511.11046}, pmid = {41555509}, issn = {1738-8872}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; Animals ; *Aging/physiology ; *Healthy Aging/physiology ; }, abstract = {Recent advances in microbiome research have highlighted that age-related physiological changes are closely shaped by shifts in the gut microbial community rather than by the passage of time alone. Aging is frequently accompanied by a decline in microbial diversity and the loss of short-chain fatty acid-producing taxa, changes that weaken the intestinal barrier and contribute to the persistent low-grade inflammation described as inflammaging. These alterations intersect with immune and metabolic pathways linked to immunosenescence, cellular senescence, and mitochondrial function. In contrast, microbial ecosystems enriched with butyrate-producing and polyamine-generating species have been associated with more stable epithelial integrity, improved metabolic flexibility, and balanced immune activity. Emerging findings also indicate that the gut microbiota communicates with peripheral organs through the gut-skin, gut-muscle, and gut-brain axes, influencing tissue-specific aging processes. Evidence from animal models and human studies shows that dietary modulation, probiotics, and other microbiota-directed approaches can partially restore microbial functions relevant to aging, although responses vary considerably across individuals. Interest is also growing in postbiotic strategies, including microbial metabolites and vesicle-based components, which may offer targeted effects without requiring colonization. By integrating these mechanistic and translational insights, this review outlines how the gut microbiota contributes to aging biology and discusses the potential for microbiome-based interventions to support healthspan.}, } @article {pmid41555501, year = {2026}, author = {Le Noir de Carlan, C and Verbruggen, E and Colaert-Sentenac, L and Cougnon, M and Sigurðsson, P and Sigurdsson, BD and Debode, J and De Tender, C}, title = {Soil microbiomes conditioned by long-term warming affect plant belowground performance.}, journal = {Plant biology (Stuttgart, Germany)}, volume = {}, number = {}, pages = {}, doi = {10.1111/plb.70182}, pmid = {41555501}, issn = {1438-8677}, support = {//European Union's Horizon 2020 framework programme for research and innovation under the Marie Skłodowska-Curie grant agreement No. 813114/ ; }, abstract = {Global change affects plant performance, both directly through warming and indirectly through changes in their biotic and abiotic surroundings. Soil microbes can critically influence plant performance, but are vulnerable to warming themselves. Disentangling direct effects of warming on plants from those intermediated by changes in microbial populations is complex under field conditions. To distinguish those effects, we monitored the performance of Agrostis capillaris and Anthoxanthum odoratum grown under uniform and controlled glasshouse conditions in soils inoculated with soil microbiomes conditioned by ambient, medium (14 years; MTW) or long-term (>55 years; LTW) geothermal warming. This was replicated under normal watering or drought conditions to additionally assess stress resistance. Furthermore, we analysed the microbiome of the inocula through metabarcoding to identify root-associated fungi and compare their relative abundance under different warming conditions. We found a decreased belowground biomass of both plant species when grown with LTW-conditioned microbiomes, with an exacerbated effect under drought for Ag. capillaris. We did not observe an associated increase in aboveground biomass, resulting in an increased aboveground biomass:belowground biomass ratio. These changes coincided with concurrent increases in the relative abundance of putative plant pathogens and arbuscular mycorrhizal fungi. We therefore conclude that soil microbes can mediate warming effects on plant performance through reduced belowground biomass.}, } @article {pmid41555483, year = {2026}, author = {Sridharan, K and Sivaramakrishnan, G}, title = {Comparative Microbiome Analysis in Ventilator-Associated Pneumonia Across Oral Care Interventions in Intubated Patients: A Systematic Review and Meta-Analysis.}, journal = {American journal of therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1097/MJT.0000000000002103}, pmid = {41555483}, issn = {1536-3686}, } @article {pmid41555453, year = {2026}, author = {Orr, RJS and Brynildsrud, O and Bøifot, KO and Gohli, J and Skogan, G and Kelly, FJ and Hernandez, MT and Udekwu, K and Lee, PKH and Mason, CE and Dybwad, M}, title = {Spatial and temporal patterns of public transit aerobiomes.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02303-7}, pmid = {41555453}, issn = {2049-2618}, abstract = {BACKGROUND: Aerobiome diversity is extensive; however, species-level community structure remains poorly resolved. Likewise, microbiomes of public transit systems are of public interest due to their importance for health, though few studies have focused on these ecosystems whilst utilising shotgun metagenomics. Aerosol studies have focused predominantly on individual cities, with limited between-city comparisons suggesting specific community structures. Longitudinal studies show aerobiome diversity as dynamic, fluctuating during seasonal and daily cycles, though interannual cycles remains to be considered. Further, a bacterial bias has limited fungal aerobiome studies, with few considering both fractions collectively. As such, the objective of this study was to examine spatial and temporal patterns in the species diversity of public transit aerobiomes, with an emphasis on bacteria and fungi.

RESULTS: Air samples taken over a 3-year period (2017-2019) from six global cities were subjected to shotgun metagenomic sequencing. Improved classification databases, notably for fungi, applying stringent parameters for trimming, exogenous contamination removal and classification yielded high species-level resolution. Microbial diversity varied substantially among cities, while human and environmental factors, recorded in parallel, were of secondary significance. Bacteria dominated the public transit aerobiome with increased presence in cities with higher population densities. All aerobiomes had complex compositions, consisting of hundreds to thousands of species. Interannual variation had limited significance on the public transit aerobiome diversity and community structure.

CONCLUSIONS: Cities were the most important factor contributing to diversity and community structure, demonstrating specific bacterial and fungal signatures. Further, possible correlation between geographical distance and genetic signatures of aerobiomes is suggested. Bacteria are the most abundant constituent of public transit aerobiomes, though no single species is globally dominant, conversely indicating a large inter-city variation in community structure. The presence of a ubiquitous global species core is rejected, though an aerobiome sub-core is confirmed. For the first time, local public transit aerobiome cores are presented for each city and related to ecological niches. Further, the importance of a robust bioinformatics analysis pipeline to identify and remove exogenous contaminants for studying low-biomass samples is highlighted. Lastly, a core and sub-core definition of contaminant aerobiome species with taxon tables, to facilitate future environmental studies, is presented. Video Abstract.}, } @article {pmid41555450, year = {2026}, author = {Ranade, AV and Bernhardt, GV and Srinivas, M and K M, DG and Ahmad, F and Ebby, S and Karim, A and Khan, NA and Jose, J and Ramachandran, G and Marzook, H and Qaisar, R}, title = {Gut microbiome- targeted intervention ameliorates structural and transcriptomic changes in the kidney of hindlimb unloaded mouse model.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {6}, pmid = {41555450}, issn = {2524-4671}, support = {23010901126//University of Sharjah/ ; }, abstract = {The human body is adapted to Earth's gravity, but space microgravity significantly alters kidney function, with the hindlimb unloaded (HU) mouse model serving as a valuable tool for studying these effects. During space travel, changes in gut microbiota can lead to health-related issues. In this study, we explored the protective role of crocodile gut microbiome media on kidney health in a HU mouse model, given the known impact of space travel on gut microbiota and related health issues. Male C57BL/6 mice (four months old) were divided into a ground-based control group (GC), HU mice fed with distilled water (HU), and HU mice fed with crocodile bacterial conditioned media (HU-CP). All groups were maintained in a controlled environment for three weeks. At the end of the experiment, mice were euthanized, kidney tissues were dissected for histopathological examination and transcriptomic analysis. Statistical analysis was performed using one-way ANOVA followed by Tukey's multiple comparison test, with p < 0.05 considered significant. Transcriptomic analysis revealed distinct gene expression profiles across GC, HU, and HU-CP groups, with HU-CP inducing both unique (4325 genes) and differential (975 genes) expression compared to HU group. The treatment partially restored glomerular morphology, reduced inflammation, and reversed gene expression alterations associated with oxidative stress, apoptosis, fibrosis, and inflammation. The crocodile bacterial conditioned media demonstrated potential therapeutic benefits in mitigating renal injury induced by simulated microgravity in HU mice. Further research is needed to elucidate the specific mechanisms involved and explore the potential clinical applications of this approach.}, } @article {pmid41555417, year = {2026}, author = {Liu, L and Spaink, HP}, title = {The function of Toll-like receptor 2 in control of transcriptome responses to the microbiome and microbiome composition.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {5}, pmid = {41555417}, issn = {2524-4671}, abstract = {BACKGROUND: Toll-like receptor 2 (TLR2) plays a pivotal role in innate immunity and has recently emerged as a critical regulator of host-microbiome interactions. However, how TLR2 influences host transcriptional responses to colonized microbiome and microbial community dynamics remains largely unclear. A comparison between germ free (GF) and conventionalized zebrafish (Danio rerio) larvae provides a valuable system to investigate how the microbiome influences host transcriptomic responses in a tlr2 mutant versus wild-type control. Vice versa, to understand the role of Tlr2 in regulating the microbiome, we have analyzed microbial community composition in both tlr2 mutant and wild-type zebrafish at larval and adult stages.

RESULTS: RNAseq analysis revealed that approximately 2.6% of the zebrafish genome (827 genes) exhibited transcriptomic alterations in tlr2 mutant larvae compared to the wild type under microbiome-colonized conditions, whereas around 2% of the genome (639 genes) showed differential expression under GF conditions. KEGG enrichment analyses show that under both microbiome-colonized and GF conditions major differences between the tlr2 mutant and wild type are related to metabolism. Furthermore, there is a striking difference in endoplasmic reticulum stress responses, including well-known markers for inflammatory bowel disease which are all downregulated in the mutant under the microbiome-colonized condition. Microbiome colonization elicited a broader transcriptional response in tlr2 wild-type larvae than in the mutant, with specifically the ferroptosis, apoptosis and inflammation related pathways differently regulated. In terms of how Tlr2 influences microbial composition, 16 S rRNA gene sequencing showed large differences in beta diversity between the tlr2 mutant and wild type. The tlr2 mutant exhibited higher microbial alpha diversity during early development, whereas alpha diversity was higher in wild-type adults. For larvae at the genus level, tlr2 mutant larvae showed increased Chryseobacterium and Flectobacillus but reduced Gracilibacteria abundance relative to wild-type controls. For adult gut samples, the relative abundance of Cetobacterium was higher in the tlr2 mutants, indicating a developmental stage-specific restructuring of the microbiome.

CONCLUSIONS: TLR2 not only modulates host transcriptional responses to microbial colonization, but also shapes gut microbial diversity, composition, and metabolic potential. Our findings highlight the critical role of TLR2 in orchestrating immune-metabolic homeostasis and provide new insights into its broader function in maintaining host-microbiota symbiosis across developmental stages.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00502-z.}, } @article {pmid41555050, year = {2026}, author = {Nakayama-Imaohji, H and Tada, A and Ogiwara, S and Munyeshyaka, E and Tabassum, N and Mori, T and Fujikawa, R and Suzuki, K and Kuwahara, T}, title = {α-Amylase in Aspergillus oryzae-fermented rice promotes the growth of human symbiotic Faecalibacterium Prausnitzii.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36928-x}, pmid = {41555050}, issn = {2045-2322}, support = {25K14867//Japan Society for the Promotion of Science/ ; }, abstract = {Diet is one of the critical factors that govern the human gut microbiome. Fermented foods provide beneficial effects for human health by supplying diverse nutrients and digestive enzymes. We aimed to investigate the effect of fermented rice extract prepared with Aspergillus oryzae on the growth of human symbiotic Faecalibacterium prausnitzii. After steamed rice was fermented by A. oryzae, a water-soluble fraction was prepared by centrifugation and used as rice-koji extract. The growth of F. prausnitzii in the media supplemented with 1% rice-koji extract was enhanced compared to that in a control medium. Fractionation of the rice-koji extract with an anion-exchange column and mass spectrometry analysis were conducted to identify the growth-promoting factors for F. prausnitzii. LC-MS/MS analysis revealed that the fractions showing a growth-promoting effect were rich in α-amylase from A. oryzae. The addition of purified A. oryzae-derived α-amylase and starch to the culture media increased the growth and butyrate production from F. prausnitzii. These findings suggest that A. oryzae-derived enzymes in fermented rice-koji possess a growth-promoting effect, enabling F. prausnitzii to efficiently uptake and utilize starch degradation products.}, } @article {pmid41554884, year = {2026}, author = {Wu, Z and Liu, Z and Wang, W and Zhang, S and Tsai, AY and Lozano-Torres, JL and Sawa, S and Zhang, L and Chen, S and Lv, X and Erb, M and Xu, J and Hu, L}, title = {Root-knot nematode Meloidogyne incognita uses secondary-metabolite-mediated soil microbiome shifts to locate host plants.}, journal = {Nature plants}, volume = {}, number = {}, pages = {}, pmid = {41554884}, issn = {2055-0278}, support = {LR25D010001//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; }, abstract = {Plant-parasitic nematodes are among the most destructive soil-dwelling pests, posing severe threats to global agriculture. However, the interplay between plant metabolites, rhizosphere microorganisms and their potential role in guiding pathogenic nematodes to their hosts remains poorly understood. Here we explored this gap by investigating the role of benzoxazinoids (BXs), a class of defensive metabolites of maize plants, in influencing the host-seeking behaviour of root-knot nematodes (RKNs). Our findings revealed that, surprisingly, BXs secreted by maize roots, particularly 6-methoxy-benzoxazolin-2-one, not only enhance RKN infection but also serve as powerful attractants. Remarkably, BX effects were observed only in the presence of a soil matrix. Further analysis demonstrated that 6-methoxy-benzoxazolin-2-one modulates the abundance and composition of rhizosphere bacteria, which in turn play a crucial role in RKN attraction and infection. We discovered that rhizosphere bacteria of BX-producing plants emit volatile compounds such as methyl ketones and 2-phenylethanol, which are then used by RKNs to locate host plants. RKNs detect these volatiles through chemosensory genes, including Mi-odr-1, Mi-odr-7 and Mi-gpa-6. Our study provides mechanistic insights into how RKNs use secondary-metabolite-shaped plant-microbe interactions to enhance their host-seeking behaviour and maximize their performance.}, } @article {pmid41554846, year = {2026}, author = {Sumithra, TG and Sharma, SRK and Gayathri, S and Gop, AP and Shravana, KS and Jagannivasan, A and Nair, AV and Sudarsan, KS and Santhosh, B and Ebeneezar, S and Gopalakrishnan, A}, title = {Egg disinfection improves larval survival and shapes the microbial community in snubnose pompano (Trachinotus blochii).}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35646-8}, pmid = {41554846}, issn = {2045-2322}, support = {BT/AAQ/3/SP28267/2018//Department of Biotechnology, Government of India/ ; }, abstract = {Early microbial colonization is crucial for immunity and survival in aquatic animals. This study evaluated the impact of egg disinfection on microbial colonization and larval performance in Trachinotus blochii, a high-value mariculture fish. Optimal egg disinfection protocols were initially identified as 20 ppm iodophor for 10 min, 400 ppm H2O2 for 10 min, and 40 ppm glutaraldehyde for 5 min to improve hatchability. Sequential analyses included 16S rRNA amplicon sequencing of larval microbiota at 10-days post hatching (DPH) and assessment of survival and antioxidant status till 25 DPH. Disinfection significantly enhanced hatchability (up to 90.88 ± 2% with 40 ppm glutaraldehyde), larval survival (up to 34.80 ± 1.1% in glutaraldehyde and 31.18 ± 1.5% in H2O2), and catalase activity. Notably, egg disinfection reshaped the larval microbiota, enriching microbial diversity measures and beneficial bacterial taxa, such as Hyphomonadaceae, Halieaceae, Nannocystaceae, and Alteromonadaceae. Improved survival correlated with enhanced taxonomic and functional metagenomic diversity, lower Proteobacteria: Bacteroidota ratio and higher combined proportions of Fusobacteriota, Firmicutes, and Bacteroidota relative to Proteobacteria. The findings suggest that egg disinfection acts as a microbiota programming strategy to promote larval health, offering a practical approach to enhance sustainability in T. blochii aquaculture.}, } @article {pmid41554833, year = {2026}, author = {Qi, Y and Huang, Y and Chen, H and Li, J and Liu, M and Xiong, W and Tang, Q and Zhang, Y}, title = {ACE2 expression by colonic epithelial cells is associated with viral infection, immunity, and energy metabolism.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36052-w}, pmid = {41554833}, issn = {2045-2322}, support = {2025A0505080010//Guangdong Province Science and Technology Innovation Strategy Special Fund/ ; 2024A04J3928//Guangzhou Science and Technology fund/ ; 91742109, 31770978, 31722003, 31770925, 31370847, 81770552//Natural Science Foundation of China/ ; 2016YFC0900102//National Key Research and Development Program/ ; 2018ZX10302205//National Science and Technology Major Project/ ; 5001-3001032//Guangzhou Women and Children's Medical Center Fund/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin I converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for SARS-CoV-2. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. We performed analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (6 controls, 6 colitis cases, 2 ulcerative colitis cases and 3 Crohn's disease cases). The single cell-RNA sequencing data was also used to conduct co-expression analysis and GO enrichment analysis. Multiplex immunofluorescence (mIF) was performed to assess the expression of ACE2, IFNA4, and RSAD2 on colon specimens obtained from patients, including non‑diseased (control) tissue, ulcerative colitis (UC) tissue and Crohn's disease (CD) tissue. We revealed that ACE2 exhibited specific and high expression levels in colonocytes. Furthermore, genes implicated in viral infection and anti-infection immunity were also found to be highly expressed in colonocytes. Additionally, we conducted an analysis of genes co-expressed with ACE2 within colonocytes, and total of 3420 and 2136 genes were identified as being positively and negatively correlated with ACE2 expression. Concurrently, through Gene Ontology (GO) enrichment analysis, it was observed that genes positively associated with ACE2 expression were significantly enriched in pathways related to viral infection, organismal immunity, and energy metabolism. Accordingly, mIF showed a significant increase in IFNA4 and RSAD2 expression in the colonic epithelial ACE2[+] cells of UC and CD patients relative to controls. Integrated data from single cell-RNA sequencing and patient's mIF highlighted the expression profile of ACE2 in colonic epithelial cells, suggesting the possible involvement of ACE2 in the intestinal tract of patients with SARS-CoV-2 pneumonia in enteroviral infection, immunity and energy metabolism functions.}, } @article {pmid41554808, year = {2026}, author = {Sugiyama, N and Kato, S and Shimizu, S and Uehara, O and Hasegawa-Nakamura, K and Shirakata, Y and Noguchi, K and Hatae, M and Kakinoki, H and Kamitomo, M and Furuichi, Y and Nagasawa, T}, title = {Association of low progesterone levels and periodontal disease with threatened preterm labor.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35944-1}, pmid = {41554808}, issn = {2045-2322}, support = {#22K10004//Grants-in-Aid for Scientific Research (C)/ ; }, abstract = {Periodontal disease has been reported to increase the risk of threatened preterm labor (TPL). However, studies analyzing the oral, vaginal, and rectal lumen commensal flora in women with TPL are limited. In this study, a total of 60 women were enrolled, including 30 with TPL and 30 without TPL. We assessed periodontal clinical parameters, salivary hormone levels, and the microbiome using next-generation sequencing. Probing pocket depth (PPD) and bleeding on probing were greater in the TPL than in the non-TPL group. The TPL group was associated with lower progesterone levels and an increase in PPD ≥ 4 mm. Significant differences in alpha diversity in only vaginal Faith's phylogenetic diversity, and significant differences in beta diversity at all sites were observed. ANCOM showed decreased Lactobacillales in the saliva and Bifidobacterium in the rectal lumen, and increased Staphylococcus in the oral cavity and vagina in the TPL group. The peptidoglycan synthesis pathway was significantly upregulated in the oral and vaginal tissues in the TPL group. Overall, the TPL group had lower progesterone levels and more severe periodontal disease; furthermore, the low progesterone levels in the TPL group were associated with oral and vaginal dysbiosis of the microbiota.}, } @article {pmid41554782, year = {2026}, author = {Holmes, LA and Veiga, PW and Pettis, JS and Guarna, MM and Hoover, SE}, title = {A non-invasive method for profiling the gut microbiome and virome of honey bee queens.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {2318}, pmid = {41554782}, issn = {2045-2322}, abstract = {UNLABELLED: High honey bee colony mortality worldwide has underscored the critical role of queen bee health in colony survival, with poor queen quality frequently linked to colony losses. The gut microbiome plays fundamental roles in immunity, nutrition, and reproduction, making its characterization essential for understanding stressors that impact queen health, longevity, and fecundity, yet its role in mediating stress responses remains poorly understood. Here, we present a novel, non-invasive method for collecting feces from queen honey bees and demonstrate its potential as a powerful tool for profiling the gut microbiome, detecting stressor exposure, and screening for viral infections. This approach permits repeated, longitudinal assessments of individual queens, providing unprecedented insights into how environmental and pathogenic pressures influence queen health, longevity, and reproductive capacity. Beyond research applications, benefits include evaluating queens before colony introduction and mitigating disease transmission risks in international trade, where pathogen spread remains a major regulatory challenge. By enabling non-destructive monitoring of queen health, this method provides a transformative tool for improving colony resilience and advancing sustainable honey bee management in the face of global challenges.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-32053-3.}, } @article {pmid41554742, year = {2026}, author = {Li, Y and Yang, L and Xu, H and Bian, X and Shi, D and Wu, W and Li, L}, title = {Restoration of ethanol-induced Bifidobacterium pseudocatenulatum depletion ameliorates alcohol-associated liver disease.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00913-z}, pmid = {41554742}, issn = {2055-5008}, support = {82502783//National Natural Science Foundation of China/ ; LQ22H030013;2022-KY1-001-039//Zhejiang Provincial Natural Science Foundation of China/ ; zz202320//State Key Laboratory for Diagnosis and Treatment of Infectious Disease Independent Project/ ; 2022499572//Young Innovative Talents Support Program of Zhejiang Medical and Health Science and Technology Project/ ; 2024025437,2024ZR152//Young Innovative Talents Support Program of Zhejiang Chinese Medicine Science Technology Project/ ; 2025ZFJH03//Fundamental Research Funds for the Central Universities/ ; }, abstract = {Alcohol-associated liver disease (ALD), characterized by gut barrier disruption and microbial dysbiosis, is associated with significant depletion of the genus Bifidobacterium in patients, as evidenced by our cohort of 127 subjects. Functional screening revealed B. pseudocatenulatum as a protective strain. In a murine ALD model established with a Lieber-DeCarli ethanol diet, oral administration of B. pseudocatenulatum for 8 weeks ameliorated hepatomegaly, steatosis, and serum transaminase levels. Probiotic intervention restored intestinal barrier function, as indicated by reduced lipopolysaccharide-binding proteins and upregulated tight junction protein expression. Microbiome analysis revealed a mitigation of dysbiosis, with a reduction in pathogenic Escherichia-Shigella and Parabacteroides and an enrichment of beneficial Bifidobacterium and Blautia, concomitant with shifts in lipid metabolism. Mechanistically, B. pseudocatenulatum-derived short-chain fatty acids downregulated the expression of hepatic lipogenic genes (Cd36, Fasn, Accα) and pro-inflammatory cytokines (Il-1β, Ccl2, Tnf-α). These results suggest that B. pseudocatenulatum is a promising probiotic candidate for ALD management.}, } @article {pmid41554738, year = {2026}, author = {Zheng, J and Zhang, C and Xiang, S and Li, M and Wang, H and Shi, K and Tondrob, D and Han, Y}, title = {Integrated metabolomics and metagenomics uncover pathogenic mechanisms of Fusarium wilt and faba bean defense responses.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-025-00673-8}, pmid = {41554738}, issn = {2396-8370}, support = {31901929//National Natural Science Foundation of China/ ; cstc2021jcyj-msxmX1021//Natural Science Foundation of Chongqing Municipality/ ; }, abstract = {Fusarium wilt diseases pose a huge threat to faba bean (Vicia faba L.) production globally, with significant outbreaks in Chongqing, China. Symptomatic plants showed wilting leaves and rotten roots, ultimately perishing in the advanced stage. Morphological features, multilocus phylogenetic analyses, and pathogenicity tests demonstrated that the primary causal agent was Fusarium oxysporum. Untargeted metabolomics of faba beans revealed substantial metabolic differences in the infected faba bean roots. Plants responded to fungal biotic stress by reprogramming key metabolic pathways, including alanine, aspartate, and glutamate metabolism, the citrate cycle, arginine biosynthesis, and jasmonic acid metabolism, which collectively underscore activated defense responses. Metagenome sequencing showed that Fusarium wilt significantly reshaped the structure of the rhizosphere microbiota and affected the abundance of genes encoding element cycling in soil. This work elucidates the pathogenic mechanisms of F. oxysporum by integrating pathogen identification, host metabolism, and microbiome ecology. Our findings offer biomarkers for disease diagnosis and targets for biocontrol, advancing sustainable management of Fusarium wilt diseases in legumes.}, } @article {pmid41554476, year = {2026}, author = {Harariya, K and Singh, TR and Kalra, A and Padhi, S and Ahamed, F}, title = {Letter to Editor regarding "Oral Microbiome Signatures as Potential Biomarkers for Gastric Cancer Risk Assessment".}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {102339}, doi = {10.1016/j.gassur.2026.102339}, pmid = {41554476}, issn = {1873-4626}, } @article {pmid41554431, year = {2026}, author = {Elechi, JOG and de Mendonça, CR and Bandeira, VCA and Da Silva, MSP and de Melo, APR and Guedes, RCA and Hirabara, SM and Cione, E and de Vasconcelos, DAA}, title = {Exploring recent insights on intermittent fasting in regulating glucocorticoid levels and diet-induced metabolic disorders with focus on MAFLD and hepatic outcomes.}, journal = {Molecular and cellular endocrinology}, volume = {614}, number = {}, pages = {112736}, doi = {10.1016/j.mce.2026.112736}, pmid = {41554431}, issn = {1872-8057}, abstract = {Consumers' risky eating behaviours aided by the current food environment have led to an increase in diet-related metabolic disorders. Metabolic (dysfunction)-associated fatty liver disease origin represents a major global health burden that is increasing at an alarming rate on an annual basis. Modifying the timing of calorie consumption, dietary composition, or caloric intake offers a promising therapeutic approach for the management of this condition. The aim of this review was to provide a concise analysis of the impact of intermittent fasting on the regulation of glucocorticoid levels and diet-induced metabolic disorders with a focus on non-alcoholic fatty liver diseases. We found that intermittent fasting primarily regulates hepatic autophagy via nutritional and hormonal pathways, aiding in the maintenance of energy equilibrium, enhancement of mitochondrial function, regulation of liver quality, preservation of cellular homeostasis, protection of cells from harmful factors, mitigation of liver metabolic disorders, and improvement of liver inflammation. Also, the physiological changes induced by intermittent fasting and their metabolic consequences arise through multiple mechanisms, including alterations in hepatic metabolism, hepatic autophagy, inflammatory responses, liver functional enzymes, hepatic steatosis, fibroblast growth factor signalling, White adipoe tissue browning, adipokines, circadian rhythms, lipid profiles, body composition, the adipose tissue-gut microbiome axis, skeletal muscle, and the autophagy process. Interestingly, we identified the complex interplay among glucocorticoids, intermittent fasting, and non-alcoholic fatty liver diseases highlighting the hepatic macrophage glucocorticoid receptor as a pivotal mediator of fasting-induced reprogramming of the macrophage secretome, including fasting-suppressed cytokines. In conclusion, existing data indicates that intermittent fasting in patients with non-alcoholic fatty liver diseases is a viable, safe, and successful strategy for weight reduction, demonstrating notable trends in the amelioration of dyslipidaemia and non-alcoholic fatty liver diseases.}, } @article {pmid41554330, year = {2026}, author = {Piñeiro, B and Kue, J and Costa, J and Santiago, A and Msaddi, J and Nuss, K and Yadav, H and Szalacha, L and Menon, U}, title = {Time-restricted eating in patients with metabolic syndrome: A protocol paper for a feasibility clinical trial.}, journal = {Contemporary clinical trials}, volume = {}, number = {}, pages = {108223}, doi = {10.1016/j.cct.2026.108223}, pmid = {41554330}, issn = {1559-2030}, abstract = {Recent studies have evaluated Time-Restricted Eating (TRE) as a promising dietary behavioral intervention for weight loss and cardiometabolic risk factor improvement. Yet the results are mixed. We describe a TRE protocol, a behavioral dietary intervention where all calorie intake is limited to 10-h eating window followed by a 14-h fasting period, without altering diet quality and quantity. This study aims to determine the feasibility and acceptability of a 12-week TRE intervention among patients with metabolic syndrome. Dietary lifestyle changes can decrease risk in metabolic syndrome, but such changes are difficult to implement and sustain. This is a pilot feasibility study with a single-arm group. A total of 40 adult patients with metabolic syndrome are being enrolled. Participants document their daily eating patterns through MyCap app. The primary outcome is to assess the feasibility and acceptability of the intervention, including recruitment, program delivery, adherence and patient satisfaction. Secondary outcome measures include changes in weight, blood pressure, sleep, quality of life, and biological measures including gut microbiome, HbA1c, lipids, and thyroid function. Findings of this pilot study will provide novel insights into improving information health markers in individuals with metabolic syndrome, as well as inform the feasibility and sustainability of this dietary intervention.}, } @article {pmid41553769, year = {2026}, author = {Kay, H and Jabbur, ML}, title = {The elusive rhythms of bacterial life.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.70287}, pmid = {41553769}, issn = {1873-3468}, support = {101166968/ERC_/European Research Council/International ; BB/Z514937/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; Institute Strategic Programme BRiC BB/X01102X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Circadian clocks are endogenous timekeeping mechanisms that are phylogenetically widespread. Despite the immense diversity of bacterial life, to date, clocks have been identified in few bacterial species. The cyanobacterial clock is understood in great detail, and the roles of its clock proteins in other types of timing mechanisms and in stress resistance are being studied in an ever-growing range of species. Studies of host-associated microbiomes have shown that host and microbial rhythmicity impact one another reciprocally. However, bacterial rhythms have primarily been studied in species in isolation or in host-associated microbiomes. Here, we summarize the state of the field of microbial chronobiology and propose the hypothesis that rhythmicity could be an emergent property of microbial interactions in free-living bacterial communities.}, } @article {pmid41553656, year = {2026}, author = {Langgeng, A and Lee, W and Hanya, G and Okamoto, M and MacIntosh, AJJ}, title = {Of hot springs and holobionts: linking hot spring bathing behavior, parasitism, and gut microbiome in Japanese macaques.}, journal = {Primates; journal of primatology}, volume = {}, number = {}, pages = {}, pmid = {41553656}, issn = {1610-7365}, support = {International Primatological Society//International Primatological Society/ ; Ministry of Education, Culture, Sports, Science, and Technology//Ministry of Education, Culture, Sports, Science, and Technology/ ; #20H03333//Japanese Society for the Promotion of Science/ ; }, abstract = {Japanese macaques at Jigokudani Snow Monkey Park, Nagano, exhibit hot spring bathing behavior (HSBB) during the cold season. HSBB is known to aid thermoregulation and reduce stress, but its impact on host-associated biota in nonhuman primates remains unexplored. In this study, conducted between December 2019 and March 2021, we investigated the relationship between HSBB and lice load, gastrointestinal (GI) parasitism, and the gut microbiome in Japanese macaques at Jigokudani. Fecal samples were collected from sixteen adult females (9 bathers and 7 non-bathers) varying by age, reproductive status, and social rank. Nit-picking rates, used to estimate lice load, differed between bathers and non-bathers in submerged and non-submerged areas. We detected four GI helminths and at least one protozoan parasite, but did not observe noticeable differences in the probability of infection or abundance of these endoparasites between bathers and non-bathers. Finally, the alpha and beta diversity of the gut microbiome did not differ between bathers and non-bathers, but we identified four microbial genera that were significantly more abundant in non-bathers. These findings suggest that HSBB may influence host-(micro)organism relationships. Further research is needed to explore potential health outcomes associated with HSBB.}, } @article {pmid41553570, year = {2026}, author = {Reinecke, K and Kleynhans, L and Ronacher, K and Loots, DT}, title = {Characterizing the tuberculosis and type 2 diabetes mellitus comorbidity in a South African cohort using untargeted GCxGC-TOFMS metabolomics.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {22}, number = {1}, pages = {19}, pmid = {41553570}, issn = {1573-3890}, mesh = {Humans ; *Diabetes Mellitus, Type 2/epidemiology/metabolism/urine ; *Metabolomics/methods ; Male ; Female ; South Africa/epidemiology ; *Tuberculosis/epidemiology/metabolism/urine ; Middle Aged ; Gas Chromatography-Mass Spectrometry/methods ; Adult ; Cohort Studies ; Comorbidity ; Aged ; }, abstract = {INTRODUCTION: Tuberculosis (TB) and type 2 diabetes mellitus (T2DM) are highly prevalent diseases resulting in high mortality rates globally. Furthermore, T2DM increases susceptibility to TB and vice versa, worsening disease outcomes. This comorbidity is, however, not well described nor understood, despite its rising prevalence globally.

OBJECTIVES: This investigation aimed to better characterize the urinary metabolic profiles of patients with the TB and T2DM comorbidity in a South African cohort, to better understand its metabolic basis and associated clinical implications.

METHODS: Using untargeted GCxGC-TOFMS metabolomics, urine samples from 17 patients with TB and T2DM and 34 healthy controls were analyzed and statistically compared to identify significantly altered urinary metabolites.

RESULTS: TB-T2DM comorbid patients were characterized by altered metabolism of: (1) tryptophan and kynurenine (reduced kynurenic acid, anthranilic acid, picolinic acid) associated with changes to NAD[+] synthesis and a redox imbalance, (2) nucleotides (reduced 3-aminoisobutyric acid, orotic acid, thymine, β-alanine, adenine, hypoxanthine), (3) tyrosine (reduced 3,4-dihydroxyphenylglycol, 4-hydroxy-3-methoxyphenylglycol, hydroxyphenylpyruvate), (4) lipids (reduced dec-2-enedioate, adipic acid, methylmalonic acid), (5) reduced concentrations of various glycine conjugates associated with glycine depletion, and (6) reduced urinary concentrations of various gut microbial metabolites indicative of microbial dysbiosis.

CONCLUSION: These results indicate several metabolic disruptions to amino acids, nucleotides, lipids, NAD⁺ homeostasis and the host microbiome, in TB-T2DM patients, mainly driven by inflammation and oxidative stress. Overall, the findings indicate synergistic amplification of metabolic stress, associated with immune suppression and TB-T2DM disease progression, and subsequently suggests how TB increases T2DM susceptibility and vice versa, as foundation for further investigations.}, } @article {pmid41553492, year = {2026}, author = {He, Q and Xie, Y and Liu, J and Li, T}, title = {Diosbulbin B attenuates propylthiouracil-induced thyroid enlargement in mice by regulating the gut microbiota-short chain fatty acids-thyroid axis.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41553492}, issn = {1432-1912}, support = {No. 2025JC-GXPT-005//Shaanxi Provincial Science and Technology Department/ ; }, abstract = {This research investigates Diosbulbin B's capacity to protect against propylthiouracil-induced thyroid enlargement in mice and examines its underlying operative principles. Propylthiouracil was administered to mice by gavage for 15 days to establish a mouse thyroid enlargement model. Meanwhile, Diosbulbin B was administered to the mice as an intervention. After the experiment, biochemical indicators were measured, and, together with non-targeted metabolomics, targeted metabolomics, 16S rDNA sequencing, and Spearman correlation analysis, the alleviating effect of Diosbulbin B on thyromegaly induced by propylthiouracil and its potential mechanism were systematically evaluated. Diosbulbin B decreased thyroid function markers and ameliorated pathological alterations in the thyroid induced by propylthiouracil. Additionally, it alleviated propylthiouracil-induced inflammatory responses and oxidative damage in thyroid tissue. Untargeted metabolomics revealed Diosbulbin B primarily normalized propylthiouracil-disrupted fatty acid metabolism. Crucially, Diosbulbin B reversed the consumption of SCFAs in feces. What is more, 16S rDNA gene sequencing analysis demonstrated that Diosbulbin B successfully rebalanced the gut microbiome by boosting the population of beneficial bacteria while cutting down on harmful microorganisms, effectively bringing the intestinal flora structure back to normal. On top of that, when we looked at the connection between fatty acids and gut bacteria, it became clear that Firmicutes, Bacteroidota, and Verrucomicrobia, along with propionic, butyric, and acetic acids, could be considered key indicators of thyroid enlargement caused by propylthiouracil. Diosbulbin B significantly improved propylthiouracil-induced thyroid enlargement by regulating the intestinal flora, increasing fatty acid production, and reducing inflammation and oxidative stress.}, } @article {pmid41553090, year = {2026}, author = {Lei, S and Tong, H and Zhou, Y and Huang, J and Zhou, X and Dai, J and Yu, Z}, title = {Gut microbiota landscape of Haemaphysalis longicornis under Borrelia burgdorferi infection.}, journal = {Insect science}, volume = {}, number = {}, pages = {}, doi = {10.1111/1744-7917.70241}, pmid = {41553090}, issn = {1744-7917}, support = {//the Innovation-Driven Research Programme of Central South University/ ; 32170071//National Natural Science Foundation of China/ ; 32170142//National Natural Science Foundation of China/ ; 32300051//National Natural Science Foundation of China/ ; 2023JJ30651//Natural Science Foundation of Hunan Province/ ; 2025JJ50101//Natural Science Foundation of Hunan Province/ ; }, abstract = {This study aimed to explore the reason for Haemaphysalis longicornis restricting Borrelia burgdorferi colonization and transmission from the perspective of gut microbiota, and to investigate the impact of different infection statuses on the Haemaphysalis longicornis microbiota and its potential role in pathogen transmission. Pathogen-free Haemaphysalis longicornis ticks and IFNAR1[-/-] mice were used to establish infection models. Ticks fed on pathogen-infected mice, and their midguts were analyzed at day 4 and 10 post-feeding. DNA was extracted from the midguts, and the V3-V4 region of bacterial 16S rRNA gene was amplified and sequenced. Analysis of microbiome data were analyzed using QIIME2 and R. After digesting the bloodmeals, the gut microbiota of ticks that ingested bloodmeal with Borrelia burgdorferi exhibited minimal structural changes, while the ticks with uninfected bloodmeal or bloodmeal with Langat virus showed the dysbiosis. The Borrelia group showed minimal temporal shifts in β-diversity, with stable co-occurrence networks and increased core microbial interactions. Neutral model analysis revealed a hybrid niche in the Borrelia group. Potential biomarkers were identified that may suppress Borrelia burgdorferi transmission. Our findings reveal that Borrelia burgdorferi infection is associated with a stabilized and functionally distinct gut microbiota in Haemaphysalis longicornis. The gut microbiota of Haemaphysalis longicornis functions as a barrier against Borrelia burgdorferi colonization and transmission through microbial regulation and resource limitation, thus providing a potential mechanistic explanation for the observed vector incompetence. These findings highlight the potential of microbiome-targeted strategies to block pathogen transmission and offer new insights into vector-borne disease.}, } @article {pmid41552974, year = {2026}, author = {Yang, XY and Zhang, ZW and Chen, GD and Yuan, S}, title = {Gut microbiome remodeling induced by microplastic exposure in humans.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2617696}, pmid = {41552974}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Microplastics/adverse effects/toxicity ; *Bacteria/classification/drug effects/genetics/isolation & purification/metabolism ; Dysbiosis/chemically induced/microbiology ; Animals ; }, abstract = {The impact of microplastics (MPs) on the diversity and composition of the gut microbiome has been extensively documented in animal studies, but evidence in humans remains limited. Recognizing the potential differences in MP effects between animal and human gut microbiomes, this review synthesizes current evidence concerning their impact on the human gut microbiota. Furthermore, the potential links between microplastic-induced dysbiosis and the pathogenesis of human diseases were analyzed. Cross-sectional studies have been conducted to explore microplastic exposures (such as in humans who consume hot foods served in disposable plastic tableware) and their associations with gut microbiome functionalities in infants, preschool children and adults. Exposure to MPs increased the abundance of Dethiosulfovibrionaceae, Enterobacteriaceae, Moraxellaceae, Actinomycetota, Pseudomonadota, and Veillonella. On the other hand, MPs decreased the abundances of Bacillota, Bacteroidota, Lactobacillales, Rikenellaceae, Parabacteroides, Roseburia, Coprococcus, Turicibacter, and Eubacterium coprostanoligenes. These changes were associated with a decrease in butyrate production and a decrease in short-chain fatty acid levels. However, for some other bacteria, both inductive (on Oscillospiraceae, Adlercreutzia, Phascolarctobacterium, and Collinsella) and repressive effects (on Streptococcus) have been documented. There are contradictory reports about MP-induced changes in Lachnospiraceae (including the Dorea genus), Alistipes and Faecalibacterium, which may be correlated with obesity, gastrointestinal dysfunction, some cancers, inflammatory bowel disease and Crohn's disease. Potential reasons for these discrepancies are proposed. This review also examines putative mechanisms, with a focus on biofilm formation on selective surfaces, and discusses the inherent limitations of current MP exposure assessments in human gut microbiota studies.}, } @article {pmid41552936, year = {2026}, author = {Lu, Y and Chang, L and Liu, S and Wang, M and Zhao, Y}, title = {Rutin alleviates dietary advanced glycation end products (AGEs)-induced insulin resistance in mice by modulation of gut microbiota.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo04604a}, pmid = {41552936}, issn = {2042-650X}, abstract = {Dietary advanced glycation end products (AGEs), formed during thermal food processing, are associated with metabolic disorders. This study investigated the efficacy of rutin in alleviating AGEs-induced insulin resistance (IR) in a mouse model. Male C57BL/6 mice were fed a high-AGEs diet for 12 weeks to induce IR, followed by 8 weeks of rutin intervention (100 mg per kg body weight per day). Rutin supplementation markedly ameliorated IR, as indicated by reduced hyperglycemia and dyslipidemia, a reduced homeostasis model assessment of insulin resistance (HOMA-IR) index, an elevated insulin sensitivity (HOMA-IS) index, and upregulation of insulin receptor substrates IRS-1 and IRS-2. Metagenomic analysis demonstrated that rutin intervention restored gut microbial richness and diversity and induced structural shifts in the microbiota composition. Specifically, rutin enriched beneficial genera, including Akkermansia, Bifidobacterium, Faecalibacterium, Lactobacillus, and Coriobacteriales, while reducing populations of IR-associated taxa such as Erysipelotrichaceae, Coprobacillus, Enterococcus, Adlercreutzia, and Allobaculum. Concurrently, rutin increased fecal concentrations of short-chain fatty acids (SCFAs), notably acetic acid and propionic acid. Spearman's correlation analysis confirmed negative associations between rutin-modulated microbiota and IR indicators. These results demonstrate that rutin mitigates AGEs-induced IR by reshaping the gut microbiome and promoting beneficial microbial metabolites.}, } @article {pmid41552834, year = {2026}, author = {Close, R and Kremer, S and Mitchem, M and Bellinghiere, A and Nirmalkar, K and Borges, CR and Krajmalnik-Brown, R and Shah, DD}, title = {A sulfotransferase from a gut microbe acts on diverse phenolic sulfate compounds, including acetaminophen sulfate.}, journal = {PNAS nexus}, volume = {5}, number = {1}, pages = {pgaf403}, pmid = {41552834}, issn = {2752-6542}, abstract = {Sulfonation is one of the two main phase II detoxification pathways in eukaryotes which transforms nonpolar compounds into hydrophilic metabolites. Sulfotransferases catalyze these reactions by transferring a sulfo group from a donor to an acceptor molecule. Human cytosolic sulfotransferases use only 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a donor to sulfonate a variety of chemicals. Less understood are microbial aryl-sulfate sulfotransferases (ASSTs), which catalyze sulfo transfer reactions, without utilizing PAPS as a donor. Currently, the identity of physiological sulfo donor substrates remains unknown and sulfo acceptor substrates are underexplored. With this study, we aim to understand the potential contribution of a gut microbial enzyme to sulfonation chemistry by uncovering its substrate preferences. Here, we show that a sulfotransferase (Bacteroides vulgatus ASST) from the prevalent gut microbe B. vulgatus (now Phocaeicola vulgatus) is a versatile catalyst that utilizes a wide range of phenolic molecules as substrates that are commonly encountered by the host. With this action, it modulates concentrations of donor phenolic sulfates such as acetaminophen sulfate, dopamine sulfate, p-cresol sulfate, and related compounds in vitro and displays broad acceptor flexibility by sulfonating diverse phenolic compounds, including p-coumaric acid, p-cresol, 4-ethylphenol, tyramine, among others. These findings suggest that gut microbial enzymes like ASSTs may contribute to host detoxification of phenolics, a role previously attributed solely to human sulfotransferases. However, further in vivo studies are necessary to understand the potential contributions of ASSTs to host detoxification processes.}, } @article {pmid41552775, year = {2026}, author = {Hodes, GE and Kropp, DR}, title = {Acute Estradiol Bridges Gut Microbiome Composition With Cognition.}, journal = {Biological psychiatry global open science}, volume = {6}, number = {2}, pages = {100662}, pmid = {41552775}, issn = {2667-1743}, } @article {pmid41552724, year = {2025}, author = {Wu, YC and Chen, BY and Duan, SZ}, title = {Oral microbiota in cardiovascular health and disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1731845}, pmid = {41552724}, issn = {2235-2988}, mesh = {Humans ; *Cardiovascular Diseases/microbiology/etiology ; *Microbiota ; *Mouth/microbiology ; Animals ; }, abstract = {Hundreds of microbial species inhabit the oral cavity and are essential to local and systemic health. Cardiovascular disease (CVD) causes a significant burden on global health, with its etiology and pathogenesis still not fully understood. Growing evidence indicates an association between the oral microbiome and CVD. However, the variability of populations, follow-up durations, and disease severity between various human investigations led to divergent conclusions. Animal studies have focused on the relationship between individual microbial species and CVD, yet gaps remain in the mechanisms between CVD and microbiome. In addition, a comprehensive understanding of the interactions between oral pathogens and the cardiovascular system has not been elucidated. In this Review, we summarize our current knowledge of basic and clinical research on potential mechanisms linking the oral microbiome to CVD and highlight the need for population-based studies with controlled baselines to establish mechanism links between oral microbial pathways and CVD.}, } @article {pmid41552720, year = {2025}, author = {Wang, Z and Zhang, T and Liu, Y}, title = {Emerging technologies and current challenges in intratumoral microbiota research.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1685862}, pmid = {41552720}, issn = {2235-2988}, mesh = {Humans ; *Tumor Microenvironment ; *Neoplasms/microbiology ; *Microbiota ; Computational Biology ; Single-Cell Analysis ; Animals ; }, abstract = {Intratumoral microbiota are now recognized as an integral component of the tumor microenvironment, affecting tumor initiation, metastatic potential, immune modulation, and treatment response. However, their extremely low biomass poses significant challenges for accurate detection, functional interpretation, and reproducibility, largely because the detection process is highly susceptible to environmental contamination. Standardization of analytical procedures has not yet been established; consequently, variability in sampling protocols, sequencing workflows, and bioinformatic pipelines further complicates cross-study comparisons and hampers the consolidation of robust evidence in this field. Recent advances in technology have begun to provide opportunities to overcome these barriers. Improved contamination-control strategies and more sophisticated decontamination algorithms have enhanced the reliability of microbial detection in low-biomass tissues. High-resolution approaches, such as single-cell RNA sequencing, spatial transcriptomics and optimized anaerobic cultivation, enable the sensitive identification, spatial localization, and mechanistic study of tumor associated microbes. Parallel developments in genome-resolved and enzyme-level analysis reveal microbial metabolic pathways that shape immune responses, drug resistance, and tumor progression. Organoid-based co-culture models further provide physiologically relevant platforms to dissect host-microbe-immune interactions and interpret microbiota-driven modulation of therapeutic responses. Integrating microbiome data with clinical and multi-omics profiles, assisted by artificial intelligence, is accelerating biomarker discovery and informing microbe-guided therapeutic strategies. Taken together, the standardization of research strategies, combined with the application of advanced detection technologies, is propelling the field beyond descriptive profiling toward mechanistic understanding and clinical translation, thereby unlocking the potential of intratumoral microbiota for precision oncology.}, } @article {pmid41552713, year = {2025}, author = {Rodríguez, ZG and Thome, SKR and Castillejos, RD and García-Reyes, ED and Martínez-Vargas, A and Nájera-Segura, NS and González, EEJ and Nivon-Torres, GF and Mascarua, EAA and Caballero-Sánchez, H and Palacios-Cruz, RL and Solórzano-Mata, CJ and Sosa-Velasco, TA and Zárate-Ortiz, C}, title = {Precision Pediatric Caries Diagnostics: Saliva-Check Mutans versus Culture for High-Density Streptococcus mutans Detection.}, journal = {Discoveries (Craiova, Romania)}, volume = {13}, number = {4}, pages = {e220}, pmid = {41552713}, issn = {2359-7232}, abstract = {The paradigm of dental medicine is shifting from a reactive surgical model to precision pediatric caries diagnostics, emphasizing early detection of pathogenic oral microbiota. Rapid point-of-care assays capable of identifying high-density Streptococcus mutans are critical to enable targeted intervention. This pilot study evaluated the diagnostic validity of a high- threshold monoclonal antibody-based lateral flow assay (Saliva-Check Mutans, SCM) relative to selective culture for identifying clinically meaningful S. mutans loads in children. Stimulated saliva samples were collected from 50 schoolchildren aged 9-13 years in Oaxaca, Mexico. Samples were analyzed using SCM and selective culture on Mitis Salivarius Agar (MSA), with presumptive S. mutans colonies confirmed biochemically. Selective culture identified 46% of participants as positive, whereas SCM detected 18% as positive. Relative to culture, SCM demonstrated 39.1% sensitivity (95% CI: 21.5%-60.1%), 100% specificity (95% CI: 87.5%-100%), and 100% positive predictive value (95% CI: 66.4%-100%), with no false positives observed. The results highlight the assay's rule-in capability for high-density pathogenic loads (>10^5 CFU/mL). The diagnostic discordance reflects divergent analytical thresholds, termed the "Threshold Gap". While SCM exhibits limited sensitivity for low-level colonization, its absolute specificity supports its use as a precision high-threshold triage tool, identifying pediatric patients with clinically significant S. mutans burdens who may benefit from intensified preventive strategies. Integration with culture or molecular approaches can enhance risk stratification and precision dentistry workflows.}, } @article {pmid41552431, year = {2026}, author = {Buonaccorsi, A and McMullen, BN and Builder, B and Drummond, K and Halteman, S and See, JC and Thomas, E and Viands, A and Worley, S and Wright, JR and Keeney, J and Lamendella, R}, title = {Metagenomic surveillance of tick-borne pathogens and microbiomes in Huntingdon County, Pennsylvania.}, journal = {One health (Amsterdam, Netherlands)}, volume = {22}, number = {}, pages = {101305}, pmid = {41552431}, issn = {2352-7714}, abstract = {The rise in tick populations across the United States has contributed to a surge in tick-borne diseases, with Pennsylvania ranking among the highest in reported cases. To better understand local pathogen prevalence and microbial community structure, an integrative study of ticks collected from ten recreational trails in Huntingdon County, Pennsylvania during the summer of 2023 was conducted. A total of 96 ticks were sampled, with 33 PCR-positive specimens selected for shotgun metagenomic sequencing. Pathogen screening via qPCR detected Borreliella burgdorferi, Borrelia miyamotoi, Babesia spp., and Anaplasma phagocytophilum. Shotgun metagenomics revealed a broader diversity of tick-borne pathogens, including Rickettsia and Ehrlichia spp., and demonstrated increased sensitivity by detecting low-abundance pathogens in samples that were PCR-negative. Co-infections were common, and multivariate statistical analysis identified significant associations between environmental variables (e.g., humidity, time of day, land cover) and microbial diversity and predicted gene function. Notably, diversity was higher in ticks collected during early afternoon and from northern sites. Co-occurrence network analysis showed Rickettsia as a central taxon with multiple significant positive associations with other microbes while other pathogens were largely absent or peripheral. These findings underscore the enhanced resolution of metagenomic approaches for pathogen detection and the value of combining molecular surveillance with ecological metadata. Our study provides critical insights into local tick microbiomes and pathogen prevalence, which may inform public health interventions and vector management strategies in central Pennsylvania.}, } @article {pmid41552224, year = {2025}, author = {Fu, X and Wang, X and Norbäck, D and Zhang, X and Sun, Y}, title = {A Comparative Analysis of Bacterial Communities in Settled Air Dust and Vacuumed Surface Dust From University Dormitories and Associations With Respiratory Health.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99514}, pmid = {41552224}, issn = {2168-8184}, abstract = {BACKGROUND: The indoor microbiome significantly impacts human health. Different sampling methods are used to characterize this environment, but it is unclear how these methods affect the resulting microbial profiles and health-related interpretations. This study aimed to compare the bacterial communities captured by two common methods, i.e., passive collection of settled air dust and active vacuuming of surface dust, and to evaluate how sampling choice influences epidemiological associations with respiratory health.

METHODS:  We collected paired settled air dust (n = 86) and vacuumed surface dust (n = 83) samples from 87 university dormitory rooms. The bacterial composition was characterized by sequencing the V3-V4 region of the 16S rRNA gene. We analyzed differences in bacterial diversity, taxonomic composition, predicted functional profiles, and associations with self-reported student health data (rhinitis, asthma, and respiratory infections).

RESULTS:  The two sampling methods captured drastically different bacterial communities (PERMANOVA R² = 0.65, p < 0.001). Vacuumed dust samples were dominated by the genus Pseudomonas (75.1% mean relative abundance), whereas air dust samples were more diverse and primarily composed of Ralstonia (15.6%), Pelomonas (11.3%), and Anoxybacillus (9.3%). Air dust samples exhibited significantly higher alpha diversity (observed taxa: 906.2 ± 179.6) compared to vacuumed dust (345.1 ± 82.3, p < 0.001). These compositional differences led to distinct predicted functional pathways and divergent associations with health outcomes. For asthma, airborne Collinsella was associated with strongly increased odds (OR 2.17, p = 0.003), while Paracoccus was associated with decreased odds (OR 0.062, p = 0.006). By contrast, associations in vacuumed dust were limited to taxa with small effect sizes, such as Peptoclostridium (OR 1.07, p = 0.004). Furthermore, while airborne genera like Slackia were associated with respiratory infections (OR 5.94, p = 0.005), no significant bacterial associations for respiratory infections were found in vacuumed dust.

CONCLUSION:  The choice between sampling settled air dust versus vacuumed surface dust provides profoundly different views of the indoor bacteriome, which can lead to contradictory conclusions in epidemiological studies of asthma and respiratory illness. Our findings underscore that the selection of an environmental sampling strategy is a critical methodological decision that can dictate the outcome and potential health implications of indoor microbiome research. Researchers must align their sampling method with a clear exposure hypothesis to ensure valid health risk assessments. Future indoor air quality standards and epidemiological studies should consider implementing multi-method sampling to capture a comprehensive profile of microbial exposure.}, } @article {pmid41551989, year = {2026}, author = {Wu, E and Li, X and Ni, Z and Zhao, F and Jia, C}, title = {Oral microbiome-SASP-aging axis: mechanisms and targeted intervention strategies for age-related diseases.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2616138}, pmid = {41551989}, issn = {2000-2297}, abstract = {BACKGROUND: Global demographic aging is intensifying the burden of age-related diseases. Cellular senescence and the accompanying senescence-associated secretory phenotype (SASP) act as key drivers of disease progression by mediating chronic inflammation. As the second largest microbial community in the human body, the oral microbiome occupies a central position in systemic aging pathologies, and its dysbiosis and interaction with SASP are critical in this process. An imbalanced oral microbiota contributes to systemic chronic conditions via metabolic activities, virulence factor release, and immune system activation, while SASP serves as a central molecular mediator linking microbial dysbiosis to chronic inflammation, with well-recognized involvement in inflammatory bowel disease, bone disorders, and neurodegenerative conditions.

OBJECTIVE: This review aims to examine the mechanism by which oral pathogens directly modulate SASP secretion via microbial metabolites and virulence factors to drive the pathogenesis of age-related diseases, propose a unifying framework of the 'oral microbiome-SASP-aging' axis, summarize therapeutic interventions targeting this axis, and suggest future development directions for precise modulation of the 'microbiome-SASP-aging' cascade.

DESIGN: A narrative review was conducted to synthesize and analyze existing literature on the interplay between the oral microbiome, SASP, and age-related diseases. The review focused on mechanisms of oral pathogen-mediated SASP modulation, therapeutic strategies targeting the 'oral microbiome-SASP-aging' axis, and potential advancements in precise therapeutic delivery and combinatorial therapies.

RESULTS: The 'oral microbiome-SASP-aging' axis serves as a unifying framework for these pathologies. SASP inhibitors, probiotics, and traditional Chinese medicine (TCM) targeting this axis show promise for age-related disease management. Additionally, spatiotemporally precise delivery systems and probiotic-TCM combinatorial therapies are proposed for precise modulation of the 'microbiome-SASP-aging' cascade.

CONCLUSIONS: The 'oral microbiome-SASP-aging' axis is a pivotal pathway driving age-related diseases. Therapeutic strategies targeting this axis hold significant promise for clinical management of these diseases. Future advancements in spatiotemporally precise delivery systems and combinatorial therapies are anticipated to enable precise modulation of the 'microbiome-SASP-aging' cascade, offering novel avenues for the prevention and treatment of age-related diseases.}, } @article {pmid41551917, year = {2026}, author = {Ling, C and Chen, X and Yang, J and Zhan, X and White, JC and Kah, M and Shen, Y and Xing, B}, title = {Multiscale Plant Defense Strategies against Ciprofloxacin Stress: From Chloroplast-Centered Adaptation to Microbiome Coordination.}, journal = {Research (Washington, D.C.)}, volume = {9}, number = {}, pages = {1082}, pmid = {41551917}, issn = {2639-5274}, abstract = {Biological stress responses operate across multiple scales, yet the coordination mechanisms remain poorly characterized. Here, we present comprehensive systems-level characterization of coordinated plant and endophytic microbiome responses during xenobiotic stress, integrating ultrastructural analysis, proteomics, and microbiome profiling in rice seedlings exposed to ciprofloxacin. We discovered a sophisticated multi-level defense system with chloroplasts as a key hub within a highly integrated cross-organellar network, comprising 36% of all differentially expressed proteins. The system operates through 3 integrated mechanisms: (a) differential cellular accumulation patterns showing 14-fold tissue-specific differences, (b) reactive-oxygen-species-associated metabolic processes with reduced toxicity of transformation products, and (c) restructuring of endophytic bacterial communities toward stress-resistant genera. This work indicates that biological systems deploy hierarchical, integrated responses spanning from organellar to ecosystem levels. The chloroplast-centered response represents a comprehensive characterization of multicompartmental responses with implications across multiple biological fields. Our findings illustrate how multidisciplinary systems approaches can uncover emergent properties of multiscale biological responses invisible to single-scale analyses, providing a framework for investigating multiscale responses across diverse biological systems.}, } @article {pmid41551788, year = {2026}, author = {Song, Q and Li, J and Liu, Y and Li, W and Li, M and Zhang, B and Guo, B}, title = {Metagenomics and volatile metabolomics reveal microbial succession and its correlations with fruity flavor volatile compounds during Mianhua industrial processing.}, journal = {Food chemistry: X}, volume = {33}, number = {}, pages = {103446}, pmid = {41551788}, issn = {2590-1575}, abstract = {Mianhua, a traditional fermentation-type staple food popular in northern China, undergoes dynamic microbial and volatile compound changes during industrial processing. 848 volatile compounds were identified using volatile metabolomics dominated by esters (18.51 %), notably hexanoic acid ethyl ester and octanoic acid ethyl ester, which confer fruity flavors. Metagenomics analysis revealed Proteus (25.93 %), Fructilactobacillus (16.63 %), Lactobacillus (10.16 %) and Companilactobacillus (7.14 %) as dominant genera. Mixing with traditional starters was critical for flavor development, driven by microbial succession and synergistic interactions between Lactobacillaceae (e.g., Fructilactobacillus sanfranciscensis and Lactobacillus helveticus) and Kazachstania during fermentation. Notably, F. sanfranciscensis and L. helveticus were significantly correlated with the formation of key esters with fruity characteristics, elucidating their roles in substrate conversion via carbohydrate metabolism and the esterification pathways. This study clarifies the microbial contributions to fruity flavor and provides insights into volatile-microbiota correlations, laying a foundation for future flavor-oriented research and industrial applications of microbiota regulation in Mianhua production.}, } @article {pmid41551650, year = {2025}, author = {Wu, Y and Li, W and Shi, J and Zhang, Z and Jing, C and Sheng, J and Li, Z and Shi, X and Liu, D and He, L and Sun, H}, title = {Microbiome-volatile metabolome analysis reveals aroma regulation driven by microbial niche competition in Jinggang honey pomelo wine.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1725554}, pmid = {41551650}, issn = {1664-302X}, abstract = {INTRODUCTION: Microbial succession in fruit wine has been reported, but the ecological mechanisms linking niche competition to aroma formation remain poorly understood. To test the hypothesis that niche competition between microbial communities significantly influences aroma formation in pomelo wine, the flesh of Jinggang honey pomelo was subjected to semi-inoculation fermentation to produce Jinggang honey pomelo wine.

METHODS: High-throughput amplicon sequencing technology was used to investigate the evolving microbial community during the fermentation process of pomelo wine. The changes in volatile compounds were measured using headspace solid phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS).

RESULTS: The dominant taxa in the wine were Weissella, Pediococcus, Lactiplantibacillus, Saccharomyces, Komagataella, Wickerhamomyces, and Aspergillus. The microbiota shifts were associated with dynamic changes in physicochemical properties, and they altered the pH, alcohol content, total soluble solids, and overall acidity. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and relative odor activity value analysis identified 17 key volatiles. A correlation network analysis revealed that Lactiplantibacillus and Aspergillus were strongly associated with various flavor molecules.

DISSCUSSION: The present findings suggested that inter-kingdom niche competition between fungi and bacteria plays a pivotal role in shaping the aroma profile of pomelo wine, offering new insights for targeted aroma regulation.}, } @article {pmid41551598, year = {2025}, author = {Verbunt, J and Jocken, J and Canfora, E and Barnett, D and Blaak, EE and Savelkoul, P and Stassen, F}, title = {Assessment of the reproducibility of bacterial membrane vesicle isolation and characterization.}, journal = {Extracellular vesicles and circulating nucleic acids}, volume = {6}, number = {4}, pages = {728-741}, pmid = {41551598}, issn = {2767-6641}, abstract = {Aim: This study aimed to evaluate the reproducibility of the isolation and characterization of feces-derived bacterial membrane vesicles. Methods: Human fecal samples (n = 12) stored at -80 °C were thawed, sampled, and then refrozen. From these samples, bacterial membrane vesicles were isolated through ultrafiltration, ultracentrifugation and size exclusion chromatography. Vesicle-associated DNA was characterized by marker [16 ribosomal DNA (rDNA)] sequencing to determine composition. The same fecal samples were thawed again after > 6 months of storage at -80 °C to repeat this procedure. Compositions and other vesicle characteristics were compared to investigate effects of storage and freeze/thawing on sample stability. In addition, for four of the fecal aliquots, the bacteria were subjected to marker gene sequencing alongside their derived membrane vesicles. Results: No significant differences were observed in the pre- and post freeze/thawing composition of feces-derived bacterial membrane vesicles [permutational multivariate analysis of variance (PERMANOVA) P = 0.356] or bacteria (PERMANOVA P = 0.721) as determined by 16S rDNA sequencing. Additionally, no significant differences were observed in vesicle size, concentration, and associated protein or DNA content. These results indicate that, long-term storage of feces at -80 °C and an additional freeze/thawing cycle does not induce compositional or qualitative changes to vesicle repertoires. Conclusion: These reproducibility findings hold great relevance for research on (gut)bacteria derived membrane vesicles. Our results indicate that fecal samples can be stably preserved at -80 °C for bacterial and vesicle isolations as their characteristics remain stable over time.}, } @article {pmid41551583, year = {2026}, author = {Chen, T and Huang, R and Huang, Y and Wang, J and Wang, Z and Zhang, X}, title = {Shared signatures of alcohol-associated dysbiosis in humans and non-human primates.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100534}, pmid = {41551583}, issn = {2666-5174}, abstract = {Alcohol use disorder (AUD) is a chronic brain disease with limited therapeutic options. Increasing evidence suggests that the gut microbiome contributes to AUD via the microbiome-gut-brain axis. Here, we conducted a cross-species investigation of gut microbiota alterations in patients with clinically diagnosed AUD and in non-human primates (NHPs) subjected to long-term alcohol (ethanol) self-administration, using metagenomic sequencing. Both cohorts showed reduced microbial diversity and conserved dysbiosis, with consistent depletion of Verrucomicrobia, Actinobacteria, Faecalibacterium, Akkermansia, Intestinibacter, Phascolarctobacterium, and Ruminococcus, alongside increased Blautia and Coprococcus. These microbial shifts correlated with liver function indices, notably positive associations between Ruminococcus and bilirubin levels in both species, suggesting a potential role in liver injury. Functional analyses revealed conserved microbial adaptations, including upregulated DNA repair pathways, fermentative energy metabolism, and downregulated glutamate/glutamine biosynthesis. Together, these results identify evolutionarily conserved microbial and metabolic alterations linking alcohol consumption, gut dysbiosis, and hepatic dysfunction. Our cross-species evidence highlights the gut microbiome as a potential biomarker and therapeutic target for AUD.}, } @article {pmid41551422, year = {2026}, author = {Cai, T and Yao, J and Jiang, H and Zou, J and Xia, T and Mou, X and Zhang, S and Tan, X and Tang, J and Xiang, W}, title = {Tetracycline residue alters the nutritional quality and bioactive composition of soybean sprouts: Evidence from transcriptomic and rhizosphere microbiota analyses.}, journal = {Food chemistry. Molecular sciences}, volume = {12}, number = {}, pages = {100345}, pmid = {41551422}, issn = {2666-5662}, abstract = {Antibiotic residues in edible crops have become an increasing food safety concern, yet their impacts on crop nutritional quality and bioactive composition remain poorly understood. Here, we investigated the effects of tetracycline, a widely used antibiotic in soil-vegetable systems, on the growth and nutritional quality and bioactive composition of soybean sprouts. Results showed tetracycline exposure significantly inhibited sprout growth and nutrient accumulation in a dose-dependent manner, with high concentrations reducing vitamin C, total flavonoids, and coumestrol contents by approximately 50 %, 30 %, and 43 %, respectively. Transcriptomic analysis revealed that these related declines were associated with disruptions in carbon, amino acid, and lipid metabolism, as well as in flavonoid and coumestrol biosynthesis pathways. In parallel, rhizosphere microbiota analysis showed that tetracycline reshaped microbial community structure by reducing nitrogen-cycling-related taxa (Dokdonella, Acidibacter) and enriching resistant genera (Acinetobacter), which were significantly correlated with changes in sprout nutritional quality and bioactive composition. Together, these results demonstrate that tetracycline residues drive substantial losses of nutritional and bioactive composition in edible crops through coordinated metabolic and microbiome-mediated mechanisms, revealing an underappreciated pathway by which antibiotic contamination threatens crop nutritional value and food quality.}, } @article {pmid41551418, year = {2025}, author = {Wark, G and Kaakoush, NO and Samocha-Bonet, D and Ghaly, S and Danta, M}, title = {Oral Microbial Diversity is Associated with Biologic Treatment and Metabolic Health Status but not with Disease Activity in Patients with Inflammatory Bowel Disease.}, journal = {Crohn's & colitis 360}, volume = {7}, number = {4}, pages = {otaf047}, pmid = {41551418}, issn = {2631-827X}, abstract = {BACKGROUND: Higher diversity of the oral microbiome has been associated with poorer oral health outcomes in the general population. We aimed to characterize the oral microbiota in patients with inflammatory bowel disease (IBD) and compare this with that of healthy controls (HC). We also sought to examine associations between IBD management and disease control, diet and metabolic disease with oral microbial diversity.

METHODS: This prospective case-control study compared participants with IBD in clinical remission with HC. Baseline anthropometry and fasting blood metabolic markers were measured, dietary intake recorded, and oral samples were collected for 16S rRNA gene amplicon sequencing.

RESULTS: There were 57 patients with IBD (Ulcerative colitis (UC) = 26, Crohns Disease (CD) = 31) and 24 HC enrolled. There were no significant differences in oral microbial diversity between the IBD and HC cohorts. Among participants with IBD, oral microbial diversity did not associate with IBD activity nor risk of subsequent disease flare (adj-P = .28), however the use of biologic medications was associated with a lower oral microbial alpha diversity (species richness P = .01). Higher plasma insulin concentrations were associated with a higher oral alpha diversity (species richness adj-P < .01) and with beta diversity (Pseudo-F: 2.05, P = .02).

CONCLUSIONS: Oral microbial diversity is not associated with IBD disease activity or course but is positively influenced by biologic treatment. Higher fasting insulin, however, is associated with more diverse "unhealthy" oral microbiota. Within the limitations of this small study, oral microbiota may be a better marker of metabolic health than of IBD activity.}, } @article {pmid41551289, year = {2025}, author = {Zhang, J and Thomas Backet, RV and Sekela, JJ and Zeller, MJ and Sellers, RS and Redinbo, MR and Gulati, AS and Bhatt, AP}, title = {Commercially Purchased and In-House Bred C57BL/6 Mice with Different Gut Microbiota Exhibit Distinct Indomethacin-Induced Toxicities.}, journal = {Gut microbes reports}, volume = {2}, number = {1}, pages = {}, pmid = {41551289}, issn = {2993-3935}, support = {R01 GM135218/GM/NIGMS NIH HHS/United States ; R35 GM155168/GM/NIGMS NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 DK122042/DK/NIDDK NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; R35 GM152079/GM/NIGMS NIH HHS/United States ; }, abstract = {Non-steroidal anti-inflammatory drug (NSAID)-induced toxicities are a significant clinical problem, yet the factors influencing these outcomes remain incompletely understood. Here, we investigated the impact of mouse vendor on indomethacin-induced injury using C57BL/6 mice from different breeding facilities (in-house "Tar Heel" and commercial Charles River). We found that Tar Heel mice exhibited significantly enhanced susceptibility to indomethacin toxicity, characterized by greater body weight loss, increased ileal ulceration, elevated fecal lipocalin-2 levels, and higher goblet cell numbers in ileum compared to Charles River mice. Importantly, whole genome metagenomic analysis revealed distinct baseline gut microbiomes between the two types of mice. Notably, Tar Heel mice showed higher abundances of β-glucuronidase (GUS)-producing bacteria, particularly those expressing Loop-1 GUS enzymes, and elevated levels of mucolytic enzyme-encoding bacteria. These differences suggest that enhanced indomethacin toxicity observed in Tar Heel mice may be related to functional changes in their gut microbiome, which may predispose to an exaggerated response to NSAID exposure. Together, our findings demonstrate that vendor-specific differences significantly influence NSAID-induced intestinal toxicity and highlight the importance of considering mouse sources and gut microbial compositions in experimental design. Moreover, we highlight potential functional roles that gut microbes play in host-indomethacin interactions.}, } @article {pmid41551178, year = {2026}, author = {Esposito, A and Valentino, V and Tagliamonte, S and Sequino, G and Vitaglione, P and Ercolini, D and De Filippis, F}, title = {Development of a synbiotic dietary supplement containing potential Next Generation Probiotics for modulation of the gut microbiome and metabolome.}, journal = {Current research in food science}, volume = {12}, number = {}, pages = {101289}, pmid = {41551178}, issn = {2665-9271}, abstract = {The term Next Generation Probiotics (NGPs) refers to microbial strains positively impacting on human health, but do not belong to common probiotic species (e.g., lactic acid bacteria, LAB). We characterized genomically and phenotypically 14 strains isolated from the gut microbiome of healthy individuals, to evaluate their ability to produce urolithins, equol and short-chain fatty acids (SCFA). The 4 most promising strains (namely Bacteroides uniformis A4, Bacteroides thetaiotaomicron A14, unclassified Bacteroidaceae A26 and unclassified Lachnospiraceae A49) were used for the production of a synbiotic formulation, containing the strains and the precursors of health-promoting molecules. This dietary supplement was administered for 2 weeks to a continuous mucosal-Simulator of the Human Intestinal Microbial Ecosystem (mSHIME) model inoculated with a faecal sample from a low fiber-consuming donor. We performed Shotgun Metagenome Sequencing on a total of 204 samples collected from lumen and mucosa compartments, and determined the concentration of SCFA, equol and urolithin. Our results highlighted that the potential NGP strains contained in the supplement persisted in the gut ecosystem during 2 weeks of washout (Wilcoxon's rank sum test, p-value <0.05). In addition, the treatment led to an enrichment in beneficial taxa and to an increase in the production of SCFAs (p-value <0.05). This study demonstrated that feeding the gut microbiota with NGPs and dietary prebiotics can modulate both the gut microbiome and metabolome, suggesting a potential beneficial impact on human health. However, further in vivo studies are needed to confirm these results.}, } @article {pmid41551170, year = {2026}, author = {Chang, CC and Pak, J and Bae, S and Kim, GD and Son, HS}, title = {Impact of low aging temperature on the microbial and metabolic dynamics of rice wine during long-term storage.}, journal = {Current research in food science}, volume = {12}, number = {}, pages = {101294}, pmid = {41551170}, issn = {2665-9271}, abstract = {This study investigated the effects of aging temperature and microbial inoculation on the physicochemical, microbiological, and metabolic properties of Korean rice wine (makgeolli) during long-term storage. Samples were aged at three different temperatures (4 °C, -1 °C, and -5 °C) for 180 days and were inoculated with Lactiplantibacillus plantarum or Saccharomyces cerevisiae to examine their respective influences on metabolite shifts during cold storage. Microbial communities were analyzed using amplicon (16S rRNA) and shotgun metagenomic sequencing, and metabolite profiles were determined by GC-MS to provide an integrative understanding of microbial and metabolic stability during long-term cold storage. Lower aging temperatures reduced fluctuations in metabolic and microbial activities, particularly among LAB, thereby contributing to a more stable physicochemical profile and extended shelf life. During rice wine aging, LAB exerted a more pronounced effect on metabolite dynamics than yeast, particularly for pyruvate, γ-aminobutyric acid, and lactic acid, underscoring their role in the aging process. Additionally, sub-zero aging temperatures preserved the initial microbial composition, limited enzymatic degradation, and stabilized organic acid profiles, reflecting enhanced chemical stability of the product during aging. While such chemical stability may have implications for sensory outcomes, this remains a hypothesis that requires direct sensory evaluation in future studies. Overall, the findings suggest that controlled storage temperatures and targeted microbial inoculation can improve the chemical and microbiological stability of rice wine during long-term storage.}, } @article {pmid41551013, year = {2025}, author = {Wang, C and Chang, K and Chen, M and Zou, X and Ni, Y and Zhang, Q and Zhao, L and Xing, B and Guo, L and Chen, W and Cao, B}, title = {Enrichment of the commensal microbiome in the lower respiratory tract is associated with improved outcomes following lung transplantation.}, journal = {Chinese medical journal pulmonary and critical care medicine}, volume = {3}, number = {4}, pages = {308-318}, pmid = {41551013}, issn = {2772-5588}, abstract = {BACKGROUND: Alterations in the respiratory microbiome are common following lung transplantation; however, the complex relationship between microbial composition and posttransplant clinical outcomes remains insufficiently characterized. This study aimed to delineate microbial signatures within the lower respiratory tract and to elucidate their associations with posttransplant outcomes in lung transplant recipients (LTRs).

METHODS: Metagenomic sequencing was performed on 138 bronchoalveolar lavage fluid (BALF) samples collected in 2023 from patients who had undergone lung transplantation between 2017 and 2023 at the China-Japan Friendship Hospital. Lung function indices, hematologic parameters, and serum cytokine levels were assessed, and patients were prospectively followed to record adverse clinical events.

RESULTS: The lung microbiome of stable LTRs formed four distinct clusters, exhibiting marked heterogeneity in both α- and β-diversity. The most prevalent cluster, enriched with oral-origin commensals, such as Neisseria subflava (N. subflava), Prevotella melaninogenica, and Streptococcus mitis (S. mitis), demonstrated the highest microbial diversity, and was associated with the lowest C-reactive protein levels, fewest adverse events, and the longest complication-free postoperative duration. In contrast, a virus-enriched cluster characterized by reduced diversity and high abundance of Torque teno virus and Cytomegalovirus human betaherpesvirus 5 was associated with poorer outcomes. BALF samples from infected LTRs exhibited more severe dysbiosis than those from immunocompetent individuals, with reduced diversity and pathogen dominance. Concurrent infections aggravated antibody-mediated rejection-related lung function decline, indicating complex microbiome-immune interactions. Integrative modeling of microbiome, hematologic, and pulmonary function data yielded superior diagnostic performance for infection detection (area under the receiver operating characteristic curve = 0.93).

CONCLUSION: The composition of the lung microbiome may serve as a prognostic biomarker for clinical outcomes after lung transplantation. The presence of diverse, commensal-dominated communities was associated with improved outcomes, whereas viral enrichment correlated with adverse events. These findings underscore the clinical importance of microbiome monitoring in posttransplant management and suggest that targeted modulation of microbial communities could improve long-term graft stability and patient prognosis.}, } @article {pmid41551009, year = {2025}, author = {Wang, B and Wang, Y and Ning, K}, title = {Unveiling the role of the respiratory microbiome in long COVID pathogenesis and therapeutics.}, journal = {Chinese medical journal pulmonary and critical care medicine}, volume = {3}, number = {4}, pages = {221-224}, pmid = {41551009}, issn = {2772-5588}, } @article {pmid41550969, year = {2026}, author = {Wei, Y and Lu, J and Wu, S and Mo, Z and He, H and Shen, Y and Zou, J and Xing, C and Huang, Y and Jiang, Q}, title = {Comparative Analysis of the Effects of Mogroside V, Epigallocatechin Gallate, and Resveratrol on Growth Performance, Blood Parameters, Rumen Microbiota, and Short-Chain Fatty Acid Metabolism in Heat-Stressed Hu Sheep.}, journal = {Food science & nutrition}, volume = {14}, number = {1}, pages = {e71455}, pmid = {41550969}, issn = {2048-7177}, abstract = {Hu sheep are highly prized for their tender meat, but heat stress (HS) caused by the high temperature and humidity in southern China severely impacts their performance. This study compared the alleviating effects of Mogroside V (Mog V), epigallocatechin gallate (EGCG), and resveratrol (RES) on HS in Hu sheep. Forty male Hu sheep were randomly divided into a control group and three treatment groups (n = 10), each with a pen. The sheep were housed under HS for 60 days. Body weight, feed conversion ratio (FCR), respiratory rate (RR), and rectal temperature (RT) were monitored. Blood physiological parameters, HSPs, antioxidant enzymes, and inflammatory factors were measured. 16S rRNA sequencing and targeted metabolomics were used to analyze the correlation between rumen microbiota and short-chain fatty acid (SCFA) metabolites. Results showed that all three extracts significantly increased final weight, total weight gain, and daily weight gain, while reducing FCR, RR, and RT. They also decreased HSP70/90, MDA, and the inflammatory factors TNF-α, IL-1β, and IL-6, and increased antioxidant enzyme activity. Microbiome and metabolome analysis revealed that RES increased Verrucomicrobia and Fibrobacterium, promoting propionic and butyric acid production; Mog V enriched Firmicutes and Clostridium succinate, promoting energy metabolism; and EGCG regulated acetate metabolism through Lactobacilli, inhibiting pathogenic bacteria. In summary, all three plant extracts alleviated the physiological damage caused by HS and improved production performance, with Mog V showing the most significant effect and possessing high potential for application.}, } @article {pmid41550964, year = {2026}, author = {Wang, AYL and Aviña, AE and Liu, YY and Kao, HK}, title = {Microbial allies in skin trauma recovery: from immune modulation to engineered probiotic therapeutics.}, journal = {Burns & trauma}, volume = {14}, number = {}, pages = {tkaf068}, pmid = {41550964}, issn = {2321-3868}, abstract = {Research shows that the microbiome of the skin is present as an active contributor to wound healing processes by moving past its historical infection-related function. The review investigates how commensal and probiotic bacteria affect immunomodulation while accelerating epithelial growth, together with tissue repair processes. Researchers use modern methods to link immunological concepts with material science along with synthetic biological techniques to study engineered probiotics which transform current wound treatments. The research study represents an extensive integration of recent findings concerning probiotic-mediated immunomodulatory operations and engineered approaches that improve probiotic delivery systems and their performance during skin wound healing procedures. Recent genetically engineered Lactobacillus reuteri strains that express chemokines like CXCL12 have been found to promote wound healing to an accelerated rate in animal models, and pre-clinical phases of clinical trials in the setting of diabetic foot ulcers (DFU) has demonstrated safety and therapeutic potential. Simultaneously, another live biotherapeutic product has been validated in terms of regenerative and immunomodulatory properties in animal models and in a clinical trial, a multi-cytokine-integrated strain of Lactococcus cremoris secreting FGF-2, IL-4, and CSF-1 promoted faster wound healing in diabetic mice and healed 83% of subjects in a Phase I DFU study. The range of probiotic therapies for trauma care expands due to advancements in probiotic delivery using materials and membrane vesicles derived from probiotics. This review builds a detailed framework that connects core immune functions with modern engineering methods for developing smart wound healing systems that combine engineered probiotics with bioresponsive materials and real-time monitoring systems. Engineered probiotics promise to become an alternative strategy for treating chronic wounds and infection-related complications that currently create significant medical problems.}, } @article {pmid41550925, year = {2025}, author = {Neff, CP and Siebert, J and Karr, M and Lippincott, R and Kvaal, R and Noe, AT and Wall, E and Nusbacher, N and Fiorillo, S and Fennimore, BP and Campbell, TB and Lozupone, C and Palmer, BE}, title = {Gut microbiome composition influences immunologic alterations in the blood and gut of HIV-positive and HIV-negative men who have sex with men.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1707736}, pmid = {41550925}, issn = {1664-3224}, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/immunology ; *HIV Infections/immunology/microbiology/blood ; *Homosexuality, Male ; Adult ; Middle Aged ; Colon/immunology/microbiology ; Immunity, Innate ; }, abstract = {BACKGROUND: HIV infection and factors associated with sexual activity among men who have sex with men (MSM) can dysregulate relationships between the gut microbiome and immune system.

METHODS: To explore these relationships in depth, blood and colonic biopsy samples from HIV+ and HIV- MSM and non-MSM were analyzed using Cytometry by Time of Flight (CyTOF). Immune profiles were then integrated with gut microbiome composition and MSM-related behaviors.

RESULTS: HIV infection status influenced immune cell composition in colonic biopsies, marked by a loss of CD4⁺ CD103⁺ and CD8⁺CD103⁺ tissue-resident T cells and group 3 innate lymphoid cells (ILC3s). In the blood, HIV status was linked to reductions in circulating group 2 innate lymphoid cells (ILC2s), and naïve CD8⁺ T cells, while mucosal-associated invariant T (MAIT) cells were reduced in MSM engaging in high-risk sexual behaviors regardless of HIV status. Network analysis revealed distinct, tissue-specific relationships between immune cell populations and gut microbial taxa, further shaped by both HIV infection and MSM-associated factors.

CONCLUSIONS: These findings provide new insights into host:microbe interactions, with implications for immune regulation, HIV persistence, and transmission among MSM.}, } @article {pmid41550814, year = {2026}, author = {Mechshanova, A and Berillo, D and Polyakov, V}, title = {Chemical composition and ecological adaptation of Populus (Salicaceae) species and hybrids depending on soil and environmental conditions.}, journal = {RSC advances}, volume = {16}, number = {4}, pages = {3368-3386}, pmid = {41550814}, issn = {2046-2069}, abstract = {This review synthesizes two decades of research on the interplay between soil properties and genotype in shaping the chemical composition and adaptive traits of hybrid poplars (Populus spp.). The present review is grounded in a comprehensive survey of peer-reviewed literature published from 2000 to 2025. Out of approximately 400 identified documents, 100 were chosen according to their scientific validity, methodological soundness, and pertinence to the study's objectives. The search strategy incorporated databases including PubMed, PubChem, Google Scholar, Scopus, and ResearchGate, using keyword combinations such as Populus species & soil, Populus species & ecological role, and Populus species & pollutant uptake. Unlike previous summaries, it advances the field by highlighting novel insights into genotype soil-metabolite interactions, demonstrating how macro- and micro-nutrient uptake influences the accumulation of flavonoids, salicylates, and other polyphenolic derivatives. It also examines how trees respond to soil pH, organic matter, and contamination, including radionuclides, and how feedback via rhizosphere microbiomes and leaf litter decomposition regulates nutrient cycling and microbial biomass. Beyond integration, the review identifies critical gaps, notably the lack of long-term field validation of soil-microbiome-metabolite linkages and the need for directed breeding of poplar varieties with specific metabolite traits. By outlining how selective breeding, metabolomics, and chemical modification of plant-derived compounds can be harnessed for bio-based materials and pharmaceuticals, and by providing region-specific case studies in urban greening, phytoremediation, bioenergy, and agroforestry, this synthesis establishes a framework for translating biochemical insights into applied strategies for ecosystem restoration and sustainable land use.}, } @article {pmid41550645, year = {2025}, author = {Wang, X and Wang, X and Cao, Y and Wang, W and Liu, D and Zhang, J and Chen, Y and Chen, D}, title = {Nanoplatforms in sepsis storm: Multimodal synergy for precision immunomodulation and pathogen neutralizations.}, journal = {Pharmaceutical science advances}, volume = {3}, number = {}, pages = {100087}, pmid = {41550645}, issn = {2773-2169}, abstract = {Sepsis, a severe global health challenge characterized by life-threatening organ dysfunction stemming from a dysregulated immune response to drug-resistant pathogens, imposes a substantial disease burden. The intricate nature of sepsis necessitates meticulous drug administration and underscores the urgency for advanced drug delivery strategies. This paper presents a comprehensive overview of recent advancements in nanotechnology-driven therapeutic interventions for sepsis, emphasizing innovative approaches such as stimulus-responsive and nano-drug delivery systems that have been applied to tackle sepsis and its associated complications. Drawing from various theories and mechanistic insights into sepsis pathogenesis, we explore novel therapeutic avenues and their potential integration with nano-delivery systems, considering factors such as the microenvironment. We demonstrate how these nano-delivery systems can enhance treatment accuracy and diversity. Furthermore, the synergy between nanomedicine and emerging technologies like CRISPR, CAR-T therapy, AI, microfluidics, microbiome research, and immunotherapy holds the promise to revolutionize sepsis diagnosis, treatment, and management strategies. However, overcoming pathogen resistance, precisely modulating excessive immune response/immunosuppression, and achieving efficient targeted delivery of nanocarriers in complex pathological environments remain core challenges. Future research needs to focus on the development of smarter and more responsive nanoplatforms and deeply explore their deep integration with multiple cutting-edge technologies in order to advance the clinical translation of precision sepsis diagnosis and treatment.}, } @article {pmid41550372, year = {2025}, author = {Tenea, GN and Jarrin-V, P and Lin, L}, title = {Editorial: Trigger the microbiome changes in foods via metagenomic technologies: from diagnostic to potential changes in product safety or quality risk profiles.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {13}, number = {}, pages = {1766291}, doi = {10.3389/fbioe.2025.1766291}, pmid = {41550372}, issn = {2296-4185}, } @article {pmid41550264, year = {2026}, author = {Ali, N}, title = {Interactions between serum uric acid and gut microbiota: implications for metabolic health.}, journal = {Metabolism open}, volume = {29}, number = {}, pages = {100438}, pmid = {41550264}, issn = {2589-9368}, abstract = {Serum uric acid (SUA), the end product of purine metabolism, is a known risk factor for developing gout; however, recent evidence suggests its broader role in metabolic disorders. The gut microbiota, a complex microbial ecosystem, plays a crucial role in influencing purine metabolism and intestinal uric acid (UA) excretion. Recent findings have uncovered a two-way relationship: certain microbes can metabolize purines and UA, while elevated UA can reduce microbial diversity, alter the production of SCFAs, and compromise intestinal barrier function. These interactions are linked to obesity, insulin resistance, T2D, NAFLD, and CVD, connecting purine metabolism with overall metabolic health. This review synthesizes current experimental and clinical evidence on SUA-microbiota interactions, with an emphasis on microbial enzymes, host urate transporters, and microbial metabolites, including bile acids and SCFAs. It also discusses therapeutic implications, spanning urate-lowering drugs to microbiota-targeted strategies, including probiotics, prebiotics, and dietary modulation. Despite progress, significant gaps remain: most human studies are cross-sectional, microbial taxa influencing SUA remain inconsistent, and interindividual microbiome variability limits the translation of findings to personalized care. Future multi-omics and longitudinal approaches are necessary to elucidate causal pathways and identify biomarkers, ultimately informing innovative strategies for the prevention and treatment of metabolic diseases beyond gout.}, } @article {pmid41550022, year = {2026}, author = {Sun, R and Chen, Y and Tang, X}, title = {Gut Microbiota-Derived Small Molecules in Atherosclerosis: Biosynthesis, Mechanistic Insights, and Translational Potential.}, journal = {Journal of natural products}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jnatprod.5c01353}, pmid = {41550022}, issn = {1520-6025}, abstract = {Atherosclerosis (AS) is the pathological foundation of most cardiovascular diseases and remains a major cause of global mortality. Increasing evidence implicates gut microbiota-derived small molecules (GMDSMs) as critical chemical modulators of lipid metabolism, vascular inflammation, and thrombosis. In this review, we summarize representative GMDSMs that have been mechanistically linked to AS, including amino acid derivatives, fatty acids, trimethylamine N-oxide, bile acids, and bacterial cell membrane compartments. For each class, we highlight representative biosynthetic enzymes, microbial taxa, and host targets that mediate atherogenic or protective effects. Mechanistic studies have established distinct microbial-host cometabolic pathways linking diet, microbiota composition, and cardiovascular outcomes. We further discuss emerging therapeutic strategies that modulate microbial metabolism or harness beneficial metabolites for AS prevention. Elucidating the biosynthetic diversity and functional logic of these molecules will accelerate the development of microbiome-based diagnostics and interventions for cardiovascular disease.}, } @article {pmid41549758, year = {2026}, author = {Ai, T and Sun, K and Jin, LN and Zhu, X and Peng, W and Huang, J and Sun, J and Zhu, L}, title = {Biotransformation of Acetaminophen in Rice Phyllosphere: Xenobiotic-Plant-Microbiota Interactions.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c10295}, pmid = {41549758}, issn = {1520-5118}, abstract = {The biotransformation of acetaminophen, a pharmaceutical contaminant widely found in crop produce, in the rice phyllosphere highlights critical xenobiotic-plant-microbiota interactions. This study investigated acetaminophen uptake, translocation, and transformation in hydroponically exposed rice shoots, revealing accumulation at 8.33 ± 0.82 μg/g and conversion into hydroxylated, glycosylated, methylated, thiomethylated, sulfonated, dimerized, and amino acid-conjugated derivatives. Specifically, these transformations may be driven by plant enzymes (cytochrome P450, glycosyltransferases, sulfotransferases, and methyltransferases) and synergistically by enriched microbial genera (Sphingomonas, Pantoea, and Pseudomonas). Furthermore, acetaminophen stress altered the rice phyllosphere metabolome (elevated linoleic acid and jasmonic acid) and reshaped microbial communities, with enhanced degradation pathways and network complexity indicating adaptive stress mitigation. Overall, this integrated transcriptome, metabolome, and microbiome profiling provides mechanistic insights into the cooperative detoxification role of plant enzymes and phyllosphere microbes, offering perspectives on leveraging plant-microbiota interactions to reduce xenobiotic impacts on crops and food safety.}, } @article {pmid41549477, year = {2026}, author = {Muradova, M and Proskura, A and Senty-Segault, V and Boichot, V and Ilina, V and Poirier, N and Gourrat, K and Chaloyard, J and Nadtochii, L and Baranenko, D and Heydel, JM and Canon, F and Lirussi, F and Schwartz, M and Neiers, F}, title = {A Human Oral Bacterial β-Glucosidase Involved in Aroma Release from Glycosides.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13712}, pmid = {41549477}, issn = {1520-5118}, abstract = {Flavor perception is driven by the interplay of gustation, olfaction, and somatosensory inputs. Among the factors influencing flavor perception, the enzymatic activity of oral bacterial glycosidases plays a role in modulating taste and aroma, generating aroma molecules from glycosidic precursors. This study investigates the in vitro capacity of oral bacterial β-glucosidases to hydrolyze glycosidic aroma precursors. Seven candidate enzymes from oral bacteria were recombinantly produced and screened for glycosidase activity. Among them, only the β-glucosidase from Prevotella sp. (PsBG1) showed hydrolytic activity toward chromogenic substrates and the aroma glucosides tested, leading to the release of salicylaldehyde, hexanol, and octanol, as confirmed by GC-MS. Structural analysis of PsBG1 revealed key residues involved in substrate recognition and catalysis. These results identify a specific oral bacterial enzyme capable of releasing aroma-active compounds from glycosides in vitro, suggesting a potential contribution of oral microbiota enzymatic activity to in-mouth aroma release.}, } @article {pmid41549467, year = {2026}, author = {C A M Fernandes, G and Rodeo, SA}, title = {Metabolic Optimization Before Orthobiologic Therapies (MOBOT): A Narrative Review.}, journal = {Sports health}, volume = {}, number = {}, pages = {19417381251409133}, doi = {10.1177/19417381251409133}, pmid = {41549467}, issn = {1941-0921}, abstract = {CONTEXT: The efficacy of orthobiologic therapies, such as platelet-rich plasma (PRP) and concentrated bone marrow aspirate (cBMA), is influenced by not only the biologic product but also the patient's systemic biological milieu. Emerging preclinical and clinical evidence suggests that modifiable metabolic factors, including obesity, insulin resistance, chronic low-grade inflammation, inflammaging, sarcopenia, dysbiosis, poor sleep, and lifestyle behaviors such as smoking and alcohol use, can impair tissue regeneration and reduce the effectiveness of orthobiologics.

EVIDENCE ACQUISITION: A structured approach guided article selection. Searches in PubMed, Embase, and Scopus through July 2025 were supplemented by reference checking. Terms included "metabolic optimization," "obesity," "insulin resistance," "inflammation," "sarcopenia," "dysbiosis," "sleep," "orthobiologics," "PRP," and "bone marrow aspirate." Preclinical and clinical studies, mechanistic reviews, and meta-analyses assessing the impact of metabolic factors on musculoskeletal regeneration and orthobiologic outcomes were included. Only English-language articles relevant to mechanisms, clinical implications, or patient optimization were considered.

STUDY DESIGN: Narrative review.

LEVEL OF EVIDENCE: Level 5.

RESULTS: Evidence-based strategies to optimize metabolic health include targeted exercise, nutritional optimization, pharmacologic interventions, sleep regulation, microbiome support, and behavioral counseling for tobacco and alcohol cessation. While clinical evidence remains limited and of low methodological rigor, preclinical and available clinical studies support the plausibility, safety, and potential efficacy of these interventions. Optimizing metabolic factors can enhance tissue responsiveness, reduce interpatient variability, and improve orthobiologic therapy outcomes.

CONCLUSION: Optimizing metabolic health before orthobiologic therapy improves the biological environment and regenerative outcomes. Screening and managing factors such as insulin resistance, chronic inflammation, and poor sleep are essential. Further randomized controlled trials and biomarker-guided studies are needed to validate strategies and personalize interventions.Strength-of-Recommendation Taxonomy (SORT):C: Supported mostly by preclinical and indirect clinical evidence.}, } @article {pmid41549355, year = {2026}, author = {Ye, L and Ruan, M and Xiao, N and Rao, C and Ming, J and Dan, H and Zeng, X and Liu, T and Wang, J}, title = {Oral Microbial Dysbiosis and Pathogenic Functional Shifts in Mucosa-Dominant Pemphigus Vulgaris and Low-Risk Mucous Membrane Pemphigoid.}, journal = {Oral diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/odi.70207}, pmid = {41549355}, issn = {1601-0825}, support = {82470983//National Natural Science Foundations of China/ ; 82270986//National Natural Science Foundations of China/ ; 82201074//National Natural Science Foundations of China/ ; }, abstract = {BACKGROUND: Mucosal-dominant pemphigus vulgaris (MD-PV) and low-risk mucous membrane pemphigoid (LR-MMP) are autoimmune bullous diseases primarily affecting the oral mucosa, yet their oral microbiome profiles remain inadequately characterized.

METHODS: Using 16S rRNA sequencing of saliva from 21 MD-PV patients, 26 LR-MMP patients, and 14 healthy controls (HC), we analyzed microbial diversity, differential taxa (LEfSe), and functional potential (PICRUSt2/BugBase).

RESULTS: Both patient groups showed significant microbial restructuring without major richness changes, featuring increased Firmicutes and decreased Proteobacteria. Disease-specific signatures included Flavobacteriia enrichment in MD-PV and Coriobacteriia/Actinobacteria in LR-MMP. Shared metabolic alterations involved "Biosynthesis of amino acids," "Phosphotransferase system," and "Ribosome" pathways, while distinct activations included "all-trans-farnesol biosynthesis" in MD-PV and "peptidoglycan biosynthesis" in LR-MMP. Phenotype prediction revealed increased Gram-positive bacteria and reduced pathogenic and stress-tolerant taxa. Microbial dysbiosis scores positively correlated with clinical disease severity.

CONCLUSION: Our study identifies distinct oral microbial dysbiosis patterns in MD-PV and LR-MMP, with conserved functional shifts and disease-specific metabolic adaptations. The microbiota-severity correlation highlights its potential role in disease mechanisms, offering new insights for therapeutic exploration.

TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR2500105460.}, } @article {pmid41549231, year = {2026}, author = {Novak, SD and Aguirre, KA and Neher, WR and Torres, AM}, title = {Bacterial endophytes journey from the seed to the seedling: an analysis of community structural shifts and bacterial localization during colonization.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08113-9}, pmid = {41549231}, issn = {1471-2229}, } @article {pmid41549174, year = {2026}, author = {Lynch, CMK and Knox, EG and Soong, D and Bastiaanssen, TFS and Trontti, K and Tofani, GSS and Ivaschuk, S and Collins, MK and Arafa, D and Nagpal, J and Hovatta, I and Lyons, DA and Clarke, G and Cryan, JF}, title = {The Microbiota Shapes Central Nervous System Myelination in Early Life.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e15671}, doi = {10.1002/advs.202515671}, pmid = {41549174}, issn = {2198-3844}, support = {SFI/12/RC/2273_P2/SFI_/Science Foundation Ireland/Ireland ; CRSII5_186346/NMS2068//Saks Kavanaugh Foundation and the Swiss National Science Foundation/ ; 22/PATH-S/10876//Science Foundation Ireland-Irish Research Council Pathway Programme/ ; GOIPD/2019/714//Irish Research Council/ ; 214244/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 108906/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; 133//MS Society Research Centre Award/ ; }, abstract = {Maturation of the gut microbiota coincides with neurodevelopmental processes such as myelination, essential for efficient neural signal transmission. While a role for the microbiome in regulating adult prefrontal cortex (PFC) myelination is known, its effects on early-life myelin formation, growth, and integrity remain unclear. Using a cross-species approach in germ-free (GF) mice and zebrafish, we examined how the microbiota influences early myelination and neural development. Multi-system, multi-level analyses showed that the microbiota impacts glial maturation and myelination across species. In GF mice, we observed sex- and age-dependent alterations in pathways linked to neuronal activity and myelination, with myelin-related transcriptomic changes correlating with functional shifts in neurotransmission- and metabolism-related metabolites over time. Myelin growth and integrity were also affected in a sex- and time-dependent manner. As microglia regulate neuronal activity and engulf myelin, we examined microbiota-microglia interactions and found altered expression of genes involved in microglia maturation and synaptic pruning in both species. In zebrafish larvae, the microbiota influenced the spatial distribution of microglia and oligodendrocytes within the brain and spinal cord. These findings reveal conserved microbiota-mediated modulation of neuronal activity, myelination, and glial maturation in early life, providing a foundation for future studies into these mechanisms.}, } @article {pmid41549150, year = {2026}, author = {Negi, R and Sharma, B and Jyothi, RS and Gupta, A and Parastesh, F and Kaur, T and Jhamta, S and Thakur, N and Singh, S and Yadav, N and Yadav, AN}, title = {Phyllosphere microbiome: Exploring the unexplored frontiers for precision agricultural and environmental sustainability.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {2}, pages = {50}, pmid = {41549150}, issn = {1573-0972}, mesh = {*Microbiota ; *Agriculture/methods ; Bacteria/classification/metabolism/genetics/isolation & purification ; Fungi/metabolism/classification ; *Plant Leaves/microbiology ; *Plants/microbiology ; }, abstract = {The phyllosphere, encompassing the aerial surfaces of plants, represents one of the largest microbial habitats on Earth and plays a pivotal yet underutilized role in sustainable agriculture and environmental health. Colonized by diverse bacterial, fungal, and yeast communities, the phyllosphere microbiome significantly influences plant growth, disease resistance, nutrient dynamics, and abiotic stress tolerance. These microorganisms engage in complex interactions with host plants, often functioning as biofertilizers, biopesticides, and stress protectants by producing phytohormones, antimicrobial metabolites, and stress-responsive compounds. Importantly, phyllospheric microbes also contribute to atmospheric and ecological balance by participating in carbon and nitrogen cycling, degrading volatile organic compounds (VOCs), and mitigating air pollution. However, despite their immense potential, the practical application of phyllospheric microbes remains limited by challenges such as environmental instability, poor field persistence, and incomplete functional characterization. The highly variable microclimate of the leaf surface poses survival barriers to both native and introduced microbial inoculants. Moreover, the specificity of plant-microbe associations and the complexity of microbial interactions necessitate precision-based approaches for successful deployment. Recent advances in omics technologies, microbial consortia engineering, and nano-enabled delivery systems provide new opportunities to overcome these limitations. A deeper understanding of phyllosphere microbial ecology, combined with innovations in synthetic biology and ecological modeling, can facilitate the development of robust microbial tools tailored to specific crops and climates. Harnessing the potential of phyllospheric microorganisms is not merely an academic pursuit, it is a strategic imperative for transitioning toward climate-resilient, low-input, and ecologically sound agricultural systems.}, } @article {pmid41548675, year = {2026}, author = {Li, D and Wang, Y and Qiang, H and Liu, Z and He, Z and Liu, W and Yue, X and Zhou, A}, title = {Tailoring microbial communities for medium chain fatty acid production from waste activated sludge: comparative performance of endogenous vs. exogenous consortia.}, journal = {Bioresource technology}, volume = {}, number = {}, pages = {134038}, doi = {10.1016/j.biortech.2026.134038}, pmid = {41548675}, issn = {1873-2976}, abstract = {Optimizing medium chain fatty acid (MCFA) production from waste activated sludge (WAS) requires tailoring microbial communities, yet it remains unclear whether combining substrate sterilization with exogenous caproate-synthesizing bacteria (CSB) can enhance chain elongation. Here, we compared the MCFA production achieved using this strategy with that driven by the endogenous microbiomes in both the solid residue and the supernatant. Among all experimental groups, this strategy achieved the highest MCFA production in the supernatants (3935 ± 21 mg COD/L). This strategy increased CSB abundance in both the solid residue and the supernatant relative to the abundance in the endogenous microbiome systems. Notably, in supernatant systems, this strategy not only enriched acidogens but also led to the highest soluble protein utilization rate, maximal CO2 release/uptake, and an increased gene abundance related to pyruvate generation. Life cycle assessment confirmed economic and environmental benefits. This work provides new insights into optimizing MCFA recovery from WAS.}, } @article {pmid41548640, year = {2026}, author = {Chen, Z and Lou, J and Yan, M and Cui, R and Jin, Y and Zhang, M and Zhang, R and Mao, S and Chen, J and Sun, L and Lu, T and Qian, H}, title = {Environmental stress and symbiotic shifts: the impact of perfluorooctanoic acid (PFOA) on soil microbe-plant networks.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {127688}, doi = {10.1016/j.envpol.2026.127688}, pmid = {41548640}, issn = {1873-6424}, abstract = {Perfluorooctanoic acid (PFOA) is a persistent per- and polyfluoroalkyl substance (PFAS) frequently detected at extremely high concentrations in soils near industrial contamination sources, yet plant-microbe responses under such extreme conditions remain poorly understood. Here, Arabidopsis thaliana was exposed to PFOA at concentrations approaching the upper levels reported in contaminated soils (1, 10, and 100 mg/kg) to investigate integrated physiological, transcriptomic, and microbiological responses over a 14-day period. Plant growth was inhibited in a clear concentration-dependent manner, with progressive reductions in fresh biomass, root length, and rosette leaf number, and the strongest suppression observed at 100 mg/kg. PFOA exposure also induced oxidative stress, as indicated by elevated reactive oxygen species (ROS) levels. Transcriptomic analysis revealed distinct dose- and pathway-specific response patterns. Only 37 differentially expressed genes (DEGs) were detected at 1 mg/kg, whereas 2184 and 4999 DEGs were identified at 10 and 100 mg/kg, respectively. 10 mg/kg PFOA exposure predominantly activated antioxidant defense and adaptive stress-response pathways, including glutathione metabolism, phenylpropanoid and flavonoid biosynthesis, MAPK signaling, and plant hormone signal transduction. In contrast, extreme exposure (100 mg/kg) was characterized by widespread repression of primary metabolic pathways, particularly photosynthesis, carbon fixation, oxidative phosphorylation, and glycolysis, indicating metabolic collapse. Rhizosphere microbial communities responded more strongly than bulk soils to PFOA stress, exhibiting reduced α-diversity, enhanced β-diversity separation, enrichment of putatively tolerant taxa (e.g., Pseudomonas, Sphingomonas, Burkholderiaceae, and Ascomycota), and increased network connectivity. Overall, these results demonstrate coordinated plant and rhizosphere microbial responses to severe PFOA contamination, providing ecological insights into PFAS hotspot soils.}, } @article {pmid41548616, year = {2026}, author = {Yang, Y and Chang, Y and Cheng, Y and Qian, Z and Zhao, J and Li, C and Zhu, X and Jia, X and Feng, L}, title = {An integrated metabolome-microbiome analysis revealed distinct regulatory effects of Xiaoer Chiqiao Qingre granules in young versus adult rats with acute upper respiratory tract infection.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121232}, doi = {10.1016/j.jep.2026.121232}, pmid = {41548616}, issn = {1872-7573}, abstract = {Xiaoer Chiqiao Qingre Granules (XECQ), officially recognized in the Chinese Pharmacopoeia (Approval No. Z20123090), represent a widely used traditional Chinese medicine (TCM) formulation for treating acute upper respiratory tract infection (AURTI) across both pediatric and adult patients.

AIM OF THE STUDY: This investigation examined XECQ's divergent regulation of endogenous metabolism and intestinal microbiome in juvenile versus mature rats, serving clinical medication to support pediatric utilization of XECQ.

MATERIALS AND METHODS: AURTI model was constructed, and serum inflammatory cytokine levels, pulmonary histopathology, and immunohistochemical analysis were assessed. Young rats served as pediatric developmental proxies. Integrated serum metabolomics and 16S rDNA sequencing methodologies elucidated XECQ's systemic modulatory actions upon host metabolism and enteric microbial communities.

RESULTS: XECQ manifested anti-AURTI efficacy across both age cohorts. Metabolites quantification identified 37 juvenile-specific and 18 adult-specific serum biomarkers. Additionally, XECQ modulated intestinal microbiome diversity and enhanced community richness across both age groups. Following XECQ treatment, the genera Subdoligranulum, Marvinbryantia, Anaerostipes, Bacillus, and Dubosiella_ag were significantly restored in young rats, while Escherichia-shigella, Parabacteroides, and Subdoligranulum showed notable recovery in adults. Species clustering analysis revealed distinct differences in intestinal microbiome modulation between age groups, with young rats exhibiting markedly different regulatory patterns for genera such as norank_f_Muribaculaceae, norank_f_Eubacterium_coprostanoligenes_group, Clostridium_sensu_stricto_1, and norank_f_Oscillospiraceae. In young rats, XECQ primarily regulated amino acid metabolism, notably pathways involving cysteine and methionine. In adult rats, the therapeutic effects were mainly associated with the modulation of pentose and glucuronate interconversion and purine metabolic pathways. Notably, glycerophospholipid metabolism emerged as a shared pathway across both age groups under normal conditions, during AURTI pathology, and following XECQ treatment.

CONCLUSION: XECQ differentially modulates the serum metabolome and intestinal microbiome between young and adult rats, highlighting the necessity of pediatric-specific studies to support the clinical application of XECQ in children.}, } @article {pmid41548440, year = {2026}, author = {Hong, EH and Hyeong, J and Ahn, JH and Han, Y and Kim, S and Kim, SM and Yoo, HH and Jeong, H and Cho, HJ and Park, JH and Chang, SY and Ko, HJ}, title = {Limosilactobacillus reuteri alleviates psoriasis via aryl hydrocarbon receptor-mediated regulation of Interkeukin-17A.}, journal = {International immunopharmacology}, volume = {172}, number = {}, pages = {116194}, doi = {10.1016/j.intimp.2026.116194}, pmid = {41548440}, issn = {1878-1705}, abstract = {BACKGROUND: Psoriasis is a chronic immune-mediated skin disorder characterized by keratinocyte hyperproliferation and interleukin-17A-driven inflammation. Growing evidence highlights the contribution of microbiome-derived factors to cutaneous immune regulation. The study aimed to evaluate the therapeutic efficacy of heat-killed Limosilactobacillus reuteri NCHBL-005 in an imiquimod-induced psoriasis-like mouse model.

RESULTS: Both topical and oral administration of NCHBL-005 significantly alleviated clinical and histological features, including reduced epidermal thickness, improved Psoriasis Area and Severity Index scores, and diminished inflammatory cell infiltration. Mechanistically, NCHBL-005 suppressed interleukin-1 beta and interleukin-17A expression in psoriatic lesions and decreased interleukin-17A-positive RAR-related orphan receptor gamma t-positive T-cells while maintaining regulatory T-cell balance. These effects were retained in Toll-like receptor 2- and nucleotide-binding oligomerization domain-containing protein 2-deficient mice but abolished in aryl hydrocarbon receptor-deficient mice, underscoring the essential role of aryl hydrocarbon receptor signaling. NCHBL-005 directly attenuated inflammatory responses in keratinocytes by suppressing the expressions of interleukin-1 beta, interleukin-17A, and tumor necrosis factor-alpha, and by inhibiting nuclear factor kappa-light-chain-enhancer activation. Liquid chromatography-tandem mass spectrometry profiling identified indole-3-acetaldehyde, indole-3-carbinol, and indole-3-lactic acid as major aryl hydrocarbon receptor ligands derived from NCHBL-005. Among these, indole-3-acetaldehyde most effectively reproduced the therapeutic effects, reducing interleukin-17A-positive cells, epidermal hyperplasia, and nuclear factor kappa-light-chain-enhancer activation.

CONCLUSIONS: NCHBL-005 and its metabolite indole-3-acetaldehyde alleviate psoriatic inflammation through modulation of the aryl hydrocarbon receptor-interleukin-1 beta-interleukin-17A axis, thereby restoring skin immune homeostasis. This study highlights postbiotic intervention in the aryl hydrocarbon receptor-interleukin-1 beta-interleukin-17A axis as a promising therapeutic strategy for psoriasis.}, } @article {pmid41548201, year = {2026}, author = {Mirmozaffari, Y and Roca, C and Martin, WJ and Heetderks, KA and Van Dorsten, A and Cook, L and Benaim, EH and Wolfgang, MC and Kimple, AJ}, title = {Species-Level Characterization of the Nasal Microbiome in Various Disease States Utilizing Third-Generation Sequencing.}, journal = {International forum of allergy & rhinology}, volume = {}, number = {}, pages = {}, doi = {10.1002/alr.70103}, pmid = {41548201}, issn = {2042-6984}, } @article {pmid41547908, year = {2026}, author = {Kim, YC and Won, SY and Jeong, BH}, title = {Identification of an altered gut microbiome and the protective effect of microbiome changer in prion diseases.}, journal = {Veterinary research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13567-025-01699-2}, pmid = {41547908}, issn = {1297-9716}, support = {2022R1C1C2004792//National Research Foundation of Korea/ ; RS-2023-00273199//National Research Foundation of Korea/ ; 2017R1A6A1A03015876//National Research Foundation of Korea/ ; B0080529001944//Gyeongbuk RISE CENTER/ ; 2021R1A6C101C369//Korea Basic Science Institute/ ; }, abstract = {Prion diseases are fatal and contagious brain disorders caused by a pathogenic prion protein (PrP[Sc]) derived from the benign prion protein (PrP[C]). To date, there are no therapeutic substances to completely block prion diseases. Thus, the development of a therapeutic substance is necessary, and the identification of a novel biomarker of prion disease is the first essential step to develop new drugs. In the present study, we carried out a metagenomic analysis to identify microbiome biomarkers for prion disease using next-generation sequencing and bioinformatics tools in intraperitoneally prion-infected mice. In addition, we evaluated the protective effects of epigallocatechin-3-gallate (EGCG), a potent microbiome changer, in prion-infected mice by western blotting and survival analysis. We found a total of 14 differentially abundant taxa between prion-infected and control mice. In addition, we found that prion diseases caused altered microbiome networks and upregulation of DNA repair-related pathways. Furthermore, we observed the protective effect of the microbiome changer EGCG against prion disease in prion-infected mice. Given previous reports of microbiome alterations in prion diseases, we further validated these associations and demonstrated the protective effects of a microbiome-modulating compound.}, } @article {pmid41547903, year = {2026}, author = {Hashmi, MA and Verma, S and Math, RGH and Muralidharan, S and Pranesh, G and Sahana, MP and Hariharan, N and N C, M and Kamath, V and Yaligod, V and Hiremath, SA and Jawali, A and Maddipati, T and Chandrasingh, S and Thomas, A and Mallnaik, N and Shanmuganand, VC and George, CE and Thomas, A and Ghosh, TS and Ramanathan, A}, title = {Integrative analysis of plasma small-molecule and gut-microbiome markers of sarcopenia in a pilot study within an Indian cohort.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35476-8}, pmid = {41547903}, issn = {2045-2322}, } @article {pmid41547860, year = {2026}, author = {Castillo-Fernandez, J and Gilroy, R and Jones, RB and Honaker, RW and Whittle, MJ and Watson, P and Amos, GCA}, title = {Waltham catalogue for the canine gut microbiome: a complete taxonomic and functional catalogue of the canine gut microbiome through novel metagenomic based genome discovery.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {25}, pmid = {41547860}, issn = {2049-2618}, mesh = {Animals ; Dogs/microbiology ; *Gastrointestinal Microbiome/genetics ; *Metagenomics/methods ; *Bacteria/classification/genetics/isolation & purification ; Metagenome ; Feces/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The canine microbiome is a vastly understudied area relative to the importance of dogs in society, particularly given the potential importance of the microbiome in veterinary medicine. This has led to a large knowledge gap in the basic taxonomy and functions of the canine gut microbiome and an overreliance on human databases for canine-specific research. Using a broad sample set, long read sequencing, short read sequencing, and metagenomic assembly approaches, we have produced the most comprehensive microbiome resource in all companion animal research.

RESULTS: Here, we describe the recovery of 240 core species that account for > 80% of the canine gut microbiome when tested on an independent validation dataset. We uncovered > 900 new canine-specific strains, 89 novel species, and 10 novel genera, providing a dramatic increase in previous knowledge of the canine microbiome and allowing for mapping rates of up to 95%, a 70% increase on historic mapping rates of ~ 25% using publicly available resources. Through detailed annotation of function, we demonstrate the potential importance of the novel species and genera to health and nutrition and provide evidence of new canine-adapted strains of existing genera and species previously unknown to inhabit canines that provide important metabolic function to the canine host. We discovered the canine microbiome has an expansive ability to metabolize carbohydrates, providing insight into how canines process diverse carbohydrates given their known limited host genomic potential. We uncovered a range of species with abilities to produce butyrate, propionate, and vitamins, highlighting the importance of the canine microbiome to host nutrition. We describe two novel Peptacetobacter species that could regulate host bile acid metabolism, an important finding in the context of chronic GI disease in pets. We demonstrated all new species and genera had no known virulence, suggesting they are commensal and, finally, provided a baseline for antimicrobial resistance in the microbiota species of healthy pets.

CONCLUSIONS: This work gives entirely new perspectives on the functional capabilities of the canine gut microbiome, suggesting the canine microbiome is distinct, presumably having evolved to its host, diet, and environment over several millennia. Video Abstract.}, } @article {pmid41547850, year = {2026}, author = {Naya-Català, F and Domingo-Bretón, R and Matias, RS and Calduch-Giner, JÀ and Belenguer, Á and Gomes, S and Guilhermino, L and Moroni, F and Valente, LMP and Pérez-Sánchez, J}, title = {Dietary rayon microfibers differentially reshape rearing water and host associated microbiomes of farmed European sea bass (Dicentrarchus labrax).}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00851-5}, pmid = {41547850}, issn = {2524-6372}, abstract = {BACKGROUND: Viscose-rayon microfibres (RFs) are cellulosic microfibres widely dispersed throughout aquatic environments. Whether ingested by or suspended in the surrounding environment, these microfibres may impact both wild and farmed animals. A previous study on European sea bass (Dicentrarchus labrax) showed that the increased presence of RFs in aquafeeds (CTRL-no RFs; RF1-0.001 g/kg; RF2-0.01 g/kg; RF3-0.1 g/kg) was linked to an exponential increase of RFs in water, intestine and skeletal muscle. This finding was associated to a fatty liver and tissue-specific transcriptional changes, depicting the up-regulation of hepatic lipogenic enzymes and intestinal/head kidney inflammatory markers. The aim of the present study was to extend this evaluation by investigating changes in associated microbial communities after the ingestion of RFs in the diet, employing a multi-layered approach for the integrative profiling of gut, skin, and environmental water microbiome using the Nanopore platform.

RESULTS: Amplicon-sequencing identified ~2800 taxa across water, skin and gut microbiomes. Gut and skin microbiomes were more similar to each other, but increasing RF exposure shifted the skin community toward the water microbiome. Moreover, RF induced the highest taxonomic variation in water (691 taxa), followed by skin (253) and gut (99), while microbial diversity Shannon and Simpson indexes declined from 4 down to 3.3 under RF2 and RF3 in a dose-dependent manner. Major exponents of this trend were the decrease of Synechococcus and Flavobacteriales in association with the increase of starch- and hydrocarbon-degrading taxa (Ardenticatenaceae and Gracilibacteria). In both gut and skin, bacterial richness decreased in fish fed low to intermediate RF doses, whereas RF3 fish resembled controls. Thus, compositional and discriminant analyses consistently grouped CTRL and RF3 samples, suggesting the existence of a dose threshold occurring in parallel with host counter-regulatory responses. Such feature was reflected by abundant skin-associated bacteria (Exiguobacterium and Planococcus) with at least the genetic potential to be linked to vitamin B6 biosynthesis and host-driven muscle regeneration markers, whereas predominant gut taxa with the same pattern (Microbacterium and Achromobacter) was associated with polysaccharide degradation and correlated with host gene inflammatory mechanisms.

CONCLUSIONS: This study revealed a concomitant dose-dependent and dose-threshold response among the bacterial communities composing the holobiont of European sea bass in response to dietary RFs ingestion, highlighting novel bacterial taxa and pathways through which microplastic exposure may differentially reshape rearing water and host-associated microbial communities.}, } @article {pmid41547827, year = {2026}, author = {Cavaliere, S and Fogolari, M and Iuliani, M and Foderaro, S and Cortellini, A and Simonetti, S and Mingo, EC and Calagna, S and Russano, M and Vincenzi, B and Tonini, G and Angeletti, S and Pantano, F}, title = {Salivary microbial signature highlighting actinomyces as a predictor of immune-checkpoint inhibitor monotherapy response in advanced non-small cell lung cancer.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-025-07570-4}, pmid = {41547827}, issn = {1479-5876}, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival in advanced non-small cell lung cancer (NSCLC), yet reliable biomarkers beyond programmed death-ligand 1 (PD-L1) expression remain limited. Increasing evidence links the gut microbiome to ICI activity, but the predictive value of the salivary microbiome is poorly defined.

METHODS: We prospectively analyzed baseline saliva from 71 stage IV NSCLC patients treated with anti-PD-1/PD-L1 (ICI) monotherapy. After quality control, 70 samples underwent 16 S rRNA gene sequencing of the V1-V3 region. Microbial diversity, differential abundance (LEfSe, Mann-Whitney/Kruskal-Wallis with false discovery rate correction) and survival associations (Kaplan-Meier; Cox proportional-hazards with LASSO-based variable selection and 1000-fold bootstrap validation) were examined. In this cohort, an exploratory genus-level cut-off was derived by receiver operating characteristic (ROC) analysis.

RESULTS: α-diversity and β-diversity did not differ between responders (progression-free survival (PFS) ≥ 12 months; n = 18) and non-responders (n = 52). Differential‑abundance profiling revealed a graded enrichment of the phylum Actinobacteria across all lower ranks, class Actinobacteria, order Actinomycetales, family Actinomycetaceae and genus Actinomyces,in non‑responders (LEfSe LDA > 3.5; p = 0.001 for each level; FDR ≤ 0.049). ROC analysis suggested an Actinomyces relative abundance of 11% (AUC = 0.768; sensitivity 0.94; specificity 0.44) as a data-driven threshold, classifying patients into low (≤ 11%, n = 46) and high (> 11%, n = 24) groups. High abundance was associated with shorter PFS (median 3 vs. 4 months; HR = 2.16, 95% CI 1.21-3.88, p = 0.009) and overall survival (OS) (median 5 vs. 9 months; HR = 2.61, 95% CI 1.48-4.61, p < 0.001) after multivariable adjustment for ECOG status, treatment line, corticosteroid and opioid use, smoking, histology and metastatic sites. Bootstrap validation supported model stability, with median bootstrap HRs of 2.56 (PFS) and 2.63 (OS), with narrow percentile CIs (PFS 1.57-4.49; OS 1.40-6.34) overlapping the original estimates.

CONCLUSIONS: In this exploratory cohort, salivary microbiome signature characterized by high Actinomyces abundance was independently associated with poorer ICI outcomes in NSCLC. Saliva profiling is non-invasive and, if validated in larger and independent cohorts, may complement tumour PD-L1 and clinical factors to refine patient stratification.}, } @article {pmid41547778, year = {2026}, author = {Park, SH and Park, SM and Suh, JW and Kim, JY and Sohn, JW and Yoon, YK}, title = {Clinical impact of altered gut microbiota and metabolite profiles on mortality in patients with candidemia: a prospective observational pilot cohort study.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12941-026-00850-x}, pmid = {41547778}, issn = {1476-0711}, abstract = {BACKGROUND: The gut microbiota plays an important role in defending against infectious diseases. However, data on the clinical implications of the microbiome profiles in patients with candidemia remain limited. In this study, we investigated the association between the intestinal microbiome and mortality in patients with candidemia.

METHODS: This prospective, observational, pilot cohort study enrolled adult patients with culture-confirmed candidemia. Fecal samples were collected within 5 days of diagnosis and analyzed using 16 S ribosomal RNA gene sequencing for microbiota profiling and gas chromatography-mass spectrometry for metabolomic analysis. Multivariate logistic regression was used to identify predictors of in-hospital mortality, defined as death during hospitalization.

RESULTS: Fifty-nine patients with candidemia were analyzed, and the in-hospital mortality rate was 40.7%. The median Shannon diversity index of the gut microbiota was significantly lower in non-survivors than that in survivors (P = 0.009). Linear discriminant analysis revealed 11 bacterial species that differed significantly between the two groups. Among the 111 fecal metabolites, only 3-isopropoxy-hexamethyl-tetrasiloxane differed significantly between the survivors and non-survivors (P = 0.007). Septic shock (adjusted odds ratio: 10.59; 95% confidence interval, 1.70-65.97), underlying malignancy (7.79 [1.41-43.10]), and Shannon diversity index (0.40 [0.19-0.84]) were significant predictors of in-hospital mortality.

CONCLUSIONS: Low gut bacterial diversity is independently associated with mortality in patients with candidemia. These preliminary findings warrant confirmation through larger, well-powered studies.}, } @article {pmid41547669, year = {2026}, author = {Isınıbılır, M and Doğan, O and Bilgin, R and Çalıcı, Z}, title = {Microbiome dynamics linked to Aurelia aurita during bloom and post-bloom periods in the Golden Horn Estuary: a snapshot via eDNA metabarcoding.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {41547669}, issn = {1614-7499}, abstract = {Jellyfish blooms are significant events in marine ecosystems, profoundly impacting carbon and nutrient cycles. During these events, decomposing jellyfish release dissolved organic matter (DOM), which fuels bacterial growth and reshapes nutrient cycling. In this study, we employed an environmental DNA (eDNA) metabarcoding approach to capture bacterial communities associated with Aurelia aurita, and in different body parts, as well as its ambient surface water column during bloom (December 2022) and post-bloom (March 2023) periods in the Golden Horn Estuary, İstanbul, Türkiye. The results reveal distinct temporal and regional variations in bacterial diversity, highlighting the pivotal role of jellyfish blooms in reshaping bacterial communities.}, } @article {pmid41547536, year = {2026}, author = {Banik, M and Bashyal, S and Ahmed, KA and Banik, K and Dua, K and Choi, JP and Paudel, KR and Majumder, R}, title = {The Gut Microbiome of Australian Cats and Dogs: Dietary Influences, Health Impacts, and Emerging Research.}, journal = {Veterinary journal (London, England : 1997)}, volume = {}, number = {}, pages = {106566}, doi = {10.1016/j.tvjl.2026.106566}, pmid = {41547536}, issn = {1532-2971}, abstract = {The gut microbiome plays a pivotal role in the health, metabolism, and behaviour of companion animals, yet comprehensive syntheses of its composition and functional relevance in cats and dogs in Australia are overlooked and remain limited globally. This review synthesises current knowledge on the gut microbial communities inhabiting the gastrointestinal tracts of dog and cats, with a particular focus on taxonomic diversity, dietary modulation, and associations with disease states within Australian context. Core phyla including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria dominate the canine and feline gut, but marked interspecies and individual variability is shaped by factors such as feeding practices, living environment, obesity, and chronic disease. Recent studies have elucidated functional signatures linked to conditions ranging from the influence of microplastics to pet gut health, as well as gut-microbiome transmission between pets and their owners, highlighting this area as a promising field of investigation. In parallel, this review contextualizes the broader landscape of pet ownership in Australia, where nearly 70% of households own pets, and significant resources are devoted to nutrition, veterinary care, and preventive health. Emerging evidence also suggests bidirectional influences between pets and their human companions' microbiota, highlighting opportunities for integrated approaches. We identify critical knowledge gaps, including the need for region-specific microbial baselines, standardized methodologies, and controlled intervention trials targeting microbiome modulation and transmission. By consolidating advances across microbial ecology, veterinary medicine, and translational research, this review provides a foundation for future studies that aim to harness the diagnostic and therapeutic potential of the pet microbiome, thereby improving health outcomes for animals and humans alike.}, } @article {pmid41547455, year = {2026}, author = {Qu, Q and Gao, H and Gao, X and Li, P and Mou, Y and Kong, X and Tan, X}, title = {Dietary inulin mediates the molecular mechanism of intestinal metabolites to alleviate high salt diet-induced chronic kidney disease in mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110269}, doi = {10.1016/j.jnutbio.2026.110269}, pmid = {41547455}, issn = {1873-4847}, abstract = {It is recognized that excessive dietary salt intake is a critical factor contributing to chronic kidney disease (CKD). A high-salt diet (HSD) disrupts the balance of the gut microbiota, but the molecular mechanisms linking gut dysbiosis to target organ damage remain unclear. This study identified dietary prebiotic inulin (INU) as a potent regulator of the gut-short-chain fatty acid-kidney axis, capable of counteracting HSD-induced CKD. Sequencing analysis showed that INU selectively enriched Bifidobacterium and Faecalibaculum while downregulating Desulfovibrio. This microbiome shift restored intestinal tight junction proteins and reduced serum lipopolysaccharide (LPS) levels, thereby inhibiting TLR4/NF-κB-mediated renal inflammation. Notably, the effects of direct SCFA supplementation align with the renal protective effects of INU, confirming the critical role of the gut-kidney axis. Our study reveals INU as a dietary strategy that combats HSD-induced CKD via SCFAs produced by the microbiota, offering new insights into the gut-SCFAs-kidney axis as a therapeutic target.}, } @article {pmid41547444, year = {2026}, author = {Shan, Y and Huang, X and Han, X and Yang, Y and Zheng, M}, title = {3'-Sialyllactose ameliorates antibiotic-associated diarrhea by shaping unique gut microbiota and metabolite composition.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-27362}, pmid = {41547444}, issn = {1525-3198}, abstract = {3'-Sialyllactose (3'-SL) is a naturally occurring prebiotic in milk, known to regulate intestinal microbiota and prevent diseases. However, the mechanisms through which 3'-SL alleviates antibiotic-associated diarrhea remain poorly understood. In this study, an antibiotic-associated diarrhea model was established through the co-administration of ampicillin and neomycin. The effects of 3'-SL supplementation on diarrhea phenotype, inflammation, intestinal permeability, and barrier function were examined in antibiotic-associated diarrhea-model mice. Moreover, gut microbiota composition, metabolite profiles, and their alterations were analyzed using genomic and metabolomic approaches. The results demonstrate that 3'-SL increased body weight and aquaporin (AQP) 3 and AQP4 levels but reduced diarrhea rate, cecal mass, and fecal water content in the model mice, indicating its therapeutic effect on diarrhea. Furthermore, 3'-SL reduced serum levels of IL-6, tumor necrosis factor (TNF)-α, and IL-1β, while increasing IL-10 levels in the mice. Moreover, 3'-SL reduced intestinal permeability by enhancing both the mechanical barrier (ZO-1 and occludin mRNA expression) and the chemical barrier (MUC2 mRNA and protein expression) in the mice. 16S rRNA analysis revealed that mice in the 3'-SL group exhibited greater abundances of Akkermansia, Bacteroides, and Dubosiella, along with a reduced relative abundance of the diarrhea-associated bacterium Alloprevotella. Furthermore, metabolomics analysis indicated that 3'-SL promoted enrichment of purine metabolism, pyrimidine metabolism, nucleotide metabolism, and the pentose phosphate pathway, which may be associated with diarrhea development, inflammation amelioration, and barrier regulation. In conclusion, our findings suggest that 3'-SL ameliorates antibiotic-associated diarrhea by modulating gut microbiota and metabolite profiles.}, } @article {pmid41547433, year = {2026}, author = {Engin, ED and Engin, AB and Engin, A}, title = {Bidirectional effect of intestinal microbiome and host in circadian rhythm disruption: Environmental factors and breast cancer development.}, journal = {Environmental toxicology and pharmacology}, volume = {}, number = {}, pages = {104939}, doi = {10.1016/j.etap.2026.104939}, pmid = {41547433}, issn = {1872-7077}, abstract = {Suppression of nocturnal circadian melatonin signaling amplitude, disruption of the host's circadian clock through diet or phase shifts, and imbalances in the gut microbiome are significant factors that increase the incidence of breast cancer. After host-derived mature microRNAs (miRNAs) are secreted from intestinal epithelial cells, they pass to the microbiota as faecal or exosomal miRNAs and modify the epigenetic profile of the microbiome. Subsequently, the profile of host miRNAs is altered by metabolites, which are derived from intestinal bacteria. Bidirectional epigenetic modulations of host and microbiota trigger the activation of oncogenic transcriptional pathways in extraintestinal tissues. However, the effect of the mutual epigenetic interactions between the gut microbiota and the host on the development of extraintestinal cancer is not clear. The aim of this review is to discuss the factors influencing bidirectional epigenetic regulation mechanisms between microbial dysbiosis and the host in breast cancer.}, } @article {pmid41546966, year = {2026}, author = {Buser-Young, J and Gardell, AM and Zalutskiy, V and Briggs, BR and Gawel, JE and Alaei, SR}, title = {Arsenic contamination drives homogenizing selection in freshwater lake periphyton.}, journal = {The Science of the total environment}, volume = {1014}, number = {}, pages = {181403}, doi = {10.1016/j.scitotenv.2026.181403}, pmid = {41546966}, issn = {1879-1026}, abstract = {Bacteria and other microbes are important contributors to arsenic biotransformation processes, which can alter the bioavailability and toxicity of arsenic within a contaminated environment. Multispecies biofilms, known as periphyton, have been identified as a significant site of arsenic bioaccumulation within shallow freshwater lakes impacted by legacy arsenic contamination. We hypothesized that prolonged arsenic exposure results in the formation of distinct prokaryotic communities within the periphyton and other environmental compartments in arsenic-contaminated lakes compared to uncontaminated lakes. We also predicted that the periphyton prokaryotic communities would be distinct from, but partially overlapping with, those found in the surrounding water column and nearby littoral sediment. To test these hypotheses, we determined the taxonomic composition and modeled the assembly processes that yielded the bacterial communities found within three environmental compartments (periphyton, littoral sediment, and water column) of three lakes that had been differentially impacted by legacy arsenic contamination. We identified unique microbiomes within these environmental compartments and observed a clear shift in microbial community composition within high arsenic-contaminated periphyton. Accumulation of arsenic (~400 ppm) in the periphyton correlated with non-random (deterministic) selection for prokaryotic taxa that are more related than expected by chance (homogenizing selection). We also identified key prokaryotic genera within the arsenic-contaminated periphyton that suggest prolonged arsenic contamination may shift iron and methane biogeochemical cycles, which may regulate arsenic accumulation and mobilization. Our results imply that legacy arsenic contamination, by altering bacterial community composition and metabolic potential at the base of the food web, may influence biogeochemical and nutrient cycles at a larger scale within a freshwater lake ecosystem.}, } @article {pmid41546896, year = {2026}, author = {He, X and Li, Z and Ji, D and Zhang, S and Shen, Z and Feng, C}, title = {Plastisphere as a unique metabolic hotspot in river water: Impact of plastic substrate biodegradability.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141168}, doi = {10.1016/j.jhazmat.2026.141168}, pmid = {41546896}, issn = {1873-3336}, abstract = {Microplastics in aquatic environments predominantly exist as carriers of plastispheres, yet the microbial community structures and co-occurrence patterns within submillimeter plastispheres (formed by approximately 100 μm plastic particles) remain poorly understood. The effects of plastic biodegradability on plastisphere microbiome assembly and function have also not been fully characterized. Hence, this study investigated the micro-ecological composition of submillimeter plastispheres in river water, focusing on plastic degradation and carbon-nitrogen biogeochemical cycling. Compared to surrounding water, these plastispheres create novel ecological niches that serve as microbial "metabolic hotspots," fostering complex, functionally interconnected networks with enhanced carbon and nitrogen metabolic potential through strong selective pressures. Plastispheres derived from biodegradable plastics create nutrient-rich environments that favor polymer-degrading taxa, promoting niche differentiation and more stable ecological networks. Higher biodegradability was associated with greater enrichment of genes encoding plastic-degrading enzymes and elevated potential for nitrogen fixation, denitrification, and methane production. In contrast, plastispheres from non-biodegradable plastics exhibited intensified interspecific competition and increased species diversity, while limited carbon availability and tight microbial interactions facilitated enrichment of methane oxidation genes. These findings highlight submillimeter plastispheres as potential hotspots for greenhouse gas emissions, providing new insights into the ecological risks of microplastics in aquatic environments.}, } @article {pmid41546711, year = {2026}, author = {Ye, L and Du, J and Huang, L and Zhao, M and Tan, F and Zhang, X and Chen, X and Xu, Q and Liu, C and Lin, Y and Zhao, X and Liu, C and Chen, L}, title = {Stability of the skin microbiome during short-term in situ and in vitro conditions: Foundational support for the potential to trace skin sites and identify individuals.}, journal = {International journal of legal medicine}, volume = {}, number = {}, pages = {}, pmid = {41546711}, issn = {1437-1596}, abstract = {As the largest human organ, the skin frequently interacts with the environment and retains abundant microbial information, making it a crucial source of forensic biological evidence. However, the temporal dynamics of microbial communities between in situ and in vitro samples, as well as the traceability of in vitro samples back to their donors based on corresponding in situ samples, remain unverified through longitudinal sampling and dynamic tracking. A total of 15 young adult volunteers participated in the study, during which skin microbiome samples were collected from their palms and cheeks. A short-term exposure experiment was designed, with a duration of between 0 and 72 hours. Fresh samples were collected at corresponding timepoints, in a synchronised manner. In this study, we utilised a combination of 16S rRNA gene (V3-V4 regions) sequencing and machine learning algorithms to analyse the environmental exposure effects on microbial community structure and their forensic applicability. The results indicated that the relative abundance of dominant genera remained largely stable, regardless of exposure status, with no significant temporal variations observed in the short term. Although individual lifestyles exerted an influence on microbiome composition, they did not affect significant alterations to the overall community architecture. The random forest model attained an accuracy of 91.33% in skin site identification, while the individual differentiation accuracy attained 97.33% when integrating palm and cheek data. These results indicate that the skin microbiome exhibits considerable structural stability under both in situ and in vitro conditions during short-term exposure and maintains high host specificity and site-specific characteristics.}, } @article {pmid41546695, year = {2026}, author = {Zhang, T and Liu, H and Huang, Z and He, Z and Fan, Y and Liu, F and Su, E and Ming, Y and Zhu, W and Wang, C and Yu, X and Niu, M and Wu, K and Sun, X and Yang, Y and He, Z and Yan, Q}, title = {Microbially Driven Organic Carbon Degradation and Nutrient Cycling during Macroalgal Decomposition.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c09758}, pmid = {41546695}, issn = {1520-5851}, abstract = {The release of labile organic carbon (OC) and nutrients during seasonal macroalgal blooms can undermine blue carbon sequestration in coastal ecosystems. Although marine microorganisms mediate OC degradation during macroalgal decay, the underlying mechanisms remain poorly defined. This study employed an integrated multiomics approach (amplicon sequencing, metagenomics, and metatranscriptomics) to investigate microbial regulation of OC degradation and coupled nutrient cycling in coastal sediments with and without decomposing Sargassaceae. Total carbon in sediments increased by over 33% in the Sargassaceae area. Microbial α-diversity in the Sargassaceae area decreased significantly (p < 0.05), while processes linked to OC degradation, carbohydrate metabolism, nitrate (NO3[-]) reduction, inorganic phosphorus utilization, and sulfur metabolism were significantly upregulated (p < 0.05). Accordingly, gene expression and extracellular hydrolase activities targeting key biopolymers (i.e., cellulose, hemicellulose, starch, and chitin) were significantly upregulated (p < 0.05) in the area with Sargassaceae. Metabolism reconstruction of metagenome-assembled genomes identified Vibrio, Pseudoalteromonas, Alteromonas, and Exiguobacterium_A as primary OC degraders, with genomic capacities enriched in NO3[-] reduction and assimilatory sulfate reduction. Key environmental drivers─including the C/N ratio, dissolved organic carbon, total dissolved nitrogen (DON), and NO3[-]─shaped microbial metabolic activities during macroalgal decomposition. Our finding demonstrates that microbially driven OC degradation is a pivotal process coupled with nutrients cycling, advancing the mechanistic understanding of microbial carbon processing and its biogeochemical linkages during macroalgal decomposition in coastal ecosystems.}, } @article {pmid41546639, year = {2026}, author = {Sun, J and He, Y and Chen, R and Li, Z and Li, X and Han, X and Li, Y and Tang, Z and Hu, L}, title = {PTEN/PI3K/AKT Axis Mediates Aflatoxin B1-Induced Intestinal Injury via Dual Regulation of Apoptosis and Necroptosis in Jejunal Epithelial Cells.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c15463}, pmid = {41546639}, issn = {1520-5118}, abstract = {Aflatoxin B1 (AFB1), the most toxic and widely distributed aflatoxin, poses considerable health hazards to both animals and humans. Following oral intake, the gastrointestinal tract is the primary site of contact. Our study shows that AFB1 exposure markedly alters the gut microbiota composition, mainly by reducing the population of beneficial bacteria. It also increases PTEN expression and suppresses the downstream PI3K/AKT signaling pathway both in jejunal and IPEC-J2 cells, promoting apoptosis and necroptosis. In addition, AFB1 impaired intestinal barrier function by decreasing expression of ZO-1 and Occludin. Notably, the PTEN-specific inhibitor VO-Ohpic can effectively alleviate the above changes induced by AFB1, confirming PTEN's key role. Our study has first elucidated the mechanism by which AFB1 induces intestinal damage through disrupting gut microbiota structure and the "PTEN/PI3K/AKT─epithelial barrier" axis, providing new targets and theoretical basis for the prevention and treatment of AFB1 poisoning.}, } @article {pmid41546540, year = {2026}, author = {Thelen, AC and Korten, NM and Blischke, L and Voelz, C and Beyer, C and Seitz, J and Trinh, S}, title = {Faecal Microbiota Transplantation in Anorexia Nervosa: A Systematic Review of Methodologies, Outcomes, and Challenges With Recommendations for Future Studies.}, journal = {European eating disorders review : the journal of the Eating Disorders Association}, volume = {}, number = {}, pages = {}, doi = {10.1002/erv.70080}, pmid = {41546540}, issn = {1099-0968}, support = {//Doktor Robert Pfleger-Stiftung/ ; START (101/23)//RWTH Aachen University/ ; START (16/22)//RWTH Aachen University/ ; }, abstract = {OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric disorder displaying an altered gut microbiome. Faecal microbiome transplantation (FMT) has emerged as a powerful research tool and potential treatment option in AN due to the microbiome-gut-brain axis. Current studies are limited and reveal variable FMT protocols. This leads to heterogeneous outcomes and complicates drawing definitive conclusions from existing literature. This review aims to compile and assess the different protocols and develop recommendations on ideal donors, handling of faeces, recipients, duration/frequency of FMT, and measuring transfer success for future FMT studies regarding AN.

METHODS: We systematically screened three databases (Pubmed, Embase, Web of Science), identifying 13 studies, including two human case reports, one human study protocol, and 10 animal studies.

RESULTS: While all studies demonstrated microbial alterations in the recipients, not all animal studies successfully induced an AN/underweight phenotype, suggesting that precise coordination of study protocol components to allow further refinement is essential.

CONCLUSION: Researchers should prioritise clear, comprehensive, and transparent documentation to ensure the interpretability and reproducibility of FMT procedures. Detailed reporting will enable more meaningful comparisons across studies, deepen our understanding of the microbiome's role in AN, and help identify methodological factors that influence outcomes. Ultimately, completeness of documentation in FMT studies in AN has substantial potential to support future clinical applications and improve patient care.}, } @article {pmid41546396, year = {2026}, author = {Xiao, Y and Chen, X and Liao, J and Wang, J and Lu, L and Chen, H and Niu, C and Wang, M}, title = {Dismantling the Necroptotic Engine: An Oral Theranostic Nanosponge for Ulcerative Colitis.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e16297}, doi = {10.1002/adma.202516297}, pmid = {41546396}, issn = {1521-4095}, support = {82400615//National Natural Science Foundation of China/ ; 82502030//National Natural Science Foundation of China/ ; 2024JJ4095//Hunan Province Outstanding Youth Fund/ ; 2022JJ40818//Hunan Provincial Natural Science Foundation of China/ ; 2025JJ60833//Hunan Provincial Natural Science Foundation of China/ ; 2025JJ70023//Hunan Provincial Natural Science Foundation of China/ ; 2024-63//Social Investment Project of Zhuzhou City in 2024/ ; }, abstract = {Ulcerative Colitis (UC) treatments often lack target specificity and have significant side effects. A key pathological driver is the excessive necroptosis of intestinal epithelial cells (IECs), which disrupts the gut barrier. To address this, we designed an intelligent oral theranostic nanoplatform, CurN@I, to dismantle the necroptosis-inflammation axis. CurN@I consists of a barium sulfate (BaSO4) core for computed tomography (CT) imaging, encapsulated within a pH-responsive silk protein nanosponge. This scaffold is co-loaded with a necroptosis inhibitor (Necrostatin-1s, Nec-1s) and an antioxidant (demethoxycurcumin, DMC). The nanostructure is condensed in the acidic stomach but swells at the neutral pH of the inflamed intestine for localized drug release. Its negative surface charge facilitates durable electrostatic adhesion to the inflamed mucosa. In murine UC models, oral CurN@I significantly outperformed first-line clinical drugs. Mechanistic analysis showed it inhibits IEC necroptosis, alleviates oxidative stress, promotes barrier regeneration, and reshapes the gut microbiome. This work presents a non-invasive, targeted oral strategy that integrates diagnosis with multi-faceted therapy to restore intestinal homeostasis, demonstrating strong potential for clinical translation.}, } @article {pmid41546197, year = {2026}, author = {Jian, L and Lin, Y and Zhao, Y and Wang, C and Li, Z and Li, Z}, title = {Low-dose undecanone from Stenotrophomonas maltophilia suppresses Astragalus root rot and shapes the rhizosphere bacterial microbiome.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.70554}, pmid = {41546197}, issn = {1526-4998}, support = {42277317//National Natural Science Foundation of China/ ; 2025QCY-KXJ-035//Shaanxi Province Technology Innovation Guidance Project/ ; }, abstract = {BACKGROUND: Astragalus membranaceus var. mongholicus is an important Chinese herbal medicine. Root rot in Astragalus caused by Fusarium oxysporum is a destructive soil-borne disease. Biocontrol agents are currently regarded as an ecofriendly strategies for controlling root rot; however, the inherent complexity of natural environments often prevents beneficial bacteria from establishing long-term residence in the plant rhizosphere. Therefore, more effective methods against pathogenic fungi are urgently needed to safeguard both the yield and quality of Astragalus, and harnessing microorganism-derived volatile organic compounds (VOCs) is a promising strategy.

RESULTS: We isolated the bacterium Stenotrophomonas maltophilia strain B45 from the Astragalus rhizosphere that exhibited effective control of root rot. The ability of strain B45 to produce antibiotics and VOCs was determined to elucidate the possible mechanisms by which B45 inhibits pathogenic fungi. The results showed that the VOCs emitted by B45 significantly inhibited both mycelial growth and conidial germination in pathogenic fungi. Among the selected VOCs, 2-undecanone demonstrated the strongest antifungal activity and caused severe structural damage to fungal cell walls. Pot experiments confirmed that 2-undecanone fumigation markedly alleviated root rot symptoms in Astragalus. Furthermore, 2-undecanone exhibited broad-spectrum antimicrobial activity with a significantly strong inhibitory effect on both fungi and bacteria. This selective pressure led to substantial shifts in the rhizosphere microbiome composition of Astragalus. Notably, fumigation with low concentrations of 2-undecanone increased the complexity of bacterial co-occurrence networks and enriched beneficial genera, including Rhizobium, Bradyrhizobium, Sphingomonas and Lysobacter.

CONCLUSION: Our results indicate that low concentrations of 2-undecanone did not compromise the disease-suppressive capacity of the rhizosphere microbial community, and support the potential application of microbial VOCs as ecofriendly strategies for managing soil-borne diseases in agriculture. © 2026 Society of Chemical Industry.}, } @article {pmid41546147, year = {2026}, author = {Cho, YT and Chu, CY}, title = {Distinct Gut Microbiome Signatures of Complete Responders to Omalizumab in Chronic Spontaneous Urticaria.}, journal = {Experimental dermatology}, volume = {35}, number = {1}, pages = {e70208}, doi = {10.1111/exd.70208}, pmid = {41546147}, issn = {1600-0625}, support = {MOST 109-2314-B-002-052-MY3//The Ministry of Science and Technology of Taiwan/ ; 108-CGN12//National Taiwan University Hospital/ ; //Novartis Taiwan Co. Ltd/ ; }, mesh = {Humans ; *Omalizumab/therapeutic use ; *Gastrointestinal Microbiome ; *Chronic Urticaria/drug therapy/microbiology/blood ; Female ; Male ; Adult ; Middle Aged ; *Anti-Allergic Agents/therapeutic use ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; Interleukin-17/blood ; }, abstract = {The gut microbiota composition of patients with chronic spontaneous urticaria (CSU) has been shown to be different from that of healthy controls. However, whether the gut microbiome is different between CSU patients with different treatment responses to omalizumab is seldom examined and is largely unknown. Antihistamine-refractory CSU patients were enrolled to receive three injections of omalizumab. The patients were divided into two groups based on their treatment responses to omalizumab determined using the weekly urticarial activity score. Demographic data, blood samples and faecal specimens were collected before, during and after omalizumab treatment. Faecal specimens underwent bacterial 16S ribosomal RNA sequencing to determine the gut bacterial microbiome. Serum biomarkers were examined using enzyme-linked immunosorbent assay. Fourteen patients were enrolled and were divided into two groups: complete responders (CRs) and non-complete responders (NCRs). At baseline, the α-diversity indices of the CR group were higher than those of the NCR group. The bacterial microbiota composition was different between the groups, but these differences became less obvious after omalizumab treatment. At baseline, the genera Bacteroides, Lactobacillus, Prevotella_9, Butyricimonas, Dialister, Megasphaera and Ruminococcaceae_UCG-002 were more abundant in the CR group. In addition, the changes in the IL-33 and IL-17 levels after omalizumab treatment were correlated with the changes in the relative abundances of Dialister (r = 0.929, p = 0.003) and Ruminococcaceae-UCG-002 (r = -0.828, p = 0.022), respectively. In conclusion, the CR patients' distinct and characteristic gut bacterial microbiota profile before treatment may contribute to their better responses to omalizumab.}, } @article {pmid41546121, year = {2026}, author = {Dib, EY and Attieh, P and Karam, K and Al Akel, L and Al Sayed, L and Charafeddine, T and Al Akel, L and Khoury, S and Khalek, WA}, title = {Blastocystis hominis infection inducing gut microbiome dysbiosis and aggravating Parkinson's disease symptoms: a case report.}, journal = {Journal of medical case reports}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13256-025-05763-5}, pmid = {41546121}, issn = {1752-1947}, abstract = {BACKGROUND: Blastocystis hominis infection in patients with Parkinson's disease may exacerbate gut microbiota dysbiosis, potentially worsening neurological symptoms; however, such associations remain speculative without microbiome data. Targeted interventions to restore gut microbial balance could mitigate disease progression and improve patient outcomes.

CASE PRESENTATION: An 86-year-old Caucasian male presented to the emergency department with severe watery diarrhea, up to six episodes per day, of 1 month duration. The patient's diarrhea was nonbloody and nonmucoid. He denied fever, nausea, vomiting, abdominal pain, bloating, loss of appetite, or anal itching. There was no history of weight loss, fatigue, or systemic symptoms. A stool sample was examined microscopically using normal saline, revealing Blastocystis hominis cysts (the burden was not quantified) and a rare white blood cell count. The sample was concentrated using acetylacetate and ether. Additional tests, including Clostridioides difficile and other common infectious pathogens, were ruled out in our patient to address alternative infectious etiologies.The patient was started on intravenous ciprofloxacin and metronidazole, resulting in an improvement in diarrhea consistency and frequency until the resolution of symptoms within 4 days of initiating intravenous therapy. The patient also reported mild improvement in his Parkinson's disease symptoms by the end of hospitalization, though objective neurologic post-treatment scoring (eg. Unified Parkinson's Disease Rating Scale) was not performed.

CONCLUSION: This case highlights the need to consider parasitic infections in patients with Parkinson's disease presenting with chronic diarrhea. While we hypothesize that B. hominis infection may transiently worsen Parkinson's disease symptoms through inflammatory or microbiota-mediated pathways, this remains speculative in the absence of microbiome sequencing or objective neurologic evaluation. Further studies integrating clinical, microbiological, and microbiome analyses are warranted.}, } @article {pmid41545888, year = {2026}, author = {Wang, J and Zhang, Z and Chen, Y and Zhou, X and Xiang, J and Yang, C and Rodionov, DA and Osterman, AL and Qiu, Q and Deng, Y and Liu, Y and Wang, C and Shang, X and Huang, L and Sun, C and Guo, J and Yang, Z and Zhai, L and Bian, Z and Lyu, A and Han, L and Jia, W and Fang, X and Zhang, L}, title = {Exploring differences in the human gut microbiome between Han Chinese and non-Chinese populations.}, journal = {Genome biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13059-026-03932-3}, pmid = {41545888}, issn = {1474-760X}, support = {No. SZ2024KF22//State Key Laboratory of Dampness Syndrome of Chinese Medicine/ ; No. 82004234//National Natural Science Foundation of China/ ; No. 2020B1111100005//Science and Technology Planning Project of Guangdong Province, China/ ; No. C2004-23Y//Young Collaborative Research grant/ ; No. 11221026//HMRF grant/ ; RCMS/24-25/03//HKBU RCMS/ ; }, abstract = {BACKGROUND: The human gut microbiota exhibits significant diversity across populations, influenced by factors such as geography, diet, and lifestyle, particularly between the Han Chinese and non-Chinese populations. While previous studies have predominantly focused on the taxonomic abundance of the gut microbiome, the impact of single nucleotide polymorphisms (SNPs) in driving population-specific differences remains largely underexplored.

RESULTS: In this study, we systematically investigated gut microbial differences between the Han Chinese and non-Chinese populations using the Human Gut Microbiome Reference Genome Catalog (HGMRGC). We observed geography was the primary driver of microbial variation of abundance and SNPs. We identified 689 population-specific genome clusters from the Collinsella genus with functional differences in carbohydrate utilization and 108 species exhibiting distinct prevalence related to vitamin biosynthesis, antibiotic resistance, and carbohydrate metabolism. Beta diversity analysis highlighted significant inter-population differences in both microbial abundance and SNPs, while alpha diversity analysis revealed that non-Chinese populations exhibited higher diversity in microbial abundance, and Han Chinese populations displayed greater diversity in SNPs.

CONCLUSIONS: This study offers a comprehensive analysis of gut microbial differences between Han Chinese and non-Chinese populations, highlighting the profound influence of population-specific traits on microbial diversity and function. We also provide a comprehensive human gut microbial reference genome catalog, with a particular focus on the Han Chinese population, laying a foundation for future research on gut microbiota genomic variations.}, } @article {pmid41545845, year = {2026}, author = {Li, X and Weiland, JE and Ohkura, M and Luster, DG and Kong, P and Hong, C}, title = {Metabarcoding-based characterization of the boxwood root-zone soil microbiome.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-025-08094-1}, pmid = {41545845}, issn = {1471-2229}, support = {2072-22000-046-000-D//USDA-NIFA the Agricultural Research Initiative/ ; 0500-00059-001-000-D//USDA ARS Floriculture and Nursery Research Initiative/ ; 0500-00059-001-000-D//USDA ARS Floriculture and Nursery Research Initiative/ ; 2020-51181-32135//USDA-NIFA SCRI/ ; }, } @article {pmid41545707, year = {2026}, author = {Řezáč, T and Vrba, R and Stašek, M and Špička, P and Klos, D and Zbořil, P}, title = {The impact of preoperative oropharyngeal microflora, decontamination, and postoperative nosocomial and opportunistic infections on the occurrence of respiratory complications in patients undergoing esophagectomy for esophageal cancer after chemoradiotherapy. A single-center cohort.}, journal = {Langenbeck's archives of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00423-026-03966-y}, pmid = {41545707}, issn = {1435-2451}, } @article {pmid41545429, year = {2026}, author = {Maharaj, SD and Nkuna, R and Matambo, TS}, title = {Shotgun metagenomic and physicochemical profiling of municipal wastewater treatment plants using activated sludge and trickling filters.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35157-6}, pmid = {41545429}, issn = {2045-2322}, abstract = {In this study, which aimed to evaluate wastewater treatment and provide data to support improved wastewater treatment plant (WWTP) design, operation and ongoing monitoring strategies, mixed liquor, return activated sludge, primary effluent and secondary effluents of two WWTPs (n = 15) and five of the industries they service (n = 15) in Emfuleni municipality, Gauteng Province, South Africa, were characterised following a 5-month monitoring study. Following physical and chemical analysis, the parameters, including the Chemical Oxygen Demand (COD), were higher than local limits (75 mg/L) for both WWTPs and extremely high for the abattoir industry (13400 mg/L). In particular, high ammonia levels were recorded in both WWTPs. Following Illumina high-throughput sequencing and analysis using the Whole Metagenome Sequencing Assembly-based (WGSA2) pipeline on the Nephele platform, Bacteria was the dominant domain in the WWTPs. The dominant phyla were Proteobacteria (87.7%), followed by Firmicutes (8.25%), Actinobacteria (2.71%) and Bacteroidetes (0.68%). Aeromonas (39.86%) was the most dominant genus, with Acinetobacter (9.29%), Pseudomonas (6.78%), Bacillus (5.99%), and Thauera following (4.78%). Total Suspended Solids (TSS), pH, Total Dissolved Solids (TDS), and DO have influenced the diversity and distribution of the microbiome. Krona charts elucidated the xenobiotics degradation and metabolism distribution potential of the microbiome of each sampled site. This study reiterates the need for constant monitoring of WWTPs due to the high pollution parameters recorded from the WWTP effluent. The metagenomic data generated in this study provides insight into the diversity and functionality of the microbiome present in WWTPs of different process configurations which can inform existing WWTP configurations and future designs.}, } @article {pmid41545383, year = {2026}, author = {Wang, X and Liu, Y and Jiang, C and Huang, Z and Yan, H and Wong, SH and Johnson, CH and Zhang, J and Ge, Y and Zhang, F and Zhang, J and Lai, R and Gao, P and Zhang, X and Shen, X}, title = {TidyMass2: advancing LC-MS untargeted metabolomics through metabolite origin inference and metabolic feature-based functional module analysis.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68464-7}, pmid = {41545383}, issn = {2041-1723}, support = {025402-00001//Ministry of Education - Singapore (MOE)/ ; }, abstract = {Untargeted metabolomics provides a direct window into biochemical activities but faces critical challenges in determining metabolite origins and interpreting unannotated metabolic features. Here, we present TidyMass2, an enhanced computational framework for Liquid Chromatography-Mass Spectrometry (LC-MS) untargeted metabolomics that addresses these limitations. TidyMass2 introduces three major innovations compared to its predecessor, TidyMass: (1) a comprehensive metabolite origin inference capability that traces metabolites to human, microbial, dietary, pharmaceutical, and environmental sources through integration of 11 metabolite databases containing 532,488 metabolites with source information; (2) a metabolic feature-based functional module analysis approach that bypasses the annotation bottleneck by leveraging metabolic network topology to extract biological insights from unannotated metabolic features; and (3) a graphical interface that makes advanced metabolomics analyses accessible to researchers without programming expertise. Applied to longitudinal urine metabolomics data from human pregnancy, TidyMass2 identified diverse metabolites originating from human, microbiome, and environment, and uncovered 27 dysregulated metabolic modules. It increased the proportion of biologically interpretable metabolic features from 5.8% to 58.8%, revealing coordinated changes in steroid hormone biosynthesis, carbohydrate metabolism, and amino acid processing. By expanding biological interpretation beyond MS[2] spectra-based annotated metabolites, TidyMass2 enables more comprehensive metabolic phenotyping while upholding open-source principles of reproducibility, traceability, and transparency.}, } @article {pmid41545381, year = {2026}, author = {Flörl, L and Schönenberger, P and Rienth, M and Bokulich, NA}, title = {Grape expectations: disentangling environmental drivers of microbiome establishment in winegrowing ecosystems.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00915-x}, pmid = {41545381}, issn = {2055-5008}, support = {310030_204275//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {Microbial communities play a central role in viticulture, influencing wine characteristics (a concept termed microbial terroir). Yet, the individual factors shaping these microbiomes remain poorly understood. We conducted a multi-year, large-scale survey of Swiss vineyards (95 sites, 680 samples), longitudinally sampling 12 sites (within 2.46 km and identical cultivar and rootstock) over three years. Using 16S rRNA gene and internal transcribed spacer (ITS) amplicon sequencing, untargeted metabolomics (GC-MS, LC-MS/MS), environmental monitoring, and sensory data, we disentangled environmental factors associated with community assembly and fermentation dynamics. Topography and climate collectively structured microbiomes but affected soil- and plant-associated communities differently. Berry-associated fungi showed the strongest site-specific signature, enabling machine-learning predictions of microclimatic variation. Climatic factors and berry chemistry selectively favor fermentative yeasts, which are each linked to distinct metabolite and aroma profiles. Plant stress metabolites were further associated with microbial and metabolite composition. Our integrative approach thereby fundamentally advances our understanding of microbial biogeography and terroir in viticulture.}, } @article {pmid41545378, year = {2026}, author = {Kaan, AM and Duijster, DD and Ujcic-Voortman, JK and Haring, LV and Volgenant, CMC and Zaura, E}, title = {Oral health assessment in a prospective birth cohort study.}, journal = {BDJ open}, volume = {12}, number = {1}, pages = {10}, pmid = {41545378}, issn = {2056-807X}, abstract = {BACKGROUND: Robust oral health data collection in birth cohort studies is needed to understand the oral microbiome in relation to oral and general health.

OBJECTIVE: The aim of this paper is to describe the collection of oral health data in toddlers participating in a birth cohort focussing on microbiome development. Hereby, we aim to support the interpretation of variance in microbiome data.

METHODS: The Amsterdam Infant Microbiome Study (AIMS, n = ~500) is a longitudinal prospective birth cohort assessing microbiota, general health status, demographics, (oral) health behaviour and dietary behaviour in children from birth up to three years. The Oral Health Study (OHS) is a sub-study of AIMS, assessing the oral health of children and their mothers. From the mothers, data on periodontal health (clinical attachment loss, gingival bleeding), oral hygiene (dental plaque, calculus) and dental caries (DMFS) is collected. In children, data on caries prevalence (ICDAS) and infection (pufa), oral hygiene (dental plaque, calculus), Obstructive Sleep Apnoea (OSA), oromuscular function, and bitter taste sensitivity are collected.

RESULTS: Enrolment in OHS started in October 2022 and is planned to continue up to December 2028. In October 2024, 64 mother-child pairs were enroled in the study.

CONCLUSIONS: Data collection is expected to be completed by January 2028. Results will be shared at international conferences and via peer-reviewed publications.}, } @article {pmid41545153, year = {2026}, author = {Luo, Y and Ding, H and Mao, X and Kang, Z and Li, B and Zhou, Y}, title = {Mechanistic insights into rhizosphere microbiome assembly in Pinus tabuliformis: The role of cross-kingdom interactions and soil salinity gradients.}, journal = {Fungal biology}, volume = {130}, number = {1}, pages = {101695}, doi = {10.1016/j.funbio.2025.101695}, pmid = {41545153}, issn = {1878-6146}, mesh = {*Pinus/microbiology ; *Rhizosphere ; *Soil Microbiology ; *Soil/chemistry ; Bacteria/classification/genetics/isolation & purification ; *Fungi/classification/genetics/isolation & purification ; *Salinity ; *Microbiota ; Plant Roots/microbiology ; High-Throughput Nucleotide Sequencing ; }, abstract = {Soil salinization caused by desertification and drought severely limits agricultural and forestry development. The rhizosphere core microbiome plays a vital role in helping host plants cope with environmental stress. However, in saline-alkali soils, it remains unclear how bacterial and fungal communities in the rhizosphere of Pinus tabuliformis interact and collectively respond to environmental factors to influence the plant. This study aims to identify the composition and functional potential of the core bacterial and fungal microbiota in the rhizosphere of P. tabuliformis in saline environments, as well as their interactions with environmental factors, thus providing a theoretical basis for utilizing core rhizosphere microbial resources. We performed high-throughput sequencing of root samples from P. tabuliformis at four locations. We analyzed the community structure and functional profiles of bacteria and fungi and their relationships with soil physicochemical properties. The environmental factors most influencing the number of core bacterial species were organic matter (OM), Na[+], and total potassium (TK). Meanwhile, total phosphorus (TP) was the most influential soil factor for core fungal species. Correlation analysis showed that TN, TP, and pH significantly affected both bacterial and fungal community variation (P < 0.05). Co-occurrence network analysis indicated complex cross-kingdom interactions between core bacterial and fungal taxa. Functional predictions suggested that bacterial communities exhibit both potential pathogenicity and stress resistance, while fungal communities are more saprotrophic and sensitive to environmental changes. Microbial communities at the SYH site displayed a "high pathogenicity-low resistance" profile, contrasting with those at the MC site. Correlation network analysis further uncovered complex mutualistic and competitive relationships among core bacterial and fungal genera. This study demonstrates that P. tabuliformis rhizosphere bacterial and fungal communities respond collaboratively to salinity stress through functional complementarity, such as bacterial enrichment in stress resistance and fungal dominance in saprotrophy. These findings may offer new insights into enhancing the adaptability of P. tabuliformis and improving sandy land ecosystems by targeted management of the soil microbiome.}, } @article {pmid41544734, year = {2026}, author = {Ge, J and Gao, L and Yu, L}, title = {Intratumoral microbiota: distribution, mechanisms, and therapeutic implications.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {105128}, doi = {10.1016/j.critrevonc.2026.105128}, pmid = {41544734}, issn = {1879-0461}, abstract = {Recent studies have increasingly highlighted the presence of microbiota within tumors and their substantial impact on tumor initiation, progression, and treatment efficacy. Intratumoral microbiota modulate tumor progression via multiple mechanisms, such as regulation of cancer cell proliferation, manipulation of immune microenvironment, and induction of the DNA damage. Notably, the distinct bacterial profiles associated with each tumor type can, in turn, promote or suppress tumor growth. Given the various mechanisms through which intratumoral microbiota influence tumor progression, a deeper understanding of their composition and functional roles in tumor dynamics is critical for the development of targeted therapies. In this review, we summarize current understanding and future perspectives of the bacterial lineages associated with different tumor types, discuss the mechanisms through which the intratumoral microbiome modulates tumor progression, and highlight emerging therapeutic strategies targeting intratumoral bacteria, including sonodynamic therapy (SDT), chemotherapy, immunotherapy, and oncolytic bacterial approaches.}, } @article {pmid41544718, year = {2026}, author = {Alexandre-Gouabau, MC and Moyon, T and Douarec, C and Moulazem, Y and Croyal, M and Gourdel, M and Roze, JC and Simon, L and Boscher, C and Billard, H and David-Sochard, A and Rezé, S and Misery, B and Bizec, BL and Guillou, S and Antignac, JP and Boquien, CY and Vigneau, E and Mahieu, B and Cano-Sancho, G}, title = {An Exploration of the Breast Milk Nutriome, Exposome and Microbiome and their Links to Early Growth in Preterm Infants.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110268}, doi = {10.1016/j.jnutbio.2026.110268}, pmid = {41544718}, issn = {1873-4847}, abstract = {BACKGROUND: Breastfeeding promotes improved growth and development in preterm infants, yet the mechanisms underlying these benefits remain unclear.

OBJECTIVE: This study explored the interplay of breast-milk nutritional, microbiological, and environmental chemical exposure on early preterm infant growth.

METHODS: In the prospective LACTACOL-cohort, growth was assessed in 137 exclusively breastfed preterm infants (including 40 twins) using Z-scores of discharge weight and fat-free mass (FFM, by air-displacement plethysmography). Breast-milk samples were analyzed for their nutriome (targeted and untargeted metabolomic and lipidomic profiling), exposome (targeting persistent organic pollutants, POPs), and microbiome (16s rRNA-sequencing). Correlation analysis and sequential random forest modelling were applied to integrate multi-omics datasets and identify determinants of discharge weight Z-score (36 observations) and FFM (21 observations).

RESULTS: The nutriome emerged as the primary contributor to the postnatal growth in preterm infants. Choline-containing lipids (sphingolipids, phosphatidylcholines and their plasmalogen forms), positively contributed to weight Z-score. Sphingomyelin enriched in nervonic acid supported positively FFM Z-score, whereas oxylipins had a negative effect. The exposome exhibited complex effects: the dioxin-like compound 1,2,3,7,8-PeCDD negatively impacted weight, while the polychlorinated biphenyl 123 positively influenced both weight and lean mass gains. Brominated flame retardants were associated with a lower FFM Z-score. Although the microbiome showed an overall minor impact, it varied with POPs and postnatal growth terciles, highlighting the co-dependencies between milk components.

CONCLUSIONS: This integrative hypothesis-generating pilot study provides novel evidence on the richness of breast-milk composition and the interplay of nutriome, exposome, microbiome in breast-milk and their joint influence on postnatal growth in preterm infants.

CLINICAL TRIAL REGISTRY: LACTACOL, ClinicalTrials.gov ID NCT NCT01493063 https://clinicaltrials.gov/study/NCT01493063.}, } @article {pmid41544710, year = {2026}, author = {Shivakoti, R and Laughton, B and Mandell, J and Barrios-Tascon, A and Rajendran, R and Glashoff, R and Bode, L and Aldrovandi, G and Kuhn, L}, title = {Limited evidence of benefits from clinical trials of human-identical milk oligosaccharides for infants.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100593}, doi = {10.1016/j.advnut.2026.100593}, pmid = {41544710}, issn = {2156-5376}, abstract = {Human milk oligosaccharides (HMOs) are complex carbohydrates unique to human milk and a wealth of observational and mechanistic studies indicate that HMOs are key to infant health by supporting gut microbiota and immune development. This review synthesizes evidence from randomized clinical trials evaluating whether supplementation with human-identical milk oligosaccharides (HiMOs), i.e. synthetic HMOs, in infants and young children improves health outcomes. We identified 12 randomized clinical trials: 8 in healthy infants, three in special populations of infants and one in young children. We selected only trials with a randomized, parallel group design; most of the included trials also had an observational human milk fed control group. The most widely evaluated HiMO was 2' fucosyllactose (2'FL) used alone or in combination with other HiMOs. In some trials, other bioactive components were included in the control and/or intervention formula groups complicating interpretation. All trials in healthy infants confirmed the non-inferiority of HiMO supplemented formula on growth and tolerability relative to control formula. Results were mixed with respect to reductions in morbidity and all studies were under-powered for more severe morbidity outcomes. Stool microbiota and biomarkers of inflammation and gut function generally shifted in a direction closer to human milk fed infants with HiMO intervention. Some growth improvements were noted in association with HiMO intervention in preterm infants and in infants with severe acute malnutrition. HiMO supplementation may be a promising intervention to improve child health, but due to the heterogeneity and limitations of the clinical trials that have been undertaken, many questions remain about the nature of the benefits and the specific populations who might benefit.}, } @article {pmid41544689, year = {2026}, author = {Ruan, W and Huang, M and Li, X and Peng, Z and Wei, Y and Mai, Z and Pan, M and Deng, J and Chen, X and Zhang, H and Meng, X and Zhang, J}, title = {Regulated cell death in COPD: Modulators, crosstalk mechanisms, and therapeutic opportunities.}, journal = {European journal of pharmacology}, volume = {1015}, number = {}, pages = {178557}, doi = {10.1016/j.ejphar.2026.178557}, pmid = {41544689}, issn = {1879-0712}, abstract = {Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory airway disorder, with emerging evidence highlighting the central role of regulated cell death (RCD) in its pathogenesis. However, the regulatory mechanisms, crosstalk between different RCD pathways, and their role in intercellular communication remain poorly understood. This review examines major forms of RCD (apoptosis, necroptosis, ferroptosis, pyroptosis, NETosis, and PANoptosis) in COPD, exploring their regulation, crosstalk, role in intercellular signaling, and potential as therapeutic targets. Mechanistically, RCD is regulated through membrane receptors, epigenetic modifications, and post-translational processes. Endoplasmic reticulum (ER) stress, reactive oxygen species, and autophagy serve as common nodes across multiple RCD types. Excessive ER stress triggers apoptosis, while impaired autophagy promotes oxidative stress, cellular senescence, and inflammation. Conversely, excessive autophagy-including mitophagy, ferritinophagy, lysosomal autophagy, ER-phagy, and chaperone-mediated autophagy-can induce apoptosis, necroptosis, and ferroptosis. Regarding inter-pathway crosstalk and RCD-mediated intercellular communication: reduced macrophage apoptosis exacerbates epithelial inflammation and apoptosis; macrophage inflammation or ferroptosis can further promote epithelial ferroptosis or inflammatory responses. Ferroptosis in airway epithelial cells aggravates their own pyroptosis, and pyroptotic epithelial cells secrete exosomes that induce macrophage pyroptosis. NETotic neutrophils release extracellular DNA, driving inflammation in airway epithelia. Therapeutically, current exploratory strategies target these death pathways through diverse approaches, including existing pharmaceuticals, hormones, phytochemicals, recombinant proteins and nucleic acids, stem cell and regenerative therapies, and modulation of the airway microbiome. Deciphering the RCD network in COPD not only enhances our understanding of disease heterogeneity but also paves the way for developing precision therapeutics.}, } @article {pmid41544466, year = {2026}, author = {Li, B and Li, Y and Wang, B and Wang, Y and Liu, W and Xu, X and Liu, M and Zhang, X and Xiu, R}, title = {Modulation of gut microbiota by the herbal formulation Intestinal Flora Balance rescues pancreatic and intestinal microvascular dysfunction to alleviate type 2 diabetes mellitus.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157828}, doi = {10.1016/j.phymed.2026.157828}, pmid = {41544466}, issn = {1618-095X}, abstract = {BACKGROUND: The potential for microbial modulation to serve as both a therapeutic and prophylactic strategy against type 2 diabetes mellitus (T2DM)-induced microvasculopathy remains underexplored. We therefore compared the efficacy of the gut-centric herbal formulation Intestinal Flora Balance (IFB, BNFF™), when used for therapeutic reversal, synergistic rescue, or prophylactic protection.

METHODS: A murine T2DM model was used to compare three arms, IFB monotherapy, IFB-metformin combination therapy, and IFB pretreatment administered prior to disease induction. Pancreatic and intestinal microcirculation was quantified using in vivo laser Doppler and fiber optic probes. Fecal microbiota composition was analyzed via 16S rRNA gene sequencing.

RESULTS: As a therapeutic agent, IFB monotherapy effectively lowered blood glucose and restored microvascular function by reversing diabetic gut dysbiosis. Combination with metformin, while not further improving glycemia, acted synergistically to provide superior rescue of pancreatic microcirculation, indicating complementary modes of action. Prophylactic administration of IFB conferred protection, preserving microbial homeostasis and significantly attenuating the onset of both hyperglycemia and microvascular damage. IFB enhanced the richness and diversity of the intestinal microbiome in T2DM mice and restored the Bacteroidetes/Firmicutes ratio.

CONCLUSIONS: By demonstrating that IFB ecologically restores the microbiome, in contrast to metformin's pharmacological modulation, our study provides a new framework for its use as a prophylactic, a restorative monotherapy, or a synergistic partner to build microcirculatory resilience.}, } @article {pmid41544465, year = {2026}, author = {Zhang, WJ and Wang, J and Liao, MY and Li, CL and Liao, XX and Su, WW}, title = {Gut microbiome-metabolomics integration explores the adjunctive effect of Naoxintong capsule on atorvastatin in ameliorating hyperlipidemia: A randomized controlled pilot study.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157799}, doi = {10.1016/j.phymed.2026.157799}, pmid = {41544465}, issn = {1618-095X}, abstract = {BACKGROUND: Naoxintong Capsule (NXT), a prescribed traditional Chinese medicine (TCM), has been widely used in combination with Western medicine to treat patients with atherosclerotic cardiovascular diseases. The purpose of this study was to preliminarily investigate the effects and mechanisms of the addition of NXT to statin therapy in patients with hyperlipidemia.

METHODS: Thirty-two hyperlipidemia patients were randomly divided into two groups, which received atorvastatin and NXT plus atorvastatin treatment for 12 weeks respectively. The primary outcome was the change of lipid metabolism. Other outcomes included changes in inflammation, endothelial function, liver function and myocardial enzyme. Microbiome and metabonomics analysis were conducted to explore the potential mechanism of the effect of the addition of NXT to atorvastatin.

RESULTS: Compared to atorvastatin monotherapy, the combination therapy demonstrated an 11.3% greater reduction in LDL-C level (2.65 vs. 2.99 mmol/l, p = 0.027), a 24.7% increase in HDL-C level (1.06 vs. 0.85 mmol/l, p = 0.011) and an 18.8% greater reduction in TG (1.77 vs. 2.18 mmol/l, p = 0.011). Systemic anti-inflammatory benefits were evidenced by an 11.8% reduction in IL-6 (69.13 vs. 78.39 ng/l, p < 0.001) and a 10.4% decrease in TNF-α (90.16 vs. 100.63 ng/l, p = 0.030). Additionally, myocardial injury biomarkers showed marked improvement, with a 19.3% decrease in LDH (193.60 vs. 239.96 U/l, p < 0.001) and a 26.2% reduction in CK-MB (31.69 vs. 42.90 U/l, p < 0.001). Some key bacteria of Streptococcus_salivarius, Veillonella_parvula, Streptococcus_thermophilus, Anaerobutyricum_hallii and Ruminococcus_sp_5_1_39BFAA were discovered to be related to the enhanced effect of NXT to atorvastatin via the correlation analysis. Several metabolic pathways, such as citrate cycle, ether lipid metabolism, propanoate metabolism, and glutathione metabolism were uncovered to be closely involved in the outcome of NXT combination treatment.

CONCLUSION: Taken together, our study demonstrates that the addition of NXT to atorvastatin could enhance the therapeutic effect against hyperlipidemia, which might be related to the composition alterations of gut microbiota and changes in plasma metabolite abundances. This study provides a novel perspective for understanding the mechanism of NXT in the combination treatment of hyperlipidemia in clinic. (Trial registration No. ChiCTR2500097533).}, } @article {pmid41544456, year = {2026}, author = {Szewc, AM and Nicholson, AC and Livingston, K and Hopper, C and McQuiston, JR}, title = {Design, validation and evaluation of a triplex real time qualitative PCR assay targeting zoonotic Capnocytophaga species in EDTA whole blood and plasma simulated clinical specimens.}, journal = {Diagnostic microbiology and infectious disease}, volume = {114}, number = {4}, pages = {117268}, doi = {10.1016/j.diagmicrobio.2026.117268}, pmid = {41544456}, issn = {1879-0070}, abstract = {Found in the oral microbiome of cats and dogs, bacteria from the genus Capnocytophaga occasionally infect humans and can cause serious disease or death if not identified and treated promptly. Described here is a real-time triplex qualitative PCR assay designed using gene targets (rplV and secY) identified as diagnostically relevant by analysis of genomes from the Capnocytophaga species. The assay was evaluated on simulated EDTA whole blood samples/plasma and is effective at detecting down to 10 copies per microliter (10000 copies per mL, 4 log/mL) for whole blood samples (rplV /secY), and 1 copy per microliter (1000 copies per mL, 3 log mL) (rplV) and 0.5 copy per microliter (500 copies per mL, 2.69 log mL) (secY) for plasma samples. Analytical sensitivity, specificity, and reproducibility were established in plasmid-spiked simulated EDTA whole blood and plasma specimens, and clinical performance in Capnocytophaga-positive patient samples remains to be determined.}, } @article {pmid41544443, year = {2026}, author = {Yang, W and Zhao, Y and Liu, X and Cai, Y and Dai, Y and Zhang, H and Chen, Y and Chen, F and Liu, F and Sun, C and Yang, N and Yan, W}, title = {Multi-omics reveals co-regulation of hepatic bile acid metabolism in laying hens by host genetics and the cecal Anaerostipes.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106388}, doi = {10.1016/j.psj.2026.106388}, pmid = {41544443}, issn = {1525-3171}, abstract = {Bile acids (BA) are central regulators of lipid metabolism and key signaling molecules within the gut-liver axis. Dysregulation of BA is implicated in fatty liver hemorrhagic syndrome (FLHS), a prevalent metabolic disorder in laying hens characterized by hepatic lipid accumulation, hemorrhage, reduced egg production, and increased mortality. However, the mechanisms governing BA regulation in poultry remain poorly understood. Here, we integrated multi-omics analyses to dissect how host genetics and gut microbiota interact to modulate hepatic total bile acids (HTBA) levels. A total of 686 hens at 90 weeks of age were profiled for HTBA, free fatty acids (FFA), triglycerides (TG), and total cholesterol (TC). We integrated single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS), liver transcriptomics, 16S rRNA profiling across different intestinal segments, and cecal metabolomics, followed by Mendelian randomization (MR) to infer causality between gut microbes and HTBA. HTBA displayed a nonlinear association with FLHS severity-lower HTBA corresponded to higher disease risk, whereas increasing HTBA aligned with reduced risk. GWAS identified 11 SNPs associated with HTBA, including a signal at 2,435,887 bp on chromosome 6 that replicated across Mixed Linear Model (MLM) and FarmCPU models and was annotated to GRID1. The hepatic expression of GRID1 showed a significant positive correlation with HTBA levels. In addition, The liver transcriptome revealed a significant downregulation in the expression of the COL4A3 and ENSGALG000005008 genes in the high HTBA group compared to the low HTBA group. These findings provide new insights into the genetic background underlying bile acid metabolism in chickens, Transcriptome analysis contrasting high- versus low-HTBA groups yielded 893 differentially expressed genes enriched for bile-acid transporters and related signaling pathways. Microbiome analyses highlighted eight genera associated with HTBA; notably, cecal Anaerostipes exhibited a strong positive causal effect on HTBA in MR (β = 9.39, P = 1.4 × 10[-10]) and coincided with metabolomic shifts in the cecum (Dehydrocholic acid and other secondary bile acids, amino acids, and lipids were elevated; while aromatic amines decreased). Collectively, these findings indicate that hepatic bile-acid metabolism in laying hens is jointly shaped by host genetics and the gut microbiota. Maintaining an appropriate HTBA range appears essential for hepatic lipid homeostasis, providing a mechanistic basis for genetic or nutritional interventions targeting bile-acid pathways to mitigate FLHS.}, } @article {pmid41544441, year = {2026}, author = {Ren, J and He, Q and Shang, H and Lu, T and Xiong, X}, title = {Host genetic and environmental determinants of chicken gut microbiota: A review.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106432}, doi = {10.1016/j.psj.2026.106432}, pmid = {41544441}, issn = {1525-3171}, abstract = {The gut microbiota is a diverse and abundant microbial community in animals; it plays a key role in nutrient absorption and immune defense and is an important factor affecting chicken health and growth performance. Understanding the composition of chicken gut microbiota and its influencing factors can provide a theoretical foundation for maintaining the diversity and microecological balance of beneficial microbial communities in the chicken intestinal tract. This review aimed to explore the recent advancements in understanding the non-genetic e.g. environmental and host genetic factors that influence the chicken gut microbiome, focusing on the gut microbial composition including host genetic kinship, heritability, microbial quantitative loci, and candidate genes. Studies on host genetic factors have identified several genes associated with gut microbial composition including lipid droplet associated hydrolase (LDAH) and apolipoprotein B (APOB) associated with Staphylococcus; TOX high mobility group box family member 2 (TOX2) significant locus linked to Veillonella, and reelin (RELN), lumican (LUM), and S-phase cyclin A associated protein in the ER (SCAPER) associated with intestinal microbial abundance. These factors are involved in host growth, development, and immune system regulation, collectively indicating that host genes play a significant role in regulating chicken gut microbiota. Furthermore, a comprehensive exploration of both non-genetic and host genetic factors could provide a solid foundation and practical strategies for improving chicken health and production performance by regulating the gut microbiota.}, } @article {pmid41544344, year = {2026}, author = {Nepal, G and Yang, D and Ojha, R and Tu, Z}, title = {Association between dairy consumption and Parkinson's disease: A systematic review and meta-analysis.}, journal = {Public health}, volume = {252}, number = {}, pages = {106143}, doi = {10.1016/j.puhe.2026.106143}, pmid = {41544344}, issn = {1476-5616}, abstract = {OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no cure and rising global prevalence. Genetic, environmental, and dietary factors may influence risk. Dairy intake, may influence risk through gut microbiome changes and alpha-synuclein spread along the gut-brain axis, though epidemiological evidence is mixed. This meta-analysis examines the association between dairy consumption and PD risk in observational studies.

STUDY DESIGN: This study is a systematic review and meta-analysis of published literature.

METHODS: PubMed and EMBASE were searched for original, peer-reviewed observational studies examining dairy intake and PD risk. Pooled risk estimates were calculated using fixed- or random-effects models depending on heterogeneity (I[2] threshold: 50 %). Subgroup analyses by dairy type and sex were conducted. This study adhered to PRISMA guidelines.

RESULTS: Nine studies (eight cohort, one case-control) comprising diverse populations from the U.S., Europe, and Asia were included. A total of 15 results from 9 observational studies were analyzed. The combined cohort studies encompassed 634,327 participants with 4285 incident PD cases, while the case-control studies included 617 individuals (368 controls and 249 PD cases). High total dairy intake was significantly associated with increased PD risk (RR = 1.211; 95 % CI: 1.071-1.37; p = 0.002), with a stronger effect in males (RR = 1.282) than females (RR = 1.019). Milk consumption was also associated with increased PD risk (RR = 1.13; 95 % CI: 1.079-1.20; p < 0.001), with consistent sex-specific results. No significant associations were found for yogurt/fermented milk, cheese, butter, or ice cream.

CONCLUSIONS: Higher consumption of total dairy and plain milk is associated with an increased risk of developing PD. Further studies involving diverse populations and ethnicities should explore this association, stratified by genetic and sporadic forms of PD.}, } @article {pmid41544313, year = {2026}, author = {Burckhardt-Bravo, V and Funes-Ferrada, R and Valenzuela, F}, title = {Update on novel acne treatments: a narrative review focused on microbiome modulation and non-pharmacological approaches.}, journal = {Anais brasileiros de dermatologia}, volume = {101}, number = {1}, pages = {501249}, doi = {10.1016/j.abd.2025.501249}, pmid = {41544313}, issn = {1806-4841}, abstract = {Acne vulgaris is a chronic inflammatory condition with multifactorial pathogenesis. Despite the availability of numerous treatment options, there remains a need for safe, well-tolerated, and microbiome-preserving therapies. This narrative review explores recent advances in non-pharmacological acne treatments, focusing on various microbiome modulation strategies. It highlights emerging therapeutic modalities and their potential impact on clinical practice. Key findings from recent studies are summarized, providing insights for future research and practical applications in dermatology.}, } @article {pmid41544076, year = {2026}, author = {Tanaka, Y and Mizushima, D and Izawa, Y and Matsumura, T and Yonekawa, C and Kato, H and Mato, T}, title = {Bacterial community associated with the surface and inside of centipede forcipules: Identification and characterization.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0341165}, pmid = {41544076}, issn = {1932-6203}, mesh = {Animals ; *Arthropods/microbiology ; *Bacteria/genetics/isolation & purification/classification ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Japan ; Phylogeny ; Bites and Stings/microbiology ; }, abstract = {BACKGROUND: In tropical to subtropical regions, centipede bites may prompt medical attention, with manifestations largely reflecting venom-related discomfort, although infections, including rare fatal necrotizing soft tissue infection (NSTI), have been reported. However, no reports are available on the commensal bacteria on centipede forcipules.

OBJECTIVES: This study aimed to investigate bacterial species residing on and in centipede forcipules and their potential role in post-bite infections.

METHODS: Nine Scolopendra mutilans, three Scolopendra japonica, and two Bothropolys rugosus were collected from three regions in Japan. The bacterial composition of their forcipules was analyzed using 16S ribosomal ribonucleic acid gene sequencing and microbiome analysis.

FINDINGS: A diverse bacterial community was observed on the centipede forcipules. Among the NSTI-associated genera examined (Escherichia, Staphylococcus, and Streptococcus), only Staphylococcus was identified as a minor population.

CONCLUSION: This study provides the first evidence that some bacteria found on centipede forcipules have been previously isolated from centipede bite infections. The risk of infection from bacteria on centipede forcipules during a centipede bite appears low. However, the presence of diverse bacterial species emphasizes the importance of thoroughly cleaning centipede bite wounds to prevent secondary infection.}, } @article {pmid41543784, year = {2026}, author = {Chen, X and Ke, Y and Huang, X and Chen, J and Chen, J and Chen, Z}, title = {Immunotherapy in clear cell renal cell carcinoma: current Status, novel Strategies, and future perspectives.}, journal = {Clinical and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10238-025-02031-0}, pmid = {41543784}, issn = {1591-9528}, abstract = {Clear cell renal cell carcinoma (ccRCC) remains a major clinical challenge, with high rates of recurrence and limited long-term survival despite surgical resection and VEGF-targeted therapy. Immune checkpoint inhibitors (ICIs)-targeting PD-1, PD-L1, and CTLA-4-have revolutionized first-line systemic treatment, particularly in combination with VEGF tyrosine kinase inhibitors or as dual ICI regimens. However, primary and acquired resistance, immune-related adverse events (irAEs), and heterogeneous treatment responses limit the durability of benefit in many patients. This review aims to address a central question: how can immunotherapy for ccRCC evolve from incremental survival extension to durable, potentially curative control? We highlight emerging strategies-including next-generation checkpoint inhibitors (LAG-3, TIM-3, TIGIT), bispecific T cell engagers, cytokine-based agents, CAR-T and TCR-T therapies, and cancer vaccines-designed to enhance and sustain anti-tumor immunity. In parallel, we examine the role of multi-omic and spatial biomarkers, such as PBRM1 mutations, interferon-γ signatures, single-cell spatial atlases, and gut microbiome profiles, in refining patient selection and predicting therapeutic outcomes. This review uniquely integrates mechanistic insights with translational advances, providing a forward-looking synthesis of precision immunotherapy in ccRCC. We also emphasize rational combination strategies, biomarker-guided personalization, and irAE management as key priorities to overcome resistance and improve long-term outcomes.}, } @article {pmid41543665, year = {2026}, author = {Fu, C and Tang, W and Lu, J and Lu, X and Huang, Y and Huang, Q and Zhao, J and Mo, L and Feng, Y and Hu, X and Tang, Y and Yi, S and Wei, H and Huang, H and Li, Q and Tan, J}, title = {Complexity of the respiratory microbiome in pediatric hMPV hospitalizations: a tNGS-based study linking microbial co-detection to severe clinical outcomes.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {41543665}, issn = {1439-0973}, support = {S2024082//Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project/ ; }, abstract = {OBJECTIVE: Human metapneumovirus (hMPV) is a significant contributor to pediatric respiratory hospitalizations. This study aimed to delineate the epidemiological patterns, clinical characteristics, and outcomes in a large cohort of hospitalized children with hMPV infection.

METHODS: From April 2021 to November 2023, 5,021 children with acute respiratory infections were enrolled at a tertiary care center. Respiratory samples underwent targeted next-generation sequencing (tNGS) for comprehensive microbial detection. Clinical, laboratory, and imaging data were analyzed to compare disease severity between cases with single hMPV detection and those with multiple microbial detections.

RESULTS: hMPV was detected in 12.5% (629/5,021) of cases. Strikingly, 94.8% (596/629) of these cases had co-detection of additional respiratory microbes, predominantly in hMPV-bacteria-virus (212/596) and hMPV-bacteria (123/596) combinations. Commonly co-detected agents included Haemophilus influenzae (40.8%, 257/629) and Mycoplasma pneumoniae (23.1%, 145/629). Cases with multiple microbial detections were associated with elevated serum amyloid A (median 26.4 vs. 5.9 mg/L, P = 0.018), prolonged hospitalization (6.0 vs. 5.0 days, P = 0.003), and higher costs (¥8,237.5 vs. ¥3,906.5, P < 0.001). Among the 629 hMPV-positive cases, 309 (49.1%) required respiratory support. Pulmonary consolidation and hypoxemia were the most common respiratory complications, while gastrointestinal dysfunction and myocardial damage were the primary non-respiratory complications. The median hospital stay was 6 days. Of these, 34 cases (5.4%) required intensive care unit (ICU) admission, and two cases (0.3%) resulted in mortality. These severe outcomes occurred exclusively in cases where multiple microbes were detected.

CONCLUSION: The respiratory microbiome in children hospitalized with hMPV is overwhelmingly complex, with frequent co-detection of multiple microbes (94.8%), which is associated with significant clinical burdens, including prolonged hospitalization, increased need for respiratory support, and higher treatment costs. tNGS, with its ability to simultaneously identify multiple microbes, shows potential diagnostic value in uncovering this complexity and could be promising for guiding clinical management and antibiotic stewardship.}, } @article {pmid41543527, year = {2026}, author = {Ibiwoye, DO and Dahunsi, SO}, title = {Amplicon sequence data from the gut microbiota of broiler chickens fed black soldier fly (Hermetia illucens) larvae-based diets.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0123025}, doi = {10.1128/mra.01230-25}, pmid = {41543527}, issn = {2576-098X}, abstract = {This manuscript describes 16S Ribosomal rRNA gene amplicon sequences from gut samples of broiler chickens fed diets containing 0%, 25%, 50%, and 100% black soldier fly larvae. The data set includes raw reads, amplicon sequence variants, and taxonomic assignments supporting microbiome analysis under insect-based feeding regimes.}, } @article {pmid41543481, year = {2026}, author = {Tanabe, G and Mack, DR and Stintzi, A}, title = {Complete genomes of Phascolarctobacterium faecium isolates obtained from pediatric mucosal-luminal interface aspirate samples.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0078925}, doi = {10.1128/mra.00789-25}, pmid = {41543481}, issn = {2576-098X}, abstract = {The bacterium Phascolarctobacterium faecium frequently colonizes the human gut and has been reported to have reduced abundance in people with Crohn's disease. Here, we report the complete genome sequences of two P. faecium strains isolated from mucosal-luminal interface samples taken from pediatric participants with/without Crohn's disease.}, } @article {pmid41543328, year = {2026}, author = {Ji, Q and Wang, Y and Huo, L and Qiao, C and Li, F and Yang, F and Pan, L}, title = {Therapeutic Mechanisms of Lactiplantibacillus plantarum NXU0014 Against Chronic Alcohol-Induced Liver Injury Mediated by Gut-Liver Axis Modulation.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {1}, pages = {e70375}, doi = {10.1002/mnfr.70375}, pmid = {41543328}, issn = {1613-4133}, support = {2023BCF01028//Key R & D Program of Ningxia Hui Autonomous Region/ ; 2023BCF01029//Key R & D Program of Ningxia Hui Autonomous Region/ ; 2024AAC05047//Ningxia Hui Autonomous Region Excellent Young Scientists Fund/ ; NYG2024042//Higher Education Scientific Research Grant, Department of Education of Ningxia Hui Autonomous Region/ ; }, mesh = {Animals ; Male ; *Lactiplantibacillus plantarum/physiology ; *Probiotics/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice, Inbred C57BL ; *Liver Diseases, Alcoholic/therapy/microbiology ; Liver/metabolism ; Mice ; Dysbiosis ; NF-E2-Related Factor 2/metabolism/genetics ; Oxidative Stress ; Bile Acids and Salts/metabolism ; Disease Models, Animal ; }, abstract = {This study investigated the protective effects of Lactobacillus plantarum NXU0014 against chronic alcoholic liver injury (CALI) and its underlying mechanisms in a mouse model. Forty-eight male C57BL/6J mice were divided into four groups: blank control, model, silymarin, and L. plantarum NXU0014. The CALI model was induced by administering 56% Hongxing Erguotou liquor. Multi-omics analyses revealed that alcohol intake induced gut microbiota dysbiosis, characterized by an increased Firmicutes/Bacteroidetes ratio and decreased abundance of probiotics (e.g., Lactobacillus and Bifidobacterium). These changes were associated with hepatic pro-inflammatory upregulation, downregulation of antioxidant genes (Nrf2, HO-1), and impaired intestinal barrier function (ZO-1). Metabolomic disturbances featured elevated fecal bile acids, reduced amino acids, and enriched pathways for ABC transporters and bile secretion. Intervention with NXU0014 restored probiotic levels (including Bifidobacterium pseudodanubicum and Lactobacillus reuteri), alleviated hepatic inflammation and oxidative stress by activating the Nrf2/HO-1 pathway, and repaired the intestinal barrier. Integrated microbiome-metabolome analysis revealed a negative correlation between Lactobacillus and toxic bile acids, and a positive correlation between Bifidobacterium and anti-inflammatory metabolites. These findings demonstrate that NXU0014 mitigates liver injury by modulating gut-liver axis metabolic interactions, highlighting its potential as a novel probiotic-based therapy for alcoholic liver disease.}, } @article {pmid41543291, year = {2026}, author = {Khan, MT and Mohanty, S and Devi, S and Sharma, S and Tripathi, P}, title = {Dietary Flavonoid, Gut Microbiota, and Intestinal Diseases: A Review With Bibliometric Trends and Research Insights.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {1}, pages = {e70368}, doi = {10.1002/mnfr.70368}, pmid = {41543291}, issn = {1613-4133}, support = {OLP-19//CSIR-Indian Institute of Toxicology Research/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Flavonoids/pharmacology ; *Diet ; Dysbiosis ; Animals ; *Intestinal Diseases/microbiology ; }, abstract = {Flavonoids are one of the bioactive compounds among polyphenols that are found in fruits and vegetables. The flavonoids mostly get metabolized in the alimentary canal, and their interaction with the gut microbiome becomes inevitable. The gut microbiota continuously interacts with dietary flavonoids and catabolizes them into more minor metabolites directly associated with the host health. The gut microbiota is resilient and highly dependent on environmental entities, such as xenobiotics, antibiotics, and diet patterns. Any abrupt alterations in these exogenous entities cause gut dysbiosis, resulting in different abnormalities and disorders. The flavonoids alter the proportion of Firmicutes to Bacteroidetes in the gut, and those bacteria play a decisive role in the host physiology. This review draws attention to how flavonoids ameliorate gut dysbiosis and inflammation. Additionally, the biomarkers and cell signaling before and after the onset of gut dysbiosis have been discussed. Ultimately, we emphasize how flavonoid-mediated gut microbiome ameliorates intestinal-related metabolic conditions such as obesity, Crohn's disease (CD), and intestinal ulcerative colitis (IUC). In the future, further studies on the clinical level and model-based studies will warrant the use of flavonoids as better therapeutics and understanding of host health correlated with the microbiome.}, } @article {pmid41543287, year = {2026}, author = {Ji, X and Wang, Y and Li, L and Yang, H and Ma, Z and Wang, C and Zhao, Y and Ding, Y and Xia, Y}, title = {Oxidative Balance Score, Genetic Predictors of the Gut Microbiome, and the Risk of Metabolic-Associated Fatty Liver Disease: A Cohort Study.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {1}, pages = {e70372}, doi = {10.1002/mnfr.70372}, pmid = {41543287}, issn = {1613-4133}, support = {XLYC2203168//Liaoning Revitalization Talents Program/ ; LJKMZ20221149//Scientific Research Project of the Liaoning Province Education Department/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Male ; Female ; Middle Aged ; *Oxidative Stress ; Prospective Studies ; Risk Factors ; Aged ; *Fatty Liver/genetics/microbiology/epidemiology ; Cohort Studies ; Genetic Predisposition to Disease ; Adult ; Proportional Hazards Models ; *Non-alcoholic Fatty Liver Disease/microbiology/genetics ; Life Style ; Diet ; }, abstract = {The oxidative balance score (OBS) integrates dietary and lifestyle factors to reflect oxidative stress. OBS has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the modifying roles of genetic predisposition and gut microbiota remain unclear. This study evaluated the prospective association between OBS and MASLD and potential modification by genetic and microbial factors. We analyzed 182 601 UK Biobank participants free of MASLD at baseline. OBS was calculated from 16 dietary and 4 lifestyle components. Incident MASLD cases were identified from hospital and death records. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). During a median 10.5 years of follow-up, 1500 participants developed MASLD. Compared with the lowest OBS quartile, adjusted HRs (95% CIs) were 0.82 (0.71-0.94), 0.71 (0.61-0.83), and 0.68 (0.58-0.81) for the second, third, and fourth quartiles (p-trend < 0.001). MASLD genetic risk score (GRS) and microbial GRSs for Ruminococcus torques and Sutterella were associated with MASLD risk but did not modify the OBS-MASLD association (all p-interaction > 0.05). Higher OBS was associated with lower MASLD risk, independent of genetic and microbial GRSs. These findings provide prospective association evidence that may inform future intervention studies.}, } @article {pmid41543263, year = {2026}, author = {Baral, B and Parajuli, M and Pinilla, J and Muniz, J and Baral, B and Cançado, GGL}, title = {Safety and efficacy of oral microbiome therapy for the treatment of recurrent Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/00365521.2026.2616310}, pmid = {41543263}, issn = {1502-7708}, abstract = {INTRODUCTION: This systematic review and meta-analysis aimed to assess the safety and efficacy of oral microbiome therapy (OMT) for the treatment of recurrent Clostridioides difficile infection (CDI).

METHODS: A comprehensive search was performed in PubMed, Cochrane library, Scopus and Embase. All randomized controlled trials (RCTs) meeting predefined inclusion criteria were included. Statistical analysis was performed using R software.

RESULTS: Three RCTs comprising 469 patients were analyzed, of whom 250 (53%) received OMT and 219 (47%) received placebo. OMT significantly reduced CDI recurrence at week 8 compared to placebo (risk ratio [RR] 0.57; 95% confidence interval [CI] 0.33-0.99; p = 0.04). In exploratory efficacy analyses, no significant differences in recurrence were observed between groups when stratified by prior fidaxomicin use (RR 0.36; 95% CI 0.03-4.01; p = 0.40) or vancomycin use (RR 0.68; 95% CI 0.30-1.55; p = 0.35). Similarly, Firmicutes engraftment at week 1 (mean difference [MD] 41.78; 95% CI -10.55 to 94.11; p = 0.12) and week 8 (MD 34.06; 95% CI -2.49 to 70.61; p = 0.07) did not show statistically significant between-group differences. Safety outcomes and adverse events were comparable between OMT and placebo.

CONCLUSION: OMT seems to reduce CDI recurrence at week 8 compared with placebo while demonstrating a comparable safety profile, supporting its role as an effective, well-tolerated therapy for recurrent CDI. New studies are necessary to confirm these findings.

REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251022230.}, } @article {pmid41543249, year = {2026}, author = {Beals, DG and Carper, DL and Hochanadel, LH and Jawdy, SS and Klingeman, DM and Piatkowski, BT and Weston, DJ and Doktycz, MJ and Pelletier, DA}, title = {Genomic signatures in Variovorax enabling colonization of the Populus endosphere.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0160525}, doi = {10.1128/msystems.01605-25}, pmid = {41543249}, issn = {2379-5077}, abstract = {Microbial colonization of plant roots involves strong selective pressures that shape the structure and function of root-associated communities. In particular, the endosphere represents a highly selective environment requiring host entry and in planta persistence. However, strain-specific microbial traits that enable endosphere colonization remain poorly understood. Here, we use a defined, genome-resolved community of 28 Variovorax strains isolated from the roots of Populus deltoides and Populus trichocarpa (poplar trees) to determine which strains partition between rhizosphere and endosphere compartments and to identify the genomic traits associated with endosphere specialization. By combining strain-resolved metagenomic profiling, comparative genomics, and functional assays, we demonstrate that dominant endosphere colonizers are enriched in genes related to nutrient metabolism, redox balance, transcriptional regulation, and a conserved L-fucose utilization pathway experimentally shown to enhance root colonization. Not all strains succeed through the same strategy. Community-wide functional profiling revealed a distinct and reduced set of traits in the endosphere, including orthogroups associated with low-abundance strains that were overlooked in strain-level analyses. These findings reveal that multiple ecological strategies, such as metabolic competition, regulatory adaptation, and niche specialization, can support endosphere colonization. Our results advance the understanding of how bacterial colonization traits are distributed and deployed within a plant microbiome and suggest that host filtering selects for distinct, and sometimes complementary, microbial strategies. This work supports a shift toward mechanistic, genome-resolved models of microbiome assembly and offers a framework for linking microbial function to host colonization success.IMPORTANCEPlants often depend on diverse microbial partners to support their growth, resilience, and adaptation to changing environments. Among these microbes, some bacteria inhabit the rhizosphere (the narrow zone around roots where microbes interact with the plant) while others are able to enter and persist within root tissues. The traits that distinguish these two lifestyles remain poorly understood. In this study, we examined a group of related Variovorax strains from poplar tree root microbiomes to ask why some rhizosphere-associated strains also become successful endosphere colonizers. We found that strains appear to succeed through different strategies: some may benefit from rapid growth on plant-derived carbon sources, while others may rely on stress tolerance or fine-tuned regulation. These results suggest that there is no single path from the rhizosphere into the root interior, but rather multiple strategies shaped by the host environment. Understanding this diversity can inform efforts to design resilient plant-microbe communities.}, } @article {pmid41543226, year = {2026}, author = {Xu, Z and Hu, J and Luo, H and Qi, X and Liu, R and Liu, Y and Zheng, Y and Li, H and Wu, B}, title = {Association between dental flossing frequency and oral microbiome in U.S. adults.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2614826}, doi = {10.1080/07853890.2026.2614826}, pmid = {41543226}, issn = {1365-2060}, mesh = {Humans ; Middle Aged ; Male ; Adult ; Female ; Cross-Sectional Studies ; *Microbiota/genetics ; United States/epidemiology ; Aged ; *Mouth/microbiology ; *Dental Devices, Home Care/statistics & numerical data ; RNA, Ribosomal, 16S/genetics ; Nutrition Surveys ; Phylogeny ; }, abstract = {BACKGROUND: The oral microbiome is vital for health, yet population-based evidence on how self-reported flossing relates to microbial communities remains limited. This study examined the association between self-reported dental flossing frequency and oral microbiome diversity in a nationally representative sample of U.S. adults.

METHODS: This cross-sectional analysis included 4,772 adults aged 30-69 from NHANES 2009-2012. Flossing frequency was categorized as non-users (0 days/week), some flossing (1-6 days/week), and daily users (7 days/week). Oral microbiome composition was profiled using 16S rRNA sequencing. α-diversity was calculated using Observed amplicon sequence variants (ASVs), Shannon, Inverse Simpson, and Faith's Phylogenetic Diversity (PD); β-diversity using Bray-Curtis and UniFrac distances. Survey-weighted linear regression and PERMANOVA were used with covariate adjustment.

RESULTS: Participants included, non-users (32%), some flossing (38%), and daily users (30%). A dose-response relationship was observed between flossing frequency and reduced microbial richness and phylogenetic diversity. Compared with non-users, daily users exhibited significantly lower richness (Observed ASVs: β = -11.46, 95% CI: -15.62 to -7.29) and phylogenetic diversity (Faith's PD: β = -0.88, 95% CI: -1.20 to -0.56). Daily flossing was associated with a modest reduction in Shannon diversity, with no significant association for the Inverse Simpson index. Inverse associations were more pronounced among younger and lower-income adults, but not among current smokers. β-diversity differed significantly across groups, although effect sizes were minimal (Bray-Curtis R[2] = 0.059%; unweighted UniFrac R[2] = 0.090%).

CONCLUSIONS: Frequent flossing was associated with reduced microbial richness and phylogenetic diversity, potentially indicating a favorable shift toward a healthier microbial community.}, } @article {pmid41543131, year = {2026}, author = {Chesneau, G and Noel, A and Bréard, D and Boulanger, A and Briand, M and Bonneau, S and Brin, C and Saux, MF and Liu, Y and Hendrickson, A and Nielsen, T and Sarniguet, A and Guilet, D and Arkin, A and Lui, L and Barret, M}, title = {Lactuchelins represent lipopeptide siderophores produced by Pseudomonas lactucae that inhibit Xanthomonas campestris.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrag003}, pmid = {41543131}, issn = {1751-7370}, abstract = {The seed is a habitat with limited resources and space. Although it is widely accepted that microbial competition is a key driver of the assembly of seed-associated microbial communities, the underlying mechanisms of this competition are not well understood. The initial objective of this work was to assess the importance of contact-independent microbial competition between the phytopathogenic bacterium Xanthomonas campestris pv. campestris 8004 (Xcc8004) and 30 strains representative of the bacterial populations most commonly associated with radish (Raphanus sativus) seeds. We identified Pseudomonas lactucae CFBP 13502 as a potent inhibitor of Xcc8004, mediated by exometabolites, specifically induced by certain seed-borne strains. Transcriptomic analysis linked this inducible activity to the upregulation of a gene cluster encoding a lipopeptide siderophore. Targeted gene deletion in P. lactucae CFBP 13502 confirmed that this cluster is essential for antagonism against Xcc8004. Furthermore, iron supplementation abolished this inhibitory effect, strongly supporting iron chelation as the underlying mechanism. Through comparative metabolomics, we elucidated the structure of a family of lipopeptide siderophores, produced by P. lactucae CFBP 13502, which we named lactuchelins. Our findings provide molecular evidence of competitive exclusion mechanisms at the seed microbiome interface, highlighting lactuchelins as a promising avenue for the development of seed-based biocontrol strategies against seed-borne phytopathogens.}, } @article {pmid41543055, year = {2025}, author = {Kozin, SV and Sigareva, AS and Moiseev, AV and Kozlova, EA and Rubailo, AD and Kravtsov, AA}, title = {[Drinking with increased deuterium content affects the gut microbiome and the antioxidant status of the organism].}, journal = {Voprosy pitaniia}, volume = {94}, number = {6}, pages = {15-27}, doi = {10.33029/0042-8833-2025-94-6-15-27}, pmid = {41543055}, issn = {0042-8833}, support = {state registration number 125011700394-5//The study was conducted within the framework of the State Task of the Southern Scientific Center of the Russian Academy of Sciences for 2025/ ; }, mesh = {Animals ; Male ; Rats ; *Deuterium/pharmacology ; Rats, Wistar ; *Antioxidants/metabolism ; *Gastrointestinal Microbiome/drug effects ; Brain/metabolism ; *Drinking ; *Oxidative Stress/drug effects ; }, abstract = {UNLABELLED: As preparations for a manned mission to Mars are currently underway, it is crucial to understand the impact of a drinking ration with a deuterium level corresponding to those found in Martian glaciers on mammals. The objective of the research was to study the dynamics of deuterium levels in laboratory animals and changes in oxidative processes following daily consumption of a drinking ration with a deuterium concentration of 6704‰.

MATERIAL AND METHODS: The experiments were conducted on male Wistar rats, which had an initial body weight 270-300 g. The response of laboratory animals to increased deuterium level was studied using 60 Wistar rats. The animals were divided into two groups (30 rats each): Group 1 consumed a drinking ration with a deuterium concentration corresponding to the natural level (-37‰); Group 2 consumed a drinking ration containing 6704‰ deuterium. Five animals were removed from the experiment on days 5, 8, 11, 16, 21 and 31. Fecal, blood and brain samples were collected during these procedures. The stress-protective activity of the drinking ration with a modified isotopic composition was studied using 3 groups of rats (7 rats each). The «Control, -37‰» group consumed water with a deuterium concentration of -37‰. Animals of the «Stress, -37‰» and "Stress, 6704‰" groups consumed water with a deuterium concentration of -37 ‰ and 6704‰, respectively, for 38 days while simulating immobilization stress (4 hours) for 3 days, starting from the 33rd day. Deuterium level in water and blood serum was determined on a NMR spectrometer (Bruker Avance NEO 700 MHz). A DELTA V Advantage isotope mass spectrometer was used to assess deuterium level in lyophilized cerebral cortex. The activity of free radical processes was assessed by the intensity of chemiluminescence of blood plasma and cerebral cortex supernatant. Catalase activity in the cerebral cortex was measured by spectrophotometry, and gene expression levels were determined using realtime polymerase chain reaction (PCR). The proportion of dominant bacterial phyla in the intestinal microbiome was assessed using polymerase chain reaction with phylum-specific primers to 16s rRNA.

RESULTS: Consuming water w ith a deuterium concentration of 6704‰ for 31 days increased its concentration in rat blood plasma from -25±4 to 4425±103 ‰, while in brain tissue, deuterium content increased from -127±7 to 667±32‰. As deuterium accumulated in the body, catalase activity increased (2.2-5.3 fold from the 8th to the 31st day, p<0.05) and the expression of several genes involved in antioxidant protection (Cat, Gclc, Nrf2) changed. Fluctuations in the composition of the intestinal microbiome were observed, especially on the 5th and 8th days of the experiment. These fluctuations resulted in a decrease in Bacteroides by 13 and 22%, respectively, and an increase in Firmicutes by 12 and 16%, respectively. These effects are the result of adaptive responses to stress caused by increased deuterium concentrations in the body's internal environment. The decrease in the intensity of oxidative stress in rat brain and blood after immobilization stress is due to the prolonged intake of water with a deuterium level of 6704‰ and the development of a cross-adaptation effect.

CONCLUSION: It has been established that increased deuterium levels in the body fluids and tissues of laboratory animals trigger a stress response, activating mechanisms for adaptation to new conditions. This results in activation of the antioxidant system, which enhances the body's protective properties during immobilization stress.}, } @article {pmid41543052, year = {2026}, author = {Pérez Pérez, M and King, J and Lawson, PA and Stubbendieck, RM}, title = {Rothia similimucilaginosa sp. nov., isolated from the human nasal cavity.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {76}, number = {1}, pages = {}, pmid = {41543052}, issn = {1466-5034}, mesh = {*Phylogeny ; RNA, Ribosomal, 16S/genetics ; Bacterial Typing Techniques ; Humans ; Fatty Acids/analysis/chemistry ; DNA, Bacterial/genetics ; Sequence Analysis, DNA ; Nucleic Acid Hybridization ; Base Composition ; *Nasal Cavity/microbiology ; *Micrococcaceae/classification/isolation & purification/genetics ; Wisconsin ; Child ; }, abstract = {Four strains of a Gram-stain-positive, coccoid, catalase-positive, non-motile bacterium were recovered from nasal lavage samples collected from children in Wisconsin during the Spring of 2008. These strains, designated RSM42[T], RSM292, RSM386 and RSM407, were subjected to a comprehensive biochemical and polyphasic taxonomic investigation. Despite the novel bacterium sharing 99.6% 16S rRNA gene sequence identity with Rothia mucilaginosa 5762/67[T], BLAST+ average nucleotide identity, MUMmer3 average nucleotide identity and digital DNA-DNA hybridization values of 91.3%, 91.9% and 43.1%, respectively, were below the cut-off values routinely used for species demarcation. Consistent with these findings, phylogenetic and pangenomic comparisons indicated that RSM42[T], RSM292, RSM386 and RSM407 form a separate lineage within the genus Rothia. Strain RSM42[T] is further distinguished from R. mucilaginosa 5762/67[T] by its unique ability among Rothia species to use fructose-6-phosphate as a sole carbon source. RSM42[T] also exhibits an enzyme activity profile consistent with R. mucilaginosa, as it is positive for valine arylamidase and negative for C4 esterase, β-glucosidase, pyrazinamidase and trypsin, a combination not observed in other Rothia species. The major fatty acids were anteiso-C15:0 (44.2%) and iso-C16:0 (14.4%), and the moderate fatty acids were anteiso-C13:0 (2.3%), iso-C14:0 (6.0%), C14:0 (2.3%), iso-C15:0 (5.9%), C15:0 (1.9%), C16:0 (9.3%) and anteiso-C17:0 (9.5%). The major polar lipids were aminoglycolipid and diphosphatidylglycerol. Based on biochemical, phylogenetic, genotypic and chemotaxonomic criteria, these isolates represent a novel species within the genus Rothia, closely related to R. mucilaginosa, for which the name Rothia similimucilaginosa sp. nov. is proposed. The type strain is RSM42[T] (=ATCC TSD-447[T]=DSM 118581[T]).}, } @article {pmid41542943, year = {2026}, author = {Broderick, C and Poulsen, CS and Hjelmsø, MH and Marrs, T and Radulovic, S and Logan, K and Li, X and Wu, Z and Sørensen, SJ and Ezzamouri, B and Alexander, H and Fyhrquist, N and Alenius, H and Bhattacharyya, M and Neumann, AU and Lack, G and Perkin, M and Bønnelykke, K and Stokholm, J and Flohr, C}, title = {Associations between early-life exposures and the infant skin microbiome.}, journal = {The British journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjd/ljaf524}, pmid = {41542943}, issn = {1365-2133}, abstract = {BACKGROUND: Factors influencing the early-life skin microbiome, and the association with atopic dermatitis (AD), are relatively unexplored.

OBJECTIVE: To evaluate associations with the infant skin microbiome during the first year of life.

METHODS: 3-month-old infants from the Enquiring About Tolerance (EAT) birth cohort were examined for AD at enrolment, 1 and 3 years of age. Parent-completed questionnaires, trans-epidermal water loss (TEWL), and filaggrin mutation status were evaluated. Bacterial swabs were collected from the elbow crease and volar forearm in 148 infants at 3 months and 1 year of age, and the microbiome composition was characterized using 16S rRNA gene sequencing (V3-V4 region).

RESULTS: Shannon diversity was significantly higher at the forearm compared to the elbow. Staphylococcus, Acinetobacter, and Streptococcus were the most abundant genera across time and body-site. Microbiome community composition was primarily associated with body-site and age (p≤0.001, both). Other significant associations were found with ethnicity (p=0.009), filaggrin status (p≤0.001), urban-vs-rural residence (p=0.005), older siblings (p=0.041), bath product usage at 3 months (p=0.011), but not with pets (p=0.159), systemic antibiotics (p=0.27) nor with bathing frequency (p=0.109). The microbiome was associated with elevated TEWL (3-months p=0.004, 1-year p≤0.001) and with concurrent AD (3-months p=0.027, 1-year p≤0.001). Streptococcus parasanguinis was significantly less abundant in non-lesional skin of infants with AD at 3 months.

CONCLUSION: In addition to age and body-site, the infant skin microbiome is associated with heritable factors, the home environment, hygiene practices, and with the presence of AD.}, } @article {pmid41542784, year = {2026}, author = {Junger, PC and Kavagutti, VS and Deutschmann, IM and Gazulla, CR and Huber, P and Menezes, M and Paranhos, R and Amado, AM and Ferrera, I and Rigonato, J and Chaffron, S and Gasol, JM and Logares, R and Sarmento, H}, title = {Ecological Processes Shaping Marine Microbial Assemblages Diverge Between Equatorial and Temperate Time-Series.}, journal = {Molecular ecology}, volume = {35}, number = {2}, pages = {e70241}, pmid = {41542784}, issn = {1365-294X}, support = {2014/13139-3//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 2017/26786-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 2020/02517-4//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 474759/2013-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ)/ ; 303906/2021-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ)/ ; 313784/2023-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ)/ ; PVE400313-2014-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ)/ ; 3213/2020-83//Fundação de Apoio Institucional ao Desenvolvimento Científico e Tecnológico (FAI/UFSCar)/ ; 862923//Horizon 2020 Framework Programme/ ; FP7-ENV-2012-308392//European Commission/ ; PID2019-105775RB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; PID2022-136281NB-I00//Ministerio de Ciencia, Innovación y Universidades/ ; CEX2024-001494-S//Ministerio de Ciencia, Innovación y Universidades/ ; 117/14//Agencia Santafesina de Ciencia, Tecnología e Innovación/ ; BJT013/2012//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Mediterranean Sea ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 18S/genetics ; *Seawater/microbiology ; Atlantic Ocean ; *Microbiota/genetics ; Ecosystem ; Biodiversity ; Seasons ; Bacteria/genetics/classification ; Temperature ; }, abstract = {Marine microbial communities are structured by a complex interplay of deterministic and stochastic processes, yet how these vary across latitudes remains poorly understood. Most long-term microbial observatories are restricted to temperate regions, limiting our ability to assess latitudinal contrasts in microbial dynamics. Here, we compare coastal microbial communities from two contrasting marine time-series stations using standardised molecular protocols: a new tropical site in the Equatorial Atlantic (EAMO, 6° S) and a well-studied temperate site in the Mediterranean Sea (BBMO, 41° N). Monthly 16S and 18S rRNA gene sequencing of two size-fractions (0.22-3 μm and > 3 μm) over 41 months (from April 2013 to August 2016) revealed marked differences in taxonomic composition, temporal variability and ecological assembly processes. Temperate communities exhibited strong seasonal turnover, higher beta-diversity and tighter coupling with environmental variables such as temperature and daylength. In contrast, tropical communities were compositionally more stable and more governed by biotic factors and stochastic processes such as historical contingency and ecological drift. These patterns were consistent across taxonomic domains and size-fractions, though selection was generally stronger in prokaryotes and the smallest size-fraction. Co-occurrence networks at the temperate site were more densely connected and environmentally responsive compared to tropical networks, where stochastic processes and putative biological interactions gain prominence. This study highlights the importance of integrating observatories from underrepresented latitudes into global microbial monitoring efforts, particularly as climate change alters the amplitude and frequency of environmental drivers across the ocean.}, } @article {pmid41542760, year = {2026}, author = {Balamurugan, J and Adeyeye, SAO}, title = {Artificial Intelligence in Nutrigenomics: A Critical Review on Functional Food Insights and Personalized Nutrition Pathways.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {39}, number = {1}, pages = {e70200}, doi = {10.1111/jhn.70200}, pmid = {41542760}, issn = {1365-277X}, mesh = {*Nutrigenomics/methods ; Humans ; *Artificial Intelligence ; *Precision Medicine/methods ; *Functional Food ; Diet ; }, abstract = {BACKGROUND: This review critically evaluates the applications of artificial intelligence in nutrigenomics, focusing on its role in interpreting functional food-gene interactions, supporting personalized nutrition strategies, and enabling evidence-based dietary interventions for improved health outcomes.

METHODS: A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies published between 2010 and 2025 addressing AI applications in nutrigenomics and functional foods. Search terms included "artificial intelligence," "nutrigenomics," "personalized nutrition," and "functional foods." Retrieved records were screened for relevance, methodological rigor, and thematic alignment. Following title, abstract, and full-text screening based on predefined inclusion criteria, 176 articles were assessed in detail, and 142 studies were included in the qualitative synthesis. Data were extracted and synthesized to identify key trends, methodological approaches, research gaps.

RESULTS: Artificial intelligence (AI) is increasingly transforming nutrigenomics by enabling personalized dietary recommendations based on genetic, metabolic, and lifestyle data. Machine learning and deep learning approaches facilitate the identification of complex gene-diet interactions, thereby improving the prediction of metabolic and disease-related outcomes. AI-based models support biomarker discovery, genotype-informed dietary guidance, and real-time monitoring through wearable and glucose-monitoring technologies, contributing to improved management of obesity, diabetes, and cardiovascular disorders. These tools enhance understanding of individual variability in dietary response and support precision nutrition strategies.

CONCLUSION: Despite challenges related to algorithmic bias, data privacy, and ethical governance, AI-driven nutrigenomics offers significant potential to advance personalized nutrition. Continued methodological refinement and responsible implementation are crucial for translating these innovations into clinically meaningful and equitable health applications.}, } @article {pmid41542635, year = {2026}, author = {Robertson, CM and Mercado-Evans, V and Larson, AB and Branthoover, H and Ottinger, S and Mejia, ME and Hameed, ZA and Serchejian, C and Ogilvie, L and Zulk, JJ and Patras, KA}, title = {Type 2 diabetes mellitus exacerbates vaginal group B Streptococcus colonization via impaired mucosal cytokine response.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.08.698441}, pmid = {41542635}, issn = {2692-8205}, abstract = {UNLABELLED: Type 2 diabetes mellitus (T2D) is a metabolic disorder that confers increased risk of microbial infections, including those caused by the opportunistic pathogen group B Streptococcus (GBS). Asymptomatic GBS carriage in the vaginal tract is a notable reservoir for infection, but the impact of T2D on the vaginal mucosa and GBS colonization is not fully understood. We employed a diet-induced mouse model of T2D paired with vaginal GBS colonization to investigate the impact of diabetes on glucose availability, bacterial composition of the vaginal microbiome, and vaginal cytokine profiles at baseline and in response to GBS. We observed that, despite experiencing hyperglycemia, diabetic mice did not exhibit elevated glucose in the reproductive tract. Regarding the vaginal microbiota, diabetic mice had minimal defining compositional characteristics with decreased Mammaliicoccus being the only significant taxonomic difference. Vaginal cytokine profiling revealed consistently depressed cytokine signaling in diabetic mice, beginning with KC at baseline and expanding to an array of eight pro-inflammatory cytokines post-GBS infection. Pairing cytokine observations with GBS colonization outcomes revealed a correlation between delayed vaginal IL-1α induction and persistent vaginal GBS, suggesting that vaginal cytokine deficiency may contribute to diabetic GBS vaginal colonization. Supplementation with intravaginal rIL-1α was sufficient to resolve GBS burden differences between diabetic mice and non-diabetic controls, confirming that deficient vaginal cytokine responses contribute to diabetic GBS vaginal persistence. These findings advance our understanding of diabetic vaginal mucosal susceptibility to pathogens and support the potential for immunological intervention in the susceptible diabetic population.

IMPORTANCE: People with T2D are more susceptible to microbial infections, but there is limited understanding of the mechanisms that drive this vulnerability. One possibility is that T2D enhances colonization of opportunistic pathogens, like GBS, in mucosal reservoirs as a precursor to infection. In this study, we used a diabetic mouse model to test whether diabetes alters the vaginal mucosa to promote GBS colonization. We found that increased vaginal GBS colonization in diabetic mice was not linked to tissue glucose availability or changes to the vaginal microbiome, but instead was associated with impaired vaginal immune responses. These findings provide a foundation for translational approaches to reduce GBS persistence and dissemination in at-risk individuals.}, } @article {pmid41542584, year = {2026}, author = {Montgomery, TL and Nelson, EA and Downs, LA and Heney, ER and Lee, MFJ and Martino, C and McDonald, D and Rahman, G and Knight, R and Krementsov, DN}, title = {Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.08.698420}, pmid = {41542584}, issn = {2692-8205}, abstract = {UNLABELLED: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) driven by genetic and environmental determinants. The gut microbiome of people with MS (pwMS) is distinct and influences disease through immunomodulatory metabolite production. Circulating metabolites are altered in pwMS, but identifying microbial-metabolic drivers remains challenging. We previously showed that colonization by the gut commensal Limosilactobacillus reuteri (L. reuteri) exacerbates disease in the experimental autoimmune encephalomyelitis (EAE) model of MS, in a tryptophan-dependent manner. Here, we integrated microbiomic and metabolomic datasets from a longitudinal EAE study utilizing high and low tryptophan diets in mice colonized or not with L. reuteri . Gut microbiome dynamics under short- and long-term alterations in tryptophan bioavailability, were affected by diet, microbiome context, or disease. During short-term dietary intervention, L. reuteri colonization exerted a greater impact on microbiome composition than tryptophan bioavailability. With longer dietary exposure and EAE progression, high dietary tryptophan and L. reuteri colonization synergized to elicit profound microbiota changes, including alterations in Lachnospiraceae, Blautia , and Akkermansia . Integration of metabolomic and microbiomic datasets using joint Robust Aitchison PCA revealed clusters of associated metabolites and microbiota enriched for functional pathways, including bile acid and tryptophan metabolism. Metabolites outperformed microbiota in predicting EAE severity, identifying p-cresols and indoles as top disease-associated metabolites. Treatment with p-cresol or 3-indoleglyoxylic acid exacerbated EAE, enhanced proinflammatory T cell responses, and increased cerebellar pathology. These data demonstrate that dietary responses are shaped by gut microbiome composition and that integrated microbiomic-metabolomic analyses can identify drivers of disease worsening in MS.

IMPORTANCE: MS is a multifactorial disease influenced not only by genetics but also by environmental factors, potentially including diet and the composition of the gut microbiome. We show that interactions between diet and commensal gut microbiota profoundly impact levels of immunomodulatory systemic metabolites, including several that are associated with disease in pwMS. Importantly, we demonstrate that individual gut microbiota produced metabolites are sufficient to worsen disease in a mouse model of MS. Integration of gut microbiome and blood metabolite datasets combined with subsequent predictive modeling, may bolster biomarker identification and the capacity to predict disease severity in pwMS, as compared to performance of individual datasets alone. These findings highlight metabolites as key mediators linking diet and the gut microbiota to neuroinflammation. Importantly, this work suggests that targeting microbial metabolites or modifying diet-microbiome interactions may represent new strategies to reduce disease activity in MS and related autoimmune disorders.}, } @article {pmid41542572, year = {2026}, author = {Hayes, AMR and Klug, ME and Sharma, M and Kao, AE and Sun, S and Lopez Gonzalez, EDJ and Zhu, H and Dent, JC and Clark, RJ and Sell, DR and Nelson, D and Monnier, VM and Tsan, L and Rea, JJ and Ahuja, A and Tanios, N and Gianatiempo, I and Shanmugam, MV and Park, Y and Yu, KB and Hsiao, EY and Schier, LA and Fodor, AA and Woodruff, TM and Shuck, SC and Gati, C and Herring, BE and Coughlan, MT and Kanoski, SE}, title = {Consumption of processed foods impairs memory function through dietary advanced glycation end-products.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.07.698065}, pmid = {41542572}, issn = {2692-8205}, abstract = {Consumption of processed foods is associated with dementia, obesity, and other negative health outcomes. Sustained heat treatment, a common food processing approach to enhance flavor, induces the chemical Maillard reaction that promotes the formation of dietary advanced glycation end-products (AGEs). The neurocognitive impacts of consuming dietary AGEs are poorly understood. Here we modeled an AGE-rich diet through heat treatment fed to rats during adolescence, a critical period of neural development, to mechanistically evaluate the long-term impact of early life dietary AGEs on behavioral and neural processes. Consuming the AGE-rich diet impaired hippocampal-dependent memory function and altered the gut microbiome without inducing obesity or nonspecific behavioral deficits. AGE-induced memory deficits were coupled with impaired hippocampal glutamatergic synaptic neurotransmission and altered expression in the synapse-pruning complement system. Hippocampal synaptic deficits likely result from direct AGE-complement interactions, as our extended studies reveal competitive antagonist action of AGEs on complement receptors. Memory impairments were prevented by administration of the AGE-inhibitor, alagebrium, and by supplementation with an AGE-inhibiting bacterial taxon, Lactococcus lactis , which was depleted in the heat-treated diet. These findings reveal a functional connection between early life dietary AGEs, the microbiome, and memory impairments, thus illuminating mechanisms through which food processing negatively impacts neurocognition.}, } @article {pmid41542410, year = {2026}, author = {Xiao, S and Wang, M and Martin, TG and Scott, B and Fang, X and Liu, X and Yang, Y and Fu, S and Truong, SD and Gugel, JF and Maas, GL and Mullen, MP and Hill, JH and Li, VL and Markhard, AL and Zhao, M and Qi, W and Reghupaty, SC and Zhao, M and Spaas, J and Wei, W and Moholdt, T and Hawley, JA and Voldstedlund, CT and Richter, EA and Chen, X and Svensson, KJ and Bernstein, D and Leinwand, LA and Xu, Y and Long, JZ}, title = {Python metabolomics uncovers a conserved postprandial metabolite and gut-brain feeding pathway.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.09.698526}, pmid = {41542410}, issn = {2692-8205}, abstract = {Most mammals consume small and frequent meals. By contrast, pythons are ambush predators that exhibit extreme feeding and fasting patterns and provide a unique model for uncovering molecular mediators of the postprandial response [1-3] . Using untargeted metabolomics, here we show that circulating levels of the metabolite para -tyramine-O-sulfate (pTOS) are increased >1,000-fold in pythons after a single meal. In pythons, pTOS production occurs in a microbiome-dependent manner via sequential decarboxylation and sulfation of dietary tyrosine. In both pythons and mice, pTOS administration activates a neural population in the ventromedial hypothalamus (VMH). In mice, these VMH neurons are required for the anorexigenic effects of pTOS. Chronic administration of pTOS to diet-induced obese male mice suppresses food intake and body weight. pTOS is also present in human blood, where its levels are increased after a meal. Together, these data uncover a conserved postprandial anorexigenic metabolite that links nutrient intake to energy balance.}, } @article {pmid41542073, year = {2025}, author = {Kapoor, S and Mehta, P and Patial, V and Pandey, R and Padwad, YS}, title = {Phloretin-induced modulation in gut microbiome, mitigates colonic inflammation and alleviates colitis-associated colorectal cancer in mice.}, journal = {Computational and structural biotechnology journal}, volume = {27}, number = {}, pages = {2730-2746}, pmid = {41542073}, issn = {2001-0370}, abstract = {Colitis associated colorectal cancer (CAC) is the fourth common cancer known to cause significant mortalities worldwide. Phloretin is a dihydrochalcone naturally found in apple, pear and strawberry. It exhibited different biological activities, namely anti-inflammatory, anticancer and anti-microbial. In the present study, the role of phloretin towards alleviating colonic inflammation and regulating gut microbiota was explored. The treatment of phloretin led to the reduction in the intestinal inflammation and maintained colon length-weight ratio by decreasing the total number of tumor nodules. We registered reduction in the colonic inflammatory cytokines levels namely TNFα, IL1β, IFNγ, and IL6 as well as expression of HSP90, Cox2, and Src found decreased. Results highlighted the restoration in the levels of tight junction proteins and the expression of Muc2 and Muc3. Further, role of phloretin in inducing apoptosis of tumor cells and the deregulation β-catenin pathway was studied. The histopathological analysis revealed normal colonic structure by decreasing leukocyte infiltration, as well as, circumvention in the reduction of the numbers of goblet cell, crypt abscess and ulceration in phloretin and 5-ASA (5-aminosalicylic acid) treated animals, compared to the diseased group. Metagenomic analysis of the gut microbiome in CAC mice revealed that phloretin significantly increased the abundance of Lactobacillus species, which exert probiotic effects and inhibit synchronous colon tumor growth by modulating β-catenin signaling. The increased abundance of L. reuteri and L. murinus was associated with regulated cellular proliferation, reduced TNF-α production, and decreased expression of COX-2, cyclin D1, and Bcl-2. In conclusion, the results obtained signify the nutraceutical potential of phloretin in restoring the intestinal barrier, maintaining the beneficial gut microbial population, and amelioration of CAC in mice.}, } @article {pmid41542055, year = {2026}, author = {Schluter, J and Maan, H and Jogia, W and Duan, C and Matheis, F and Nishimoto, E and Zhang, C and Sullivan, A}, title = {Sugar ABC transporter repertoires predict ecological dynamics in gut microbiome communities.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-8380132/v1}, pmid = {41542055}, issn = {2693-5015}, abstract = {The gut microbiome plays a central role in human health, but modern diets and lifestyles alter its composition. Increased sugar consumption is a hallmark of modern diets, yet its impact on the microbiome remains poorly understood. Here, we combine comparative genomics, experiments, and longitudinal human diet-microbiome records to show that the response of the microbiome to dietary sugars is explained by the carriage of sugar ABC (ATP-binding cassette) transporters. Bacteria encoding these transporters exhibit enhanced growth and consistently outcompete others in both monocultures and complex consortia across contexts. Targeted deletion of sugar transporter genes in Escherichia coli, a model gut pathobiont of the expanded Oligo-Mouse-Microbiota (OMM15) consortium, reveals that a specific sugar ABC transporter gene is required to compete, and invade this community. In gnotobiotic mice colonized with the OMM15 consortium, dietary sugar supplementation selectively increases the expansion of sugar ABC transporter-positive bacteria, including E. coli. Paired human diet-microbiome data reveal that intake of dietary sugars significantly correlates with the expansion of sugar ABC transporter-positive genera. Taken together, our work identifies a genomic predictor of microbiome responses to dietary sugars and suggests ways to anticipate major shifts in the abundances of important gut bacteria.}, } @article {pmid41542043, year = {2026}, author = {Johnson, E and Bañuelos, P and Comrie, J and Richter, A and Le, H and Thompson, S}, title = {Characterization of dietary choline uptake by the gut microbiome reveals choline assimilating microbes and influences on host choline metabolism.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-8491198/v1}, pmid = {41542043}, issn = {2693-5015}, abstract = {Choline is an essential nutrient with diverse roles in host metabolism; however, the current understanding of its microbial fate is largely restricted to trimethylamine production. Here, we apply the BioOrthogonal-labeling, Sorting, Sequencing, and mass Spectrometry (BOSSS) workflow to map dietary choline-specific gut microbial interactions. Using an alkyne-modified choline analog (propargylcholine) in mice, we fluorescently label and flow-sort choline-assimilating gut bacteria, identifying a varied set of taxa enriched in probiotic species, including Limosilactobacillus reuteri (L. reuteri). In vitro studies confirm that L. reuter i assimilates choline and converts it to long chain fatty acylcholines. Metabolomic and transcriptomic profiling revealed that L. reuteri colonization, with a choline sufficient diet, selectively elevates serum choline and increases lysophosphatidylcholine production, findings corroborated by transcriptomic evidence of upregulated hepatic genes involved in lipid metabolism. These findings uncover a new metabolic fate for dietary choline, expand the known repertoire of microbiome-derived lipids, and illustrate how specific host-microbe-diet interactions can influence host status.}, } @article {pmid41541710, year = {2026}, author = {Yang, RZ and Lin, S and Huang, LT and Weng, J and Liu, QM and Chen, HS and Ruan, N and Zeng, K}, title = {Effect of Targeted Probiotics on Anesthesia-Induced Sleep Disturbances via Modulating the Gut Microbiome and Metabolites.}, journal = {Food science & nutrition}, volume = {14}, number = {1}, pages = {e71447}, pmid = {41541710}, issn = {2048-7177}, abstract = {Post-operative/post-anesthesia sleep disturbances are a major concern to patients, impacting recovery and overall well-being. Probiotics may offer potential benefits for sleep promotion by modulating microbial diversity and abundance. This study aimed to investigate the effect of targeted probiotic treatment on anesthesia-induced sleep disturbances and its impact on the microbiota and metabolites in the gut and lungs. Eight-week-old male SD rats received a continuous inhalation of isoflurane, combined with oral yogurt treatment without or containing probiotic Lactobacillus and Bifidobacteria. Rats underwent electrode implantation and 7 days of polysomnography. 16S rRNA sequencing and untargeted metabolomic analysis from fecal and BALF samples were used to investigate the changes in the gut and lung microbiota and their metabolites. Isoflurane exposure led to sleep disturbances associated with a significant reduction in Lactobacillus and Bifidobacteria in the gut. Targeted probiotic supplementation improved post-anesthesia sleep quality (NREM sleep time on day 1: Yogurt+ISO group 597.25 ± 100.15 vs. Probiotic+ISO group 772.77 ± 29.36 min, p = 0.002), increased the abundance of beneficial gut bacteria, and reduced wake-related metabolites in both the gut and lungs. Correlation analysis revealed significant negative correlations between the abundance of beneficial gut flora and wake-related metabolites (all p < 0.05). The present study first indicated that targeted probiotic treatment alleviated post-anesthesia sleep disturbances by modulating both the gut and lung microbiota and their metabolites. These findings suggest that peri-anesthesia probiotic treatment may be a viable strategy for improving sleep disturbances, although further clinical research into the underlying mechanisms is needed.}, } @article {pmid41541603, year = {2026}, author = {Cheung, SLY and Kenway, LC}, title = {Pathophysiological Mechanisms and Nonpharmacological Interventions in Irritable Bowel Syndrome: Current Insights and Future Directions.}, journal = {Journal of nutrition and metabolism}, volume = {2026}, number = {}, pages = {4520019}, pmid = {41541603}, issn = {2090-0724}, abstract = {Irritable bowel syndrome, diagnosed using the ROME IV diagnostic criteria, is one of the most common dysfunctional disorders of the gastrointestinal system with a high global prevalence. Although symptom presentation is diverse, symptoms primarily manifest as abdominal pain, bloating, and alterations to bowel habits, negatively impacting quality of life but without an associated increase in mortality risk. Disruptions to the gut-brain axis, the bidirectional communication system between the central nervous system and the enteric nervous system, are hypothesised to be at the core of irritable bowel syndrome. Dysfunction may also be associated with stress and anxiety, as well as dietary factors, among other aspects related to physical and social environment, genetic predisposition and medical history. Patients with irritable bowel syndrome have also demonstrated increased vulnerability to neurotransmitter imbalances, with abnormalities associated with changes in gastrointestinal motility, low-grade inflammation and visceral pain. Moreover, chronic stress and anxiety may significantly exacerbate symptoms through the upregulation of cortisol secretion, disrupting the gut microbiome and elevating visceral sensitivity. While the gut microbiome maintains the integrity of the gut-brain axis and intestinal barrier, decreases in its diversity heighten susceptibility to intestinal inflammation. Although there is currently no known cure for irritable bowel syndrome, research supports stress management and behavioural therapies, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, and probiotic supplementation as key interventions to alleviate symptoms. Additionally, faecal microbiota transplantation emerges as a promising intervention that addresses some of the limitations in current interventions. This literature review explores the pathophysiological mechanisms relating to irritable bowel syndrome, with insight into current interventions and future directions to directly address the underlying factors driving symptomology.}, } @article {pmid41541500, year = {2025}, author = {Broedlow, CA and Swanson, E and Cherenack, EM and Basting, C and Nogueira, NF and France, M and Yue, P and Chakrawarti, A and Salazar, A and Acosta, L and Raccamarich, P and Gale, M and Ravel, J and Fein, LA and Holm, J and Alcaide, ML and Klatt, NR}, title = {Common cervicovaginal sequencing methods result in discordant molecular diagnoses of bacterial vaginosis and reveal strain level effects of Gardnerella vaginalis.}, journal = {npj women's health}, volume = {3}, number = {}, pages = {}, pmid = {41541500}, issn = {2948-1716}, support = {P30 AI073961/AI/NIAID NIH HHS/United States ; R01 AI138718/AI/NIAID NIH HHS/United States ; }, abstract = {Bacterial vaginosis (BV) is associated with HIV transmission and pre-term birth, yet the etiology of BV remains unknown. Our analysis addressed that knowledge gap by comparing diagnostic techniques and using Bayesian inference to find species-specific associations with clinical indicators. We also assessed the effect of sequencing methodology on the results of molecular BV profiling. We observed significant differences in microbial diversity within BV-associated CSTs based on clinical diagnosis. CST assignments were substantially influenced by sequencing methodology, with concordance between methods as low as 59% for metatranscriptomic and metataxonomic-based CST assignment. We also found that Gardnerella has a strain-dependent association with individual Amsel's criteria, and that Dialister micraerophilus and Parvimonas micra are positively associated with Amsel's criteria while Lactobacillus is negatively associated. These results highlight the challenge of characterizing a condition without a single etiological agent, reinforcing the need for more granular diagnoses and treatments that are sensitive to BV variability.}, } @article {pmid41541221, year = {2026}, author = {Cai, Z and Wang, M and Xian, Z and Hu, Y and Pan, Y and Feng, X and Sun, B and Deng, M and Li, Y and Liu, G and Hu, W and Liu, D and Guo, Y}, title = {Effects of inactivated Lactobacillus acidophilus on growth performance, blood parameters, fecal fermentation and microbiota in neonatal Holstein calves.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {24}, number = {}, pages = {1-16}, pmid = {41541221}, issn = {2405-6383}, abstract = {Inactivated probiotics can exhibit beneficial properties similar to live probiotics while offering greater stability and safety. However, the understanding of how inactivated probiotics affect the growth, health, and gut microbiota of neonatal calves is still limited. This study investigated the effect of inactivated Lactobacillus acidophilus (ILA, ≥1 × 10[8] CFU equivalents/mL) on growth performance, blood parameters, and fecal fermentation and microbiota of neonatal dairy calves. Forty female Holstein calves (37.92 ± 2.04 kg; 2.45 ± 0.96 d) were randomly assigned to a basal diet supplemented with 0 (CK), 2, 4, or 6 mL/d of ILA (ILA2, ILA4, and ILA6) until 54 d of age. The results showed that while ILA supplementation did not affect body weight or feed efficiency, it linearly increased structural growth indices (body length and heart girth) at both 30 and 54 d of age (P < 0.05). Crucially, ILA significantly reduced fecal scores (P < 0.001) and diarrhea incidence (P = 0.019), particularly in the ILA4 group. Serum analysis revealed that ILA elevated the levels of immunoglobulins A, G, and M (P < 0.001), as well as total protein, globulin, glucose, and superoxide dismutase (P < 0.05), indicating improved immune status and metabolic health. Furthermore, ILA modulated fecal fermentation, inducing a quadratic response in acetic acid (P = 0.005) and total volatile fatty acids (P = 0.010). Microbiome analysis indicated linear increases in Firmicutes, Proteobacteria, and the genus Faecalibacterium, coupled with linear decreases in Bacteroidota, Spirochaetota, and Rikenellaceae_RC9_gut_group (P < 0.05). This ILA-induced microbial shift enriched functional pathways associated with transport, transcription, replication, and butanoate metabolism compared with the CK group (P < 0.05). Spearman correlation analysis identified significant correlations between fecal microbiota composition and host growth, metabolism, and health. Collectively, the beneficial effects of ILA on structural growth, diarrhea reduction, fecal fermentation, and metabolic health in calves are closely related to dynamic changes in fecal microbiota. These beneficial effects may stem from ILA's ability to modulate the composition, diversity, and function of the gut microbiota. This study offers a scientific basis for the application of ILA in calf production.}, } @article {pmid41541069, year = {2025}, author = {Jafari-Nakhjavanlou, A and Irajian, P and Zahedi Bialvaei, A}, title = {Potential mechanisms linking bacterial factors to the development and progression of multiple sclerosis.}, journal = {Infectious medicine}, volume = {4}, number = {4}, pages = {100219}, pmid = {41541069}, issn = {2772-431X}, abstract = {Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease of the central nervous system (CNS). While the exact etiology remains unclear, emerging evidence suggests that bacterial toxins play significant roles in MS pathogenesis and progression. We aimed to review mechanisms by which bacterial toxins influence MS development, focusing on molecular mimicry, epitope spreading, bystander activation, and blood-brain barrier (BBB) disruption. Specific toxins, including Clostridium perfringens epsilon toxin, Staphylococcus aureus superantigens, and Chlamydia pneumoniae heat shock proteins, demonstrate distinct pathogenic mechanisms in promoting CNS inflammation. Crucially, several toxins disrupt BBB integrity, making it easier for immune cells and cytokines that promote inflammation to enter the CNS and exacerbate neural inflammation. Furthermore, through molecular mimicry and epitope dissemination, bacterial antigens can initiate cross-reacting immune responses that may lead to autoimmune attacks on myelin. This review highlights the complex interplay between bacterial toxins, immune modulation, and genetic susceptibility in MS. Understanding these toxin-mediated pathways reveals the complex interplay between the microbiome and MS pathogenesis, potentially leading to novel therapeutic interventions targeting bacterial contributions to autoimmune neurodegeneration.}, } @article {pmid41540767, year = {2026}, author = {Yoo, E and Uchida, AM}, title = {Response to: An Overview of Predictive Biomarkers and Detection Approaches for Immunotherapy Response in GI Malignancies.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.70242}, pmid = {41540767}, issn = {1440-1746}, } @article {pmid41540666, year = {2026}, author = {Munyaneza, V and Zhang, W and Haider, S and Ren, L and Song, H and Yi, B and Wang, C and Shi, L and Xu, F and Kant, S and Ding, G}, title = {Soil Microorganisms as Drivers of Pollutant Degradation, Metal Detoxification, and Sustainable Agriculture.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13543}, pmid = {41540666}, issn = {1520-5118}, abstract = {Soil microorganisms are essential drivers of ecosystem functioning and mediate pollutant degradation, metal detoxification, and nutrient cycling. This review aims to synthesize recent mechanistic advances in understanding how microbes degrade organic contaminants, transform or immobilize metals, mitigate toxic effects on plants through chelation, redox reactions, sequestration, and support soil structure and fertility. Microbial consortia and rhizosphere-associated taxa accelerate pollutant breakdown, reduce metal toxicity, and enhance plant resilience in acidic or contaminated soils. Integration of microbial processes with amendments such as biochar and organic matter further improve remediation efficiency and sustainability. Key insights reveal that microbial signaling networks, biofilm formation, and plant-microbe interactions are critical for maintaining the ecosystem stability under stress. These findings underscore the potential of microbial driven strategies to restore degraded soils, minimize reliance on chemical inputs, and promote sustainable agricultural practices, although field-scale persistence and ecological interactions warrant further research.}, } @article {pmid41540554, year = {2026}, author = {Busby, PE and Apigo, A and Sirova, D and Pérez-Pazos, E and Gervers, KA and Neat, A and Romero-Jiménez, MJ and Anderegg, LDL and Taylor, G}, title = {Do stomatal traits modulate leaf microbiome assembly?.}, journal = {The New phytologist}, volume = {}, number = {}, pages = {}, doi = {10.1111/nph.70914}, pmid = {41540554}, issn = {1469-8137}, support = {2022-67013- 37437//National Institute of Food and Agriculture/ ; 2020-67013-31797//National Institute of Food and Agriculture/ ; 2209329//Directorate for Biological Sciences/ ; 2319568//Division of Emerging Frontiers/ ; 2146552//Division of Integrative Organismal Systems/ ; CZ.02.01.01/00/22_010/0003414//Ministry of Education, Youth and Sports: MSCA Fellowship/ ; }, abstract = {Elucidating the factors controlling plant microbiome assembly is a major research goal in plant biology given a growing awareness of microbial community contributions to host plant health and fitness. While stomata have long been recognized to influence pathogen colonization, less is known about whether or how stomatal traits regulate diverse communities of nonpathogenic microbes that make up the majority of the leaf microbiome. In this Viewpoint, we propose that stomata are a primary filter by which plants influence the assembly of leaf-associated microbial communities. We discuss three nonmutually exclusive hypotheses for how stomatal traits influence leaf microbes, including preliminary support for each based on published studies of foliar fungi and bacteria. The stomatal density hypothesis argues that a greater density of pores increases the rate of microbial entry into the leaf, while the stomatal function hypothesis posits that the duration and speed of stomatal opening and closing regulate microbial access into the leaf. The stomatal covariation hypothesis recognizes that many other leaf traits covary with stomatal traits and thus could contribute to observed relationships between stomatal traits and leaf microbiome structure. Finally, we propose research priorities to improve our understanding of stomatal control over leaf microbiome assembly.}, } @article {pmid41540478, year = {2026}, author = {Premathilaka, C and Godakumara, K and Peffers, MJ and Clarke, EJ and Dorbek-Sundström, E and Orro, T and Kodithuwakku, S and Fazeli, A}, title = {Cryptosporidium spp. infection drives distinct alterations in the faecal extracellular vesicles metaproteome of calves.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {8}, pmid = {41540478}, issn = {1674-9782}, support = {857418 "COMBIVET"//Horizon 2020/ ; 101079349 "OH-Boost"//Horizon 2020/ ; P17019VLKM//Eesti Maaülikool/ ; }, abstract = {BACKGROUND: The gut is primarily responsible for digestion and nutrient absorption, plays essential roles in immune regulation and metabolic balance, and is supported by a diverse microbiome essential for digestion, absorption, and defence from pathogens. Understanding gut physiology and pathophysiology in pre-weaned calves is essential, as infections like cryptosporidiosis can lead to gut dysbiosis, impair growth, and negatively affect long-term productivity. Faeces are considered easily accessible biological specimens that can be used to monitor gastrointestinal disorders. The methods employed in this study aimed to investigate the potential use of faecal extracellular vesicles (fEVs) as a non-invasive tool for assessing gut health and infections in calves. Particularly, considering Cryptosporidiosis as a model for gut infectious disease.

RESULTS: The analysis using a hybrid reference-based metaproteomic approach revealed that the proteomic profiles of fEVs significantly differed from that of faecal crude (FC) suspensions. Both sample types contained microbial and host proteins, which are important for maintaining gut defence and microbial homeostasis. However, Cryptosporidium spp. infection significantly shifted the fEV proteome, reducing both host and microbial proteins involved in gut defence. It also reduced proteins from microbes that are important for maintaining microbial homeostasis, while increasing stress-related proteins. Further, lyophilisation of fEVs significantly altered the protein profiles.

CONCLUSION: These findings underscore that fEVs contain host and microbial proteins that are a valuable resource for studying gut physiology, pathophysiology, host-microbe-pathogen interactions, and microbiome dynamics. Changes in the proteomic profile of fEVs during Cryptosporidium spp. infection demonstrates the pathogen's ability to manipulate host immune defences and microbiome composition for its survival and replication. Overall, these findings support the utility of fEV proteomics as a non-invasive platform for biomarker discovery and advancing research in gastrointestinal health and disease in livestock.}, } @article {pmid41541076, year = {2023}, author = {Nwafor, DC and Brichacek, AL and Rallo, MS and Bidwai, N and Marsh, RA}, title = {Subarachnoid hemorrhage: New insights on pathogenesis.}, journal = {Frontiers in stroke}, volume = {2}, number = {}, pages = {1110506}, pmid = {41541076}, issn = {2813-3056}, abstract = {Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke characterized by high morbidity and mortality. Saccular intracranial aneurysms account for most cases of SAH. While the role of hemodynamic stress and inflammation have been extensively studied in SAH, little is known about the role of the microbiome in SAH despite recent studies uncovering new insights on the effects of microbiome alteration in ischemic stroke. This review presents the current knowledge around the role of the microbiome in intracranial aneurysm formation and rupture. We also highlight the influence of diet on intracranial aneurysm formation and provide evidence that corroborates the targeting of inflammatory pathways as a potential strategy to curb SAH-associated neurological dysfunction.}, } @article {pmid41540332, year = {2026}, author = {Wang, Y and Wu, C and Zhu, Q and Fan, C and Zhu, Y and Chen, Y and Wei, X and Feng, L}, title = {Comparative metagenomic characterization of gut microbiota and antibiotic resistome in multi-facility SPF mice.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04699-6}, pmid = {41540332}, issn = {1471-2180}, abstract = {Specific pathogen-free (SPF) mice are pivotal preclinical models linking basic microbiology to clinical translation, yet comprehensive high-resolution profiling of their gut microbiome, especially antibiotic resistance genes (ARGs), remains limited. To address this gap, metagenomic sequencing was conducted on cecal contents from C57BL/6 and BALB/c SPF mice from five Shanghai laboratory animal facilities, generating 141 Gbp high-quality sequencing data. From 1,761,909 predicted genes, 1,048,575 non-redundant genes were identified for analysis. Taxonomic annotation identified Bacillota (73.0%), Bacteroidota (16.6%), and Actinomycetota (2.9%) as dominant phyla. At the genus level, microbial communities varied markedly across facilities, with Muribaculaceae prevailing in SHA/SHD and Blautia or Enterococcus enriched in SHB/SHE. Beta diversity analysis showed communities clustered by facility, indicating breeding environment had a stronger impact on gut microbiota diversity than host strain. KEGG, COG, and GO functional annotation revealed broad metabolic and molecular diversity. Antibiotic resistome profiling identified 11 ARG categories, predominantly associated with glycopeptides (18.1%) and tetracycline (11.3%) resistance. The most enriched ARG carriers were Pseudomonadota (acrD, emrB, mdtB etc.), Bacillota (tet(44), tet(M), tet(O) etc.), Bacteroidota (tet(Q), mel, tet(X) etc.), and Actinomycetota (rpoB, ileS). Furthermore, ARGs resistance mechanisms varied between facilities with distinct beta-diversity clustering: SHB and SHE mice mainly employed antibiotic target alteration against glycopeptides, whereas SHA, SHD, and SHC-C57BL/6 primarily utilized antibiotic target protection against tetracyclines. This study presents a high-resolution comparison of gut microbiota and ARGs in SPF mice from multiple facilities, highlighting facility-dependent microbial and resistome variation and providing valuable references for preclinical microbiological standardization and risk assessment.}, } @article {pmid41540252, year = {2026}, author = {Jo, Y and Joshi, NR and Chellappa, K}, title = {The microbiome at the centre of NAD[+] supplementation.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {41540252}, issn = {2522-5812}, } @article {pmid41540124, year = {2026}, author = {Nickols, WA and Kuntz, T and Shen, J and Maharjan, S and Mallick, H and Franzosa, EA and Thompson, KN and Nearing, JT and Huttenhower, C}, title = {MaAsLin 3: refining and extending generalized multivariable linear models for meta-omic association discovery.}, journal = {Nature methods}, volume = {}, number = {}, pages = {}, pmid = {41540124}, issn = {1548-7105}, support = {U19AI110820//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; T32GM135117//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {Microbial community analysis typically involves determining which microbial features are associated with properties such as environmental or health phenotypes. This task is impeded by data characteristics, including sparsity (technical or biological) and compositionality. Here we introduce MaAsLin 3 (microbiome multivariable associations with linear models) to simultaneously identify both abundance and prevalence relationships in microbiome studies with modern, potentially complex designs. MaAsLin 3 can newly account for compositionality either experimentally (for example, quantitative PCR or spike-ins) or computationally, and it expands the range of testable biological hypotheses and covariate types. On a variety of synthetic and real datasets, MaAsLin 3 outperformed state-of-the-art differential abundance methods, and when applied to the Inflammatory Bowel Disease Multi-omics Database, MaAsLin 3 corroborated previously reported associations, identifying 77% with feature prevalence rather than abundance. In summary, MaAsLin 3 enables researchers to identify microbiome associations more accurately and specifically, especially in complex datasets.}, } @article {pmid41539935, year = {2026}, author = {Vizon, C and Hochart, C and Galand, PE and Nugues, MM}, title = {Impacts of Nearby Algae on Recruitment Success and Early Microbiome Development of the Coral Acropora cytherea.}, journal = {Environmental microbiology}, volume = {28}, number = {1}, pages = {e70241}, doi = {10.1111/1462-2920.70241}, pmid = {41539935}, issn = {1462-2920}, support = {ANR-18-CE02-0009-01//Agence Nationale de la Recherche/ ; }, mesh = {*Anthozoa/microbiology/growth & development ; Animals ; *Microbiota ; Coral Reefs ; *Bacteria/classification/genetics/isolation & purification ; Larva/microbiology/growth & development ; Symbiosis ; *Dinoflagellida/physiology ; Ecosystem ; }, abstract = {The persistence of coral reefs is dependent on the arrival and settlement of coral larvae followed by their post-settlement growth and survival. Despite evidence showing that benthic algae have variable effects on corals, it is still unclear how benthic communities of the coral nursery habitat impact the early development of the coral microbiome and if these impacts relate to the survival and growth of newly settled corals. Here, we tested whether the survival and growth of Acropora cytherea recruits are impacted by surrounding algae, and whether specific algae influence their associated bacterial and Symbiodiniaceae communities. A 6-month survey of coral larvae experimentally settled near different algae showed that crustose coralline algae enhanced recruit survival. However, despite variation in their microbiome, the presence of different algae did not impact the coral microbial community composition. The recruit microbiome was colonised by bacteria shared among all benthic substrates rather than bacteria unique to specific algae. Furthermore, the microbiome of coral larvae was different from that of the recruits. We conclude that the microbiome of corals in their early life stages is structured by host ontogeny rather than by their surrounding benthos, but that the surrounding benthos contributes to the transfer of opportunistic bacteria.}, } @article {pmid41539801, year = {2026}, author = {Zhang, X and Zang, X and Zhuang, J and Cheng, Y and Qin, Y and Jiang, J and Liang, Y and Song, Y and Liu, Y}, title = {Construction of a synthetic microbial community model for the predicting of characteristic aromas in Penglai Cabernet Sauvignon wines.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118162}, doi = {10.1016/j.foodres.2025.118162}, pmid = {41539801}, issn = {1873-7145}, mesh = {*Wine/analysis/microbiology ; Fermentation ; Saccharomyces cerevisiae/metabolism/genetics ; *Odorants/analysis ; *Vitis/microbiology ; *Microbiota ; Food Microbiology ; *Microbial Consortia ; Volatile Organic Compounds/analysis ; }, abstract = {To address the challenge of achieving targeted flavor formation in traditional fermented foods by overcoming the unpredictability of spontaneous fermentation, this study introduces a novel approach using Chinese Penglai Cabernet Sauvignon wines as a model system. First, the study identified and selected a collection of core functional microbial strains, including key Saccharomyces cerevisiae genotypes and non-Saccharomyces, from the indigenous spontaneous fermentation microbiome. By reconstituting them into a defined synthetic microbial community, we successfully developed a mathematical model that quantitatively correlates microbial community structure with characteristic aroma compounds. This model enables the accurate prediction and targeted shaping of desired aroma profiles through the rational design of starter cultures. This work provides a methodological framework that moves beyond the descriptive analysis of spontaneous fermentations towards the engineering of synthetic microbial consortia for targeted wine style. The core microbial resources and the predictive model presented here offer a concrete strategy for enhancing regional typicity and quality consistency in Penglai Cabernet Sauvignon production.}, } @article {pmid41539791, year = {2026}, author = {Liu, P and Gao, C and Li, S and Wu, D and Zhang, Z and Chen, W and Li, W and Shao, F and Wang, HD and Yang, Y}, title = {A novel Fucose-specific lectin from Morchella esculenta modulates gut-liver Axis to alleviate non-alcoholic fatty liver disease.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118106}, doi = {10.1016/j.foodres.2025.118106}, pmid = {41539791}, issn = {1873-7145}, mesh = {*Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Diet, High-Fat/adverse effects ; *Lectins/pharmacology/chemistry/isolation & purification ; *Liver/metabolism/drug effects ; Mice, Inbred C57BL ; Male ; *Fucose/metabolism ; Lipid Metabolism/drug effects ; Disease Models, Animal ; }, abstract = {Morchella esculenta is an underexplored source of lectins with diverse bioactivities. In this study, a novel fucose-specific lectin (MEP5) was isolated from M. esculenta, with a molecular weight of 33.12 kDa and a characteristic carbohydrate-recognition domain. Structural analysis revealed that MEP5 predominantly consists of random coils and extended strands, with α-helix as a minor component. In a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) mouse model, MEP5 treatment significantly ameliorated NAFLD by normalizing lipid profiles (TG, TC, LDL-C, HDLC), repairing adipose tissue morphology, and reducing hepatic lipid accumulation. Mechanistically, MEP5 exerted hepatoprotective effects through transcriptional modulation of key lipid metabolic regulators (PPARα, SREBP-1, Fasn, Hmgcr, G6pc1, UCP-1, CD36, ABCA1, PRDM16). Network pharmacology and experimental validation indicated that MEP5 alleviated hepatic steatosis by inhibiting the MAPK signaling pathway. Additionally, integrated metabolomic and 16S rRNA sequencing analyses identified alterations in the gut microbiome, with enrichment of Duncaniella, CAG-485, and UBA3282, and depletion of Desulfovibrio-R, which were linked to MEP5's protective effects. This study highlights the potential of M. esculenta lectins as a therapeutic tool, advancing our understanding of gut-liver interactions and metabolic regulation.}, } @article {pmid41539761, year = {2026}, author = {Long, M and Wang, H and Zhang, F and Ran, Y and Li, Y and Luo, J and Chen, Z and Tian, Z and Tan, S and Liu, X}, title = {Nanogel-encapsulated Rosa roxburghii Tratt fruit polyphenols ameliorated ulcerative colitis by regulating gut microbiota and PI3K/Akt and NF-κB pathways.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118149}, doi = {10.1016/j.foodres.2025.118149}, pmid = {41539761}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/microbiology ; Animals ; NF-kappa B/metabolism ; *Polyphenols/pharmacology/chemistry ; Proto-Oncogene Proteins c-akt/metabolism ; *Fruit/chemistry ; Signal Transduction/drug effects ; *Rosa/chemistry ; Phosphatidylinositol 3-Kinases/metabolism ; Nanogels/chemistry ; Male ; Mice ; Anti-Inflammatory Agents/pharmacology ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Antioxidants/pharmacology ; }, abstract = {Rosa roxburghii Tratt fruit polyphenols (RP) possess antioxidant, anti-inflammatory, and immunomodulatory properties, showing potential for ulcerative colitis (UC) treatment. However, their efficacy is limited by bioavailability and targeting efficiency. To address this, RP were encapsulated into acylated chitosan-crosslinked carboxymethyl konjac glucomannan (ACs-CKGM) nanogel (RPNG). Experimental results demonstrated that RPNG significantly enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1, Occludin and Claudin-3) and mucus secretion (MUC2). It effectively mitigated oxidative stress by restoring antioxidant enzymes (SOD, GSH-Px and CAT) while reducing MPO, COX-2 and iNOS activation. Through integrated ELISA, western blot, and transcriptomic analyses, we emonstrated that RPNG specifically inhibited PI3K/Akt/mTOR and NF-κB signaling pathways, decreasing inflammatory cytokines (e.g., TNF-α, IL-6) while increasing anti-inflammatory mediators (e.g., IL-10). Gut microbiome analysis showed RPNG reversed DSS-induced dysbiosis by enriching beneficial bacteria (e.g., Muribaculum sp.) and suppressing pathogens (e.g., Escherichia coli). These findings highlight RPNG as a novel targeted strategy for UC management, supported by multi-omics mechanistic insights.}, } @article {pmid41539751, year = {2026}, author = {Zhou, M and Xia, C and Jing, B and Duan, J and Li, H and Che, H}, title = {Sepia pharaonis ink derived melanin ameliorated high-fat diet induced lipid dysmetabolism: Insights from microbiome and hepatic transcription.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118086}, doi = {10.1016/j.foodres.2025.118086}, pmid = {41539751}, issn = {1873-7145}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Liver/metabolism/drug effects ; *Melanins/pharmacology ; *Lipid Metabolism/drug effects ; Male ; *Sepia/chemistry ; Mice ; Mice, Inbred C57BL ; }, abstract = {Sepia pharaonis ink melanin (MSI) is a natural eumelanin-rich compound with anti-inflammatory activities and gut microbiota-regulating effects. However, its impact on lipid dysmetabolism triggered by high-fat diet (HFD) remains unclear. This study sought to investigate the improvement and the underlying mechanisms of MSI on lipid metabolism through biochemical indicators, liver transcriptomics, and intestinal microbiota analyses. The results demonstrated that MSI administration obviously reduced weight gain and fat accumulation, and reduced anomalous lipid levels in liver and serum. Liver transcriptome analysis suggested that MSI mainly affected PPARα signaling pathway and fatty acid degradation to enhance lipid metabolism. Furthermore, MSI lowered hepatic and intestinal inflammation, and boosted the levels of ZO-1 and occludin in a dose-dependent manner. Concurrently, 16S rRNA sequencing of gut microbiota showed that MSI treatment decreased the Firmicutes/Bacteroidetes ratio and increased dominant bacterial of Muribaculum, Alistipes and Odoribacter. Collectively, these findings suggested that MSI alleviated HFD-induced lipid accumulation by modulating inflammation, intestinal barrier function and gut microbiota. This comprehensive study offered a basis for the development and utilization of MSI in tackling lipid dysmetabolism.}, } @article {pmid41539628, year = {2026}, author = {Peng, Y and Liu, H and Xing, T and Zhen, F and Wu, D and Sun, Y}, title = {Instability mechanisms of overloaded anaerobic digestion: Insights from volatile fatty acid metabolism.}, journal = {Bioresource technology}, volume = {444}, number = {}, pages = {134006}, doi = {10.1016/j.biortech.2026.134006}, pmid = {41539628}, issn = {1873-2976}, abstract = {To clarify the mechanisms driving process instability under overload stress, a long-term semi-continuous overload instability simulation experiment was conducted. High-throughput sequencing and metagenomics were used to determine the response of the process parameters, community composition, and volatile fatty acid (VFA)-related metabolic functional genes to the organic loading rate (OLR). When the OLR increased to 12.5 kg VS/m[3]/d, the methane yield remained low at 226.40 ± 10.78 mL CH4/g VS. Further increasing the OLR to 20 kg VS/m[3]/d completely destabilized the reactor, resulting in a final methane yield as low as 0.29 mL CH4/g VS, a hydrogen partial pressure as high as 357.37 Pa, and concentrations of butyrate, propionate, and acetate of 4328.49 ± 538.18, 1036.13 ± 75.48, and 9939.67 ± 427.68 mg/L, respectively. Organic overload stress caused reactor instability mainly by blocking VFA metabolism. When the OLR was ≥ 11 kg VS/m[3]/d, the relative abundances of key genes (aceE, buk, ptb, atoD) in the butyrate and propionate metabolic pathways decreased, resulting in the accumulation of butyrate and propionate. Despite a shift in syntrophic acetate oxidation metabolism from the methyl to the carbonyl branch under overload, the latter's recovery was insufficient to compensate for the severe impairment of the methyl branch, ultimately leading to acetate accumulation. VFA accumulation caused severe inhibition of acetogens and some methanogens, while hydrolytic and acidogenic bacteria dominated the microbiome (relative abundance: 94.18 %). As a result, the microbial metabolic balance was broken. Our results provide new insights into the mechanisms driving process instability under overload stress.}, } @article {pmid41539609, year = {2026}, author = {Yang, D and Ren, D and Zhang, Y and Hao, Y and Yue, Y and Li, Q and Fan, Q and Sun, C and Cui, M and Zhang, M}, title = {The Gut Microbiota Dysbiosis in Geriatric Multimorbidity: Pharmacotherapeutic Implications, Pathophysiological Mechanisms, and Precision Modulation Strategies.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {103023}, doi = {10.1016/j.arr.2026.103023}, pmid = {41539609}, issn = {1872-9649}, abstract = {Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these reasons, the gut microbiota is becoming an important therapeutic target for optimizing precision medicine strategies in treating patients with geriatric multimorbidities. In this narrative review, we systematically synthesize the evidence regarding how gut dysbiosis leads to decreased efficacy of multi-drug regimens through the interplay between metabolism, immune response, and barrier function in aging patients with multimorbidities, and we evaluate targeted interventions. Furthermore, we demonstrate that current interventions (e.g., probiotics, prebiotics, fecal microbiota transplants (FMT), phage therapy, and dietary modulation) have unique benefits but are limited by inter-individual variability, safety concerns, and a lack of proven long-term efficacy. Thus, many areas of microbiota-drug interactions in older adults with multimorbidity should be explored through future research. Key areas to address are: the establishment of large, multicenter longitudinal cohorts of older adults with multimorbidity that would allow for repeated collection of microbiota profiles, medication use, and health outcomes to identify the evolving interaction between multimorbidity, microbiota, and polypharmacy; the urgent need for standardized and integrated databases of microbiome-drug interactions that harmonize data formats, provide metabolic annotations and medication identifiers in order to support reproducible cross-study validation; and the further validation and application of artificial intelligence (AI) and machine learning (ML) in clinical trials. High-dimensional data collected from cohorts and databases will enable the development of predictive algorithms to identify individual drug responses and how effective microbiota-targeted interventions will be; these algorithms must then be prospectively validated. Ultimately, these initiatives are necessary to move toward the personalized management of microbiota-drug interactions in older adults with multimorbidity, providing greater safety of polypharmacy and promoting healthy aging.}, } @article {pmid41539598, year = {2026}, author = {Wei, S and Li, W and Ran, S and Zhang, J and Zhang, Z and Yang, Z and Tian, F and Chen, L and Hu, P and Yuan, J and Lin, H}, title = {Multi-organ metabolic dysregulation and cecal microbiota alterations following black carbon exposure.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.01.027}, pmid = {41539598}, issn = {2090-1224}, abstract = {BACKGROUND: Black carbon (BC) has been linked to adverse health outcomes, yet underlying mechanisms remain unclear. Integrating metabolomic and metagenomic data across tissues may clarify BC-induced biological pathways.

METHODS: We performed human epidemiology and mice experimental approaches. We included 248,288 participants with annual BC exposure estimates and plasma metabolomic profiles. Elastic net regression identified BC-associated metabolites. Male C57BL/6J mice were exposed to filtered air or BC (1 mg/m[3], 1 h/day, 5 days/week, 12 weeks). Multi-tissue metabolomics and cecal contents microbiota sequencing were conducted, with histology and gene expression measurements.

RESULTS: In humans, long-term BC exposure significantly altered plasma metabolites, notably increasing saturated fatty acids (β = 0.048), while decreasing docosahexaenoic acid (β = -0.002). Amino acid metabolism was broadly disrupted, involving elevated valine (β = 0.011) and reduced glutamine (β = -0.006). In mice, metabolomic profiling showed organ-specific shifts, including increased glutathione and cortisol in the liver (2.88-fold and 2.06-fold), increased PC(16:0/18:1(9Z)) in the heart (3.22-fold), elevated anandamide and arachidonic acid in the kidney (2.35-fold and 1.48-fold), and decreased multiple fatty acids and lysophospholipids across organs. Cecal microbiota exhibited reduced alpha-diversity (Shannon: 3.67 vs. 4.50, P < 0.05) and taxonomic shifts, including an increased abundance of g_Akkermansia and decrease in g_Bacteroides. Multi-omics integration revealed significant microbiota-metabolome correlations in the cecum and plasma (Mantel r = 0.276, P = 0.012). Histological examination confirmed organ injuries, notably lung inflammation, cardiac edema, and neuronal condensation. Gene expression analysis showed increased Il-6 in the lung (5.35-fold, P = 0.047), increased Mb in the heart (5.18-fold, P = 0.010), and increased Igfbp7 in the kidney (3.03-fold, P = 0.001), while Tjp1 expression in cecum was reduced (0.42-fold, P = 0.004).

CONCLUSIONS: Our findings suggest that BC exposure may alter systemic metabolism and gut microbiota, potentially contributing to tissue injury and inflammation. The gut-organ axis could be a target for mitigating BC-related health effects.}, } @article {pmid41539591, year = {2026}, author = {Pravin, V and Vellapandian, C and Naveen Kumar, V}, title = {The oral-gut-brain axis in periodontitis: microbial signaling in systemic and neuroinflammatory disease.}, journal = {Brain research}, volume = {}, number = {}, pages = {150168}, doi = {10.1016/j.brainres.2026.150168}, pmid = {41539591}, issn = {1872-6240}, abstract = {Periodontitis, a chronic inflammatory disease of the oral cavity, has been identified as a modifiable risk factor of the development of systemic and neurological disorders via a complicated interplay of microbiological, immunological, and neural interactions. Periodontal pathogens breach local immune homeostasis, are translocated to the gut and brain, and trigger a cascade of immune deregulation, leaky gut, and blood-brain barrier, thereby forming a tri-directional communication network that links local oral inflammation to systemic and neurovascular conditions. This review synthesizes existing evidence on how oral dysbiosis, can spread to the gut and trigger systemic inflammation, leading to neuroinflammation and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Mechanistically, the OGB axis acts through various processes, such as hematogenous spread, retrograde axonal transport, immune cell trafficking (Trojan horse mechanism), and extracellular vesicle-based signaling corresponding to the causes of neuroinflammation, microglial activation, and the pathology of tau and amyloid. The diagnostic and therapeutic implications of the OGB axis provide new pathways toward early intervention with precision medicine, microbiome remodeling, immune-based therapy, and neuroprotective approaches. Emerging technologies, including AI-based diagnostics and biosensing technologies, offers noninvasive tools to track host-microbial interactions and inflammatory biomarkers. This integrative view underscores the central importance of oral health in systemic homeostasis and the development of neurodegenerative conditions, necessitating collaborative approaches between dentistry, neurology, and immunology to cooperate to deliver efficacy in disease elimination and mitigation.}, } @article {pmid41539578, year = {2026}, author = {Chehadeh, C and Nakatsuji, T and Gallo, RL}, title = {Staphylococcus aureus in Atopic Dermatitis: How a common bacterium exploits and drives disease.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.12.1009}, pmid = {41539578}, issn = {1097-6825}, abstract = {The role of Staphylococcus aureus (S. aureus) in atopic dermatitis (AD) has been extensively studied. Although its role in the pathophysiology of AD was previously controversial, current evidence now shows that it is a major factor promoting the disease and is responsible for significant morbidity. Its influence in AD stems from widespread exposure since S. aureus is common on healthy skin and is frequently part of the normal human skin microbiome. In AD, S. aureus and the closely related S. epidermidis gain a selective growth advantage over most other members of the skin microbiome due to a complex relationship involving the skin's innate immune system, other members of the microbiome, and skin barrier properties. Disruption in the functioning of those components or changes in their interactions leads to dysbiosis, skin barrier damage, and the progression of skin disease. This review summarizes research findings on these relationships and highlights the interactions and factors that promote S. aureus survival on skin and its participation in the pathogenesis of AD.}, } @article {pmid41539526, year = {2026}, author = {Uddin, G and Song, J and Lu, Z and Chaofie, Z and Sajjad, W and Li, P and Fan, Q}, title = {Microbial Taxonomic and Functional Responses to Heavy Metal Gradients in Mining-Impacted Stream Sediments.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123778}, doi = {10.1016/j.envres.2026.123778}, pmid = {41539526}, issn = {1096-0953}, abstract = {Legacy heavy metal pollution from historical mining restructures sediment microbial composition and function directly impacting contaminant fate and ecosystem health. The Dongdagou stream (Baiyin, China) possesses a pronounced geochemical gradient caused by long-term discharge of potentially toxic metals including Cd, Cu, Pb, and Zn. We employed this natural gradient to characterize microbial taxonomic and functional responses to metal stress. Sediment samples from four zones along the contamination gradient were analyzed for geochemistry, metal concentrations, and microbial composition (bacteria, archaea, and fungi) via high-throughput amplicon sequencing, with functional potential inferred using PICRUSt2. We found that microbial community structure and function were primarily shaped by metal concentration, with db-RDA explaining 18.1%, 12.4%, and 12.9% of the variance for bacteria, archaea, and fungi, respectively. Cadmium was identified as the strongest individual predictor for both bacterial (r[2] = 0.50, p = 0.001) and fungal (r[2] = 0.38, p = 0.001) communities. Bacterial diversity increased significantly downstream as contamination declined, with Shannon diversity increasing from 5.17 in the Source Zone to 6.28 in the Distal Zone (Tukey's multiple comparison test, p < 0.05). Upstream sediments were dominated by metal-tolerant taxa such as Sulfurifustis (17.4%) and Acidithiobacillus (5.0%), while downstream taxa shifted to heterotrophic genera like Gallionella (4.8%) with diverse metabolic capabilities. Despite cadmium being a key predictor, archaeal and fungal communities demonstrated greater compositional stability than bacteria, as shown by their lower beta-dispersion (ANOSIM R = 0.3152 and 0.5762, respectively, compared to 0.7222 for bacteria), indicating potential functional redundancy. Metagenomic predictions revealed a significant enrichment of genes for metal detoxification, anaerobic respiration, and oxidative stress response in polluted zones. These findings establish that microbial communities are both sensitive bioindicators and key mediators of contaminant dynamics, providing a framework for using microbial signatures to assess sediment health and monitor remediation efficacy.}, } @article {pmid41539436, year = {2026}, author = {Berube, LT and Wang, C and Curran, M and Pompeii, ML and Hu, L and Barua, S and Li, H and St-Jules, DE and Schoenthaler, A and Segal, E and Bergman, M and Popp, CJ}, title = {Personalized dietary feedback mediates the association of dietary self-monitoring adherence and weight loss: a post-hoc analysis of the Personal Diet Study.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101364}, doi = {10.1016/j.tjnut.2026.101364}, pmid = {41539436}, issn = {1541-6100}, abstract = {BACKGROUND: Dietary self-monitoring is central to effective personalized nutrition, providing critical data to inform tailored feedback and support behavior change.

OBJECTIVE: To examine the impact of dietary self-monitoring adherence and the indirect effect of personalized scores to predict postprandial glycemic response (PPGR) on weight loss.

METHODS: Post-hoc analysis of the Personal Diet Study that investigated the impact of a machine algorithm-based diet that integrates clinical and microbiome features (Personalized) compared to a standard, low-fat diet (Standardized) on weight loss. All participants received behavioral counseling and were encouraged to self-monitor dietary intake via a smartphone app. Personalized received algorithm-based scores (1 to 5) on predicted PPGR to foods logged (PPGR score; 1-2 indicating optimal; 3-5 suboptimal). Dietary self-monitoring adherence was the percentage of days logging ≥50% of target calories, classified as high or low. PPGR score quality was calculated by the proportion of optimal predicted PPGR scores per day; defined as "high-PPGR quality" days when this exceeded the group average. Mediation analysis assessed whether PPGR quality mediated the relationship between dietary self-monitoring adherence and weight loss.

RESULTS: Participants with high self-monitoring adherence lost an average of 4.2% of their baseline weight, compared to 1.9% among those with low adherence (p=0.016). High self-monitoring adherence was associated with a greater likelihood of achieving ≥5% weight loss (aOR=3.67, 95% CI: 1.63-8.50). Within Personalized, high PPGR quality mediated 53.4% of the total effect of self-monitoring adherence on weight loss (p<0.001).

CONCLUSION: Consistent self-monitoring coupled with personalized feedback may significantly enhance weight loss in a precision nutrition approach.

CLINICAL TRIAL REGISTRATION: NCT03336411.}, } @article {pmid41539328, year = {2026}, author = {Meduri, GU and Lannini, S and Smit, JM}, title = {Limitations in the Design of Critical Care Studies and Suggestions for Future Research Directions.}, journal = {Seminars in respiratory and critical care medicine}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2762-8278}, pmid = {41539328}, issn = {1098-9048}, abstract = {Glucocorticoid (GC) therapy has been a cornerstone of critical care; however, its full potential has been constrained by fixed-dose regimens and trial designs that predate current insights into the dynamic, phase-specific functions of glucocorticoid receptor α (GRα). This study shifts focus from mechanistic pathways to the clinical implications of phase-adaptive care, emphasizing how GC therapy can be optimized through individualized, response-guided strategies tailored to illness trajectory and biological variability. Rather than reiterating GRα's mechanistic role, which is discussed in Chapter 3, this work highlights its practical relevance in therapeutic decision-making across the three sequential phases of critical illness: priming, modulatory, and restorative. In this clinically oriented framework, phase-specific treatment adjustments are informed by real-time changes in systemic stress markers, immune dynamics, and metabolic indicators. Earlier randomized controlled trials were instrumental in establishing safety but often failed to account for evolving physiological demands or receptor variability, contributing to inconsistent outcomes. To bridge this translational gap, this study proposes the integration of response-guided protocols utilizing accessible clinical biomarkers-such as C-reactive protein, interleukin-6, D-dimer, and lactate-allowing for adaptive dosing and tapering strategies aligned with patient-specific recovery patterns. Moving beyond pharmacologic dosing, the study outlines adjunctive clinical strategies-including targeted micronutrient supplementation and microbiome-supportive therapies-not as theoretical possibilities but as practical co-interventions that can be incorporated into intensive care unit protocols. Furthermore, it explores how artificial intelligence-enabled clinical decision systems and adaptive trial designs can operationalize precision care by dynamically stratifying patients and tailoring interventions to shifting biological profiles. Together, these applied strategies support a transition from static treatment paradigms to a precision medicine model in critical care-one that aligns GC therapy with individualized recovery trajectories, maximizes therapeutic responsiveness, and reduces treatment-related risks through multimodal, phase-responsive interventions.}, } @article {pmid41539295, year = {2026}, author = {Zhang, H and Liao, C}, title = {Illuminating the functional dark matter of the gut microbiome.}, journal = {Cell host & microbe}, volume = {34}, number = {1}, pages = {12-14}, doi = {10.1016/j.chom.2025.12.004}, pmid = {41539295}, issn = {1934-6069}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Bacteria/genetics/enzymology ; Bacterial Proteins/metabolism/chemistry ; Bacteriophages ; Host Microbial Interactions ; }, abstract = {In this issue of Cell Host & Microbe, Liu et al. provide a roadmap for decoding the gut microbiome's functional dark matter through a structural atlas of gut phage and bacterial proteins, validating structure-guided functions from endolysins to microbial-host isozymes, and developing an alignment-free method for detecting bacteria-human remote homologs.}, } @article {pmid41539238, year = {2026}, author = {Sitthipunya, A and Uthaipaisanwong, P and Sinwat, N and Kanjanavaikoon, K and Cheevadhanarak, S and Kusonmano, K}, title = {Metagenomic insights into the effects of Clostridium butyricum and Bacillus subtilis probiotics on the gut microbiome and metabolic pathways of industrial broilers in Thailand.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106371}, doi = {10.1016/j.psj.2026.106371}, pmid = {41539238}, issn = {1525-3171}, abstract = {Probiotic supplementation has become increasingly important in broiler production due to its safety and well-documented health benefits. The gut microbiome of broilers plays a vital role in feed digestion and maintaining intestinal homeostasis, which directly influences the efficacy of probiotics under specific farm conditions. This study aims to investigate the effects of single Bacillus subtilis probiotics and double-strain probiotics of Clostridium butyricum and B. subtilis supplementation on the gut microbiome of broilers in industrial farms. We evaluated sequencing data obtained from broilers supplemented with these probiotics through amplicon sequencing and metagenomic analysis. Our study revealed that probiotics significantly influence the cecal microbiome and its functionality in broilers. The use of double-strain probiotics increased butanoate metabolism, as well as the metabolism of glycine, serine, and threonine. This suggests their contribution from microbial gut species, including Alistipes onderdonkii, Alistipes finegoldii, Bacteroides uniformis, and Phocaeicola dorei. Supporting this finding, network analysis shows more connections between probiotics and commensal cecal microbiota, highlighting a cascade-linked association with butanoate-producing microbiota. Furthermore, single-strain B. subtilis probiotic supplementation uniquely enhanced arginine and proline metabolism, likely due to the presence of species such as Bacteroides sp. zj-18, Bacteroides cellulosilyticus, and Parabacteroides distasonis. Overall, our findings indicate that double-strain probiotics increased richness in the cecal microbial community, reshaped the microbial network, and enriched short-chain fatty acid and amino acid metabolism, contributing to improved gut health and performance in broiler production.}, } @article {pmid41539110, year = {2026}, author = {Shrivastav, K and Pandey, M and Gor, H and Nema, V}, title = {Gut virome plays an extended role with bacteriome in neurological health and disease.}, journal = {Journal of the neurological sciences}, volume = {481}, number = {}, pages = {125754}, doi = {10.1016/j.jns.2026.125754}, pmid = {41539110}, issn = {1878-5883}, abstract = {The gut-brain axis (GBA) is a complex two-way communication system that links the gastrointestinal tract and the central nervous system (CNS) through neural, immune, hormonal, and microbial pathways. The microbiota-gut-brain axis (MGBA), a more specific concept, focuses on how gut microorganisms, including bacteria, viruses, and other microbes, modulate this communication and influence neurological health. This comprehensive review examines the intricate mechanisms through which gut microorganisms modulate neural function and contribute to neurological health and disease pathogenesis. The gut microbiota, comprising bacteria, viruses, fungi, and bacteriophages, produces essential neuroactive compounds including neurotransmitters- Gamma-Aminobutyric Acid (GABA), serotonin (5-HT), dopamine (DA), short-chain fatty acids (SCFAs), and metabolites that directly influence brain physiology through vagal, hormonal, and immunological pathways. Dysbiosis of the gut microbiota has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorders, and schizophrenia. In healthy conditions, beneficial bacterial strains such as Lactobacillus species synthesize GABA and regulate mood, while SCFA-producing bacteria like Fecalibacterium prausnitzii maintain blood-brain barrier integrity and exert neuroprotective effects. Conversely, pathological states demonstrate altered microbial compositions, reduced bacterial diversity, and compromised production of beneficial metabolites. Emerging evidence highlights the previously underexplored role of the gut virome, particularly bacteriophages, in regulating bacterial populations and influencing neurodevelopment. Viral dysbiosis correlates with cognitive impairment and neurodegenerative processes through modulation of bacterial metabolism and inflammatory responses. Understanding these complex host-microbiome-virome interactions provides novel therapeutic opportunities for neurological disorders through targeted interventions including probiotics, fecal microbiota transplantation, and phage-based therapies, representing a paradigm shift toward microbiome-centered approaches in neurological medicine.}, } @article {pmid41539094, year = {2026}, author = {Wang, L and Xiong, Z and Chen, J and Liu, J and Liu, M and Yan, X and Fang, Z}, title = {Synergistic gut microbiome-host lipid axis underlies the antihypertensive effect of Qianyang Yuyin formula.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157804}, doi = {10.1016/j.phymed.2026.157804}, pmid = {41539094}, issn = {1618-095X}, abstract = {BACKGROUND: Prehypertension (Pre-HTN) is highly prevalent and substantially increases the risk of developing hypertension and cardiovascular disease. Gut microbiota (GM) dysbiosis and altered lipid metabolism are increasingly recognized as critical regulators of blood pressure (BP). Traditional Chinese Medicine (TCM) formulas, such as Qianyang Yuyin Granules (QYYY), offer multi-target interventions, yet their preventive mechanisms in Pre-HTN remain unclear.

PURPOSE: This study aimed to investigate the antihypertensive effects of QYYY and elucidate its underlying mechanisms in a prehypertensive rat model.

METHODS: Prehypertensive spontaneously hypertensive rats (SHRs) were treated with QYYY for four weeks. Multi-omics analyses, including metagenomics, plasma metabolomics, and transcriptomics, were conducted. Causal involvement of GM was tested using antibiotic-induced pseudo-germ-free SHRs with fecal microbiota transplantation (FMT) from QYYY-treated donors, administered alone or in combination with QYYY. Gut barrier integrity, systemic inflammation, and vascular function were evaluated by histology, immunofluorescence, transmission electron microscopy, and ELISA.

RESULTS: QYYY significantly lowered SBP and DBP, reversed GM dysbiosis, normalized the Firmicutes/Bacteroidetes ratio, and modulated differential bacteria including Frisingicoccus and Blautia. These microbial shifts correlated with restoration of lysophosphatidylethanolamines (LPEs), inversely associated with BP, revealing a GM-lipid-BP axis. FMT alone was insufficient, whereas the combination of FMT+QYYY produced the strongest antihypertensive effect, restoring intestinal barrier integrity, enhancing ZO-1 expression, and normalizing Ang-II and NO levels. Transcriptomic analyses suggested PPAR and ROS signaling pathways as potential mechanisms mediating the antihypertensive effect of QYYY.

CONCLUSION: QYYY prevents BP elevation in Pre-HTN via synergistic microbiota-dependent and independent mechanisms, offering a comprehensive strategy for early hypertension prevention.}, } @article {pmid41537815, year = {2025}, author = {Aoki, LR and Graham, OJ and Yoshioka, RM and Maher, R and Alma, L and Hofmann, EE and Burge, CA and Harvell, D and Groner, ML}, title = {Wasting disease of a marine foundation species links community interactions to disease dynamics.}, journal = {Biology letters}, volume = {21}, number = {12}, pages = {}, doi = {10.1098/rsbl.2025.0579}, pmid = {41537815}, issn = {1744-957X}, support = {//National Science Foundation/ ; //William Calver Postdoctoral Fellowship/ ; }, mesh = {*Zosteraceae/microbiology/parasitology/physiology ; *Ecosystem ; Animals ; Climate Change ; Microbiota ; *Plant Diseases/parasitology ; }, abstract = {Infectious disease plays a key role in shaping marine communities, including in seagrass meadows, which form biodiverse coastal habitats. Eelgrass (Zostera marina) is the most widespread seagrass species and is susceptible to seagrass wasting disease, caused by the protist Labyrinthula zosterae. As a foundation species, eelgrass strongly influences ecosystem structure, function and services; recent work has begun to explore the links between critical community interactions and seagrass wasting disease. Here, we highlight recent advances about how the eelgrass community regulates and responds to seagrass wasting disease, from the microbiome to herbivores and filter feeders. We further show how efforts to model seagrass wasting disease progression can build on prior efforts to predict eelgrass growth and productivity and can inform our understanding of ecosystem health, resilience and vulnerability. As climate change alters environmental conditions, potentially favouring the wasting disease pathogen, efforts to integrate community interactions with disease ecology will be critical to forecast ecosystem dynamics and to develop effective coastal management strategies. We offer guidance on addressing major knowledge gaps in the study of eelgrass wasting disease in order to deepen both ecological theory and applied practices and identify how an integrated marine-disease-community ecology can inform a broader, cross-cutting understanding of disease.}, } @article {pmid41538371, year = {2026}, author = {Alves, G and Hamaneh, MB and Ogurtsov, AY and Yu, YK}, title = {Taxonomic-Level Protein Quantification in Metaproteomics Using a Biomass-Constrained Expectation-Maximization Approach.}, journal = {Journal of the American Society for Mass Spectrometry}, volume = {}, number = {}, pages = {}, doi = {10.1021/jasms.5c00332}, pmid = {41538371}, issn = {1879-1123}, abstract = {Microbiome communities are found across diverse environments and play critical roles in both ecosystem function and human health. Mass-spectrometry-based metaproteomics provides a powerful means for directly identifying and quantifying microbial proteins. However, its application is hindered by the shared peptide problem, where peptides map to multiple proteins across taxa, complicating taxon-protein quantification. To address this challenge, we extend a previously published modified expectation-maximization algorithm that incorporates taxonomic biomass constraints into the Microorganism Classification and Identification (MiCId) workflow. This enhanced expectation-maximization algorithm is used to quantify taxon-protein pairs derived from clusters of identified taxon-protein pairs, thereby enabling more accurate quantification and representation of taxonomic-level proteomes. The performance of the approach is evaluated using synthetic datasets consisting of simple mixtures with known relative species abundances, a more complex 24-species synthetic dataset, and a clinical human stool microbiome dataset. It is shown that, in simple synthetic datasets, fold changes computed for species-protein pairs closely match the expected values and are consistent with those obtained from MaxQuant. Using the 24-species synthetic dataset, we show that the algorithm accurately redistributes peptide extracted ion count among taxon-protein pairs that share peptides. Finally, analyzing the clinical stool microbiome dataset, we demonstrate that MiCId's results are accurate and consistent with previously reported findings. These results demonstrate the robustness of MiCId's algorithm for quantifying taxon-protein pairs in complex microbial communities. By resolving the shared peptide problem, the method enables accurate representation of taxonomic-level proteomes, thereby advancing the application of metaproteomics in microbiome research.}, } @article {pmid41538368, year = {2026}, author = {Dame-Teixeira, N and Melo, JLMA and Parolo, CCF}, title = {Caries Microbiome: time to move from blame to balance.}, journal = {Caries research}, volume = {}, number = {}, pages = {1-23}, doi = {10.1159/000550472}, pmid = {41538368}, issn = {1421-976X}, abstract = {BACKGROUND: Advances in next-generation sequencing(NGS) and multi-omics approaches reinforced the concept of functional diversity within biofilm communities, revealing roles beyond bacterial taxonomy and highlighting metabolic and ecological mechanisms operating at the individual level rather than within isolated caries lesions. Moving toward new clinical solutions will require broader perspectives; to this end, we propose key directions to advance the translational potential of caries microbiome research. We present a perspective that connects ecological theory, molecular evidence, and clinical implications through three central topics: (I)microbial composition, (II)microbial function, and (III)individual-level characteristics.

SUMMARY: From a compositional perspective, caries microbiome research should move beyond the search for bacterial culprits and instead consider the broader microbial ecosystem, including low-abundance and non-bacterial members (such as archaea). Within this framework, microbial taxa and functions should not be viewed as inherently "good" or "bad," but rather as context-dependent components of a dynamic ecosystem shaped by sustained environmental pressures. Functionally, the recurrent enrichment of pathways related to carbohydrate metabolism, sugar transport, and acid production likely reflects microbial adaptation to persistent sugar exposure rather than intrinsic virulence traits. This perspective suggests that progress in caries research depends on moving beyond disease-centered models toward understanding how microbial stability preserves oral health. At the individual level, individuals with previous caries experience may retain disease-associated microbial or functional signatures during remission, a phenomenon referred to here as a microbiological dysbiosis scar. This ecological memory may help explain why past caries experience remains one of the strongest predictors of future lesions and highlights the importance of incorporating individual history into the design and interpretation of caries microbiome studies. Integrating detailed clinical metadata with advanced bioinformatic approaches, including artificial intelligence, will be essential for establishing meaningful biological links.

KEY MESSAGES: Progress in caries microbiome research depends on refining study design across microbial composition, functional, and individual levels. Strengthening the resilience of the oral microbiome rather than eliminating specific pathogens or the microbiome should be the central goal of caries microbiology. Moving from blame to balance is not merely semantic; it represents a fundamental shift in how we study, prevent, and manage dental caries.}, } @article {pmid41537975, year = {2026}, author = {Sless, T and Chau, K and Nguyen, P and Rehan, S}, title = {Microbial communities of wild bees and comparative phylogenetics of key bacterial taxa across the bee tree of life.}, journal = {Proceedings. Biological sciences}, volume = {293}, number = {2062}, pages = {}, doi = {10.1098/rspb.2025.1823}, pmid = {41537975}, issn = {1471-2954}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; Bees/microbiology ; Phylogeny ; *Bacteria/classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics/analysis ; *Microbiota ; *Fungi/classification/genetics/isolation & purification ; DNA Barcoding, Taxonomic ; }, abstract = {Recent years have seen a rapidly growing interest in the study of microbiomes to understand the health and well-being of host animals. Within bees, much of this work has focused on managed species of agricultural importance, such as honeybees and bumblebees. However, unmanaged wild bees are also vital to both agricultural and natural systems, and studying their microbial associates is essential to understanding the impacts of microbiomes on bee health. We used metabarcoding based on 16S rRNA and internal transcribed spacer region (ITS1) loci to identify bacterial and fungal associates of adult bees from 16 species, 10 genera and 5 families, representing a diverse sampling of wild bees common to eastern North America. Overall, Apilactobacillus was the largest component of bacterial communities, while fungal communities were dominated by Cladosporium. Alpha diversity of both bacteria and fungi differed significantly across genera and species, while beta diversity varied at all taxonomic levels. Additionally, we conducted a broad phylogenetic comparison of bacterial communities across bees using previously published 16S rRNA datasets and contrasted these findings with functional traits across the bee tree of life. Several bacterial taxa showed evidence of strong phylogenetic signal in prevalence, while the presence of corbiculae was more strongly associated with bacterial community composition than sociality or nesting habit. This study provides expanded insights into the microbial associates of wild bees, as well as the broadest investigation to date into patterns of phylogenetic conservation in bacterial communities across a total of 42 species representing the five most diverse bee families.}, } @article {pmid41537600, year = {2026}, author = {Li, Y and Stieh, DJ and Droit, L and Kim, AH and Rodgers, R and Mihindukulasuriya, KA and Wang, L and Pau, MG and Yuan, O and Virgin, HW and Barouch, DH and Baldridge, MT and Handley, SA}, title = {Associations between the microbiome and immune responses to an adenovirus-based HIV-1 candidate vaccine are distinct between African and US cohorts.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0143525}, doi = {10.1128/msystems.01435-25}, pmid = {41537600}, issn = {2379-5077}, abstract = {Optimization of prophylactic vaccine regimens to elicit strong, long-lasting immunity is an urgent need highlighted by the COVID-19 pandemic. Stronger vaccine immunogenicity is frequently reported in individuals living in high-income countries compared to individuals living in low- and middle-income countries. While numerous host genetic and immune factors may influence vaccine responses, geographic restrictions to vaccine effectiveness may also be influenced by the intestinal microbiota, which modulates host immune systems. However, the potential role of the gut microbiota on responses to HIV-1 vaccines has not yet been explored. We analyzed the bacteriome by targeted 16S sequencing and the virome by virus-like particle sequencing of 154 fecal samples collected from healthy individuals in Uganda, Rwanda, and the United States early (week 2) and late (week 26) after vaccination with multivalent adenovirus serotype 26 (Ad26)-vectored mosaic HIV-1 vaccines. Vaccination did not affect the enteric bacteriome or virome regardless of geographic location. However, geography was the major driver of microbiota differences within this cohort. Differences in overall bacterial and viral diversity and in specific microbial taxa, including Bacteroidota and Bacillota, between participants from the United States and East African countries correlated with differential immune responses, including specific antibody titers, antibody functionality, and cellular immune responses to vaccination regimens. These findings support the microbiota as a putative modifier of vaccine immunogenicity.IMPORTANCEOur research examined how gut bacteria might influence vaccine effectiveness in different parts of the world. We studied adults from the United States, Rwanda, and Uganda who received an experimental HIV vaccine. We found that participants from East Africa had more diverse gut bacteria than those from the United States, but their immune responses to the vaccine were weaker. This is the first study to directly show this relationship between higher gut bacterial diversity and reduced vaccine effectiveness in the same group of people. We also identified specific types of bacteria that were linked to either stronger or weaker immune responses. These findings are particularly relevant now as we use vaccines globally to fight diseases like COVID-19, as they suggest that regional differences in gut bacteria Bacteroidota and Bacillota might help explain why vaccines work better in some places than others. This could inform how we design and test future vaccines.}, } @article {pmid41537573, year = {2025}, author = {Roos, NDB}, title = {The microbiome in mind: Reflections on antibiotic prescription in primary care.}, journal = {South African family practice : official journal of the South African Academy of Family Practice/Primary Care}, volume = {67}, number = {1}, pages = {e1-e4}, doi = {10.4102/safp.v67i1.6238}, pmid = {41537573}, issn = {2078-6204}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *Primary Health Care ; *Antimicrobial Stewardship ; Child ; *Microbiota ; *Practice Patterns, Physicians' ; }, abstract = {In this opinion piece, the author critically reflects on his own antimicrobial stewardship practices in primary care and the complex factors influencing antibiotic prescription, specifically in children.Contribution: In light of emerging evidence of the role of the microbiome in both health and disease, this piece raises a key question: Are we doing more harm than good?}, } @article {pmid41537554, year = {2026}, author = {Deyett, E and DiSalvo, B and Massonnet, M and Ashworth, V and Cantu, D and Lindow, S and Rolshausen, PE and Roper, MC}, title = {Grapevines Pre-Treated with Biocontrol Bacteria Have an Altered Transcriptional Response to Xylella fastidiosa and a Reduction in Pierce's Disease Severity.}, journal = {Molecular plant-microbe interactions : MPMI}, volume = {}, number = {}, pages = {}, doi = {10.1094/MPMI-12-25-0166-R}, pmid = {41537554}, issn = {0894-0282}, abstract = {In a previous DNA-based microbiome study of grapevines in areas of Pierce's Disease (PD) pressure, we determined that taxa belonging to the Pseudomonas and Achromobacter genera negatively associated with PD severity and titer of the causal agent, Xylella fastidiosa, leading us to hypothesize that these taxa suppress PD and could be deployed as biocontrols. Here we tested this hypothesis using two bacterial isolates from the grapevine endosphere, Pseudomonas viridiflava and Achromobacter vitis. We demonstrate that pre-treatment with these two isolates significantly reduced PD symptoms and X. fastidiosa titer, comparable to that of a known PD biocontrol agent, Paraburkholderia phytofirmans PsJN. We monitored early spatial transcriptional responses using genome-wide transcriptional profiling in vines that were pre-treated with the biocontrol strains and then inoculated with X. fastidiosa. We coupled this with phenotyping of internal tylose development and external disease symptoms and bacterial titer and determined that grapevines pre-treated with the biocontrols A. vitis and PsJN developed fewer tyloses and PD symptoms and underwent major transcriptional reprogramming in response to X. fastidiosa. These included up-regulation of genes in auxin- and ethylene-signaling pathways linked to tylose development. In contrast, P. viridiflava pre-treatment also resulted in a reduction of tyloses and PD symptoms but did not induce major transcriptional changes in vines, suggesting it likely has a direct inhibitory effect to X. fastidiosa through antibiosis. Using this data, we propose a model that incorporates timely and effective deployment of tyloses driven by induction of ethylene and auxin pathways as a key factor in PD resistance.}, } @article {pmid41537461, year = {2026}, author = {Choi, KY and Kang, S and Cook, S and Li, D and Choi, YY and Seo, EH and Han, X and Park, JE and Lee, S and Lee, S and Chung, JY and Chong, A and Choi, SM and Ha, JM and Song, MK and Lee, JS and Choo, IH and Kim, JH and Song, HC and Kim, BC and Kim, H and Farrer, LA and Gim, J and Jun, GR and Lee, KH}, title = {The Gwangju Alzheimer's & Related Dementias (GARD) cohort: Over a decade of Asia's largest longitudinal multimodal study.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {22}, number = {1}, pages = {e70981}, pmid = {41537461}, issn = {1552-5279}, support = {25-BR-03-05//the KBRI Basic Research Program through the Korea Brain Research Institute, funded by the Ministry of Science and ICT/ ; NRF-2014M3C7A1046041//the Original Technology Research Program for Brain Science of the National Research Foundation funded by the Korean government, MSIT/ ; RS-2024-00407198//Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea/ ; 2023-ER1007-01//Korea National Institute of Health research project/ ; //by the Technology Innovation Program (20022810, Development and Demonstration of a Digital System for the evaluation of geriatric Cognitive impairment) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea)/ ; RS-2024-00433283//the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy, Republic of Korea/ ; HR22C141105//Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea/ ; }, mesh = {Humans ; Longitudinal Studies ; Male ; *Alzheimer Disease/epidemiology/diagnostic imaging/genetics/diagnosis ; Female ; Aged ; *Cognitive Dysfunction/epidemiology/diagnostic imaging ; Disease Progression ; Republic of Korea/epidemiology ; Cohort Studies ; Middle Aged ; Biomarkers ; Magnetic Resonance Imaging ; Aged, 80 and over ; Neuroimaging ; Proteomics ; Genomics ; }, abstract = {INTRODUCTION: Alzheimer's disease (AD) is a major public health concern in Korea, with a high prevalence among older adults. A community-based longitudinal study is essential for tracking disease progression, identifying biomarkers, and developing targeted prevention and treatment strategies. The Gwangju Alzheimer's & Related Dementias (GARD) cohort was established to address these needs through a multimodal approach.

METHODS: Participants aged ≥60 years undergo comprehensive clinical evaluations, neuroimaging, and biospecimen collection for multi-omics analyses (genomics, transcriptomics, proteomics, and metagenomics) at baseline and systematic follow-up visits.

RESULTS: From over 17,000 screened individuals, 12,877 were enrolled. Baseline diagnoses include 5,123 cognitively unimpaired (CU), 3,250 mild cognitive impairment (MCI), and 2,125 AD dementia. The resource includes magnetic resonance imaging scans (n = 10,843) and extensive multi-omics data: genomic (n = 10,775), proteomic (n = 116), and microbiome (n = 595).

DISCUSSION: The integrated GARD dataset provides a powerful and scalable resource for identifying novel biomarkers, understanding disease heterogeneity, and advancing precision medicine for AD.

HIGHLIGHTS: Gwangju Alzheimer's & Related Dementias (GARD) is a large-scale, longitudinal, community-based cohort study in South Korea. The study focuses on early detection and monitoring of dementia progression. GARD includes cognitive testing, imaging, biospecimens, and multi-omics data. We aim to identify Korean-specific biomarkers predictive of cognitive decline. Supports East Asian insights and fills gaps in global Alzheimer's research.}, } @article {pmid41537394, year = {2026}, author = {Zhang, L and Li, B and Ye, F and Li, LZ and Xiong, S and Lei, SS}, title = {Effect of Puerarin on Chronic Alcoholic Encephalopathy by Modulating the "Microbiota-Gut-Brain Axis" Lipopolysaccharides/Toll-Like Receptors 4/Nuclear Factor Kappa-B Inflammatory Pathway.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.70197}, pmid = {41537394}, issn = {1099-1573}, support = {LKLY25H270003//Joint Fund of Zhejiang Provincial Natural Science Foundation of China/ ; KJTYSZX2025//Zhejiang Provincial Department of Science and Technology Research Institute Support Program/ ; WJ2023M173//the General project of the Health Commission of Hubei Province/ ; 2023YFZD043//Key science and technology project of Jingmen/ ; 2024-XK-59//Key Discipline Construction Plan for Traditional Chinese Medicine/ ; }, abstract = {Chronic alcoholic encephalopathy (CAE) is a condition induced by alcohol consumption, with a huge demand for research on its prevention and treatment drugs. Puerarin, the principal active compound found in Pueraria lobata, has been traditionally utilized in ethnopharmacology to mitigate alcoholic brain injury and rectify imbalances in intestinal flora. The study was aimed to investigate the mechanism by which puerarin exerts its anti-CAE effect. The CAE mice model induced by alcohol were treated with oral administration of puerarin. First, the effects of puerarin on cognitive function, motor ability, and hippocampal tissue pathology along with the expression of TLR4, Myd88, NF-κB, IL-1β, and IL-6 of brain and fecal LPS were investigated. Finally, the composition of the gut microbiome of fecal and TJs (Claudin-1 and Occludin) in the intestine and colon, focusing on the production and transporter of LPS, were measured. The findings revealed that puerarin administration significantly ameliorated motor deficits, anxiety-like behaviors, and cognitive impairments in CAE mice. Histopathological analysis revealed puerarin reduced hippocampal damage and decreased Iba1 immunoreactivity, indicating attenuated neuroinflammation. Puerarin treatment downregulated the protein expression of IL-1β, IL-6, TLR4, Myd88, and NF-κB in brain. Notably, puerarin restored intestinal barrier integrity by upregulating Claudin-1 and Occludin expression. Intestinal flora analysis demonstrated that puerarin treatment increased the abundance of beneficial bacteria (e.g., norank_f_Eubacterium_coprostanoligenes_group) while reducing pathogenic bacteria (e.g., Escherichia-Shigella). The study showed that puerarin exerts a treatment CAE effect, which may be related to modulation of the "microbiota-gut-brain axis" LPS/TLR4/NF-κB inflammatory pathway.}, } @article {pmid41537224, year = {2026}, author = {Liang, D and Wang, Y and Li, Y and Chen, Z and Zeng, Q and Ha, S and Zhou, X and Wu, D}, title = {Elevated Prevalence of Oral HPV Infection Among Females with Periodontitis: A Cross-Sectional Study.}, journal = {Oral health & preventive dentistry}, volume = {24}, number = {}, pages = {1-11}, doi = {10.3290/j.ohpd.c_2446}, pmid = {41537224}, issn = {1757-9996}, mesh = {Humans ; Female ; Cross-Sectional Studies ; *Papillomavirus Infections/epidemiology/complications ; *Periodontitis/epidemiology/microbiology/virology/complications ; Adult ; Middle Aged ; Prevalence ; Male ; Microbiota ; Risk Factors ; Nutrition Surveys ; Young Adult ; Aged ; United States/epidemiology ; }, abstract = {PURPOSE: This study investigated the association between periodontitis and oral HPV infection, while exploring the role of oral bacterial microbiota diversity.

METHODS AND MATERIALS: Data from 4,685 adults in the NHANES 2009-2012 cycles were analysed. Periodontitis was defined based on clinical examination, and oral HPV infection was identified using PCR from oral rinse samples. Multivariable logistic regression models were employed to assess the relationship, adjusting for body mass index (BMI), age, sex, ethnicity, education, smoking, alcohol consumption, daily dental flossing, and history of systemic diseases. Subgroup analyses were stratified by age, sex, and education. Mediation analysis was performed to evaluate whether the oral microbiome acts as a mediator in the relationship between periodontitis and oral HPV infection.

RESULTS: No statistically significant overall association was found between periodontitis and oral HPV infection (P > 0.05). However, females with moderate to severe periodontitis exhibited increased odds of oral HPV infection (P 0.05). Oral HPV infection was associated with greater microbial diversity (higher operational taxonomic units [OTUs]). No significant mediating effect of the oral microbiome was observed.

CONCLUSION: Moderate to severe periodontitis appears to be associated with higher odds of oral HPV infection in females. These findings highlight the potential relationship between oral health, microbial diversity, and oral HPV infection.

CLINICAL IMPLICATION: In the general population, periodontitis does not appear to be a major risk factor for oral HPV; however, female with moderate to severe periodontitis and individuals with higher educati-on showed increased odds of oral HPV infection, suggesting that maintaining periodontal health may be particularly important for HPV related risk management in these subgroups.}, } @article {pmid41537047, year = {2026}, author = {Locher, JA and Wise, A and Strehlau, R}, title = {Intimate hygiene practices during pregnancy with demographic and preterm birth associations: a large cohort study.}, journal = {AJOG global reports}, volume = {6}, number = {1}, pages = {100592}, pmid = {41537047}, issn = {2666-5778}, abstract = {BACKGROUND: Intimate hygiene practices during pregnancy can influence maternal and neonatal health outcomes. Limited data exist on these practices among South African women. This study aimed to characterize intimate hygiene practices among pregnant women in Johannesburg and examine associations with demographic factors and preterm birth.

METHODS: A secondary analysis was conducted on data from 18,076 pregnant women enrolled in the Group B Streptococcus Correlates of Protection Cohort Study in Johannesburg, South Africa. Participants completed questionnaires detailing their intimate hygiene practices, including frequency, methods, and products used. Statistical analyses assessed the prevalence of these practices, their association with demographic characteristics (age, race, education, occupation, dwelling type, parity, and HIV status), and preterm birth outcomes.

RESULTS: The mean age was 28.4 years (range 18-49). Most participants were Black (93.0%), single (80.4%), unemployed (64.7%), and resided in urban areas (70.7%). They reported a median intimate cleaning frequency of 14 times per week (IQR 8-14). Over half (53.3%) practiced douching, and 48.4% added products to their bathwater.Race was significantly associated with adding bathwater products (P<.00001). White women (44.3%) had the highest proportion adding products. Tertiary-educated mothers were more likely to add products (27.0%, P=.0041). Students had the highest rate of product use (28.7%, P=.0018). Urban participants were more likely to add products (25.2%) than semi-urban women (23.2%, P=.025).Douching was also significantly associated with race (P<.00001), with the "Other" category (65.1%) reporting the highest rate. Women with no schooling had the highest douching rate (53.2%, P=.0006). Semi-urban mothers douched the most frequently (53.4%, P<.00001). Marital status was significantly associated with douching (P<.00001), with the highest prevalence among single women (45.8%). Occupation was also significantly associated with douching (P=.016), with students having the highest douching prevalence (28.7%).A significant association was observed between gestational age and the addition of products to bathwater for deliveries between 34 and <37 weeks compared to term deliveries (P=.045). Women who did not add products were more likely to deliver at term, while those who added products had a higher likelihood of delivering preterm. For deliveries <34 weeks compared to 34-<37 weeks, women who did not add products were more likely to deliver at 34-<37 weeks (P=.02).For deliveries at <34 weeks compared to 34-<37 weeks, women who douched were less likely to deliver at <34 weeks, while those who did not douche had lower proportions of deliveries at 34-<37 weeks (P=.035).In the combined preterm category (<37 weeks) compared to term deliveries, a statistically significant association was observed (P=.035), with women who douched being more likely to deliver preterm. Although some early preterm categories were more frequent among those who douched, overall no consistent statistically significant associations were found between hygiene practices and preterm birth outcomes.

CONCLUSION: Intimate hygiene practices are prevalent among pregnant women in Johannesburg and are significantly associated with various demographic factors. While some associations with preterm birth were identified, no consistent significant association was established, warranting further studies.}, } @article {pmid41536683, year = {2025}, author = {Wu, F and Lu, W and Wu, D and Zhou, Y and Lu, H and Ying, L and Wu, G}, title = {[Effects and Mechanisms of Yangyin Yiqi Huoxue Formula on the Oral Microecology in Sjögren's Syndrome Model Mice].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {56}, number = {6}, pages = {1556-1565}, pmid = {41536683}, issn = {1672-173X}, mesh = {Animals ; *Sjogren's Syndrome/microbiology/drug therapy ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Disease Models, Animal ; *Microbiota/drug effects ; Female ; Saliva/microbiology ; *Mouth/microbiology ; RNA, Ribosomal, 16S/genetics ; Hydroxychloroquine/pharmacology ; }, abstract = {OBJECTIVE: To investigate the effect of the Yangyin Yiqi Huoxue formula on the oral microecology in a mouse model of Sjögren's syndrome (SS), and to explore the underlying mechanisms.

METHODS: A total of 12 8-week-old non-obese diabetic (NOD) mice were randomly assigned to a model group, a traditional Chinese medicine (TCM) group, and a hydroxychloroquine (HCQ) group, with 4 mice in each group. In addition, 4 BALB/c mice were used as the normal control group. The TCM group was administered Yangyin Yiqi Huoxue formula (15 g/[kg·d]) via gavage and the HCQ group received HCQ (0.08 g/[kg·d]) via gavage. The normal control and model groups were maintained under standard feeding conditions without intervention. After 8 weeks of treatment, saliva samples were collected for 16S rRNA gene sequencing to analyze the oral microbiota. Alpha diversity, beta diversity, and functional prediction analyses were performed.

RESULTS: Alpha diversity analysis showed that the Yangyin Yiqi Huoxue formula significantly increased oral microbiome diversity in NOD mice (P < 0.05). Species composition analysis indicated that the formula increased the abundance of the phylum Proteobacteria and decreased the abundance of the phylum Firmicutes (P < 0.01), while HCQ led to an abnormal decrease in the abundance of the phylum Firmicutes. Beta diversity analysis revealed distinct microbial clustering in the treatment groups and the model group, with the TCM group showing clustering in the phylum Proteobacteria and exhibiting lower intragroup dispersion than the HCQ group did. According to the functional prediction analysis, both the TCM and HCQ groups demonstrated regulatory potential in terms of amino acid transport and metabolism, transcription, and other related functions. KEGG analysis found greater microbial enrichment in cellular processes, environmental information processing, and disease-related pathways in the TCM group compared to the HCQ group (P < 0.05).

CONCLUSION: The Yangyin Yiqi Huoxue formula can restore oral microbiome diversity and improve the colony structure in in a mouse model of SS, providing experimental evidence for the advantages of TCM in regulating oral microecological functions.}, } @article {pmid41536544, year = {2026}, author = {Stø, K and Skagen, KR and Holm, K and Ueland, T and Vestad, B and Bjerkeli, V and Halvorsen, B and Trøseid, M and Hov, JR and Skjelland, M}, title = {Oral Eikenella as a potential new biomarker of symptomatic carotid atherosclerosis.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2613521}, pmid = {41536544}, issn = {2000-2297}, abstract = {INTRODUCTION: Oral microbiota dysbiosis is linked to cardiovascular disease, and oral pathogens have been detected in atherosclerotic plaques. We aimed to investigate the relationship between the oral microbiota and carotid atherosclerosis, and the occurrence of oral pathogens in plaques.

PATIENTS AND METHODS: Oral swab and saliva samples from patients with severe carotid atherosclerosis (≥50% stenosis) were compared with those from controls. The oral microbiome was analyzed by 16S rRNA amplicon sequencing targeting the V3‒V4 region. Carotid plaques were investigated for five oral bacterial species by qRT-PCR.

RESULTS: Compared with controls, patients exhibited different inter-individual (beta) diversity (r = 0.02, p = 0.002), reduced intra-individual (alpha) diversity (p = 0.026) and 22 bacterial genera differed in relative abundance. Furthermore, abundances of five bacterial genera, including Eikenella, were increased in patients with recent cerebrovascular symptoms compared to asymptomatic patients. Eikenella corrodens was detected in all 30 carotid plaques.

CONCLUSION: Oral microbiota diversity and composition differ between patients with carotid atherosclerosis and controls. A higher relative abundance of the genus Eikenella in symptomatic versus asymptomatic patients and the detection of the species Eikenella corrodens in all carotid plaques, might suggest that Eikenella is important in atherogenesis and plaque instability. Oral Eikenella could possibly serve as a potential new biomarker.}, } @article {pmid41536244, year = {2026}, author = {Girdhar, K and Dedrick, S and Rhodes, L and Kim, D and Powis, A and Mahon, C and Chapdelaine, H and Obaid, L and McNamara, M and Altindis, E}, title = {Diet, gut microbiome, and type 1 diabetes: from risk to translational opportunity.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2614039}, doi = {10.1080/19490976.2026.2614039}, pmid = {41536244}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 1/microbiology/therapy/etiology/immunology ; Animals ; *Diet ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Fecal Microbiota Transplantation ; }, abstract = {The incidence of type 1 diabetes (T1D) has risen sharply in recent decades, implicating the role of environmental factors in disease pathogenesis. Diet, a primary driver of gut microbiome development and composition, along with other environmental exposures, has emerged as a potential modulator of T1D risk and progression. While nutrients, such as certain vitamins, may exert protective effects, the roles of other dietary factors (e.g., early exposure to dietary antigens) remain unclear. Importantly, diet shapes the gut microbiome, which produces immunomodulatory metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), and others that directly influence immune responses. This review presents evidence on how specific dietary factors, including macronutrients (fats, carbohydrates, proteins, such as gluten and milk proteins), fibers, and breastfeeding, affect the gut microbiome and T1D. We also discuss the effects of microbiome-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, on T1D and their potential as future therapeutic strategies. Although animal studies provide compelling mechanistic insights, the results from human trials remain inconsistent, underscoring the urgent need for longitudinal and interventional studies to establish causality. Understanding the complex interplay between diet, the gut microbiome, and immune homeostasis is essential for developing personalized strategies to prevent and treat T1D and delay-related complications.}, } @article {pmid41536238, year = {2026}, author = {Corona-Cervantes, K and Urrutia-Baca, VH and Gámez-Valdez, JS and Jiménez-López, B and Rodríguez-Gutierrez, NA and Chávez-Caraza, K and Espiricueta-Candelaria, F and Villalobos, UAS and Ramos-Parra, PA and Uribe, JAG and Brunck, M and Chuck-Hernández, C and Licona-Cassani, C}, title = {Maternal obesity alters human milk oligosaccharides content and correlates with early acquisition of late colonizers in the neonatal gut microbiome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2607043}, doi = {10.1080/19490976.2025.2607043}, pmid = {41536238}, issn = {1949-0984}, mesh = {Humans ; *Milk, Human/chemistry ; Female ; *Oligosaccharides/analysis/metabolism ; *Gastrointestinal Microbiome ; Infant, Newborn ; Feces/microbiology ; Longitudinal Studies ; Adult ; Pregnancy ; *Bacteria/classification/genetics/isolation & purification/metabolism ; *Pregnancy in Obesity/microbiology/metabolism ; Infant ; Male ; Body Mass Index ; Mexico ; }, abstract = {Metabolic and immune development in neonates are shaped by the succession of the gut microbiome. Maternal obesity can perturb this process by altering interactions of human milk bioactive elements, including oligosaccharides (HMOs), microbial populations, and metabolites. We conducted a longitudinal study of Mexican mother-infant dyads to examine maternal BMI-associated variations in HMOs and infant fecal microbiota. Breastmilk samples from 97 mothers were collected at 48 h, one month, and three months postpartum. We used targeted and untargeted metabolomics to profile breastmilk samples, while shotgun metagenomics was used to analyze infant fecal microbiome composition in a subset of samples. Mothers with obesity showed decreased concentration of key HMOs shortly after birth, correlating with an altered succession of their infant's gut microbiota. This included reduced early colonizers (Enterobacteriaceae) and increased abundance of intermediate and late colonizers (Bifidobacterium and members of the Lachnospiraceae family), over subsequent months. These taxa negatively correlated with HMOs such as 6'SL, LNnT, and LNT. Additionally, functional profiling revealed alterations in metabolic pathways related to polyamine biosynthesis, suggesting changes in microbial metabolism linked to maternal BMI. Despite the cohort's size, our study offers unique insights into the relationship between maternal obesity, HMO composition, and early infant microbial colonization in Latin-American mothers. This exploratory research serves as proof of concept, underscoring the need for larger-scale studies to validate these findings and better understand their implications for infant health. More importantly, our results highlight the interplay between maternal BMI and human milk bioactives, underscoring the importance of correlating microbial succession with maternal metabolic health to better understand early immune development in neonates.}, } @article {pmid41536172, year = {2026}, author = {Carboni, S and Asangba, AE and Melin, AD}, title = {Microbial Contributions to Primate Reproduction.}, journal = {Evolutionary anthropology}, volume = {35}, number = {1}, pages = {e70023}, pmid = {41536172}, issn = {1520-6505}, mesh = {Animals ; *Primates/microbiology/physiology ; Female ; *Reproduction/physiology ; *Microbiota/physiology ; Male ; Humans ; Pregnancy ; Anthropology, Physical ; Sexual Behavior, Animal ; Biological Evolution ; Copulation/physiology ; }, abstract = {Reproduction is a complex process, and microbes play a far greater role than previously imagined. This review explores the ways that microbiomes influence the rich tapestry of reproductive processes and outcomes within the primate lineage, including pre-copulatory and post-copulatory mechanisms. We discuss microbiomes in a sexual selection framework, specifically how they might influence mate choice and sexual competition across multiple sensory modalities. We then consider how copulatory behavior and mating systems may in turn shape reproductive microbiomes. Moving to post-copulatory processes, we discuss the potential impact of microbes on cryptic choice and sperm competition and call for additional research in this area. Finally, we explore the influence of microbes on pregnancy outcomes, emphasizing evolutionary perspectives often overlooked in clinical research. Importantly, we compare human studies to those on nonhuman primates, bridging the two areas of inquiry and outlining future research directions. Our aim is to highlight the vast potential for microbes to contribute to all stages of reproduction, and to inspire creative, synthetic future research that moves forward this fascinating area of inquiry.}, } @article {pmid41536169, year = {2026}, author = {Abdulkareem, AA and Gul, SS and Abdulbaqi, HR and Sha, AM and Preshaw, PM}, title = {Assessing Evidence to Include Filifactor alocis as a Novel Candidate in Socransky's Complexes.}, journal = {Molecular oral microbiology}, volume = {}, number = {}, pages = {e70018}, doi = {10.1111/omi.70018}, pmid = {41536169}, issn = {2041-1014}, abstract = {Socransky's complexes have identified a range of bacteria as key contributors to the onset and progression of periodontal disease. However, advancements in microbiological detection methods have allowed for exploration of the microbiome in periodontal health/disease in greater detail. In recent years, Filifactor alocis has emerged as a potential periodontal pathogen. Therefore, the aim of this review was to investigate whether this bacterium could be included in Socransky's model by summarizing the available evidence. A comprehensive literature search performed using PubMed, ScienceDirect, and Scopus databases was undertaken. The retrieved articles were filtered according to defined eligibility criteria, which yielded 24 studies. Data were extracted from these observational and clinical studies to synthesize findings. Findings regarding the host immune response were derived from in vitro and experimental animal models and narratively summarized. Observational studies and clinical trials showed heterogeneity and a lack of standardized outcomes. However, the general trend indicated a higher prevalence of F. alocis at diseased sites than at healthy sites. In addition, periodontal treatment was found to significantly reduce F. alocis levels and was associated with improvements in clinical periodontal parameters. Experimental models and in vitro studies showed that F. alocis exhibits a range of virulence attributes and pathogenic behavior similar to that of putative pathogenic periodontal bacteria. The evidence is not sufficient to include F. alocis as a new member of Socransky's model. However, this review suggests that this bacterium has the potential to be included in Socransky's complexes in the future after further research which would require to be highly standardized to enhance comparability and generalizability of findings.}, } @article {pmid41536161, year = {2026}, author = {Turnlund, AC and O'Brien, PA and Rix, L and Ferguson, S and Boulotte, N and Jeong, SY and Webster, NS and Diaz-Pulido, G and Wahab, MA and Lurgi, M and Vanwonterghem, I}, title = {Bacterial Communities Associated With Crustose Coralline Algae Are Host-Specific.}, journal = {MicrobiologyOpen}, volume = {15}, number = {1}, pages = {e70213}, pmid = {41536161}, issn = {2045-8827}, support = {//Australian Government Research Training Programme/ ; //UQ Graduate school/ ; //the Reef Restoration and Adaptation Programme/ ; }, mesh = {*Rhodophyta/microbiology/classification ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; Phylogeny ; *Microbiota ; Symbiosis ; Coral Reefs ; DNA, Bacterial/genetics/chemistry ; Sequence Analysis, DNA ; *Anthozoa/microbiology ; DNA, Ribosomal/genetics/chemistry ; }, abstract = {Crustose coralline algae (CCA) comprise hundreds of different species and are critical to coral reef growth, structural stability and coral recruitment. Despite their integral role in reef functioning, little is known about the diversity and structure of bacterial communities associated with CCA. We address this knowledge gap by characterising the surface microbial communities of 15 Indo-Pacific CCA species across eight different families from the Great Barrier Reef, using 16S rRNA amplicon sequencing. CCA microbial community composition was distinct and found to primarily differentiate by algal host species. When looking at the core bacterial communities, divergence across CCA microbiomes was additionally correlated to host phylogeny. CCA from similar light environments and depths also had more similar microbial communities, suggesting the potential role of environmental parameters in influencing microbial community organisation. The fundamental descriptions of CCA bacterial communities for a wide range of Indo-Pacific species presented here provide essential baseline information to further inform CCA microbial symbiosis research.}, } @article {pmid41536159, year = {2026}, author = {Morgan, L and Tilzey, A and El-Ajouz, M and Dong, J and Daley, C and Olivares, CI}, title = {Surface water microbiome response to pyrogenic carbon after a wildland-urban interface fire.}, journal = {Environmental science. Processes & impacts}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5em00803d}, pmid = {41536159}, issn = {2050-7895}, abstract = {Fires in the wildland-urban interface (WUI) introduce pyrogenic organic contaminants to surface waters, but their impacts on microbial dynamics have not been evaluated. We studied the interactions between microbial communities and pyrogenic carbon during post-fire storms in a WUI fire-impacted creek in Orange County, CA. The first storms following the fire (low intensity) brought about the highest discharges of polycyclic aromatic hydrocarbons (PAHs), e.g. benzo[a]pyrene, benz[a]anthracene. Dissolved organic carbon (DOC) loads reached up to 11.2 g-C s[-1] during the more severe storms. PAHs correlated with each other but not with DOC or fluctuations in turbidity, suggesting these two variables might not be good predictors of PAH flushes, especially in low-intensity storms. Microbial genera with known PAH-degrading members were differentially abundant during post-fire storms (Pseudomonadota, Bacteroidota, Cyanobacteriota, Actinobacteriota, Bacillota). In addition, predicted metabolic pathways related to the PAH biodegradation intermediates, catechol and protocatechuate, increased significantly at sites downstream of the fire. Overall, our findings suggest pyrogenic carbon from the fire resulted in a detectable shift in microbial community function and composition to favor PAHs degradation just a few months after the fire. This response suggests that PAH-degrading microorganisms are readily found after WUI fires.}, } @article {pmid41536136, year = {2026}, author = {Yu, J and Zhang, Y and Wells, JCK and Wei, Z and Nielsen, DS and Fewtrell, M}, title = {Maternal and infant microbiota in early infancy: Longitudinal findings from a randomised controlled trial.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70342}, pmid = {41536136}, issn = {1536-4801}, support = {//NIHR Great Ormond Street Hospital Biomedical Research Centre/ ; }, abstract = {OBJECTIVES: To characterise early postnatal microbial development across maternal gut, breast milk, and infant gut compartments, and explore potential modulation by maternal stress in a cohort of Chinese mothers practising traditional postpartum confinement.

METHODS: This secondary analysis draws on a randomised controlled trial of a maternal relaxation intervention in late preterm and early-term dyads. Vaginally delivered mothers (34 + 0 to 37 + 6 weeks) and their exclusively breastfed infants were followed from 1 to 8 weeks postpartum. Maternal stool, breast milk, and infant stool samples were collected at both time points and analysed via 16S rRNA gene amplicon sequencing. Changes in gut microbiome diversity and composition (alpha andbeta diversity metrics) and the relative abundance of dominant genera were assessed overall and by intervention group.

RESULTS: Microbiome diversity (alpha diversity metrics) remained stable across all sample types. However, we observed a compositional temporal shift in breast milk microbiota (p = 0.039), driven primarily by changes in the control group. Infant gut microbiota showed increased Bifidobacterium and decreased Staphylococcus and Enterobacteriaceae with time. A significant reduction in Staphylococcus was observed in breast milk of the intervention group only. Maternal gut microbiota remained stable.

CONCLUSIONS: Microbial composition in breast milk and infant gut shifted over the first 8 weeks postpartum, while maternal gut remained stable. Findings suggest maternal stress-reduction interventions may influence breast milk microbiota. Further research is warranted to confirm these effects and investigate mechanisms.}, } @article {pmid41535980, year = {2026}, author = {Wang, Z and Guo, H and He, J and Zhang, Z and Huws, S and Guo, T and Shen, W and Wan, F}, title = {Responses of rumen bacterial microflora to aflatoxin B1 challenge: potential roles of AHLs/AI-2 mediated quorum sensing.}, journal = {Animal microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s42523-026-00515-2}, pmid = {41535980}, issn = {2524-4671}, support = {32302764//National Natural Science Foundation of China/ ; 2024JJ5179//Hunan Provincial Natural Science Foundation/ ; 2024JJ5179//Hunan Provincial Natural Science Foundation/ ; XJSLSW-2023001//Key laboratory for the feed and biology technique of Xinjiang Uygur Autonomous Region/ ; XJSLSW-2023001//Key laboratory for the feed and biology technique of Xinjiang Uygur Autonomous Region/ ; XJSLSW-2023001//Key laboratory for the feed and biology technique of Xinjiang Uygur Autonomous Region/ ; XJSLSW-2023001//Key laboratory for the feed and biology technique of Xinjiang Uygur Autonomous Region/ ; 2022A02001-1//Science and Technology Department of Xinjiang Uygur Autonomous Region/ ; }, } @article {pmid41535879, year = {2026}, author = {Xu, Y and An, L and Xie, J and Luo, C and Zhang, H and Zhang, Q and Luo, G}, title = {Investigating the impact of gut microbiota-derived metabolites on benign prostatic hyperplasia using network pharmacology approaches.}, journal = {BMC pharmacology & toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40360-025-01059-y}, pmid = {41535879}, issn = {2050-6511}, abstract = {BACKGROUND: The gut microecosystem represents the most abundant and complex microbial ecosystem in the human body. Maintaining homeostasis of gut microbiota and their metabolites is essential for human health. As a chronic metabolic disorder, the association between benign prostatic hyperplasia (BPH) and gut microbiota remains unclear. Growing evidence suggests that modulating the composition and function of gut microbiota may influence the gut-prostate axis, thereby affecting the development and progression of prostatic hyperplasia. In this study, we employed network pharmacology to systematically elucidate the complex interactions among gut microbiota, microbial metabolites, and BPH-related therapeutic targets.

METHODS: In this study, we first retrieved information on gut microbial metabolites from the gutMGene database. Subsequently, we identified overlapping targets of these metabolites using the SEA and STP databases. To further clarify targets related to BPH, we integrated data from authoritative databases such as Genecard and OMIM. Based on this information, we constructed a protein-protein interaction (PPI) network to screen for core targets. In addition, we performed systematic GO and KEGG functional enrichment analyses of these targets using the DAVID database. we constructed a network model to illustrate the interactions among microbiota, substrates, metabolites, and targets.Finally, molecular docking validation was performed between the core targets and gut microbiota metabolites.

RESULTS: We identified 43 overlapping targets between gut microbial metabolites and BPH. Subsequently, we selected AKT1, IL-6, and IL-1B as core therapeutic targets for BPH. By constructing an MSMT comprehensive network, we found that these three core targets exert therapeutic effects on BPH through interactions with 11 metabolites, 2 substrates, and 4 gut microbial species. Furthermore, GO analysis revealed that gut microbial metabolites influence prostatic hyperplasia by regulating inflammation, immune responses, and the activation of oxidoreductase activity. KEGG analysis indicated that the AGE-RAGE signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, C-type lectin receptor signaling pathway, and PI3K/Akt signaling pathway are the major pathways involved in BPH.The molecular docking results demonstrated that butyrate may influence prostatic hyperplasia by modulating the AKT1 gene.

DISCUSSION: This study employs a network pharmacology approach to elucidate the intricate "Microbiota-Substrate-Metabolite-Target" (M-S-M-T) network in Benign Prostatic Hyperplasia (BPH), identifying key hub genes (AKT1, IL-6, IL-1B), signaling pathways (PI3K/Akt, AGE-RAGE, HIF-1), and gut microbiota-derived metabolites (butyrate, propionate, TMAO) as central regulators. It further characterizes the functional significance of the Bifidobacterium-tryptophan and Clostridium sporogenes-tyrosine axes, highlighting their probiotic potential for microbiota-targeted BPH therapy. While demonstrating the therapeutic promise of modulating the gut microbiome, the study underscores the need for future experimental validation to decipher the precise mechanistic links within the M-S-M-T network and its role in BPH pathogenesis CONCLUSION: IL-6, AKT1, and IL-1B serve as the primary targets through which gut microbiota metabolites exert their therapeutic effects on benign prostatic hyperplasia.}, } @article {pmid41535843, year = {2026}, author = {Pappert, FA and Newrzella, N and Roth, O}, title = {Parental fasting effects on offspring immune gene expression, epigenetic patterns, and gut microbiota in a species with male pregnancy (Syngnathus typhle).}, journal = {BMC biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12915-026-02509-7}, pmid = {41535843}, issn = {1741-7007}, support = {RTG 2501 TransEvo//Deutsche Forschungsgemeinschaft/ ; MALEPREG: eu-repo/grantAgreement/EC/H2020/755659//HORIZON EUROPE European Research Council/ ; CRC 1182 Origin//Metaorganisms/ ; }, abstract = {BACKGROUND: Intermittent fasting is widely promoted for its potential to improve health and extend lifespan, yet these benefits may come at a reproductive cost, potentially reducing parental fitness and offspring quality. While the inter- and transgenerational effects of fasting are increasingly studied, they remain poorly understood in species with unconventional reproductive roles. Investigating such effects in these systems is crucial, as the evolutionary trade-offs between somatic maintenance and reproductive investment may differ from those in species with conventional reproductive roles. In this study, we investigated the effects of intermittent fasting (IF) in a species with male pregnancy, Syngnathus typhle, by exposing mothers and fathers to either IF or ad libitum (AL) feeding before mating. Upon transfer of maternal eggs to paternal brood pouches, males remained on their assigned diets throughout pregnancy.

RESULTS: Offspring from all parental diet combinations AL(p) × AL(m), IF(p) × IF(m), AL(p) × IF(m), and IF(p) × AL(m) (with p = paternal and m = maternal) were analyzed at birth before first feeding alongside parents for morphology, immune and epigenetic candidate gene expression, and gut microbiota composition. Mothers under IF showed greater condition loss, leading to reduced offspring condition regardless of paternal diet, highlighting the importance of maternal provisioning through eggs. However, IF fathers exhibited increased immune activation and microbiome shifts that were mirrored in offspring, suggesting paternal priming via epigenetic and microbial inheritance. Offspring from mismatched parental diets showed disrupted immune-microbiome correlations, indicating that aligned parental cues support more stable offspring development.

CONCLUSION: These findings highlight how parental nutritional history differentially shapes offspring phenotype through maternal and paternal pathways in a species with male pregnancy. Our results emphasize the value of studying species with diverse reproductive strategies and life histories to understand the full spectrum of trans-generational plasticity in nature.}, } @article {pmid41535719, year = {2026}, author = {Almonte, AA and Thomas, S and Iebba, V and Kroemer, G and Derosa, L and Zitvogel, L}, title = {Gut dysbiosis in oncology: a risk factor for immunoresistance.}, journal = {Cell research}, volume = {}, number = {}, pages = {}, pmid = {41535719}, issn = {1748-7838}, support = {INCA_16698//CNIB (INCA)/ ; 955575//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; }, abstract = {The gut microbiome is recognized as a determinant of response to immune checkpoint inhibitor (ICI) therapies in cancer. However, the clinical translation of microbiome science has been hampered by inconsistent definitions of dysbiosis, inadequate biomarker frameworks, and limited mechanistic understanding. In this review, we synthesize the current state of knowledge on how gut microbial composition and function influence ICI efficacy, highlighting both correlative and causal evidence. We discuss computational approaches based on α-diversity or taxonomic abundance and argue for more functionally and clinically informative models, such as the topological score (TOPOSCORE) and other dysbiosis indices derived from machine learning. Using retrospective analyses of metagenomic datasets from thousands of patients and healthy controls, we examine microbial patterns that distinguish responders from non-responders. We also explore how dysbiosis perturbs immunoregulatory pathways, including bile acid metabolism, gut permeability, and mucosal immunomodulation. Finally, we assess emerging therapeutic strategies aimed at correcting microbiome dysfunction - including dietary modification, bacterial consortia, and fecal microbiota transplantation - and describe how they are being deployed in multiple clinical trials. We conclude with a brief discussion of the ONCOBIOME initiative, which works with international partners to incorporate microbiome science into oncology workflows. By refining our understanding of gut-immune interactions and translating it into action, microbiome-informed oncology may unlock new therapeutic potential for patients previously resistant to immunotherapy.}, } @article {pmid41535594, year = {2026}, author = {Govender, P and Cason, E and Ghai, M}, title = {Characterization of the oral microbiome in the diverse South African population by PacBio HiFi sequencing.}, journal = {Applied microbiology and biotechnology}, volume = {110}, number = {1}, pages = {23}, pmid = {41535594}, issn = {1432-0614}, mesh = {Adult ; Humans ; South Africa ; *Microbiota/genetics ; *Mouth/microbiology ; Middle Aged ; Young Adult ; RNA, Ribosomal, 16S/genetics ; Adolescent ; *Bacteria/classification/genetics/isolation & purification ; Male ; Female ; DNA, Bacterial/genetics ; Sequence Analysis, DNA ; Phylogeny ; Biodiversity ; }, abstract = {Mounting evidence supports population-specific variation in the microbiome. This study applied PacBio HiFi 16S rRNA amplicon sequencing to profile the oral microbiome of 62 individuals (aged 18-55 years) from the four major South African population groups (Black, Coloured, Indian and White). Bioinformatics analysis was performed using QIIME2 with taxonomic classification based on the SILVA database. Across all groups, Firmicutes was the most dominant phylum (80.92%), followed by Proteobacteria (8.94%) and Bacteroidota (4.22%). A total of 236 genera and 376 species were identified. Veillonella was the most abundant genus (27.57%), followed by Streptococcus (25.08%) and Granulicatella (15.54%). Streptococcus (30.40%) and Veillonella (41.82%) were the most abundant in the Indian and Coloured populations, respectively. Significant microbiome variation was observed between groups (β-diversity, p < 0.001), highlighting distinct population-specific microbial profiles. The Coloured population exhibited the highest microbiome diversity, likely due to complex genetic makeup and diverse cultural influences. The White population displayed the lowest microbiome diversity, likely due to more uniform lifestyle patterns. Despite these differences, three bacterial species, namely, Streptococcus salivarius, Veillonella atypica, and Prevotella melaninogenica were present in the majority of individuals across the populations, suggesting a core component of the South African oral microbiome. No significant associations were observed between factors such as sex, age, diet antibiotic use, lifestyle and oral microbiome variation. Several undetermined factors, such as psychological factors, stress, level of exercise, host genetics and immunity, could have contributed to the observed diversity. Our results present the first report of oral microbiome analysis of healthy South African populations by PacBio HiFi sequencing and warrant further research to provide insight into how these differences influence health disparities and potential application in forensics. KEY POINTS: • First report of the oral microbiome of healthy South Africans by PacBio HiFi sequencing • S. salivarius, P. melaninogenica and V. atypica define South Africa's core oral microbiome • Population-specific microbiome signatures can guide forensics and health research.}, } @article {pmid41535558, year = {2026}, author = {Zhang, M and Ding, R and Jia, T and Wu, Z and Hussain, M and Wang, L and Gan, GY and Zhang, J}, title = {Synergy of FeNPs and PGPR Strain Enhances Nitrogen Fixation by Linking Root Metabolites and Rhizosphere Microbiome Assembly in Alfalfa.}, journal = {Plant, cell & environment}, volume = {}, number = {}, pages = {}, doi = {10.1111/pce.70387}, pmid = {41535558}, issn = {1365-3040}, support = {32471768//National Natural Science Foundation of China/ ; 22ZD6NA007//Key Science & Technology Project of Gansu Province, China/ ; }, abstract = {Increasing evidences show plant growth-promoting rhizobacteria (PGPR) benefit legume-rhizobium symbiosis, and iron-based nanoparticles (FeNPs) act as rhizobia microenvironment stabilizers. However, few studies explored if their combination exerts synergistic effects on the symbiosis in legume. Here, we compared the effects of FeNPs, Pseudomonas rhizovicinus M30-35, and their co-application (Fe + M) on alfalfa growth, nitrogen fixation, root metabolites, and rhizosphere microbiome. Compared with FeNPs and M30-35, Fe + M increased shoot height, root length, root activity, chlorophyll content, and net photosynthetic rate (Pn) by 63.2% and 45.4%, 61.1% and 70.6%, 56.2% and 47.1%, 20.1% and 18.6%, and 41.1% and 30.6%, respectively; the nodule number, nitrogenase activity, ureide content, and leghemoglobin content rose by 29.6% and 31.4%, 58.5% and 78.7%, 20.4% and 15.1%, and 9.7% and 12.4%, respectively. Metabolomic analysis showed that Fe + M enhanced the accumulation of benzenoid compounds in roots, while microbial co-occurrence network analysis indicated reduced complexity and connectivity of rhizosphere bacterial and fungal communities. Importantly, core microbes, such as Hydrogenophaga, Nocardioides, unidentified_Mitochondria, and Scedosporium, were positively associated with benzenoid compounds, which contribute to nutrient cycling in the rhizosphere. Our findings demonstrate that FeNPs and PGPR strain together achieve synergistic effects on the nitrogen fixation in alfalfa.}, } @article {pmid41535415, year = {2026}, author = {Sambolín-Pérez, CA and Montes-Jiménez, SM and Montes-Jiménez, HM and Rosa-Morales, Y and Aybar-Batista, R and Núñez-Marrero, ÁR and Rivera-Vicéns, RE and Ríos-Velázquez, C and Negrón-Berríos, JA}, title = {Revealing and characterizing bacterial communities of in vitro Musa species through 16S rDNA metabarcoding and culture dependent approaches.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35510-9}, pmid = {41535415}, issn = {2045-2322}, support = {Award No. P031S220125//U.S. Department of Education/ ; }, abstract = {Bananas and plantains, part of the Musa genus, are key global food crops that are threatened by various factors, including hurricanes and microbial infections. The production of phytopathogen-free plants in Temporary Immersion Bioreactors (TIB) has gained attention due to improved yield and health. However, the impact of TIB on Musa spp. microbiomes remains poorly understood. Thus, elucidating the role of in vitro Musa spp. microbiome is crucial for developing healthier plantlets with beneficial microbes, such as plant growth-promoting bacteria (PGPB), which are essential for plant development and might help Musa spp. thrive in abiotic and biotic stresses after in vitro development. To reveal the potential association of PGPB, we aimed to identify and characterize the bacterial communities from in vitro (TIB) Musa spp. varieties (Maiden, Dwarf, and Maricongo) pseudostems using both culture-independent (16S rDNA-metabarcoding) and culture-dependent methods to elucidate their diversity and roles in plant health. Our results identified four bacterial phyla, with Bacillota being the most dominant, followed by Pseudomonadota, Actinobacteriota, and Bacteroidota. Brevibacillus sp. and Xylella sp. were the dominant genera. The isolates included Lysobacteraceae and Terribacillus spp., and the microbiomes metabolic pathways featured cofactors and amino acid biosynthesis. These findings enhance the understanding of bacterial communities in Musa spp. under in vitro conditions, highlighting the potential effects of artificial environments on host microbiomes, and encouraging innovative research into bacterial-plant interactions. This may aid in identifying specific bacteria with potential PGPB traits in Musa spp., offering new ways to enhance production and protection.}, } @article {pmid41535303, year = {2026}, author = {Hall, AN and Manuja, S and Payling, LM and Romero, LF and Hoerr, FJ and Shields, J and Hofacre, C and Susanti, D and Gangaiah, D and Plata, G and Kumar, A}, title = {Lactobacillus-vectored nanobodies improve broiler productivity under sub-clinical necrotic enteritis with associated microbiome and transcriptome changes.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00916-w}, pmid = {41535303}, issn = {2055-5008}, abstract = {Sub-Clinical Necrotic Enteritis (SCNE), caused by toxin-producing Clostridium perfringens, is a major challenge in poultry production. SCNE has traditionally been managed with in-feed antibiotics; however, increasing concerns about the spread of antimicrobial resistance call for antibiotic-free strategies for its control. We recently described an NE control strategy leveraging Limosilactobacillus reuteri probiotic strains genetically engineered to deliver nanobodies against alpha toxin and NetB from C. perfringens in the poultry gut. Here, in a controlled study under SCNE conditions, we found that the engineered strains significantly improved feed conversion ratios and weight gain of broilers, outperforming treatment with either a prophylactic antibiotic or the wild-type probiotic strains. To investigate the systemic factors contributing to these performance differences, we analyzed histomorphometrics of the small intestine, microbial metatranscriptomics of jejunal contents, and gene expression from the jejunum and liver tissues. Our results confirmed the in situ expression of the nanobodies and provided evidence that nanobody delivery mitigates SCNE-associated inflammation in the jejunum and toxin-induced damage in the liver, leading to a more quiescent immune state, lower oxidative stress, and improved growth performance. Our findings demonstrate the potential of probiotic-vectored nanobody delivery as an effective strategy for targeting gut antigens across a range of diseases.}, } @article {pmid41535289, year = {2026}, author = {Panah, FM and Støving, RK and Sjögren, M and Micali, N and Maschek, S and Reis, KD and Mirsepasi-Lauridsen, HC and Petersen, AM and Nielsen, DS and Helms, M and Rasmussen, MA and Barfod, KK}, title = {Impact of a single fecal microbiome transplantation in adult women with anorexia nervosa: an open-label feasibility pilot trial.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68455-8}, pmid = {41535289}, issn = {2041-1723}, support = {R370-2021-863//Lundbeckfonden (Lundbeck Foundation)/ ; }, abstract = {Anorexia nervosa (AN) is a severe mental disorder characterized by restrictive eating and disturbance in the way one's body weight or shape is experienced, often accompanied by depression and anxiety. Current evidence-based treatments for AN have limited efficacy, with less than half of the patients achieving full recovery in long-term follow-up studies. Recent findings have identified gut microbiota (GM) dysbiosis as a potential contributor to AN pathology through the gut-brain axis. This open-label, non-randomized, feasibility trial (Clinicaltrials.gov Identifier: NCT05834010) evaluated the feasibility of utilizing fecal microbiota transplantation (FMT) to modify the GM and GM-associated signaling in females with AN and to examine biological effects following a single FMT procedure. Adult female participants diagnosed with AN were recruited. FMT was administered either orally via capsules or as rectal enema. Stool and blood samples were collected pre- and one week post-FMT to assess GM composition, hormonal changes, and biomarkers. Primary endpoints: Feasibility of FMT in individuals with AN and preferred route of FMT. Secondary endpoints: A single FMT treatment can alter GM composition in individuals with AN short term and relevant gut brain signaling in serum. 18/22 participants (81%) completed FMT and sampling and 19/22 participants chose oral capsules, with no serious adverse effects reported. GM analysis showed significant shifts toward donor composition 1-week post-FMT, with improved stool consistency. No significant changes were observed in psychopathology measures or appetite-related biomarkers. Oral FMT is a feasible intervention for adult women with AN, leading to changes in GM profile. Future studies should focus on placebo-controlled trials to assess the efficacy of repeated oral treatments and explore long-term effects on GM, appetite, body weight, sex hormones, disorder-specific symptoms, and overall well-being.}, } @article {pmid41535271, year = {2026}, author = {Klümpen, L and Mantri, A and Philipps, M and Seel, W and Schlautmann, L and Yaghmour, MH and Wiemann, V and Stoffel-Wagner, B and Coenen, M and Weinhold, L and Hasenauer, J and Fließwasser, T and Burgdorf, S and Thiele, C and Stehle, P and Simon, MC}, title = {Cholesterol-lowering effects of oats induced by microbially produced phenolic metabolites in metabolic syndrome: a randomized controlled trial.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {598}, pmid = {41535271}, issn = {2041-1723}, support = {01EA1707//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 432325352 - SFB 1454, EXC 2151-390873048//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 432325352 - SFB 1454//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; *Avena/metabolism/chemistry ; *Metabolic Syndrome/diet therapy/blood/microbiology/metabolism ; Male ; Coumaric Acids/blood ; Middle Aged ; Female ; *Phenols/metabolism ; Adult ; *Cholesterol/blood ; Gastrointestinal Microbiome ; }, abstract = {Oats have various positive effects on human health, but the underlying mechanisms are not fully understood. To identify oat-microbiome-host interactions contributing to metabolic improvements, we conducted two randomized controlled dietary interventions in parallel-design in individuals with metabolic syndrome, comparing a short-term, high-dose and a six-week, moderate oat intake with respective controls (DRKS00022169). Both oat diets lead to an increase in plasma ferulic acid (0.64 [0.26, 1.02], P = 0.002; 0.55 [0.21, 0.89], P = 0.003), while the high-dose oat-diet also increased dihydroferulic acid (1.23 [0.44, 2.01], P = 0.003). Here we show that microbial phenolic metabolites are driving factors for the cholesterol-lowering effect of oats, which might be of relevance since short-term, high-dose oat-diet is a suitable approach to alleviate obesity-related lipid disorders.}, } @article {pmid41534821, year = {2026}, author = {Cadaxo, AS and Cotrin, JC and Valente, AP and Lopes, FG and Veras, RP and Torres, DS and Molina da Costa, RQ and Dos Santos Junior, GC and Santos-Rebouças, CB}, title = {Multi-biofluid metabolomics coupled with gene network reveals stage-specific alterations in mild cognitive impairment and Alzheimer's disease in an ethnically mixed cohort.}, journal = {Brain research}, volume = {1874}, number = {}, pages = {150167}, doi = {10.1016/j.brainres.2026.150167}, pmid = {41534821}, issn = {1872-6240}, abstract = {Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide. A prodromal stage, often manifested as Mild Cognitive Impairment (MCI), can precede dementia onset. Metabolomics provides a powerful approach to detect metabolic alterations capturing combined genetic, epigenetic, dietary, gut microbiota, and environmental influences on AD pathogenesis and progression from MCI to AD. In this study, we analysed plasma, urine, and saliva metabolomes of 94 ethnically diverse Brazilian individuals (30 AD, 16 MCI and 48 healthy controls), all comorbidity-free, using Nuclear Magnetic Resonance (NMR)-based metabolomics. Cross-sectional analysis employed multivariate modelling (PLS-DA) and univariate Mann-Whitney U tests. We identified distinct group-specific metabolic signatures involving amino acids (phenylalanine, glutamine, asparagine, valine, alanine), energy-related metabolites (pyruvate, citrate, glucose), compounds linked to lipid/redox pathways (acetate, glutamate, aspartate), epigenetic regulation (betaine), neuroinflammation, immune fitness, and gut microbiome-influenced metabolites (scyllo-inositol). Valine increased progressively (controls < MCI < AD), while alanine showed a biphasic pattern (reduced in MCI, elevated in AD). These consistent, biofluid-spanning alterations highlight their potential as minimally invasive biomarkers for diagnosis and monitoring. Integration of metabolite data with AD-associated genes from genome-wide association studies (GWAS) revealed six genes (CYCS, NFAT5, GRIN2B, SLC43A2, MAPT, and SLC38A1) common to all biofluids, reinforcing convergent systemic pathways. Collectively, these findings underscore the importance of integrating metabolomics with genetic networks to enhance understanding of AD pathophysiology, identify potential therapeutic targets, and guide future clinical validation and precision medicine strategies for dementia in ethnically mixed populations.}, } @article {pmid41534759, year = {2026}, author = {Deng, L and Tian, L and Su, D and Li, Y and Zhang, S and Wang, S and Liu, Z}, title = {(R)-bambuterol ameliorates DSS-induced colitis in mice fed a high-fat diet via modulating immune response, intestinal barrier integrity, gut microbiota, and metabolomic profiles.}, journal = {Archives of biochemistry and biophysics}, volume = {777}, number = {}, pages = {110734}, doi = {10.1016/j.abb.2026.110734}, pmid = {41534759}, issn = {1096-0384}, abstract = {The consumption of a high-fat diet is currently thought to be closely related to the onset of ulcerative colitis. (R)-bambuterol ((R)-BMB) has anti-inflammatory effects in the treatment of respiratory system related diseases. However, the therapeutic effect of (R)-BMB against in high-fat diet-related colitis remain undocumented. Therefore, in this study, the alleviation effect of (R)-BMB in mice with dextran sulfate sodium (DSS)-induced colitis fed a high-fat diet and its potential mechanism was explored. The results demonstrated that (R)-BMB markedly ameliorated the symptoms of colitis, such as body weight loss, spleen swelling and colon shortening. Moreover, (R)-BMB obviously mitigated the levels of inflammatory cytokines. Further research exhibited that (R)-BMB inhibited the NF-κB signaling pathway, regulated the balance of Th17 and Treg cells, elevated activated the Nrf-2/HO-1 signaling pathway, and increased the expression of related to tight junction proteins to increase the integrity of the intestinal barrier. In addition, 16S rDNA sequencing results indicated that (R)-BMB regulated the structure of the intestinal microbiome and relieved imbalances in this microbiome, and non-targeted metabolomics analysis revealed that (R)-BMB reversed the metabolic changes in mice with colitis fed a high-fat diet. In summary, these results indicate that (R)-BMB can serve as a novel alternative strategy for treating colitis in the context of high-fat diet consumption.}, } @article {pmid41534752, year = {2026}, author = {van der Merwe, L and Bester, M and Serem, J and Apostolides, Z}, title = {Alleviation of adverse effects associated with α-glucosidase inhibitors by Ocimum basilicum L., Matricaria chamomilla L., and Salvia officinalis L. reveals novel selective inhibition of Bacillus α-glucosidase by acarbose.}, journal = {Journal of ethnopharmacology}, volume = {360}, number = {}, pages = {121182}, doi = {10.1016/j.jep.2026.121182}, pmid = {41534752}, issn = {1872-7573}, abstract = {Ocimum basilicum L., Matricaria chamomilla L., and Salvia officinalis L. have literature-supported ethnobotanical claims of reducing hyperglycaemia and gastrointestinal discomfort. Thus, they contain potent potential for reducing gastrointestinal adverse side effects associated with the use of the type 2 diabetes medication, acarbose. The adverse effects are predominantly theorised to be caused by excess carbohydrate fermentation by gut bacteria. Therefore, the aim of this study was to subject herbal extracts as well as compounds identified in the herbs to in silico and in vitro investigation for selective inhibition of a gut bacterial enzyme, Bacillus α-glucosidase, compared with human α-glucosidase. In silico molecular docking was employed to filter and select top performing compounds that exhibited the highest selective Bacillus α-glucosidase inhibition, followed by pharmacokinetic examination of the selected compounds. In vitro enzyme kinetics, hepatocellular carcinoma cell line cytotoxicity and the reduction of hepatic lipid accumulation in a hepatocellular carcinoma/oleic acid cellular model of metabolic dysfunction-associated fatty liver disease was examined. A metabolomic study on the concentration of the selected compounds in the herbs as well as a comparative analysis on abundant metabolites between herbs were analysed through an ultra-performance liquid chromatography-mass spectrometry-based study. Molecular docking revealed cinnamic acid, coumaric acid, epicatechin, hesperetin, linalool, menthol, octenol, terpineol, umbelliferone, and vanillic acid as the top predicted compounds with the highest predicted selective inhibition of Bacillus α-glucosidase. These findings were validated through in vitro assessment, in which the primary finding and the most unexpected result was obtained through enzyme kinetics, where compared with all compounds, acarbose exhibited the most potent inhibition and selectivity towards Bacillus α-glucosidase. Only umbelliferone significantly reduced cell viability and therefore validated its predicted toxicity that was obtained through pharmacokinetic studies. O. basilicum, M. chamomilla, and S. officinalis were evaluated against Camellia sinensis (L.) Kuntze for cytotoxic effects, where only M. chamomilla produced a significantly higher EC50, substantiating the herbs potent anti-cancerous abilities. Compounds and herb extracts were not found to reduce hepatic lipid accumulation. The novel finding was related to acarbose inhibition and specifically its potent selectivity of Bacillus α-glucosidase which discredits and disproves the theory that excess bacterial fermentation is the cause behind acarbose's reported adverse effects. Thus, this research study rather proves that acarbose negatively affects gut bacterial enzymes, promoting microbiome dysbiosis and therefore future research should at the forefront focus on the rehabilitation of diabetic patients' gut microbiome and intestinal health.}, } @article {pmid41534698, year = {2026}, author = {Baldi, S and Bertorello, S and Cei, F and Iurato La Rocca, A and Scianaro, V and Bartolucci, G and Mannaioni, G and Amedei, A and Gerace, E}, title = {Gender-Specific Gut Microbiota Alterations in Adolescent C57BL/6 Mice Following Prenatal Alcohol Exposure.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {115929}, doi = {10.1016/j.fct.2026.115929}, pmid = {41534698}, issn = {1873-6351}, abstract = {Fetal Alcohol Spectrum Disorder (FASD), caused by prenatal alcohol exposure (PAE), produces lasting physical, cognitive, and behavioral impairments. The present study examined effects of early PAE on the gut microbiome (GM) in adolescent mice to identify targets for early intervention. Female C57Bl/6 dams received 10% ethanol during the first 10 days of gestation while controls received water. Fecal and blood samples from adolescent offspring were profiled by 16S rRNA sequencing and gas chromatography-mass spectrometry to characterize microbial composition and short-chain fatty acids (SCFAs). PAE reduced microbial alpha diversity and produced distinct beta diversity patterns versus controls. Metabolomic profiling revealed increased fecal acetate and reduced anti-inflammatory SCFAs in PAE mice, though circulating SCFA levels remained unchanged. Sex-stratified analyses showed that these alterations were driven predominantly by males, who exhibited greater microbial and metabolic disruptions, enrichment of pro-inflammatory genera (Parasutterella, Parabacteroides, Clostridioides), and elevated serum medium-chain fatty acids. Cluster analysis of PAE males identified a dysbiotic subgroup with severe alpha diversity loss, increased pro-inflammatory taxa, diminished beneficial SCFAs, and enrichment of catabolic and fatty acid biosynthesis pathways. Together, the results reveal sex- and individual-specific susceptibility to PAE-induced GM dysbiosis and justify further mechanistic studies to develop sex-tailored microbiota-targeted strategies for FASD.}, } @article {pmid41534598, year = {2026}, author = {Irfan, Z and Halder, J and Giri, S and Molla, EA and Khanam, S}, title = {Therapeutic potential of prebiotics in modulating postprandial GLP-1, GLP-2, and glucose homeostasis in type 2 diabetes mellitus: Targeting gut dysbiosis and insulin resistance.}, journal = {Diabetes research and clinical practice}, volume = {}, number = {}, pages = {113102}, doi = {10.1016/j.diabres.2026.113102}, pmid = {41534598}, issn = {1872-8227}, abstract = {Type 2 diabetes mellitus is associated with gut dysbiosis, decreased microbial diversity, short-chain fatty acid synthesis, and altered GLP secretion, which are crucial for intestinal integrity, insulin sensitivity, and postprandial glucose control. Evidence from peer-reviewed mechanistic studies, observational research, clinical trials, and meta-analyses was summarised in this review. Prebiotics, an emerging potential treatment, increase the formation of SCFA during fermentation, thereby enhancing the release of GLP through FFAR2/3 signalling. This chain of events enhances glucose-dependent insulin production, inhibits glucagon secretion, delays stomach emptying, strengthens the intestinal barrier, and reduces inflammation throughout the body. Human trials demonstrate statistically significant but clinically modest improvements in HbA1c, postprandial glucose fluctuations, and an increased response to incretin-based treatments, with meta-analytic evidence reporting decreased fasting glucose and HbA1c levels. Prebiotics effect on incretin hormones in humans appears to be diverse, depending on the type, dose, duration, and baseline microbiota composition. Resistant starch and inulin-type fructans have the most consistent effects for lowering postprandial glucose. Prebiotics are viable supplementary therapy for improving glycaemic management by regulating the gut microbiota-SCFA-incretin axis. While the molecular evidence is substantial, clinical effects are moderate and diverse. Long-term microbiome-specific trials are required to understand therapeutic potential and optimise tailored therapies fully.}, } @article {pmid41534526, year = {2026}, author = {Jalkanen, J and Zhong, J and Nono Nankam, PA and Bhalla, N and Elmastas, M and Luo, J and Weinbrenner, S and Frendo-Cumbo, S and Pesti, B and Gourash, W and Courcoulas, A and Yang Loureiro, Z and Dietrich, A and Bäckdahl, J and Thorell, A and Buggert, M and Kalucka, J and Emont, MP and Rosen, ED and Blüher, M and Kovacs, P and Ståhl, PL and Massier, L and Rydén, M and Mejhert, N}, title = {Cytoarchitectural multi-depot profiling reveals immune-metabolic crosstalk in human colon-associated adipose tissue.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.12.008}, pmid = {41534526}, issn = {1932-7420}, abstract = {While it is well established that the cellular composition of white adipose tissue (WAT) varies between depots, the functional relevance of this heterogeneity remains unclear. By combining spatial and single-nucleus RNA sequencing, we provide a comprehensive map of subcutaneous and visceral (omental, mesenteric, mesocolic, and epiploic) WAT in both men and women. Our analyses reveal shared features, such as the spatial organization of adipogenesis, alongside depot-specific characteristics, including distinct cell-type enrichments and unique cell-cell communication routes. Epiploic WAT stands out by harboring high proportions of serum amyloid A expressing fat cells (encoded by SAA1/SAA2) and several leukocyte populations. Through mechanistic studies, we demonstrate that adipocyte SAA1/SAA2 expression is induced by inflammatory signals, including lipopolysaccharide, and that SAA1 activates immune responses in adipose-resident myeloid cells. Collectively, our findings suggest that visceral WAT exhibits distinct cytoarchitectural properties, with those located near the colon adapting by developing specialized adipocytes and immune cell populations.}, } @article {pmid41534266, year = {2026}, author = {Yang, SB and Kwack, KH and Lee, JH and Moon, JH}, title = {Oral live microbial therapeutics: A synthetic biology roadmap toward durable oral microbiome-based therapies.}, journal = {Archives of oral biology}, volume = {183}, number = {}, pages = {106515}, doi = {10.1016/j.archoralbio.2026.106515}, pmid = {41534266}, issn = {1879-1506}, abstract = {OBJECTIVES: Oral live microbial therapeutics (LMTs) show promise for halitosis, caries, and adjunctive periodontal care, yet benefits often fade after dosing stops. We synthesized evidence across indications and reframed development around quantifying and engineering persistence at intraoral sites, while outlining safety-by-design and delivery considerations for the oral niche.

DESIGN: This narrative review integrated randomized trials, observational studies, and in vitro/ex vivo investigations to characterize clinical outcomes, persistence-related metrics, and engineering principles relevant to oral LMT development. Sources included PubMed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, with backward/forward citation tracking. We included studies on LMTs in oral or gut contexts when mechanistically informative for oral applications (e.g., persistence, delivery, or biocontainment). Eligibility required clinical outcomes or persistence-related readouts. Two reviewers screened records and resolved disagreements by consensus. Reporting and assay principles were informed by STORMS and MIQE to support transparent, reproducible methods.

RESULTS: Across indications, effects typically peak during dosing and attenuate after cessation, varying with strain, delivery format, and co-interventions (e.g., tongue dorsum debridement; standardized periodontal care). Persistence is rarely co-measured with clinical endpoints, limiting mechanistic interpretation. We outline a site-resolved measurement set, including time above the limit-of-detection, colonization area under the curve, apparent half-life (t½), and t½ under oral-mimetic shear, together with an engineering toolkit combining mucoadhesive/enamel-interactive carriers, single-cell coatings, and multilayer biocontainment (e.g., logic-gated/CRISPR kill switches, synthetic auxotrophy), and chemistry, manufacturing, and controls considerations.

CONCLUSIONS: Embedding persistence metrics and safety-by-design into study protocols may support more durable outcomes, and standardized, site-resolved reporting will be essential for clinical translation.}, } @article {pmid41534185, year = {2026}, author = {de Torres, CS and Elias, E and Vaghi, C and González, NS and García, A and Alcaraz, A and Rodríguez-Castells, M and Baraibar, I and Ros, J and Salvà, F and Tabernero, J and Élez, E and Sanz-Garcia, E}, title = {Exploring resistance to immune checkpoints inhibitors in mismatch repair-deficient or microsatellite-instable colorectal cancer.}, journal = {Cancer treatment reviews}, volume = {143}, number = {}, pages = {103089}, doi = {10.1016/j.ctrv.2026.103089}, pmid = {41534185}, issn = {1532-1967}, abstract = {Colorectal cancer (CRC) with mismatch-repair deficiency (dMMR) or high microsatellite instability (MSI-H) represents a distinct molecular subtype highly sensitive to immune checkpoint inhibitors (ICIs). Landmark clinical trials have established ICIs as standard-of-care in this setting, demonstrating durable responses and improved survival. However, up to one-third of patients will exhibit primary or acquired resistance, highlighting the urgent need for predictive biomarkers and novel therapeutic strategies. This review summarizes the clinical evidence supporting ICIs in dMMR/MSI-H CRC, explores mechanisms of resistance-including intrinsic and extrinsic modulators-and evaluates the role of potential predictive biomarkers of response. Finally, we discuss innovative therapeutic approaches to overcome resistance, including combination strategies, DNA repair pathway inhibitors, immune-oncology drugs beyond checkpoint inhibitors and microbiome-targeted interventions. Together, these insights aim to refine patient selection, optimize therapeutic benefit, and guide the development of next-generation therapies for dMMR/MSI-H CRC.}, } @article {pmid41534145, year = {2026}, author = {Das, M and Rath, S and Gorepatti, R and Dash, R and Akella, A and Gaur, AS and Venugopal, G and Khan, ZH and Ramadass, B and Nayak, P}, title = {Microbiome-linked transcriptomic signatures in NMIBC: Toward personalized uro-oncology.}, journal = {Urologic oncology}, volume = {44}, number = {3}, pages = {110977}, doi = {10.1016/j.urolonc.2025.12.013}, pmid = {41534145}, issn = {1873-2496}, abstract = {BACKGROUND: Nonmuscle Invasive Bladder Cancer (NMIBC) is a prevalent malignancy marked by high recurrence and progression rates. Emerging evidence suggests that demographic and environmental factors may alter the bladder's native oncobiome, influencing tumor behavior. This exploratory pilot study examined whether paired tumor and adjacent normal bladder mucosa exhibit distinct host transcriptomic and microbial signatures that may illuminate early tumor-microbiome interactions in NMIBC.

METHODS: A meta-transcriptomic analysis was conducted on paired tumor and adjacent normal bladder mucosa from 6 NMIBC patients. Shotgun RNA sequencing was used to profile differential gene expression and microbial composition. Functional annotation and correlation analyses were performed to explore gene-microbe interactions.

RESULTS: Fifty-seven differentially expressed genes (DEGs) across 6 patients and 12 paired samples were identified, including 45 downregulated and 12 upregulated genes, primarily involved in extracellular matrix organization and structural integrity. Tumor tissues exhibited significantly reduced microbial species richness compared to the adjacent normal mucosa (P = 0.026). Propionibacterium acnes showed increased abundance in tumor sites (23.88%) versus the adjacent normal mucosa (13%), suggesting a protumorigenic role. Veillonella dispar and Corynebacterium durum were strongly associated with matrix-regulating genes, while Bifidobacterium longum-more abundant in the adjacent normal tissues-correlated with genes linked to extracellular homeostasis, indicating a potential protective role.

CONCLUSION: This pilot study reveals distinct transcriptomic and microbial signatures in NMIBC, highlighting the role of microbial dysbiosis, which denotes an altered microbial community; reduced diversity and shifts in key taxa relative to the adjacent bladder mucosa, in extracellular matrix remodeling and tumor progression. These host-microbe interactions may contribute to disease pathogenesis and recurrence. Further studies are warranted to elucidate the underlying mechanisms and therapeutic implications.}, } @article {pmid41534121, year = {2026}, author = {Zalomova, LV and Fesenko, EE}, title = {Effectiveness of FBS-DMSO cryoprotectant composition in artificial microbiome models mimicking key gut microbiota enterotypes.}, journal = {Cryobiology}, volume = {122}, number = {}, pages = {105582}, doi = {10.1016/j.cryobiol.2026.105582}, pmid = {41534121}, issn = {1090-2392}, abstract = {The ratio of microorganisms in the composition of the microflora of the small and large intestines plays a crucial role in human health. Therefore, it is essential to preserve the original proportions of species over an extended period for their further therapeutic application. It has previously been established that three primary enterotypes dominate the human gut microbiota: Bacteroides, Prevotella, and Ruminococcus. However, there is no precise information on how their species ratios are affected by deep freezing. In our study, we examined the preservation of the ratios of microorganisms in the human gut before and after cryopreservation, represented as distinct clusters consisting of four different bacterial species dominant in the gut microbiome. Using photometric registration of optical density and fluorescent staining methods, we demonstrated that the viability of most bacteria remained high in the cryoprotective medium of 5 % Me2SO/FBS. Additionally, the calculation of the Pattern Comparison Index (PCI) showed good results in maintaining the community structure of bacteria in each of the artificial models. Thus, this modeling of microbiocenoses allows for the identification of patterns in the preservation of their quantitative composition during long-term storage in liquid nitrogen.}, } @article {pmid41533849, year = {2026}, author = {Su, T and Cai, W and Shen, T and Yu, D and Zhu, M and Liu, C and Yu, J}, title = {Comprehensive Analysis of the Conjunctival Sac Microbiome in Patients With Evaporative Dry Eye and Mixed Dry Eye.}, journal = {Translational vision science & technology}, volume = {15}, number = {1}, pages = {4}, pmid = {41533849}, issn = {2164-2591}, mesh = {Humans ; *Microbiota/genetics ; *Dry Eye Syndromes/microbiology ; Female ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; *Conjunctiva/microbiology ; Adult ; *Bacteria/genetics ; Aged ; DNA, Bacterial/genetics ; }, abstract = {PURPOSE: This study aimed to investigate the differences in the microbial community of the conjunctival sac (CS) between patients with evaporative dry eye (EDE) and patients with mixed dry eye (DE), then, to compare it with previously reported ocular surface microbial of healthy people.

METHODS: CS swabs were collected from 10 patients with EDE and 10 patients with mixed DE. Bacterial DNA from these swabs were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Alpha diversity analysis assessed the microbial community diversity, while beta diversity was evaluated. Bioinformatic analysis of relative abundances and the functional annotations were performed at the genus level.

RESULTS: Results indicated no significant difference in alpha diversity, but a significant difference in beta diversity was observed (P = 0.001). Notably, Ralstonia and Corynebacterium exhibited significant differences. At the species level, the colonization rates and abundances of bacteria, including Comamonas denitrificans, Raoultella planticola (R. planticola), Pseudomonas mosselii, and Pseudomonas aeruginosa were significantly different. Functional annotation revealed that disparities in the microbial composition from CS between the two groups were accompanied by differences in the expression levels of genes involved in carbohydrate metabolism and histidine kinases, which were elevated in the mixed DE group.

CONCLUSIONS: The microbial community structure of the EDE group was comparable to that of the mixed DE group. However, notable differences were observed in the relative abundance and colonization rate of certain specific microorganisms. These variations were associated with alterations in carbohydrate metabolism and histidine kinase expression.

TRANSLATIONAL RELEVANCE: Corynebacterium, and Ralstonia may play important roles in the pathogenesis of dry eye disease (DED).}, } @article {pmid41533724, year = {2026}, author = {Li, H and Jin, YT and Ye, DX and Liu, Q and Su, X and Zhang, HQ and Yang, H}, title = {Machine Learning-based Diagnostic Potential of Bipolar Disorder Using Gut Microbiota Signatures.}, journal = {IET systems biology}, volume = {20}, number = {1}, pages = {e70056}, doi = {10.1049/syb2.70056}, pmid = {41533724}, issn = {1751-8857}, support = {32270786//National Natural Science Foundation of China/ ; 62371403//National Natural Science Foundation of China/ ; 62402207//National Natural Science Foundation of China/ ; 2024D008//the Municipal Government of Quzhou/ ; }, mesh = {*Bipolar Disorder/diagnosis/microbiology ; *Gastrointestinal Microbiome ; *Machine Learning ; Humans ; RNA, Ribosomal, 16S/genetics ; Biomarkers ; Male ; Female ; Adult ; }, abstract = {Bipolar disorder (BD) is a chronic psychiatric illness associated with significant cognitive and social dysfunction, contributing substantially to the global disease burden. Recent evidence suggests that the gut microbiota may play a role in the pathophysiology of BD through the microbiota-gut-brain axis. To clarify this potential link and explore diagnostic applications, we investigated gut microbial alterations in BD and evaluated their predictive value using 16S rRNA sequencing and machine learning approaches. We first assessed microbial diversity and composition, revealing significantly reduced α-diversity and altered β-diversity in BD compared to healthy controls (HC), alongside weakened microbial co-occurrence network connectivity. Given these compositional differences, we systematically benchmarked 12 classification algorithms to discriminate BD from HC. Ensemble-based models, particularly the random forest (RF) classifier, achieved the best diagnostic performance. To further improve predictive accuracy, we compared multiple feature selection methods: RF feature importance ranking, independent t-tests and MaAsLin2 analysis, identifying 35 optimal microbial biomarkers based on RF. This feature set demonstrated excellent classification performance (AUC = 0.9316, AUPR = 0.9497). Furthermore, based on the taxonomic findings, we applied PICRUSt2 functional prediction using KEGG and MetaCyc annotations, which revealed marked alterations in pathways related to neurodegeneration, lipid metabolism and heme biosynthesis. Finally, to capture both compositional and functional aspects of microbial dysbiosis, we combined these functional features with the selected microbial biomarkers in an RF model, achieving further improved diagnostic performance (AUC = 0.9499, AUPR = 0.9586). In conclusion, our results demonstrate substantial compositional and functional disturbances in the gut microbiota of BD and highlight the value of machine learning-driven, microbiome-based models for noninvasive BD diagnosis. The identified microbial and metabolic markers also provide mechanistic insights into the microbiota-gut-brain axis, offering promising directions for precision psychiatry and microbiome-targeted interventions.}, } @article {pmid41533698, year = {2026}, author = {Vargas-Robles, D and Yap, YR and Singha, B and Tien, J and Purandare, M and Rojas-Correa, M and Madziar, C and Picker, M and Dumont, T and Leftwich, HK and Frisard, CF and Ward, DV and Peter, I and Olendzki, B and Maldonado-Contreras, A}, title = {Association of vaginal IL-4, IL-6, IL-8, IL-17, IFN-γ, and dietary intake with IBD status and vaginal microbiota in pregnant individuals.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0335178}, pmid = {41533698}, issn = {1932-6203}, mesh = {Humans ; Female ; Pregnancy ; *Vagina/microbiology/metabolism ; Adult ; *Inflammatory Bowel Diseases/microbiology/metabolism ; *Microbiota ; Interferon-gamma/metabolism ; Diet ; Interleukin-6/metabolism ; Interleukin-4/metabolism ; Interleukin-17/metabolism ; Interleukin-8/metabolism ; *Cytokines/metabolism ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {BACKGROUND: Pregnant individuals with inflammatory bowel diseases (IBD) exhibit gut inflammation and dysbiosis; however, there is limited knowledge about their vaginal environment. This is important as vaginal inflammation and high vaginal microbiota diversity are associated with adverse pregnancy outcomes.

OBJECTIVES: We aimed to compare vaginal inflammatory markers and microbiota diversity of pregnant individuals with and without IBD in their third trimester of pregnancy and determine the role of diet in the vaginal microbiota diversity.

METHODS: We recruited pregnant individuals who provided vaginal swabs at 27-29 weeks of pregnancy. We characterized the vaginal microbiota by sequencing the V3-V4 region of the 16S rRNA and surveyed nine key pro and anti-inflammatory cytokines by qRT-PCR from the vaginal mucosa. Participants completed three validated interviewer-led nutrition assessments of 24-hour dietary intake around the same time as the collection of vaginal samples. The nutritional assessments were used to estimate dietary quality using the validated Healthy Eating Index (HEI-2015).

RESULTS: The cohort included 23 pregnant individuals with IBD (18 with Crohn's disease and 5 with ulcerative colitis) and 25 healthy controls (HC); 56.5% of the IBD cases were in remission. Vaginal microbiota diversity and composition did not differ significantly between individuals with IBD and HC. However, the vaginal mucosa of the IBD individuals showed increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) and decreased expression of Th1 (IFN-γ) and Th2 (IL-4) compared to HC. Expression of IL-6 and TNF- α correlated positively with vaginal microbial diversity. The beneficial Lactobacillus crispatus dominated the vaginal microbiota of individuals with either high dietary quality or those consuming more vegetables or low added sugar, regardless of IBD status. In IBD cases, consumption of vegetables and added sugars were associated with reduced expression of the pro-inflammatory IFN-γ and an increased expression of anti-inflammatory IL-4.

CONCLUSION: The vaginal microbiome did not differ between individuals with IBD and HC; however, IBD cases exhibit a pro-inflammatory tone in the vagina (high IL-6) that is associated with higher vaginal microbial diversity. Regardless of IBD status, healthier diets are positively associated with an increased abundance of the beneficial L. crispatus in the vagina.}, } @article {pmid41533261, year = {2026}, author = {Aron, S and Meagher, M and Azari, S and Baker, B and Nasseri, R and Bagrodia, A and Stewart, T and Liss, M and Salmasi, A}, title = {Beyond Sterility: the Urinary Microbiome in Bladder Cancer Carcinogenesis and Treatment.}, journal = {Current urology reports}, volume = {27}, number = {1}, pages = {8}, pmid = {41533261}, issn = {1534-6285}, mesh = {Humans ; *Urinary Bladder Neoplasms/microbiology/therapy ; *Microbiota ; *Carcinogenesis ; }, abstract = {PURPOSE OF REVIEW: Emerging evidence has challenged the paradigm of bladder sterility, opening new opportunities for understanding bladder cancer biology.

RECENT FINDINGS: Disruption of commensal intravesical bacterial communities appears to increase risk of carcinogenesis, while the presence of specific bacterial strains has been linked to differential treatment responses. However, the interplay between urinary microbiome and bladder cancer remains incompletely defined. This review summarizes the current literature regarding the role of urinary microbiome in the pathogenesis and treatment outcomes, highlights limitations of existing studies, and outlines future directions for incorporating microbiome profiling into personalized management strategies.}, } @article {pmid41532953, year = {2026}, author = {Maggo, J and Ng, HM and Bayer, SB and Wall, CL and Hoad, CL and Marciani, L and Mullaney, J and Cabrera, D and Fraser, K and Cooney, JM and Günther, CS and Trower, T and Tang, J and Gasser, O and Milan, A and McNabb, WC and Spiller, R and Conner, T and Frampton, C and Foster, M and Roy, NC and Gearry, RB}, title = {Normalization of Gastrointestinal Symptoms in Adults With Constipation With Daily Green Kiwifruit Consumption: Protocol for an Open-Label Intervention Study.}, journal = {JMIR research protocols}, volume = {15}, number = {}, pages = {e75286}, pmid = {41532953}, issn = {1929-0748}, mesh = {Humans ; *Actinidia ; *Constipation/diet therapy ; Adult ; *Irritable Bowel Syndrome/diet therapy/complications ; Female ; Male ; *Fruit ; Middle Aged ; Abdominal Pain/diet therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC) have significant personal, health care, and social impacts, affecting patients' quality of life. Treatment of these conditions is challenging. While green kiwifruit is a promising natural alternative to laxatives, its effectiveness in managing abdominal pain and the underlying mechanism of action is yet to be substantiated.

OBJECTIVE: This study investigates the effect of consuming 2 green kiwifruit daily for 4 weeks (the habitual serving) on abdominal pain and discomfort in individuals with IBS-C and FC.

METHODS: This study is a 2-arm parallel, open-label, placebo-controlled randomized study. This study's duration was 9 weeks, with a 3-week lead-in phase, a 4-week intervention phase, and a 2-week follow-up phase. A total of 60 participants with IBS-C and FC were randomized to consume either 2 Zespri green kiwifruit (Actinidia deliciosa "Hayward," ~150 g per serving, ~90 kcal) or maltodextrin (calorie-matched to the fruit, ~25 g per serving, ~90 kcal) per day for 4 weeks. The participants completed validated questionnaires assessing digestive and general health and well-being parameters, underwent magnetic resonance imaging to determine colon physiological measures, ingested a blue food dye, provided blood and fecal samples to measure microbial, immunological, and biochemical parameters, and ingested wireless motility devices (selected participants only) to assess physiological processes.

RESULTS: Recruitment for this study began in May 2021 and was completed in May 2022. A total of 63 participants were randomized, and 57 were analyzed using intention-to-treat analysis. Data analysis is complete, and full results are expected to be published in a peer-reviewed journal by April 2026.

CONCLUSIONS: This study aims to evaluate the effectiveness of green kiwifruit consumption in managing abdominal pain in individuals with IBS-C and FC. It will provide new insights into the mechanisms behind the habitual consumption of green kiwifruit for digestive comfort in this population.}, } @article {pmid41532887, year = {2026}, author = {Liao, Z and Parumasivam, T and Xiao, Z and Zhu, X and Yeoh, YK and Ye, X and Tan, TC}, title = {Emerging therapeutic and cosmeceutical applications of phenylalanine and its metabolites.}, journal = {Cutaneous and ocular toxicology}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/15569527.2026.2612999}, pmid = {41532887}, issn = {1556-9535}, abstract = {OBJECTIVE: This review aims to comprehensively examine and integrate the extant knowledge pertaining to phenylalanine (Phe) and its key metabolites, namely tyrosine (Tyr), phenylpyruvic acid (PPA), phenyllactic acid (PLA), and phenylacetic acid (PAA). The primary focus of this review will be on the emerging pharmacological and cosmetic applications of these metabolites.

RATIONALE: Phe-derived compounds have garnered increasing attention due to their diverse pharmacological effects, including antioxidant, antimicrobial, anti-inflammatory, and neuromodulatory properties. Their relevance to skin health, pigmentation regulation, microbiome modulation, and mood-related dermatoses provides a compelling basis for reviewing their functional potential in both therapeutic and cosmetic contexts.

METHODS: A systematic literature review was conducted using PubMed, Web of Science, and Scopus up to 2025. The review was guided by predefined keywords related to Phe and its metabolites. The inclusion criteria were tailored to encompass experimental, clinical, and translational studies that explore pharmacological or cosmetic applications of Phe.

MAIN FINDINGS: The review presents compelling evidence substantiating the bioactivity of Phe and its metabolites across multiple skin-related pathways. These compounds exhibit promising efficacy in preserving skin homeostasis, regulating pigmentation, harmonizing cutaneous microbiota, and mitigating psychosomatic skin conditions. Their structural and functional diversity renders them versatile agents with extensive translational potential.

CONCLUSIONS AND IMPLICATIONS: The multifunctional nature of Phe-derived compounds presents substantial potential for incorporation into advanced skincare and pharmaceutical formulations. However, limitations persist in safety and toxicological data, particularly concerning prolonged human exposure. Future research should prioritize (i) mechanistic elucidation of biological effects, (ii) standardized toxicological and clinical validation, and (iii) formulation optimization to facilitate safe and effective applications. These endeavors have the potential to bridge the gap between biochemical research and practical innovation, thereby fostering novel solutions for skin health and emotional well-being.}, } @article {pmid41532678, year = {2026}, author = {Le Dréan, ME and Ganachaud, B and Rebion, M and Marchix, J and Le Berre-Scoul, C and Hulin, P and Feyeux, M and Talon, S and Neunlist, M and Caillaud, M and Boudin, H}, title = {The Microbiota-Derived Metabolite Deoxycholic Acid Regulates Enteric Neuron Activity and Connectivity.}, journal = {Journal of neurochemistry}, volume = {170}, number = {1}, pages = {e70351}, doi = {10.1111/jnc.70351}, pmid = {41532678}, issn = {1471-4159}, support = {R20056NN//Conseil Régional des Pays de la Loire/ ; R23066NN//Conseil Régional des Pays de la Loire/ ; //Fondation SantéDige/ ; //Ministère de l'enseignement supérieur, de la recherche et de l'espace/ ; ANR-10-INBS-04//Agence Nationale de la Recherche/ ; ANR-22-CE14-0043//Agence Nationale de la Recherche/ ; }, mesh = {Animals ; *Neurons/drug effects/metabolism/physiology ; *Enteric Nervous System/drug effects/metabolism ; Rats ; *Deoxycholic Acid/pharmacology/metabolism ; *Gastrointestinal Microbiome/physiology ; Cells, Cultured ; Receptors, G-Protein-Coupled/metabolism ; Rats, Sprague-Dawley ; }, abstract = {Secondary bile acids (BAs) are metabolites produced by the gut microbiota and shown to impact digestive functions, at least in part through the enteric nervous system (ENS). In the ENS, enteric neurons express the BA receptor Takeda G protein-coupled receptor 5 (TGR5), making them potential direct cellular targets of secondary BAs, although their effects on enteric neuronal functions remain poorly understood. Enteric neuronal activity and connectivity form the basis of the regulatory control exerted by the ENS on gut functions. Yet, the influence of microbiota-derived metabolites, such as secondary BAs, on enteric neuron connectivity and synaptic activity remains largely unexplored. To address this question, we studied the effects of secondary BAs on neuronal connectivity using a model of rat primary culture of enteric neurons. We found that exposure to deoxycholic acid (DCA) increased the expression of key presynaptic proteins, synapsin-1 and synaptophysin, and enhanced synaptic density in enteric neurons. Moreover, DCA enhanced synaptic activity by increasing synaptic vesicle exocytosis upon KCl depolarisation, potentially through amplified phosphorylation of synapsin-1 at the Ser62-67 sites. In addition, we found that DCA modulated the intracellular Ca[2+] response induced by acetylcholine, a major excitatory neurotransmitter in enteric neurons, through a mechanism mediated by the TGR5 receptor. Overall, this study identifies DCA as a microbiota-derived compound capable of reshaping the enteric neuronal functional network. These findings highlight the potential of bacterial metabolites like DCA to link the microbiome with modulation of enteric neuronal activity and connectivity, supporting the relevance of secondary BAs in digestive physiology and their possible roles in gastrointestinal disorders.}, } @article {pmid41532647, year = {2026}, author = {Cuozzo, M and O'Connor, C and Power, E and Gleeson, E and O'Mahony, S}, title = {Gut-Brain Communication in Menopause: Insights into Neuroendocrine and Microbiome Interactions.}, journal = {The Proceedings of the Nutrition Society}, volume = {}, number = {}, pages = {1-35}, doi = {10.1017/S0029665126102201}, pmid = {41532647}, issn = {1475-2719}, abstract = {This review synthesizes current evidence linking alterations in the gut microbiome to menopausal transition. The gut microbiota plays a crucial role in numerous physiological processes, particularly due to its bidirectional communication with the brain via multiple neural, endocrine, and immune pathways. Menopause-associated oestrogen decline disrupts this axis, influencing not only gastrointestinal function and microbial diversity but also mood, cognition, and inflammation.The estrobolome is a community of gut bacteria capable of modulating circulating estrogen levels. Taken together, research suggests a complex dynamic interplay between the intestinal microbiota and sex hormones, potentially contributing to menopausal symptoms and related comorbidities.Understanding these interactions offers promising avenues for intervention, as dietary strategies (such as isoflavones), lifestyle modifications, and targeted probiotic and prebiotic therapies may help restore balance within the gut-brain axis and optimize brain health by influencing neurotransmitter synthesis, stress responses, and hormonal regulation during and after the menopausal transition.Here, we highlight the importance of an integrative, microbiome-informed approach to midlife women's health, emphasizing innovative, non-pharmacological strategies to promote long-term well-being in women.}, } @article {pmid41532636, year = {2026}, author = {Jangra, M and Travin, DY and Kaur, M and Hackenberger, D and Koteva, K and Polikanov, YS and Wright, GD}, title = {An Acetyltransferase Conferring Self-Resistance of the Producer to Lasso Peptide Antibiotic Lariocidin.}, journal = {ACS infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsinfecdis.5c00885}, pmid = {41532636}, issn = {2373-8227}, abstract = {The soil microbiome, a reservoir of antibiotic-producing bacteria, also harbors resistance determinants encoded within antibiotic biosynthetic gene clusters (BGCs). Studying self-resistance mechanisms, which have evolved in producers to protect against their own toxic metabolites, provides critical insights into the evolution of resistance and the potential vulnerabilities of new antibiotics and can facilitate the production of natural products in heterologous hosts. Here, we describe the self-resistance mechanism to lariocidin (LAR), a recently discovered lasso peptide antibiotic that inhibits the ribosomal machinery and exhibits antibacterial activity against key pathogens. We identified and characterized an N-acetyltransferase enzyme (LrcE) encoded within the LAR BGC that mediates self-resistance in LAR-producing Paenibacillus sp. M2. LrcE is a member of the GCN5-related N-acetyltransferase (GNAT) superfamily and performs site-specific acetylation of LAR at a critical lysine residue. This modification disrupts ribosomal binding, thereby reducing LAR's antibacterial activity. Using in silico modeling, we predicted a conserved acetyl-CoA-binding motif and an LAR-binding region on LrcE. Bioinformatic analysis revealed LrcE homologues in environmental but not clinically relevant pathogens, suggesting a limited risk of horizontal gene transfer and, therefore, supporting the further development of LAR as a next-generation antibiotic.}, } @article {pmid41532519, year = {2026}, author = {Zhu, M and Huang, K and Wang, X and Yang, F and Ni, K}, title = {Enhanced Nitrogen Use Efficiency and Reshaped Phyllosphere Microbiome through Biochar Application and Nitrogen Fertilizer Reduction.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c10538}, pmid = {41532519}, issn = {1520-5118}, abstract = {Paper mulberry (Broussonetia papyrifera), a high-protein forage species, exhibits low nitrogen use efficiency (NUE) under conventional nitrogen fertilization. This study conducted a field experiment to systematically evaluate the effects of coapplying biochar with reduced nitrogen fertilizer on paper mulberry by integrating plant physiological measurements, soil property analysis, and phyllosphere microbiome profile. Results demonstrated that moderate biochar addition significantly enhanced plant growth, forage quality, and soil health, while improving NUE. Notably, coapplying biochar with a 15% reduced nitrogen emerged as a sustainable fertilization strategy, reducing nitrogen inputs without compromising plant performance. 16S rRNA gene sequencing revealed that biochar treatment reshaped the phyllosphere microbiome by increasing diazotroph abundance, suppressing pathogens, and enhancing microbial network complexity. Overall, this study demonstrates that coapplying biochar with 15% reduced nitrogen not only improves NUE, but also enhances plant performance and soil properties, while reshaping the phyllosphere microbiome into a more plant-beneficial community.}, } @article {pmid41532472, year = {2026}, author = {Lim, S and Kim, SH and Jeong, HJ and Park, S and Koo, BK and Lee, JH and Shin, W}, title = {Gastric cancer organoids and their convergence in engineering approaches.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.70272}, pmid = {41532472}, issn = {1873-3468}, support = {RS-2023-00221122//National Research Foundation of Korea/ ; RS-2024-00414004//National Research Foundation of Korea/ ; RS-2025-23022973//National Research Foundation of Korea/ ; IBS-R021-D1//Institute for Basic Science/ ; }, abstract = {Gastric cancer research has rapidly progressed due to interdisciplinary advances in stem cell biology and bioengineering. Gastric organoid models, particularly those derived from adult stem cells, have emerged as powerful tools that recapitulate the cellular complexity of the human stomach. This review highlights the development of various gastric organoid platforms, with a specific focus on the convergence of engineering strategies to overcome the limitations of conventional organoid systems. We explore how CRISPR-based functional genomics, matrix innovations, co-culture systems, microphysiological systems (MPS), and big data integration are collectively enhancing organoid models. Furthermore, we examine how artificial intelligence may refine the clinical relevance and precision of gastric organoid models. By assessing both current capabilities and future directions, this review offers a perspective on how gastric organoid systems may reflect human physiology more accurately and improve therapeutic outcomes.}, } @article {pmid41532467, year = {2026}, author = {Ruan, C and Zheng, X and Wang, L}, title = {Letter to the Editor: integrating oral microbiome biomarkers into global disease burden assessments to enhance early-onset type 2 diabetes prevention strategies.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000004750}, pmid = {41532467}, issn = {1743-9159}, } @article {pmid41532465, year = {2026}, author = {Ferri, A and Schneider, E and Lucey, A and Hennessy, Á and Cotter, PD and Balasubramanian, R and Clarke, G and Cryan, JF}, title = {Development and Validation of a Food Frequency Questionnaire to Assess Fermented Food Consumption in Adults.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {39}, number = {1}, pages = {e70183}, pmid = {41532465}, issn = {1365-277X}, support = {SFI/12/RC/2273_P2//Science Foundation Ireland grant to APC Microbiome Ireland through the Irish Government's National Development Plan/ ; }, mesh = {Humans ; Adult ; Male ; Middle Aged ; Female ; *Fermented Foods/statistics & numerical data ; Young Adult ; Surveys and Questionnaires/standards ; Reproducibility of Results ; Adolescent ; *Diet/statistics & numerical data ; United Kingdom ; *Diet Surveys/methods/standards ; Ireland ; Australia ; *Feeding Behavior ; New Zealand ; United States ; Canada ; }, abstract = {BACKGROUND: Fermented foods can confer benefits to human health and modulate the microbiota-gut-brain axis. Fermented foods are gaining popularity in Western cultures, with increasing calls for their inclusion in national dietary guidelines. As no specific validated measure to capture fermented food intake exists, this study aimed to develop and validate a fermented food intake questionnaire (FFIQ) to assess habitual intake in adults from the United States, Canada, the United Kingdom, Ireland, Australia and New Zealand, aged 18-60 years.

METHODS: A 32-item self-administered FFIQ, informed by available international food consumption data for adults, was developed and subsequently validated in an online sample of 167 adults using six online 24-h automated dietary recalls (intake24.com) as the reference method. Correlation and Bland-Altman analyses were used to assess agreement and bias between the FFIQ and the 24-h dietary recalls.

RESULTS: The most frequently consumed fermented foods were cheeses, yoghurt, kefir and kombucha. Median (Interquartile range) intake of total fermented food was 85.4 (42.3, 143.0) g/day for the FFIQ and 54.9 (20.8, 112.1) g/day for the average of the 24-h dietary recalls, respectively and showed good agreement for total fermented food consumption (r = 0.56, p < 0.001) and for most individual fermented foods and food categories. The FFIQ classified 93.4% of participants in the same or adjacent tertile of total fermented food intake. Bland-Altman plots for total intake of fermented food demonstrated good agreement between the FFIQ and the 24 h recalls. The FFIQ also showed good to excellent reliability upon re-administration for most fermented foods as indicated by the intraclass correlation coefficients.

CONCLUSIONS: The FFIQ provides a robust estimate of fermented food consumption among adults from English-first language countries. This will be a valuable resource with potential applications in clinical and epidemiological research aimed at exploring associations between fermented foods and health outcomes.}, } @article {pmid41532096, year = {2025}, author = {Xie, L and Li, X and Liu, L and Zhao, J and Luo, L and Qiao, W and Chen, L}, title = {Oral administration of Lacticaseibacillus rhamnosus HM126 alleviates DNFB-induced atopic dermatitis in BALB/c mice by modulating immunity, gut microbiota, and metabolites.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1739967}, pmid = {41532096}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Dermatitis, Atopic/immunology/chemically induced/therapy/metabolism/microbiology ; *Lacticaseibacillus rhamnosus/immunology ; Administration, Oral ; *Probiotics/administration & dosage ; Mice ; Disease Models, Animal ; Mice, Inbred BALB C ; Cytokines/blood ; Female ; Feces/microbiology ; Metabolomics ; }, abstract = {INTRODUCTION: Probiotics have emerged as a promising and safe alternative therapy for atopic dermatitis (AD) by regulating the gut microbiota-immune axis, correcting type 1/type 2 imbalance, and repairing the skin barrier.

METHODS: A mouse model of AD was established using diphenylnitromethane (DNFB). Low, medium, and high doses of human milk-derived Lacticaseibacillus rhamnosus HM126 were administered to investigate its effects on the model. We observed the scratching frequency and skin lesion scores after 28 days of continuous oral administration. Serum biochemical indicators and inflammatory cytokines were measured using ELISA, whereas the gut microbiota in feces was analyzed using 16S rDNA sequencing. Non-targeted metabolomics was used to assess the changes in fecal metabolites.

RESULTS AND DISCUSSION: Compared to the DNFB group, high-dose L. rhamnosus HM126 significantly reduced scratching frequency in AD mice. The low-dose group showed significantly reduced IgE levels. Additionally, the IFN-γ/IL-4 ratio significantly increased, indicating that L. rhamnosus HM126 modulates type 1/type 2 immune factors toward equilibrium. 16S rDNA analysis revealed that L. rhamnosus HM126 significantly reduced the ACE index and Chao 1 index of the gut microbiota in mice with AD, thereby reshaping the composition of the gut microbiome. Metabolomics analysis suggested that L. rhamnosus HM126 may improve AD by influencing the levels of asiatic acid, phytosphingosine, Ser-Glu, prostaglandin F2 alpha ethylamide (PGF(2α)EA), argininosuccinic acid, L-rhamnose, and gamma-L-glutamyl-L-glutamic acid. This study demonstrated that L. rhamnosus HM126 maintains the type 1/type 2 balance and effectively modifies the gut microbiota structure and metabolic changes to improve AD. Our findings provide a scientific basis for the development of probiotic therapeutics to prevent and treat this condition.}, } @article {pmid41532068, year = {2026}, author = {Aghdam, R and Shan, S and Lankau, R and Solís-Lemus, C}, title = {A hybrid framework for disease biomarker discovery in microbiome research combining Bayesian networks, machine learning, and network-based methods.}, journal = {Biology methods & protocols}, volume = {11}, number = {1}, pages = {bpaf089}, pmid = {41532068}, issn = {2396-8923}, abstract = {Microbiome research faces two central challenges, namely constructing reliable networks, where nodes represent microbial taxa and edges represent their associations, and identifying significant disease-associated taxa. To address the first challenge, we developed CMIMN, a novel R package that applies a Bayesian network framework based on conditional mutual information to infer microbial interaction networks. To further enhance reliability, we construct a consensus microbiome network by integrating results from CMIMN and three widely used methods, including Sparse Inverse Covariance Estimation for Ecological Association Inference (SPIEC-EASI), Semi-Parametric Rank-based correlation and partial correlation Estimation (SPRING), and Sparse Correlations for Compositional Data (SPARCC). This consensus approach, which overlays and weights edges shared across methods, reduces inconsistencies and provides a more biologically meaningful view of microbial relationships. To address the second challenge, we designed a multi-method feature selection framework that combines machine learning with network-based strategies. Our machine learning pipeline applies distinct algorithms and identifies key taxa based on their consistent importance across models. Complementing this, we employ two network-based strategies that prioritize taxa based on centrality differences between networks constructed from healthy samples and disease-affected samples, as well as a composite scoring system that ranks nodes using integrated network metrics. We applied CMIMN on soil microbiome data from potato fields affected by common scab disease. Bootstrap analysis confirmed the robustness of CMIMN, and the consensus network further improved stability and interpretability. The multi-method framework enhances confidence in identifying soil microbial taxa associated with potato disease. Notably, we identified Bacteroidota, WPS-2, and Proteobacteria at the Phylum level; Actinobacteria, AD3, Bacilli, Anaerolineae, and Ktedonobacteria at the Class level; and C0119, Defluviicoccales, Bacteroidales, and Ktedonobacterales at the Order level as key taxa associated with disease status.}, } @article {pmid41531645, year = {2026}, author = {Fernandes, LA and de Souza, AO and Nukui, Y and Marcusso, RM and de Oliveira, ACP and Casseb, J and Clissa, PB and Villas-Boas, SG and Sanabani, SS}, title = {Gut Microbiome Dysbiosis is Associated With Human T-Lymphotropic Virus Type 1 (HTLV-1) Infection and Disease Progression to HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Cross-Sectional Study.}, journal = {Smart medicine}, volume = {5}, number = {1}, pages = {e70024}, pmid = {41531645}, issn = {2751-1871}, abstract = {Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease. Given the established role of the gut-brain axis in other neurological diseases such as multiple sclerosis, the role of the gut microbiome in the pathogenesis of HAM/TSP remains a critical unexplored area. The aim of this study was to characterize alterations in the gut microbiome associated with HTLV-1 infection and its clinical stages. We performed a cross-sectional analysis of the gut microbiome from 112 Brazilian individuals, including 24 healthy controls and 88 HTLV-1-infected individuals at different disease stages: 38 HAM patients, 17 patients with intermediate syndromes, and 33 asymptomatic carriers. Fecal samples were collected and analyzed using Illumina MiSeq sequencing to assess bacterial composition and diversity. Functional analysis was performed to identify differentially enriched gene categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) modules. Significant dysbiosis was observed in HTLV-1-infected individuals, characterized by reduced bacterial diversity, an inverted Firmicutes/Bacteroidetes ratio, and specific changes in bacterial genera. Notably, HAM patients exhibited decreased Faecalibacterium and increased Ruminococcus_g2 abundance. These associations should be interpreted with caution, as patient cohorts were significantly older and differed in sex distribution from healthy controls. Functional analysis revealed 13 differentially enriched gene categories and five KEGG modules that were more abundant in HAM patients, indicating alterations in metabolic processes. These findings provide the first comprehensive insight into gut microbiome changes associated with HTLV-1 infection and disease progression. This study provides the first comprehensive insight into gut microbiome changes associated with HTLV-1 infection and disease progression. The identified microbial signatures and functional alterations highlight potential diagnostic and therapeutic targets for HTLV-1-associated diseases, particularly HAM. These findings open new avenues for further research and clinical applications.}, } @article {pmid41436826, year = {2025}, author = {Biţă, A and Turcu-Ştiolică, A and Scorei, IR and Pisoschi, CG and Biţă, CE and Rău, G and Ciocîlteu, MV and Ştefănescu, S and Dincă, L and Neamţu, J and Rogoveanu, I and Mogoşanu, GD and Gheonea, DI}, title = {Targeting biological age with bioactive, microbiota-accessible nutritional complexes: a pilot study on healthspan extension in medically healthy adults.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1901}, pmid = {41436826}, issn = {2045-2322}, support = {The Article Processing Charges were funded by the University of Medicine and Pharmacy of Craiova, Romania.//Universitatea de Medicină şi Farmacie din Craiova/ ; }, abstract = {UNLABELLED: Microbiota-accessible nutritional complexes (MAC), a formulation comprising prebiotics, postbiotics, autophagy stimulators, senolytic activators, and natural probiotics, may influence systemic biomarkers and biological aging in healthy individuals. This pilot interventional study aimed to evaluate the effects of a 60-day MAC supplementation on serum biomarkers and biological age (BioAge) in medically healthy adults. Methods: Of 13 screened, 12 enrolled; 3 were excluded from the final analysis. Nine participants (five females, four males; mean age 61 ± 9.29 years) completed 60 days of daily MAC supplementation and were included in the analyses. Serum biomarkers were measured at baseline and post-intervention. BioAge was estimated using three machine-learning regressors: Support Vector Regression (SVR), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost). Feature importance analysis was conducted to identify key predictors of BioAge. Results: No adverse events occurred. A significant reduction in high-sensitivity C-reactive protein (hs-CRP) levels was observed from 2.66 ± 4.65 to 0.84 ± 0.54 mg/L (-69%; p = 0.009; Cohen’s d ≈ 0.55; post-mean 95% CI: 1.44 to 5.10), indicating decreased systemic inflammation. Lactate dehydrogenase (LDH) also declined significantly from 171.11 ± 21.32 to 159.44 ± 26.86 U/L (-6.8%; p = 0.038; Cohen’s d ≈ 0.22; post-mean 95% CI: 0.97 to 22.37). Other biomarkers, including gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and glucose, showed trends toward improvement without reaching statistical significance. Stratified analysis revealed that females experienced a significant reduction in hs-CRP (p = 0.043) and a mild increase in creatinine (p = 0.042), whereas males exhibited non-significant trends toward improved inflammatory and metabolic markers. AI modeling indicated a reduction in BioAge for several participants. The XGBoost model consistently captured moderate improvements (e.g., Participant 7: 3.3 years), while the RF model showed more variability. SVR did not detect significant changes. An independent empirical model confirmed a statistically significant reduction in BioAge post-intervention (p < 0.0001). Top predictors were low-density lipoprotein cholesterol (LDL-C), glucose, and total cholesterol (TC) as key predictors in the RF and SVR models, while ferritin and hs-CRP ranked highest in the XGBoost model. Conclusions: Sixty days of MAC was safe and associated with clinically relevant hs-CRP reductions and small LDH decreases, alongside AI-inferred BioAge improvements most stably detected by XGBoost. Limitations include small sample size (n = 9), single-arm design, 60-day duration, non-fasting sampling, and a multicomponent intervention that precludes mechanistic attribution, with no microbiome/postbiotic readouts. Larger randomized trials with microbiome/metabolomic profiling and pre-registered, externally validated AI pipelines are required to confirm causality. Trial registration: ISRCTN, ISRCTN85957759. Registered 04 February 2025, https://www.isrctn.com/ISRCTN85957759.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-31590-1.}, } @article {pmid41531549, year = {2026}, author = {Barnea, ER and Nazareth, A and Purandare, CN and Pinheiro-Borovac, A and Carluccio, RD and Purandare, NC and McAuliffe, FM and , }, title = {Optimizing Maternal Microbiome: Role in Improved Conception and Pregnancy Outcome.}, journal = {Reproductive medicine and biology}, volume = {25}, number = {1}, pages = {e70014}, doi = {10.1002/rmb2.70014}, pmid = {41531549}, issn = {1445-5781}, abstract = {PURPOSE: To evaluate the role of optimizing the maternal microbiome in improving pregnancy outcomes, focusing on preconception and early gestation, and to propose practical diagnostic and preventive strategies, particularly in low- and middle-income countries (LMIC).

METHODS: A comprehensive review of peer-reviewed literature was conducted, analyzing the impact of vaginal, endometrial, gastrointestinal, urinary, and oral microbiomes on fertility and pregnancy. Key factors included microbial dysbiosis, sexually transmitted infections (STIs), and lifestyle interventions. Diagnostic approaches (cultures, gene sequencing) and preventive measures (nutrition, probiotics, vaccinations) were assessed for efficacy in optimizing the microbiome.

RESULTS: An optimized microbiome, particularly with Lactobacillus crispatus dominance, enhances fertility and reduces pregnancy complications like miscarriage, preterm birth, and congenital infections. Dysbiosis, linked to obesity, antibiotic overuse, and poor nutrition, increases STI susceptibility and pregnancy risks. Preconception screening and targeted treatments (e.g., antibiotics for STIs, probiotics) improve outcomes. Nutritional interventions, including Mediterranean diets and supplements, support microbial health. LMIC face challenges due to limited access to care and nutrition, exacerbating adverse outcomes to be addressed.

CONCLUSIONS: Preconception microbiome optimization through diagnostics, lifestyle changes, and targeted therapies significantly improves pregnancy outcomes. Simple, cost-effective measures are critical also in LMIC to prevent and reduce maternal and fetal morbidity and mortality.}, } @article {pmid41531391, year = {2026}, author = {Liang, J and Li, S and Dai, Y and Pi, Z and Liu, J and Li, P and Sun, W and Jiang, T and Xu, T and Yu, P}, title = {Integrating Transcriptomics and Gut Microbiota Analysis Reveals the Anti-Osteoporotic Mechanisms of Wine and Oil Co-Processed Epimedium.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {2}, pages = {e71319}, doi = {10.1096/fj.202501534RR}, pmid = {41531391}, issn = {1530-6860}, support = {20230204034YY//Jilin Provincial Scientific and Technological Development Program (Jilin Scientific and Technological Development Program)/ ; 2024128//Administration of Traditional Chinese Medicine of Jilin Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Epimedium/chemistry ; Female ; *Osteoporosis/drug therapy/metabolism/microbiology ; *Transcriptome/drug effects ; Ovariectomy ; *Wine ; *Drugs, Chinese Herbal/pharmacology ; STAT3 Transcription Factor/metabolism ; Mice, Inbred C57BL ; Gene Expression Profiling ; }, abstract = {Wine- and suet oil co-processed Epimedium (WSOEP) is a traditional Chinese herbal preparation produced by processing raw Epimedium with wine and suet oil as adjuvants. Although WSOEP has been used clinically for the treatment of osteoporosis, its precise therapeutic indications and underlying molecular mechanisms remain incompletely defined. This study integrates transcriptomic profiling with gut microbiota analysis to systematically elucidate the anti-osteoporotic efficacy of WSOEP and its mechanistic basis. In a mice model of osteoporosis induced by bilateral ovariectomy (OVX), WSOEP administration significantly attenuated bone loss and improved multiple key bone parameters compared to the Mod group. Mechanistically, WSOEP treatment markedly downregulated SRC protein expression while simultaneously upregulating both total STAT3 and p-STAT3, indicating restoration of the dysregulated SRC/STAT3 signaling axis. Furthermore, WSOEP effectively modulated gut microbial homeostasis by enriching beneficial taxa, including Bacilli, Verrucomicrobiae, and Bacteroidales, while suppressing potentially detrimental lineages such as Proteobacteria, Clostridia, and Akkermansia. This is the first study to demonstrate that WSOEP exerts robust protective effects against OVX-induced osteoporosis through dual modulation of the SRC/STAT3 pathway and the gut microbiome. These findings not only position WSOEP as a promising candidate for osteoporosis therapy but also offer a novel paradigm for multi-component herbal interventions targeting the gut-bone axis in metabolic bone diseases.}, } @article {pmid41531341, year = {2026}, author = {Mellor, D and McArdle, P and Spiro, A and Stanner, S and Marsland, N and Kudzin, S and Twenefour, D}, title = {Summary of the Development of a Joint Position Statement on Low and No-Calorie Sweeteners (LNCS) From the British Dietetic Association (BDA), British Nutrition Foundation (BNF) and Diabetes UK.}, journal = {Nutrition bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1111/nbu.70044}, pmid = {41531341}, issn = {1467-3010}, abstract = {Low and no-sugar sweeteners (LCNS) are used in the food supply, notably within the beverage industry in many countries, where sugar reduction is a key public health concern. In the UK, following the announcement and implementation of the Soft Drinks Industry Levy (SDIL), nearly 9 out of 10 soft drinks contain < 5 g sugar per 100 mL, most of which now contain LNCS. In 2023, the World Health Organisation (WHO) issued a guideline with a conditional recommendation advising that LNCS should not be used as 'a means of achieving weight control or reducing the risk of non-communicable disease' (NCDs). This recommendation potentially conflicted with existing recommendations from several authoritative sources at the time, including the Diabetes UK position statement published in 2018 (developed in collaboration with the British Dietetic Association, BDA and the British Nutrition Foundation, BNF), as well as information on the NHS website, which suggests that LCNS can be helpful in reducing sugar intake. More recently, a working group comprising the BDA, BNF and Diabetes UK produced an updated insight document. This review included a re-evaluation of the WHO's systematic review and meta-analysis, alongside the Scientific Advisory Committee on Nutrition (SACN) statement on the guideline. The narrative review outlines the relationship between LNCS and a range of public health outcomes, including weight management, dental health, cardiovascular disease, type 2 diabetes (T2D), cancer and related risk markers such as appetite and gut microbiome composition. The insights document also considered the safety of LNCS and their impact on overall dietary quality. The insight document informed a subsequent joint position statement from the three organisations, highlighting research gaps and providing practical guidance for healthcare professionals to support individuals living with obesity and diabetes in reducing sugar intake. It also includes recommendations for policymakers and identifies actions for the food industry. The Position Statement emphasises that, while LNCS may not directly promote weight loss or reduce disease risk, they can serve as a useful tool for reducing sugar intake at both individual and population levels, at least acting as a 'stepping stone' from sugar-sweetened foods and unsweetened food and beverages.}, } @article {pmid41530974, year = {2026}, author = {Xu, XY and Wang, CL and Xu, JY and Dong, CJ and Tan, C and He, YX and Hu, HW and Shu, K and Dai, CC and Chen, ZH and Sun, K}, title = {Seed-microbiome interactions: Mechanistic insights and utilization toward seed performance for sustainable agriculture.}, journal = {Plant communications}, volume = {}, number = {}, pages = {101716}, doi = {10.1016/j.xplc.2026.101716}, pmid = {41530974}, issn = {2590-3462}, abstract = {Global climate change poses increasing threats to seed production and thus food security. The seed microbiome plays an essential role in regulating the whole seed life cycle. Specific seed endophytes and spermosphere microorganisms orchestrate the maintenance and termination of dormancy towards the synchronization of germination plasticity to meet agricultural demands. In this review, we summarize recent advances by linking seed-microbiome interactions with seed processes. We review the sources of seed microbiomes and their physiological regulation on dormancy and germination in response to environmental changes with a focus on phytohormone crosstalk. We also discuss the molecular mechanisms by which seed-microbe interactions affect seed destiny. Finally, we explore emerging precision applications of microbiomes in the seed industry by integrating cutting-edge technologies such as microbial seed coatings and artificial intelligence (AI) in seed science and technology. In conclusion, harnessing microbiome-based strategies to manipulate seed life cycle holds immense promise for sustainable food production in a changing global climate.}, } @article {pmid41530889, year = {2026}, author = {Bonacolta, AM and Keeling, PJ}, title = {Modern microbialites harbor an undescribed diversity of chromerid algae.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-026-00852-4}, pmid = {41530889}, issn = {2524-6372}, support = {GBMF9201//Gordon and Betty Moore Foundation/ ; }, abstract = {BACKGROUND: Chromerid algae are the closest photosynthetic relatives of apicomplexan parasites. While chromerids have been central to understanding the evolutionary transition from free-living algae to parasitism within Apicomplexa, their ecology remains poorly understood. Although often considered coral-associated symbionts, emerging evidence suggests this link is incidental and that chromerids may be more broadly associated with calcium carbonate environments, including microbialites. These microbial structures represent modern analogues of ancient reef-like ecosystems but are difficult to study due to their rarity and protected status as world heritage sites. Prokaryotic members of the microbialite microbiome have been studied at length, while the microeukaryotes associated with these environments have gone mostly ignored. To further investigate the link between microbialites and chromerid algae, we re-analyzed previously published microbialite sequencing data with the aim of investigating chromerid diversity and distribution.

RESULTS: Through a novel plastid-focused metagenomic binning workflow combined with re-analysis of rRNA metabarcoding data, we reveal that chromerid algae are consistent associates of microbialites across diverse marine and freshwater environments worldwide. Most notably, we report the first recovery of plastid genomes from microbialite-associated chromerids: a complete Vitrella brassicaformis plastid genome and a second, partial plastid genome from a previously undescribed Chromera-related lineage in Highborne Cay thrombolites. This partial plastid genome contained photosystem genes, confirming this novel Chromera-related lineage as a photosynthetic chromerid. These findings not only expand the known ecological and biogeographic range of chromerids but also provide evidence for their overlooked diversity.

CONCLUSIONS: Our analyses prove that this overlooked algal lineage is not found exclusively associated with corals, but instead occurs across a wide range of microbialite habitats, including those found in freshwater. By extending their known distribution beyond coral hosts and the marine environment, our results not only highlight the diversity and ecological range of the most recently discovered algal lineage but also broaden our understanding of the ancestral lifestyles that may have preceded apicomplexan evolution. This research underscores the value of targeted mining of public sequencing datasets to address specific ecological questions, particularly in rare or hard-to-access environments such as microbialites.}, } @article {pmid41530845, year = {2026}, author = {Liu, CM and Erikstrup, LT and Edslev, SM and Park, DE and Salazar, JE and Aziz, M and Rendboe, AK and Pham, T and Dinh, KM and Roach, K and Onos, A and Sung, E and Weber, NO and Andersen, PS and Ullum, H and Skov, R and Hungate, BA and Stegger, M and Erikstrup, C and Price, LB}, title = {Composition and dynamics of the adult nasal microbiome.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02250-3}, pmid = {41530845}, issn = {2049-2618}, abstract = {BACKGROUND: The nasal microbiome, a dynamic assemblage of commensals and opportunistic pathogens, is crucial to human health.

RESULTS: Using cross-sectional data from 1,608 adults and longitudinal sampling of 149 individuals over 8-22 months, we identified nine nasal community state types (CSTs), defined by bacterial density and indicator taxa, with varying stability and transition patterns. Core taxa such as Staphylococcus epidermidis and Cutibacterium acnes were highly stable, while opportunistic pathogens like Staphylococcus aureus and Moraxella catarrhalis had shorter residence times. Interactions between Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum/propinquum were linked to reduced S. aureus colonization. Host factors, including age and biological sex, significantly shaped microbiome dynamics: men exhibited higher bacterial densities and pathogen colonization, while women showed more stable commensal-dominated CSTs. Aging was associated with shifts in CST frequencies, with declining S. aureus and increasing Enterobacterales.

CONCLUSIONS: These findings reveal potential strategies by modulating nasal microbiome dynamics to reduce pathogen colonization and improve health. Video Abstract.}, } @article {pmid41530829, year = {2026}, author = {Yan, D and Yu, Y and Liang, C and Cui, Z and Shi, L and Li, G and Ren, C}, title = {Intratumoral microbiome: the double-edged sword in remodeling cancer immunotherapy.}, journal = {Molecular cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12943-025-02566-6}, pmid = {41530829}, issn = {1476-4598}, support = {82172345//National Natural Science Foundation of China/ ; BK20221281//Natural Science Foundation of Jiangsu Province/ ; SBJC22003//Crosscooperation project of Subei Peoples' Hospital of Jiangsu Province/ ; }, abstract = {Emerging evidence reveals that intratumoral microbial (ITM) communities within the tumor immune microenvironment (TIME) critically influence tumor progression and immunotherapy response. Studies have shown that resident bacteria within tumors, such as Sphingobacterium multivorum, regulate the secretion of chemokines like CCL20 and CXCL8, promoting the infiltration of regulatory T cells (Tregs) and inhibiting the function of cytotoxic T cells (CD8[+] T cells)-thereby weakening the efficacy of immune checkpoint inhibitors. Additionally, microbial metabolites may serve as potential biomarkers for predicting sensitivity to immunotherapy. Concurrently, engineered bacteria (e.g., oncolytic mineralizing bacteria) demonstrate significant antitumor effects by activating innate immunity and enhancing antitumor-specific immune responses, providing new strategies to overcome immunotherapy resistance. These findings highlight the dual role of ITM in tumor immune evasion and immunotherapy sensitivity, laying an important theoretical foundation for developing novel immunotherapy strategies targeting tumoral microbiota metabolism.}, } @article {pmid41530817, year = {2026}, author = {Li, R and Liao, X and Fu, X and Li, X and Liao, X and Cen, S and Zeng, J and Huang, L and Chi, H and Zou, Y}, title = {Microbiota-driven tryptophan metabolism and AhR triggered intestinal stem cell differentiation: mechanisms of huangqin decoction in ulcerative colitis repair.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {33}, pmid = {41530817}, issn = {1749-8546}, support = {2022A1515140011//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023A1515010012//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 20231800936162//Dongguan Science and Technology of Social Development Program/ ; 20221800905632//Dongguan Science and Technology of Social Development Program/ ; }, abstract = {BACKGROUND: Promoting intestinal barrier repair and epithelial regeneration is a core therapeutic objective in managing ulcerative colitis (UC). Intestinal stem cell (ISC) differentiation is pivotal in sustaining epithelial renewal and mucosal homeostasis. Huangqin decoction (HQD), a classical herbal formulation comprising Scutellaria baicalensis, Ziziphus jujuba, Paeonia lactiflora, and Glycyrrhiza uralensis, is clinically used for inflammatory bowel disease. Nevertheless, how HQD precisely regulates ISC differentiation to promote UC repair remains unclear.

PURPOSE: This research sought to assess whether HQD ameliorates UC by concurrently modulating the gut microbiome, tryptophan metabolism, aryl hydrocarbon receptor (AhR) activation, and ISC differentiation.

METHODS: Mice developed colitis after drinking water with a 3.5% (w/v) concentration of dextran sulfate sodium. We evaluated HQD effects on colon length, weight trajectory, disease activity index score, histological damage, and colonic inflammatory mediator abundance. Metagenomic sequencing resolved microbiota restructuring, while UPLC-MS/MS quantified fecal tryptophan metabolites such as indole derivatives. AhR pathway activity (AhR, CYP1A1), its downstream cytokine IL-22, and ISC fate were mapped by combining immunofluorescence, ELISA, Western blot, and RT-qPCR, probing Lgr5 for stem-cell identity and MUC2, LYZ, and ChgA for lineage-specific differentiation. The involvement of AhR and gut microbiota was investigated using AhR inhibitors and broad-spectrum antibiotics.

RESULTS: High-dose HQD significantly alleviated colitis symptoms, reduced colon damage, and corrected gut dysbiosis. HQD increased the abundance of related bacteria that elevated colonic levels of indole-3-propionic acid, indole-3-acetamide, and tryptamine, acting as AhR ligands that upregulate AhR and its downstream targets CYP1A1 and IL-22. Crucially, HQD promoted a shift in expression from the ISC marker Lgr5 toward differentiation markers MUC2, LYZ, and ChgA, indicating enhanced ISC differentiation and improved barrier function. These effects were effectively blocked by AhR inhibition or antibiotic treatment.

CONCLUSION: HQD restores intestinal mucosal integrity and attenuates colonic inflammation by modulating gut microbiota composition, increasing microbial tryptophan metabolites with AhR-agonist activity, activating the AhR signaling pathway, and promoting ISC differentiation into functional epithelial cells. This work reveals a novel "microbiota-tryptophan metabolism-AhR-ISC differentiation" axis underlying HQD's therapeutic efficacy in UC.}, } @article {pmid41530663, year = {2026}, author = {Yu, HL and Elsheikha, HM and Liang, HR and Qin, SY and Peng, P and Liu, J and Tang, Y and Guo, L and Ni, HB and Xie, LH and Lei, CC and Su, JW and Yu, MY and Qin, Y and Jiang, J and Liu, J and Xu, Y and Zhang, XX}, title = {Blastocystis infection enhances vitamins B and K2 biosynthesis in the Tibetan antelope (Pantholops hodgsonii) gut microbiota.}, journal = {BMC genomics}, volume = {27}, number = {1}, pages = {40}, pmid = {41530663}, issn = {1471-2164}, support = {2023YFF1305403//the National Key Research and Development Program of China/ ; 2022KJ169//the Shandong Province Higher Education Institutions "Youth Innovation Team Plan"/ ; }, } @article {pmid41530658, year = {2026}, author = {Kaloterakis, N and Braun-Kiewnick, A and Rashtbari, M and Giongo, A and Babin, D and Zamberlan, PM and Razavi, BS and Smalla, K and Reichel, R and Brüggemann, N}, title = {Bacillus seed coating mitigates early growth reduction in successive winter wheat without altering rhizosphere bacterial and archaeal communities.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-026-08128-2}, pmid = {41530658}, issn = {1471-2229}, abstract = {The soil legacy of successively grown winter wheat (WW) often leads to lower plant growth and yield. In this study, we assessed the effect of Bacillus pumilus seed inoculation on the early growth of successively grown WW. We conducted an outdoor experiment using newly designed temperature-regulated rhizotrons. WW was grown in soil from two rotational positions, i.e., first WW after oilseed rape (W1) and second WW after oilseed rape (W2), until the end of tillering. We measured several plant and soil biochemical parameters. In addition, amplicons of the 16S rRNA gene were sequenced to account for bacterial and archaeal community shifts in the rhizosphere, and functional genes involved in the nitrogen cycle were quantified to estimate possible changes in N cycling due to B. pumilus inoculation. B. pumilus seed coating significantly compensated for the early growth reduction of W2, and this effect was primarily linked to changes in root plasticity with a higher root length density and a smaller specific root length in inoculated W2 compared with non-inoculated W2. There was a higher LAP activity in the rhizosphere of inoculated W2 plants than in the rhizosphere of non-inoculated W2 plants and this was followed by a reduction in soil NO3[-], most probably due to an enhanced plant N uptake capacity. This was also shown in the increased potassium content of the inoculated W2 plants compared with their non-inoculated counterparts. B. pumilus seed coating did not influence the bacterial and archaeal alpha and beta diversity, but differential abundance analysis identified differences in the relative abundance of certain taxa between non-inoculated and inoculated W2. While B. pumilus seed coating significantly improved root growth and nutrient uptake in W2, this was not accompanied by a higher absolute abundance of bacterial or archaeal genes involved in N-cycling. Our study suggests that certain plant-beneficial microbes can reverse the negative plant-soil feedback in successive WW rotations and provides strong evidence of B. pumilus seed coating to promote WW productivity under such rotations.}, } @article {pmid41530607, year = {2026}, author = {Miller, CB and Bader, GA and Kay, CL}, title = {Fecal Microbiota Transplantation in 2025: Two Steps Forward, One Step Back.}, journal = {Current gastroenterology reports}, volume = {28}, number = {1}, pages = {5}, pmid = {41530607}, issn = {1534-312X}, mesh = {*Fecal Microbiota Transplantation/trends/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; *Clostridium Infections/therapy ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {PURPOSE OF REVIEW: This review summarizes the history and current landscape of fecal microbiota transplantation (FMT), with an emphasis on use of the therapy for Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). We clarify indications, evidence, and current recommendations for FMT-highlighting major advances and minor setbacks that have led to the state of FMT in 2025.

RECENT FINDINGS: After decades of steady progress, the U.S. Food and Drug Administration (FDA) approved the first FMT-based therapies: fecal microbiota, live-jslm and fecal microbiota spores, live-brpk-in 2022 and 2023, respectively. The 2024 American Gastroenterological Association (AGA) Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases made specific recommendations for conventional FMT and these FDA-approved therapies for multiple CDI presentations, as well as for IBD and IBS. Conventional FMT remains an option for CDI; however, OpenBiome's halt of shipped, frozen FMT preparations on December 31, 2024, has made access more challenging in 2025. Although first reported almost seventy years ago, extensive efforts over the last two decades have placed FMT in routine algorithms for many patients with CDI. While understanding of the intestinal microbiome's role in other gastrointestinal conditions is expanding, and FMT may modulate these pathways, additional evidence is needed before FMT becomes routine outside CDI.}, } @article {pmid41530574, year = {2026}, author = {Deng, YH and Liu, Q and Luo, XQ}, title = {The gut-kidney axis in pediatric acute kidney injury: a review of pathophysiological mechanisms and therapeutic frontiers.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {41530574}, issn = {1432-198X}, support = {2024JJ6595//Natural Science Foundation of Hunan Province/ ; }, abstract = {Acute kidney injury (AKI) is a frequent and severe condition in hospitalized children, leading to significant morbidity, mortality, and long-term risk of chronic kidney disease. This review explores the gut-kidney axis, a concept describing the bidirectional relationship between the gut microbiome and kidney function, as a critical driver of pediatric AKI. In critically ill children, interventions such as broad-spectrum antibiotics and necessary nutritional support strategies (e.g., parenteral nutrition or fasting) can cause profound gut microbial imbalance (dysbiosis). This dysbiosis initiates a deleterious feedback loop, exacerbating kidney injury. Key mechanisms include the disruption of the intestinal barrier (leaky gut), which allows bacterial endotoxins to enter the bloodstream, triggering renal inflammation via Toll-like receptor 4 signaling. Concurrently, the dysbiotic gut increases production of directly nephrotoxic gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, while failing to produce protective anti-inflammatory metabolites like short-chain fatty acids. While therapies targeting the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, are theoretically promising, their clinical use in pediatric AKI is unsupported by evidence and carries substantial risks, particularly iatrogenic infection. A significant knowledge gap exists due to a relative lack of pediatric-specific clinical research. The conclusion emphasizes an urgent need for longitudinal, multi-omics studies in children to understand this axis, identify functional biomarkers, and develop safe, targeted therapies to improve outcomes.}, } @article {pmid41530533, year = {2026}, author = {Ning, J and Zhao, Y and Lu, G and Wei, L}, title = {Melatonin Alleviated Cadmium Induced Microbiota-Gut-Brain Disorder in Adult Zebrafish: Insights from Transcriptomic and Microbiome Analysis.}, journal = {Biological trace element research}, volume = {}, number = {}, pages = {}, pmid = {41530533}, issn = {1559-0720}, support = {KYQD(ZR)21138//Scientific Research Start-up Fund of Hainan University/ ; }, abstract = {Cadmium (Cd), a toxic metal, poses significant threats to ecological and human health due to its neurotoxic and gut toxicity effects. However, the mechanisms by which Cd disrupts brain-gut axis interactions remain unclear, and strategies to mitigate these effects are limited. Melatonin (MT), known for its anti-inflammatory and antioxidant properties, has shown promise in counteracting heavy metal toxicity. This study investigated the protective mechanisms of MT against Cd-induced toxicity in adult zebrafish using histopathological analysis, 16 S rRNA sequencing, RNA-sequencing, and qRT-PCR. Results showed that MT significantly alleviated Cd-induced structural damage in brain spongiosa and restored intestinal villi integrity. 16 S rRNA sequencing revealed that MT reduced pathogenic bacteria and increased beneficial bacteria in the gut microbiota. Transcriptomic analysis identified 31 differentially expressed genes (DEGs) in brain, KEGG enrichment analysis showed these DEGs are associated with neurodegenerative diseases pathways. Concurrently, 8 DEGs in gut were linked to oxidative phosphorylation signaling pathways. Correlation analysis showed pathogenic Legionella and Aeromonas were positively correlated with htr2b, il21r.2, il2rb, il21r.2, cyp46a1.3 cyp2ad3, cyp46a1.3 in brain, Candidatus_Protochlamydia was positively correlated with il7r, drd3 in gut, those are down regulated DEGs, whereas beneficial Acinetobacter and Achromobacter were positively correlated with cyp2 × 8 in gut, this is up regulated DEG. These suggests that Legionella, Candidatus_Protochlamydia, Achromobacter and Acinetobacter may be key bacterial that mediate the MT reduction in neurotoxicity and immunotoxicity induced by Cd. These findings highlight MT's potential to mitigate Cd-induced toxicity by modulating the gut microbiota, offering therapeutic insights for reducing Cd toxicity risks in aquaculture.}, } @article {pmid41530470, year = {2026}, author = {El-Sayed, ASA and Mohamed, NZ and Safan, S and Yassin, MA and Shaban, L and Shindia, AA and Shad Ali, G and Sitohy, MZ}, title = {Retraction Note: Restoring the Taxol biosynthetic machinery of Aspergillus terreus by Podocarpus gracilior Pilger microbiome, with retrieving the ribosome biogenesis proteins of WD40 superfamily.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1752}, doi = {10.1038/s41598-026-35501-w}, pmid = {41530470}, issn = {2045-2322}, } @article {pmid41530275, year = {2026}, author = {Wöber, D and Wernicke, M and Cerqueira, F and Wechselberger, K and Hansel-Hohl, K and Manhalter, S and Molin, EM}, title = {Intestinal microbiome interactions influence Metarhizium-based biocontrol efficacy against the sugar beet weevil.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36038-8}, pmid = {41530275}, issn = {2045-2322}, abstract = {The sugar beet weevil is considered one of the most economically important insect pests in sugar beet cultivation. A promising biological control strategy involves the natural interaction between entomopathogenic fungi and arthropods. The successful application of M. brunneum as part of integrated biological control strategies against the sugar beet weevil has already been demonstrated resulting in lethal mycosis. However, the efficacy of this strain is affected by multiple factors. The intestinal microbiome of insects harbours beneficial microbes that possess various functions, such as defence mechanisms against insect-pathogens. Thus, investigating intestinal microbial interactions in combination with Metarhizium-application could reveal microbes that modulate susceptibility to pathogens. This study investigated whether intestinal microbial interactions influence mycosis caused by M. brunneum and M. robertsii. We analysed the intestinal microbiome of both treated and untreated sugar beet weevils, distinguishing between mycotic and non-mycotic individuals at the time of death. Notably, Pantoea and Enterobacter were significantly associated with mycotic individuals and may act as a potential antagonist to Metarhizium. In contrast, healthy individuals harboured diverse microbial communities that may provide a protective barrier against entomopathogens. However, the intestinal microbiome of non-mycotic specimens also comprised genera with presumed insecticidal properties, including Serratia, Penicillium and Cladosporium. The last two were also observed in the intestines of male individuals, which were generally at a higher risk of mortality. Further investigation is needed to confirm their insecticidal potential in the sugar beet weevil. A combined application could improve the efficacy of Metarhizium-based biocontrol, contributing to more sustainable pest management strategies.}, } @article {pmid41530269, year = {2026}, author = {Ludyga, S and Pedrini, L and Sarbach, L and Topyürek, B and Köhler, H and Furlano, R and Légeret, C}, title = {A comparative study of cognitive function among children with coeliac disease and healthy controls.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-34500-7}, pmid = {41530269}, issn = {2045-2322}, abstract = {Coeliac disease (CD) is an immune-mediated systemic disorder triggered by gluten in genetically predisposed patients. The only available treatment is a strict life long gluten-free diet (GFD), which has been linked to a reduced quality of life (QOL) and causes alterations in the gastrointestinal microbiome. Abnormal compositions of the microbiome are now recognized as factors in the pathogenesis of neuropsychological disorders via gut-brain-axis. The aim of this study was to assess the QOL and the mental performance of children and teenagers with CD and compare it to healthy controls (HC). Children between the ages of 6 and 18 years with CD and age-and-sex-matched healthy controls (HC) filled in a questionnaire to assess QOL and performed the Flanker task, a standardized test to assess cognitive performance. A total of 444 children (210 CD patients and 234 HC) were included in the study. CD patients reported feeling statistically significantly more comfortable at school (p = 0.02) and being less exposed to bullying (p = 0.01); otherwise, no difference in QOL and sleep pattern was found compared to HC. The analysis of Flanker task revealed no difference in accuracy (HC: mean 0.97, CI 0.96-0.97; CD patients: mean 0.96, CI 0.96-0.97; p = 0.79), but there was a difference in reaction time (HC: mean 495.4 ms, CI 476.34-514.46; CD patients: mean 514.03, CI 493.68-534.39; p = 0.19). Children with CD in Switzerland have the same QOL as HC. There was a statistically non-significant difference in reaction time, therefore this study suggests that a GFD is not associated with impaired cognitive function.}, } @article {pmid41530203, year = {2026}, author = {Huang, X and Xu, B and Lei, Y and Qin, H and Zheng, J and Xu, Y and Zhao, D and Su, J and Li, J and Zhao, J}, title = {Bacillus velezensis mitigates deoxynivalenol-induced intestinal inflammation and liver injury via modulating the gut microbiota.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00707-9}, pmid = {41530203}, issn = {2396-8370}, abstract = {Deoxynivalenol (DON), a prevalent mycotoxin in food and feed, induces gastrointestinal and liver damage. The potential probiotic Bacillus velezensis may mitigate DON toxicity, though its precise mechanisms remain unknown. Our study demonstrates that B. velezensis WMCC10514 effectively survives and degrades DON within simulated gastrointestinal fluid. Fluorescently labeled WMC10514-GFP colonized murine intestines and persisted in simulated intestinal fluid (SIF), confirming its colonization capacity. In vivo, WMCC10514 alleviated DON-induced anorexia, restored murine growth, and reduced liver injury. Furthermore, the strain elevated ZO-1 and Occludin expression, enhanced intestinal barrier integrity and reduced DON accumulation in host tissues. Integrated transcriptomic and microbiome analyses revealed that the strain suppressed TLR4/NF-κB pathway activation in the intestine and liver, increased Lactobacillus abundance, restored SCFAs level, and modulated liver energy metabolism. These findings elucidate B. velezensis's role in mitigating mycotoxin toxicity through gut microbiota-driven regulation of the gut-liver axis.}, } @article {pmid41530166, year = {2026}, author = {Zhang, Q and Chen, B and Zhang, Z and Yu, Y and Jin, M and Lu, T and Zhang, Z and Pang, Q and Xu, N and Sun, J and Chen, J and Wang, J and Zhu, D and Qian, H and Penuelas, J and Zhu, YG}, title = {Cobamide-producing microbes as a model for understanding general nutritional interdependencies in soil food webs.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-68255-6}, pmid = {41530166}, issn = {2041-1723}, support = {2022C02029//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; 42307158//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Nutrient crossfeeding critically governs microbiome-host interactions and ecosystem stability. Cobamides, synthesized only by prokaryotes, offer a powerful and tractable model for studying nutrient-mediated interdependencies in soil food webs; however, their ecological role in sustaining soil health remains unclear. Here, we construct the Soil Cobamide Producer database (SCP v.1.0) by integrating over 48,000 metagenomic and genomic datasets from 1,123 sampling sites. This database catalogs phylogenetically diverse prokaryotes (19 phyla, 302 genera) with cobamide biosynthetic potential. Using this resource, we identify host-specific colonization patterns of cobamide-producing microbes in fauna. These microbes also carry diverse functional traits that may contribute to trophic cascades and microbial community stability. In an Enchytraeid model, these colonizers support host development, modulate gene expression, and promote gut stability through transkingdom interactions, with cobamide biosynthesis serving as one representative trait among multiple microbial functions. At macroecological scales, cobamide-producing microbes occur across relatively high trophic levels, reflecting a broader principle of nutrient transfer that may also apply to other essential metabolites. This framework provides a general basis for studying nutritional microbes in soil food webs and advances One Health research.}, } @article {pmid41530018, year = {2026}, author = {FitzGerald, JA and Lester, KL and O' Sullivan, N and Crispie, F and Lawton, EM and Cotter, PD and McNally, P and Cox, DW}, title = {Parallel metagenomic- and culture-based approaches show nasal swabs are a good proxy for broncho-alveolar lavage in children with cystic fibrosis.}, journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcf.2025.12.011}, pmid = {41530018}, issn = {1873-5010}, abstract = {BACKGROUND: Broncho-Alveolar Lavage (BAL) is the reference standard for airway surveillance in clinical management of cystic fibrosis (CF), but is invasive and requires general anaesthesia in children. Non-invasive alternatives can lack specificity (Oropharyngeal swabs; OPS), or evaluation in paediatric CF (Middle meatus sampling; MMS). We sought to determine if MMS via nasal-swabs performed better than OPS at representing the microbiological attributes of BAL.

METHODS: In a stable preschool CF cohort attending a single specialist centre, we evaluated the microbiological yield of BAL, MMS, and OPS sampling using both standard clinical culturing, and shotgun metagenomic sequencing (Illumina NextSeq 500).

RESULTS: Matched BAL, MMS, and OPS from 30 preschool children provided 88 samples. While both culture and metagenomic surveillance performed well at detecting S. pneumoniae in BAL, MMS performed better at detecting S. aureus, M. catarrhalis and Escherichia coli, while OPS performed better at detecting H. Influenzae. Metagenomics revealed a significantly more diverse microbiome in OPS than BAL or MMS. While agreement on pathogen profiles varied widely between metagenomics and culture methods, MMS more accurately represented BAL, particularly for Streptococcus, M. catarrhalis, and Escherichia.

CONCLUSIONS: MMS and OPS cultures performed well as proxies for BAL in relation to certain pathogens. Metagenomics detected pathogens in many samples that were unobserved in culture, and showed the oropharynx microbiome to be much more diverse. Lung and nares microbiomes were more similar in composition and diversity. Our data suggest that nasal sampling of the middle meatus may be a more accurate surrogate for lower airway samples.}, } @article {pmid41530012, year = {2026}, author = {Lechien, JR}, title = {Emerging Microbiome Findings in Laryngopharyngeal Reflux Disease: A Scoping Review.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2025.12.023}, pmid = {41530012}, issn = {1873-4588}, abstract = {OBJECTIVE: To review the current literature linking laryngopharyngeal reflux disease (LPRD) with microbiome impairments.

METHODS: Two independent investigators conducted a systematic literature search for studies reporting microbiome findings in LPRD patients through PubMed, Scopus, and Cochrane Library databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Population, Intervention, Comparison, Outcome, Timing, and Setting (PICOTS) framework were followed. A methodological bias analysis was conducted with the Tool to Assess the Risk of Bias in Cohort Studies.

RESULTS: Of the 585 identified papers, eight studies met the inclusion criteria, including 245 patients with suspected or confirmed LPRD. Two studies using objective diagnostic approaches confirmed that LPRD is associated with significantly reduced alpha and beta diversities compared to controls. Streptococcus and Actinomyces emerged as key taxa consistently differentiating LPRD patients from controls across multiple studies. However, significant methodological heterogeneity was observed in LPRD diagnosis, microbiome assessment methods, and control group definitions.

CONCLUSION: Preliminary literature suggests that patients with suspected or confirmed LPRD exhibit salivary microbiome alterations characterized by reduced diversity and selective microbial shifts. Future high-quality methodological studies are needed to elucidate the mechanistic relationship and clinical consequences of LPRD-related dysbiosis.}, } @article {pmid41529744, year = {2026}, author = {Li, J and Tang, G and Xie, Z and Yang, L and Zhou, Z and Guo, K}, title = {Identification of oral microbial biomarkers for prediabetes in young adults: A two-stage population-based study.}, journal = {Diabetes research and clinical practice}, volume = {}, number = {}, pages = {113101}, doi = {10.1016/j.diabres.2026.113101}, pmid = {41529744}, issn = {1872-8227}, abstract = {AIM: This study aims to identify oral microbial signatures associated with prediabetes in young adults and to investigate potential oral risk factors for early-onset diabetes, as well as to pinpoint targets for monitoring and intervention.

METHODS: The study involved a large cross-sectional analysis of 3,142 participants from two independent cohorts. The discovery cohort consisted of 334 prediabetes cases and 1,266 controls, while the validation cohort had 325 prediabetes cases and 1,217 controls. We compared the basic and clinical characteristics of the different groups. Additionally, 16S rRNA gene sequencing was conducted on oral rinse samples.

RESULTS: Prediabetes-enriched taxa comprised Bacteroidetes, Prevotella_7, and Veillonella. In contrast, normoglycemic controls showed a higher presence of Firmicutes and Streptococcus. The combined models, constructed from indicators identified by LASSO regression, including BMI, HOMA-IR, and specific microbiota (Prevotella_7 or Veillonella), demonstrated discriminatory performance. In the discovery set, the AUC values were 0.761 and 0.758, respectively, whereas in the validation set, the AUC values were 0.693 and 0.696, respectively.

CONCLUSION: Reproducible alterations and enrichment of Prevotella_7 and Veillonella are linked to prediabetes in young adults. Furthermore, the combined interaction between specific bacterial genera and core clinical indicators may be crucial in the development of prediabetes in young individuals.}, } @article {pmid41529362, year = {2026}, author = {Le, VV and Taj, M and Esterhuizen, M and Kim, YJ and Jung, MY and Lee, SA}, title = {Shape-driven toxicity of polystyrene microplastics: Impacts on physiology and gut microbiota in Daphnia magna.}, journal = {Marine pollution bulletin}, volume = {225}, number = {}, pages = {119218}, doi = {10.1016/j.marpolbul.2026.119218}, pmid = {41529362}, issn = {1879-3363}, abstract = {Microplastic pollution has emerged as a global issue that poses serious risks to aquatic ecosystems. Although Daphnia spp. are widely used as model organisms to study the effects of microplastics on their fitness, their microbiome response remains largely unexplored. This study investigated the effects of ground polystyrene microplastics (G-PS; fragments below the EC10 value) and commercial polystyrene microplastics (C-PS; beads below the EC10 value) on the physio-biochemical responses and gut microbiota of Daphnia magna. The toxicity of polystyrene microplastics to D. magna was shape-dependent, with G-PS being more toxic than C-PS. Exposure to G-PS and C-PS triggered Reactive oxygen species (ROS) production in D. magna. Although G-PS increased the abundance of both harmful (Fusobacterium) and beneficial bacteria (Blautia and Subdoligranulum) in the gut microbiota of Daphnia, C-PS only increased the abundance of beneficial bacteria (Lactobacillus, Ligilactobacillus, and Aerococcus), which may mitigate the toxicity of microplastics. Functional predictions based on amplicon sequencing suggested that altered microbiota may support the growth of D. magna by modulating associated metabolic pathways. D. magna exposed to G-PS exhibited a significantly higher abundance of gut microbiota pathways and enzymes associated with the detoxification of harmful compounds than those exposed to C-PS. This suggests that the higher toxicity of G-PS requires a stronger adaptive response from the gut microbiota. Overall, these findings highlight microplastic shape as a key factor influencing toxicity in D. magna and its associated microbiota.}, } @article {pmid41529347, year = {2026}, author = {Singh, S and Bajaj, A and Manickam, N}, title = {Microbiome of soil waste dumpsite and adjacent river habitat harbors dynamic plastic degrading bacterial diversity and abundant functional enzymes.}, journal = {The Science of the total environment}, volume = {1014}, number = {}, pages = {181331}, doi = {10.1016/j.scitotenv.2025.181331}, pmid = {41529347}, issn = {1879-1026}, abstract = {Landfill leachates and adjacent riverine ecosystems are usually the reservoirs of plastic-derived contaminants and other xenobiotics. Yet these sites are still less explored for their degradation potential. This study employed a whole metagenome analysis to characterize microbial communities and functional genes from the Ghaila municipal dumpsite and the Gomti river, Lucknow, India. Physicochemical analyses revealed neutral to slightly alkaline pH and elevated BOD and COD in downstream river sites, indicating high organic and plastic-associated pollutant loads. Taxonomic profiling identified 57 phyla, dominated by Proteobacteria, Bacteroidetes, Chloroflexi, and Firmicutes, with occurrence of key genera such as Pseudomonas, Acinetobacter, Flavobacterium, and Sphingomonas in abundance. Functional annotation of the metagenomic sequences detected 31 enzymes targeting 24 polymeric substances, including PETase, MHETase, urethanases, laccases, and nylon hydrolases in both dumpsite leachate and sludge (p < 0.05) samples. Antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) were widely distributed, particularly in leachate and sludge, underscoring their role as resistance reservoirs. These findings demonstrate that municipal dumpsite ecosystems are hotspots for plastic and xenobiotic degradation, highlighting their potential as genetic resources for bioremediation and advancing understanding of contaminant-driven microbial adaptation at landfill-river interfaces. NUCLEOTIDE SEQUENCE ACCESSION NUMBER: The complete metagenome sequence has been deposited at NCBI GenBank having accession no: SAMN42678420 to SAMN42678429 (BioProject).}, } @article {pmid41529345, year = {2026}, author = {Chinthalapudi, DPM and Narayana, NK and Nekkalapudi, L and Sinha, N and Shanmugam, SG}, title = {Soil microbial diversity, stability, and function are enhanced by cover cropping: A machine learning-based pooled analysis of Mississippi agroecosystems.}, journal = {The Science of the total environment}, volume = {1014}, number = {}, pages = {181365}, doi = {10.1016/j.scitotenv.2026.181365}, pmid = {41529345}, issn = {1879-1026}, abstract = {Cover cropping has emerged as a pivotal strategy to enhance soil health and microbiome functionality across diverse agroecosystems. However, the extent to which cover crops reshape microbial diversity, composition, functional capacity, and ecological stability remains insufficiently understood, particularly within heterogenous environments like Mississippi. In this study, we conducted a comprehensive pooled analysis of 473 soil samples collected from multiple independent cover crop trials (2020-2024) across diverse cropping systems and edaphic contexts in Mississippi. Amplicon sequencing (16S rRNA and ITS2) coupled with machine learning, co-occurrence network modeling, and functional prediction tools were employed to evaluate microbial community responses to cover cropping. Results revealed that cover crops significantly elevated bacterial and fungal α-diversity, altered community composition, and enriched taxa associated with nitrogen fixation, organic matter turnover, and pathogen suppression. Notably, Proteobacteria, Acidobacteriota, and Chloroflexi were more abundant under cover cropping, whereas Firmicutes and Actinobacteriota dominated control plots. Fungal communities under cover cropping exhibited higher relative abundance of Rozellomycota and Chytridiomycota, indicating enhanced saprotrophic and decomposition potential. Functional predictions showed increased cellular and environmental processing functions in cover-cropped soils, alongside a marked reduction in KEGG pathways linked to human diseases and pathotroph dominance. Co-occurrence network analysis indicated increased connectivity, modularity, and robustness under cover cropping, suggested enhanced microbial interaction strength and ecological stability. Sloan's neutral model fitting and increased migration rates further revealed that stochastic processes played a greater role in microbial assembly under cover cropping. Random Forest model identified Bradyrhizobium, Bryobacter, and Solirubrobacter as top bacterial biomarkers enriched in cover-cropped soils, while Talaromyces, Purpureocillium, and Clonostachys were the most predictive fungal genera, known for their biocontrol and nutrient cycling roles. These findings underscore the ecological potential of cover crops to enhance soil microbial networks and sustainability within Mississippi production systems, while insights may inform similar humid, subtropical agroecosystems elsewhere.}, } @article {pmid41528771, year = {2026}, author = {Wittle, L and Ocius, KL and Chordia, MD and van Wagoner, C and Bullock, TNJ and Pires, MM}, title = {Identification and Evaluation of Benzimidazole- Agonists of Innate Immune Receptor NOD2.}, journal = {ACS infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsinfecdis.5c00737}, pmid = {41528771}, issn = {2373-8227}, abstract = {Emerging evidence has demonstrated the importance of pattern recognition receptors (PRRs), including the nucleotide-binding and oligomerization domain receptor 2 (NOD2), in human health and disease states. NOD2 activation has shown promise with aiding malnutrition recovery, lessening irritable bowel disease (IBD) symptoms, and increasing the efficacy of cancer immunotherapy. Currently, most NOD2 agonists are derivatives or analogs of the endogenous agonist derived from bacterial peptidoglycan, muramyl dipeptide (MDP). These MDP-based agonists can suffer from low oral bioavailability and cause significant adverse side effects. With the goal of broadly improving NOD2 therapeutic interventions, we sought to discover a small molecule capable of activating NOD2 by screening a library of total 1917 FDA approved drugs in a phenotypic assay. We identified a class of compounds, benzimidazoles, that act as NOD2 agonists, with the most potent member of this class being nocodazole. Nocodazole activates NOD2 with nanomolar potency and causes the release of cytokines canonically associated with MDP-induced NOD2 activation, suggesting its potential to elicit similar therapeutic immune effects as MDP and potentially offer improved pharmacological properties.}, } @article {pmid41528651, year = {2026}, author = {He, YQ and Xue, WQ and Diao, H and Zhan, JY and Ji, MF and Yang, DW and Zhao, Y and Deng, CM and Wu, ZY and Zhou, T and Liao, Y and Zheng, MQ and Zhang, WL and Jia, YJ and Yuan, LL and Luo, LT and Li, DH and Wang, TM and Tong, XT and Du, Y and Tang, LL and Huang, JW and Huang, CL and Zhao, ZY and Wu, YX and Cao, LJ and Dong, SQ and Wang, F and Jiang, CT and Xiao, RW and Zhang, WB and Chen, XY and Wang, QL and Liu, QY and Zhao, YZ and Tang, CL and Ma, L and Zheng, XH and Zhang, PF and Li, XZ and Zhang, SD and Hu, YZ and Yu, X and Wu, BH and Li, FG and Wu, JH and Deng, BS and Liang, XJ and Jia, WH}, title = {Guangdong Biobank Cohort (GDBC) study.}, journal = {European journal of epidemiology}, volume = {}, number = {}, pages = {}, pmid = {41528651}, issn = {1573-7284}, support = {2023ZD0501000//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 2016YFC1302700//National Key Research and Development Program of China/ ; 82473703//National Natural Science Foundation of China/ ; 82273705//National Natural Science Foundation of China/ ; 82373656//National Natural Science Foundation of China/ ; 82404339//National Natural Science Foundation of China/ ; 2024A04J00693//Science and Technology Planning Project of Guangzhou, China/ ; 2024A04J4560//Science and Technology Planning Project of Guangzhou, China/ ; YSTTGDPMAA202502//Young Science and Technology Talent Support Program of Guangdong Precision Medicine Application Association/ ; 24qnpy292//Sun Yat-sen University/ ; 24ykqb002//Sun Yat-sen University/ ; YTP-SYSUCC-0081//Young Talents Program of Sun Yat-sen University Cancer Center/ ; YTP-SYSUCC-0076//Young Talents Program of Sun Yat-sen University Cancer Center/ ; CIRP-SYSUCC-0017//Cancer Innovative Research Program of Sun Yat-sen University Cancer Center/ ; }, abstract = {The global rise of non-communicable diseases (NCDs) presents an urgent public health challenge, particularly in regions undergoing rapid economic and demographic transitions. Guangdong Province, China's most populous and economically advanced region, is experiencing a substantial and accelerating burden of NCDs. However, large-scale, population-based cohorts from this region remain scarce, limiting insights into region-specific disease determinants and prevention strategies. The Guangdong Biobank Cohort (GDBC) was established in 2017, enrolling 35,081 participants aged 40-84 years from urban and rural areas of Zhongshan City in the Pearl River Delta. At baseline, comprehensive data on 346 variables-including lifestyle, environmental exposures, medical histories, physical examinations, and laboratory profiles-were collected via a cloud-based member management information system (MMIS), alongside blood and saliva samples for biobanking. A sub-cohort underwent genome-wide genotyping (N = 2,530) and oral microbiome profiling via 16 S rRNA sequencing (N = 2,049). During dynamic follow-up, 44.2% (N = 15,499) completed Phase I resurvey with repeated measurements and updated biospecimens. Disease outcomes, including hypertension, diabetes, and cancer, were ascertained through active surveillance and regional registry linkage until December 2023. Baseline prevalence of hypertension, diabetes, and cancer was 25.3%, 8.0%, and 3.6%, respectively. Over follow-up, 1,767 hypertension cases, 814 diabetes cases, and 558 cancers were recorded, yielding crude incidence rates of 1,804.6, 649.7, and 423.1 per 100,000 person-years, respectively. The GDBC provides a comprehensive, dynamically updated resource to dissect gene-microbiome-environment interactions and develop precision prevention strategies to inform public health policies.}, } @article {pmid41528513, year = {2026}, author = {Muhammad, A and Sun, C and Shao, Y}, title = {Ecological and functional dynamics of gut microbiota in the model insect, silkworm Bombyx mori.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {1}, pages = {39}, pmid = {41528513}, issn = {1573-0972}, support = {32250410276//National Natural Science Foundation of China/ ; SKLRI-ORP202401//State Key Laboratory of Resource Insects/ ; CARS-18//China Agriculture Research System of MOF and MARA/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Bombyx/microbiology ; Probiotics ; Bacteria/classification/genetics/metabolism/isolation & purification ; Symbiosis ; Antimicrobial Peptides/metabolism ; Host Microbial Interactions ; }, abstract = {The silkworm (Bombyx mori) has emerged as a powerful invertebrate model for gut microbiome research due to its simple yet representative gut microbiota, cost-effective rearing, and established germ-free systems. This review synthesizes current knowledge on the ecological drivers and functional roles of silkworm gut microbiota, emphasizing its interaction with host health, environmental adaptation, and biotechnological applications. The microbial community of silkworms is highly plastic, shaped by various intrinsic (developmental stage, sex) and extrinsic (diet, environmental conditions) factors. Key microbial taxa, including Enterococcus, Bacillus, Acinetobacter, Pseudomonas, and Staphylococcus, form a dynamic core community with demonstrated probiotic attributes. These microbes contribute to nutrient metabolism (such as cellulose digestion and amino acid synthesis), immune modulation (through the production of antimicrobial peptides), and detoxification (by degrading xenobiotics). Meanwhile, their dysbiosis correlates with reduced growth, silk yield, and pathogen resistance. Notably, several gut symbionts produce or stimulate natural antimicrobial proteins, including bacteriocins (such as enterococcin LX) and host-derived antimicrobial peptides, which exhibit activity against microbial pathogens. Understanding these microbial associations is crucial for developing microbe-based probiotic formulations, antimicrobial therapies, and enzyme-driven bioprocesses to enhance sericultural productivity and sustainability. Despite progress, significant gaps remain in our understanding of host-microbe coevolution, immune-microbiota crosstalk, and the genetic basis of microbial resilience. Future research integrating multi-omics approaches and gnotobiotic models will unravel mechanistic insights, enabling targeted manipulation of the silkworm microbiota for agricultural, environmental, and medical innovations.}, } @article {pmid41528365, year = {2026}, author = {Johnsen Stefani, L and Wohlgemuth, S and Schütte, L and Halbgebauer, R and Bergmann, CB and Huber-Lang, M and Wohlgemuth, L}, title = {Macrophages on demand: How tissue trauma shapes their role.}, journal = {European journal of trauma and emergency surgery : official publication of the European Trauma Society}, volume = {52}, number = {1}, pages = {17}, pmid = {41528365}, issn = {1863-9941}, mesh = {Humans ; *Macrophages/immunology/physiology ; *Wounds and Injuries/immunology ; *Wound Healing/immunology ; *Inflammation/immunology ; Regeneration/immunology ; }, abstract = {Macrophages, renowned for their plasticity, are central to both the immune response and tissue repair following physical trauma. This review delineates how tissue trauma dynamically modulates macrophage function across organs, highlighting their dichotomous roles in promoting inflammation versus regeneration. After injury, macrophages shift along a continuum from pro-inflammatory to pro-regenerative states, influenced by local and systemic cues, injury type, and microenvironmental factors, including damage-associated molecular patterns, and cytokines leading to pronounced organ-specific differences. The temporal and spatial dynamics of macrophage recruitment - from resident pools or via monocyte influx - dictate not only healing outcomes but also the risk of organ dysfunction and chronic inflammation. Emerging immunomodulatory strategies, encompassing stem cell therapies, pharmacological phenotype modulation, and microbiome-targeted approaches, underscore the clinical potential of precise macrophage-targeted interventions. Understanding macrophage adaptability post-trauma is crucial for devising organ- and context-specific therapies to optimize tissue repair and minimize adverse outcomes.}, } @article {pmid41528150, year = {2026}, author = {Guo, M and Xia, Z and He, X and Wan, S and Wang, Y and Fan, S and Pérez-Moreno, J and Yang, Z and Yang, C and Liu, D and Yu, F}, title = {High-throughput sequencing reveals endophytic bacterial differentiation of common truffles (Tuber spp.) in China: diversity, biogeographical patterns, and fungal health implications.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0186625}, doi = {10.1128/spectrum.01866-25}, pmid = {41528150}, issn = {2165-0497}, abstract = {UNLABELLED: As valuable hypogeous fungi, truffles depend on fruiting-body-associated microorganisms for lifecycle functions like growth and nutrient cycling. This study sampled fruiting bodies of 10 Tuber species from 16 sites across six major truffle-producing provinces in China, characterizing endophytic bacterial communities via high-throughput sequencing and multivariate analysis. Proteobacteria dominated the endophytic bacteria, with Bradyrhizobium as the prevalent genus. Significant genus-level compositional differences occurred across provenances and species: Bradyrhizobium reached 99.80% relative abundance in Tuber sinense from Mengzi, Yunnan, versus 7.90% in Tuber shii from Dali (12.6-fold difference). Shannon diversity indices (n = 48) revealed striking species- and altitude-related variations (P < 0.001): Tuber lijiangense (5.111) and T. shii (5.091) had the highest diversity, while T. sinense (1.336) had the lowest (3.8-fold gap). Subtropical Dali samples exhibited a sevenfold higher diversity compared to those from the Mengzi region, which is geographically closer to the tropics. Non-metric scaling and principal coordinates analysis identified environmental factors (soil, climate) and host species as primary drivers, with species effects potentially overriding environment. Five core taxa (all Rhizobiales) suggested nitrogen-fixing roles, while Variovorax (via linear discriminant analysis effect size) emerged as an external-disturbance-sensitive opportunist. This study clarifies endophytic bacterial variation patterns and drivers, identifies key taxa, and informs truffle ecological interactions, providing a scientific basis for sustainable resource management and conservation.

IMPORTANCE: This study underscores the critical importance of truffle endophytic bacteria in mediating fungal health and ecological resilience, addressing a major knowledge gap in hypogeous fungal microbiome research. By integrating high-throughput sequencing across 10 Tuber species in China, we reveal how bacterial communities (dominated by Bradyrhizobium) shape biogeographical patterns and functional roles like nitrogen fixation. These findings advance understanding of microbe-fungal symbioses, with direct applications for sustainable truffle cultivation (e.g., microbial inoculants) and climate-resilient management-aligning perfectly with AEM's focus on applied microbial ecology and biotechnological relevance.}, } @article {pmid41528122, year = {2026}, author = {McMurray-Jones, A and Spann, K and Yarlagadda, PKDV and Fernando, J and Roberts, LW}, title = {Environmental surveillance of bacteria in a new intensive care unit using plate sweeps.}, journal = {Microbial genomics}, volume = {12}, number = {1}, pages = {}, pmid = {41528122}, issn = {2057-5858}, mesh = {*Intensive Care Units ; *Bacteria/genetics/isolation & purification/classification/drug effects ; Humans ; Queensland ; *Environmental Monitoring/methods ; Drug Resistance, Bacterial/genetics ; Microbiota/genetics ; Metagenomics/methods ; Cross Infection/microbiology ; }, abstract = {The hospital environment plays a critical role in the transmission of infectious diseases. Surveillance methods often rely on selective enrichment or deep metagenomic sequencing, which both have significant drawbacks in terms of community resolution and cost. Plate sweeps provide a practical moderate approach to cultivate a wide range of bacteria, capturing more diversity than a single colony pick without high sequencing costs. Here, we use this approach to characterize a newly built hospital intensive care unit (ICU) in Queensland, Australia. Between November 2023 and February 2024, we sampled 78 sites within an 8-bed private hospital ICU pre- and post-patient introduction to the environment. Samples were enriched on non-selective media before DNA was extracted from whole plate sweeps and sequenced using Illumina. We assessed species, antimicrobial resistance (AMR) genes, virulence genes and transmission across all samples and between the pre- and post-patient samples using Kraken2, AbritAMR and Tracs. While the rate of positive microbial growth within the ICU environment did not change significantly pre- and post-patient introduction, the post-patient microbiome consisted of largely different bacterial species; of 22 genera identified, only 3 genera were represented at both timepoints. Post-patient samples were enriched in AMR genes, including resistance to fosfomycin, quinolones and beta-lactams. Common genera identified post-patient were Pseudomonas, Delftia and Stenotrophomonas, often associated with areas of plumbing. Cluster analysis identified 17 possible transmission links from a single timepoint, highlighting several areas in the ICU (e.g. communal bathrooms) as key areas for transmission. We demonstrate the utility of plate sweeps as a means of economical non-selective environmental surveillance and highlight their ability to identify hotspots of transmission within a hospital ward that could be targeted by infection control prior to an outbreak of a more serious pathogen.}, } @article {pmid41527932, year = {2026}, author = {Connell, E and Le Gall, G and McArthur, S and Lang, L and Breeze, B and Liaquat, M and Pontifex, MG and Sami, S and Pourtau, L and Gaudout, D and Müller, M and Vauzour, D}, title = {A novel Mediterranean diet-inspired supplement reduces hippocampal amyloid deposits and microglial activation through the modulation of the microbiota gut-brain axis in 5xFAD mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2614030}, doi = {10.1080/19490976.2026.2614030}, pmid = {41527932}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Microglia/drug effects/metabolism ; *Hippocampus/metabolism/drug effects/pathology ; Mice ; Male ; *Diet, Mediterranean ; Mice, Transgenic ; *Alzheimer Disease/metabolism/diet therapy/microbiology ; Female ; *Dietary Supplements ; Disease Models, Animal ; Amyloid beta-Peptides/metabolism ; Humans ; Brain-Gut Axis ; Brain/metabolism ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is projected to increase in prevalence, heightening the need for strategies to alleviate its neuropathological burden. The bioactive constituents of a Mediterranean-style diet are well-recognised for their neuroprotective properties. Due to their capacity to alter the gut microbiome composition, these benefits may involve modulation of the microbiota-gut-brain axis. In this study, we investigated whether a novel supplement enriched with key Mediterranean diet-derived bioactives (Neurosyn240) could reduce amyloid deposition and microglial activation in 5xFAD mice, a transgenic model of AD, through microbiota-mediated mechanisms.

METHODS: Male and female 5xFAD transgenic mice (n = 16 per sex) were randomly assigned to receive either a standard control diet or a diet supplemented with Neurosyn240 for 12 weeks. Employing a multi-omics approach, gut microbiota composition was profiled using 16S rRNA ampliconsequencing, serum metabolites were quantified via targeted metabolomics, and hippocampal gene expression was analysed through qPCR and RNA sequencing. Neuropathological markers, including amyloid-β deposition and microglial activation, were evaluated using immunofluorescence staining. Statistical analyses were performed using two-way ANOVA to examine the main effects of diet and sex and their interaction.

RESULTS: Neurosyn240 significantly shifted the gut microbiome composition, which was associated with increased circulatory serotonin levels and decreased kynurenine and bile acids (TCA, HDCA, TDCA, CDCA and LCA) concentrations. In the brain, Neurosyn240 consumption led to a significant reduction in hippocampal amyloid deposits and Iba-1 positive microglia (p<0.05), which were associated with decreased LCA and increased serotonin, respectively. Hippocampal RNA sequencing further highlighted the upregulation of genes involved in promoting amyloid beta clearance mechanisms.

CONCLUSIONS: Together, these findings highlight novel neuroprotective effects of Neurosyn240 in modulating metabolite-mediated pathways of the microbiota-gut-brain axis, accentuating its therapeutic potential against AD progression.}, } @article {pmid41527485, year = {2026}, author = {Cheng, Q and Nolz, J and Karr, T and Dorn, N and Readhead, B and Krajmalnik-Brown, R and Mastroeni, D}, title = {Gut proteome and microbiome alterations: Analysis of transverse colon samples from pathologically confirmed Alzheimer's disease patients.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {22}, number = {1}, pages = {e71021}, doi = {10.1002/alz.71021}, pmid = {41527485}, issn = {1552-5279}, support = {U24 NS072026/NS/NINDS NIH HHS/United States ; P30AG19610//the National Institute on Aging/ ; P30AG072980//the National Institute on Aging/ ; 211002//the Arizona Department of Health Services/ ; 4001//the Arizona Biomedical Research Commission/ ; 0011//the Arizona Biomedical Research Commission/ ; 05-901//the Arizona Biomedical Research Commission/ ; and 1001//the Arizona Biomedical Research Commission/ ; //the Michael J. Fox Foundation for Parkinson's Research/ ; //Arizona Alzheimer's Consortium/ ; //Biodesign Center for Health Through Microbiomes/ ; }, mesh = {Humans ; *Alzheimer Disease/pathology/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Proteome/metabolism ; Female ; Male ; *Colon/microbiology/metabolism/pathology ; Aged ; Proteomics ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism ; }, abstract = {INTRODUCTION: Alzheimer's disease (AD) has been regarded as a brain-first disorder. Emerging evidence suggests that the gut may influence central nervous system pathology, but the mechanisms remain unclear.

METHODS: We conducted a proteomic and microbial analysis of transverse colon samples from clinically and pathologically confirmed AD and control cases.

RESULTS: In the AD gut samples, antimicrobial humoral response and oxidative stress response were downregulated, while catabolic processes and insulin signaling were upregulated. Several complement (e.g., C5) and synaptic (e.g., synaptophysin) proteins were downregulated. Amyloid beta 42 was detected at higher levels. Christensenellaceae, Desulfovibrio, and Candida tropicalis amplicon sequence variants were higher in abundance, while Streptococcus, Lachnospiraceae, Blautia, and Nakaseomyces were lower. In general, bacterial composition correlated with AD clinical variables such as plaque and tangle burden.

DISCUSSION: These findings underscore the gut's possible involvement in AD pathogenesis and provide new insights into potential biomarkers and therapeutic targets.

HIGHLIGHTS: This study provides the first in-depth analysis of the proteome and microbiome in AD transverse colon tissues. Multiple immune and oxidative stress response pathways were downregulated in AD, while metabolic pathways were upregulated. Synaptic protein, complement protein, and Aβ42 levels were significantly different between AD and controls. Transverse colon microbial composition was associated with AD clinical variables.}, } @article {pmid41527479, year = {2026}, author = {Zhang, T and Yu, Y and Bu, F and Li, J and Zhou, M and Lin, L and Zheng, L and Cheng, Y}, title = {Biodegradation of polypropylene by yellow mealworm (Tenebrio molitor) larvae: response of gut microbiome and metabolome to plastic polymers.}, journal = {Insect science}, volume = {}, number = {}, pages = {}, doi = {10.1111/1744-7917.70223}, pmid = {41527479}, issn = {1744-7917}, support = {No. 2024J08148//Natural Science Foundation of Fujian Province/ ; No.MEEST-2023-05//MNR Key Laboratory of Eco-Environmental Science and Technology, China/ ; No.2021N040//Science and Technology Plan Project of Quanzhou City/ ; No.JAT220031//Education and Research Foundation of the Ministry of Education of Fujian Province for Young Teachers/ ; }, abstract = {The widespread use and improper disposal of polypropylene (PP) facemasks have resulted in persistent environmental pollution, posing urgent challenges for waste management. This study added bran-PP mixture, which increased the survival rate, consumption rate and removal rate of Tenebrio molitor feeding solely on PP. The average consumption of the larvae fed with the edible bran-PP mixture was 61.54% higher than those fed only PP. The removal rates were 39.26% and 36.14%, respectively. Fourier-transform infrared spectroscopy, thermal gravimetric analysis, gel permeation chromatography, and nuclear magnetic resonance confirmed the production of oxygenated compounds in the larval gut, indicating partial oxidation and degradation of PP masks within the intestinal tract. HT-GPC analysis revealed significant reductions in molecular weight parameters, with the number-average (Mn), weight-average (Mw), and Z-average (Mz) molecular weights decreasing by 51.07%, 33.60%, and 32.99%, respectively. High-throughput 16S rRNA sequencing revealed that feeding on PP enhanced gut microbiota richness and diversity. The bran-PP mixture group exhibited significantly higher relative abundances of Enterobacter and Spiroplasma, whereas the bran group was dominated by Lactobacillus. PICRUSt functional predictions indicated upregulation of plastic degradation-associated oxidases (alkane 1-monooxygenase, cyclohexanone monooxygenase) and hydrolases (chitinase, carboxylesterase) in larvae fed PP or bran-PP diets. Metabolomic profiling revealed significant enrichment in pathways related to histidine, glycerophospholipid, choline and steroid hormone metabolism in PP-fed larvae. These findings demonstrate that PP can be biodegraded in T. molitor larvae through gut microbe-mediated depolymerization involving a diverse microbial community.}, } @article {pmid41527353, year = {2026}, author = {Lu, Y and Zhang, CQ and Xu, XM and Zhu, WB and Hu, CY and Gong, T and Meng, YH}, title = {Novel Methylenetransferase from Human Gut Strain L. longoviformis Initiates Sesamin Conversion and Its Catalytic Mechanism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13970}, pmid = {41527353}, issn = {1520-5118}, abstract = {Gut microbiota governs lignan bioactivation, yet the specific enzymes involved remain poorly characterized. Here, we identified a novel sesamin methylenetransferase from Lactonifactor longoviformis, LacAMT, that catalyzes the methylenedioxy bridge cleavage of sesamin (SESA) into catechol metabolites, with Km and kcat values of 1.203 mM and 0.83 min[-1]. LacAMT homologues are rare in human gut microbes, mainly in the Lachnospiraceae and Clostridiaceae families. Structural and mutational analyses revealed that LacAMT employs a unique catalytic mechanism distinct from those of typical GcvT methyltransferases and hepatic P450s. LacAMT cleaves SESA's methylenedioxy bridge and transfers the methylene group to tetrahydrofolate through Y218 and H222, acting as an acid-base pair. Moreover, enhanced substrate binding with Y218 likely facilitates proton transfer, resulting in 3.33-fold and 2.12-fold increases in catalytic efficiency for W107E and V94A, respectively. These findings elucidate how the human gut microbiome activates plant secondary metabolites, advancing our understanding of the interplay among the diet, gut microbiota, and human health.}, } @article {pmid41527254, year = {2026}, author = {London, RE}, title = {Microbiome-generated antifolates.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.70252}, pmid = {41527254}, issn = {1873-3468}, support = {ZIA ES050111/ES/NIEHS NIH HHS/United States ; }, abstract = {The folate biosynthesis activity of the human microbiome provides reduced folate metabolites that are readily absorbed from the gastrointestinal (GI) tract. The bacterial folate biosynthesis enzyme dihydropteroate synthase (DHPS), which adds p-aminobenzoate (pABA) to an activated pterin precursor, is an important antibiotic target. Both the broad-spectrum p-aminobenzenesulfonamide antibiotics, and the drug p-aminosalicylate (PAS, 2-hydroxy-pABA) with high selectivity for Mycobacterium tuberculosis, are competitive DHPS substrates. The adducts formed from these drugs, DHP-sulfonamides (sulfapterins) and 2'-hydroxyfolate metabolites, respectively, have been reported to exhibit antifolate activity in studies of microorganisms. The presence of these DHP-adducts and their effects on the host organism are largely undetermined; however, their close structural relationship to dihydrofolate (DHF) suggests that they are likely to mediate some side effects reported for these antibiotics. Naturally occurring pABA analogs that probably function similar to DHPS-targeted antibiotics have been identified in carrots and bacteria. Impact statement pABA analogs represent an important class of antibiotics, that are converted into dihydrofolate analogs by organisms present in the human microbiome. These analogs may mediate reported side-effects associated with these antibiotics. Several naturally occurring pABA mimics have been identified that are likely to exhibit antibiotic activity.}, } @article {pmid41527156, year = {2026}, author = {Buffoni, M and Kerkvliet, JJ and Enting, H and Kers, JG and Rogers, M and Visser, JAGM and Paganelli, FL and Willems, RJL and Schürch, AC}, title = {Coccidiosis prevention strategies shape the microbiome, resistome and mobilome composition in the broiler gut.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {3}, pmid = {41527156}, issn = {2524-4671}, abstract = {BACKGROUND: Coccidiosis is a parasitic infection in the gut of livestock that poses a significant health challenge in poultry farming, underscoring the important role of intervention and prevention strategies in the poultry industry. The use of anticoccidial drugs raises concerns about antimicrobial resistance (AMR) due to their antimicrobial properties and the ability of bacteria to evolve resistance to these drugs. Whether anticoccidial drug resistance could extend beyond coccidiostats, leading to cross-resistance and co-selection against other antimicrobial resistance genes (ARGs), is currently under discussion. Also, it is not well understood to what extent coccidiosis reduction strategies may enable the emergence of ARGs in farm environments and transmission of ARGs to other environments through bacterial clonal transfer or horizontal transmission via mobile genetic elements (MGEs) like plasmids or transposons.

RESULTS: In this study, we used metagenomic sequencing of caecal and faecal dropping samples from broiler chickens to investigate how two anticoccidial prevention strategies (vaccination and coccidiostat drugs) influence bacterial taxonomic composition and ARG profiles. We also explored the mobile resistome, ARGs located on mobile genetic elements (MGEs) such as plasmids, which are capable of disseminating, investigating ARGs identifying with the potential to disseminate within and beyond farm settings. Our exploratory findings in bacterial composition, as well as resistome composition with 21 differentially abundant ARGs, illustrating the potential impact of anticoccidial strategies on the chicken gut microbiome and resistome. We also identified 14 plasmid fragments containing ARGs in faecal dropping samples, highlighting mobile ARGs potentially able to disseminate to other environments, including humans.

CONCLUSIONS: Our findings demonstrate the impact of anticoccidial strategies on the chicken gut microbiome and resistome with potential consequences for the dissemination of ARGs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00497-7.}, } @article {pmid41527141, year = {2026}, author = {Liu, YY and Xia, F and Yimuran, R and Nuermamaiti, A and Yang, Y and Zhou, JT}, title = {Assessing whether rectal swabs reflect appendiceal microbiota profiles in acute appendicitis: a 16S rRNA-based comparative study.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-025-00794-1}, pmid = {41527141}, issn = {1757-4749}, support = {2023D01A93//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; }, abstract = {BACKGROUND: Acute appendicitis is associated with characteristic changes in the intestinal microbiota, but direct sampling of appendiceal contents is invasive and cannot be performed in healthy controls. We therefore evaluated whether rectal swabs could partially capture appendiceal microbiome signatures in adults with acute appendicitis.

METHODS: In a prospective cross-sectional study, we enrolled adults with acute appendicitis and healthy volunteers between October 2023 and December 2024. Four types of samples were collected: feces from healthy controls (HC), appendiceal luminal contents from patients with acute appendicitis (AC), intraoperative rectal swabs from patients with acute appendicitis (RS), and initial postoperative feces from patients with acute appendicitis (IF; first stool within 24 h after surgery). 16 S rRNA gene (V3-V4) sequencing was performed, and reads were processed with QIIME2. Alpha and beta diversity, differential taxonomic composition, and PICRUSt2-based functional predictions were compared across matrices. Genus-level and functional concordance between paired AC-RS samples was assessed.

RESULTS: After quality control, 64 AC, 34 RS, 24 IF, and 29 HC samples were included. Phylogenetic diversity (PD whole-tree) was higher in AC and RS than HC, with AC also higher than RS; IF showed lower PD than AC. Bray-Curtis principal coordinate analysis showed AC forming a distinct cluster separated from HC and RS along PC1, whereas IF overlapped with HC and RS. AC, RS, and IF were enriched for Escherichia/Shigella and Fusobacterium and depleted in butyrate-producing genera such as Faecalibacterium compared with HC. In the 21 paired AC-RS cases, genus-level relative abundances and several predicted functional pathways showed concordance, indicating that RS captured many but not all appendiceal dysbiosis features.

CONCLUSIONS: Our findings suggest that intraoperative rectal swabs may partially reflect appendiceal microbiome alterations at the genus and pathway levels and may serve as a minimally invasive adjunct for microbiome profiling in acute appendicitis. However, these associations are inferred from 16 S amplicon data in a modestly sized, antibiotic-exposed cohort and should be validated using shotgun metagenomics in larger, clinically stratified populations.}, } @article {pmid41527126, year = {2026}, author = {Zhu, H and Li, M and Lu, C and Wang, J and Ouyang, K and Zhang, J and Li, X and Chen, WH and Xiao, M}, title = {Efficacy of very low calorie diet in the intervention of obesity and the changes in oral microbiota: a prospective cohort study.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-025-07087-w}, pmid = {41527126}, issn = {1479-5876}, support = {No.82274352//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Very Low Calorie Diet (VLCD) is a stringent caloric restriction regimen used in the short-term management of obese patients, which can effectively reduce body weight and blood glucose levels. This prospective study aimed to evaluate the short-term impacts of a VLCD on body composition, metabolic parameters, and oral microbiota in obese adults, exploring its therapeutic potential for metabolic dysfunction and inflammation-related comorbidities.

METHODS: This prospective study was conducted on the basis of a cohort of overweight/obese individuals at Affiliated Hospital of Hubei University of Chinese Medicine. Patient eligibility for inclusion in this study was determined by the adoption of a complete short-term VLCD therapy following their entry into the cohort. The study aimed to explore the improvements in body composition, blood glucose, blood lipids, and inflammatory markers post-VLCD intervention, as well as the safety of the treatment. Additionally, it analyzed the changes in the microbiota of the upper gastrointestinal tract, specifically the oral coating. The study was concluded on December 31, 2023.

RESULTS: In the per-protocol cohort (n = 101), the VLCD intervention induced rapid, clinically meaningful reductions in body weight, body fat mass(BFM), body mass index (BMI), and visceral fat area(VFA). Skeletal muscle mass(SMM) decreased modestly. Metabolic parameters improved significantly, with decreases in fasting blood glucose (FBG), fasting insulin (FIns), and homeostasis model assessment of insulin resistance (HOMA-IR). Lipid profiles showed transient increases in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (CHOL) at day 5, normalizing by two-week follow-up, alongside reduced triglycerides (TG). Systemic inflammation markers declined after resuming normal diet, including alanine aminotransferase (ALT) and high-sensitivity C-reactive protein (hs-CRP); uric acid (UA) peaked transiently during the VLCD before falling below baseline. Tongue-coating microbiota exhibited increased Shannon diversity and shifted community structure, with 12 reduced species associated with 19 systemic diseases.

CONCLUSIONS: The VLCD intervention shows significant short-term benefits in weight loss and body fat reduction. Furthermore, it shows potential for reducing the risk of chronic diseases by modulating systemic inflammation and altering the oral microbiome. Further studies are warranted to assess long-term efficacy and sustainability.

TRIAL REGISTRATION: Chinese Clinical Trail Registry (No. ChiCTR2200063126, date of registration: 31 August 2022), https://www.chictr.org.cn/hvshowproject.html?id=188695&v=1.2.}, } @article {pmid41527105, year = {2026}, author = {Pang, T and Wang, C and Jiao, G and Fan, X and Huang, D and Long, Z and Xiao, M and Sun, L and Chen, W and Zhang, F}, title = {Therapeutic potential of Sheng-Xian-Tang in doxorubicin-induced chronic heart failure by regulation of phenylalanine metabolism disruption.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {29}, pmid = {41527105}, issn = {1749-8546}, support = {2022YFC3501700//National Key Research and Development Program of China/ ; 82274059//National Natural Science Foundation of China/ ; SL-33//Naval Military Medical University Far East Talent Project/ ; NO. CPA-Z05-ZC-2024-003//Talent Project established by Chinese Pharmaceutical Association Hospital Pharmacy department/ ; }, abstract = {BACKGROUND: Sheng-Xian-Tang (SXT), a traditional Chinese medicine, ameliorates doxorubicin (DOX)-induced chronic heart failure (CHF), yet its molecular mechanisms remain elusive.

OBJECTIVE: To elucidate SXT's cardioprotective mechanisms against DOX-induced CHF.

METHODS: In vivo, cardioprotection was evaluated via echocardiography, oxidative stress assays, and histopathology. Integrated metabolomic and 16S rRNA sequencing identified metabolic disruptions. Serum pharmacochemistry analysis identified hepatic bioactive compounds targeting phenylalanine hydroxylase (PAH). Molecular docking, CETSA, SPR, and enzyme activity assay validated neomangiferin-PAH interactions.

RESULTS: SXT dose-dependently improved DOX-induced cardiac dysfunction in rats. Metabolomic and microbiome analyses confirmed phenylalanine metabolic disorder in the CHF rats. DOX exposure elevated phenylalanine levels in plasma, urine, and heart, reducing hepatic PAH expression and function while inducing ectopic phenylalanine catabolism in the heart. Phenylalanine administration exacerbated the cardiac abnormalities, whereas SXT effectively prevented attenuated DOX-induced cardiac toxicity. CETSA and SPR revealed a strong binding of neomangiferin to PAH, stabilizing its interaction with cofactor BH4 and preventing DOX-induced PAH inhibition.

CONCLUSIONS: SXT mitigated DOX-induced CHF through hepatic PAH modulation. Neomangiferin could enhance PAH stability via competitive binding. Targeting PAH-phenylalanine metabolism emerged as a novel therapeutic strategy for DOX-induced cardiac dysfunction.}, } @article {pmid41526999, year = {2026}, author = {Xu, L and Zhu, S and Sun, HZ and Yan, Y and Wang, X and Li, X and Bu, D}, title = {Intracellular microbial signals in the gastrointestinal tract of dairy cattle.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02319-z}, pmid = {41526999}, issn = {2049-2618}, support = {ZR2025MS327//Natural Science Foundation of Shandong Province/ ; ZR2024QC105//Natural Science Foundation of Shandong Province/ ; 25-1-1-251-zyyd-jch//Qingdao Natural Science Foundation/ ; 32102553//National Natural Science Foundation of China/ ; LR23C170001//Natural Science Foundation of Zhejiang Province/ ; }, abstract = {BACKGROUND: The presence of intracellular microbiota in epithelial cells of gastrointestinal tracts (GITs) of dairy cows, as well as their associations with rumen development, remains unclear.

RESULTS: Using a single-cell analysis of host-microbiome interactions (SAHMI) within a single-cell atlas derived from ten GITs tissue types collected from new-born (NB) and adult (AD) cows, we found that 20.5% of the single-cell RNA sequencing reads aligned to reference microbial genomes after filtering low-quality single cells and doublets. Comparative analysis revealed that abomasum tissue exhibited the highest proportion of cells detected microbial signals, with Paneth cells possessing the most genes classified as both marker genes and those related to microbial signals. In the NB rumen, Basal cells demonstrated the greatest overlap between differentially expressed genes in AD vs. NB comparison and the microbial signal-related genes. Notably, these microbiota-associated genes, which are mainly linked to Aliiroseovarius crassostreae, Enterobacter sp. T2, and Enzebya pacifica, are implicated in nucleotide excision repair mechanisms, including DNA replication and the cell cycle. Furthermore, bacterial fluorescence in situ hybridization (FISH) analysis indicated that these three microbial species were partially localized within the cytoplasm and nucleus of rumen epithelial cells in NB cattle.

CONCLUSIONS: These findings provide substantial evidence supporting the existence of an intracellular microbiome within the GITs of dairy cattle and highlight their potential relationships with rumen development. This research enhances our understanding of the crosstalk between hosts and microbiome during the maturation of ruminants. Video Abstract.}, } @article {pmid41526953, year = {2026}, author = {Quijia-Pillajo, J and Naik, S and Chapin, LJ and Owen, JS and Jones, ML}, title = {Calcium phosphate-solubilizing bacteria promote growth and alleviate phosphorus deficiency in French marigold with minimal impact on the rhizosphere microbiome.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-025-00844-w}, pmid = {41526953}, issn = {2524-6372}, support = {2021-09976//NIFA Agriculture and Food Research Initiative - Foundational Knowledge of Agricultural Production Systems/ ; }, abstract = {BACKGROUND: Plant roots are surrounded by communities of microbes that influence plant growth, development, and disease resistance. In soilless culture, microbial diversity in root-associated communities primarily originates from the substrate, irrigation water, and applied microbial inoculants. Phosphate solubilizing bacteria (PSB) capable of mobilizing phosphate from insoluble Ca3(PO4)2 were identified from a greenhouse rhizobacteria collection. Plant growth promoting efficacy was investigated at different substrate pH. The influence of the inoculum composition on plant growth responses to the bacteria was also evaluated. Finally, we analyzed the impact of PSB inoculation on microbiome composition and function.

RESULTS: From 1044 isolates in the rhizobacteria collection, 14 solubilized more than 25% of the phosphorus provided in vitro. Only eight bacterial strains resulted in growth promotion benefits in planta when inoculated as a substrate drench onto marigolds grown in a peat-based substrate (pH 7.0) and fertilized with insoluble Ca3(PO4)2. In a follow up experiment, two newly identified (Pantoea sp. C2G6 and Enterobacter soli C4A1) and three previously identified PSB (Pantoea trifolii C2B11, Pantoea formicae C8D10, and Bacillus velezensis) that have demonstrated superior phosphate-mineral solubilization were evaluated. The PSB were tested at a substrate pH of 6.0 and 6.5 using water, 1% glucose, 2% Micromate, or 0.1X Luria-Bertani (LB) broth as inoculant supplements. All five bacteria promoted growth and improved plant health at both pH levels. A greater benefit to marigold growth and health was observed in plants growing at pH 6.5. C2B11, C8D10, C2G6, and B. velezensis treatment resulted in a significant increase in shoot P content. Microbiome diversity and community structure exhibited no significant alterations in response to PSB treatment. Genes enriched in PSB treated rhizospheres were mostly related to colonization, competition, and biofertilization traits.

CONCLUSIONS: PSB isolated from the rhizosphere of floriculture crops grown in soilless substrates promoted growth and enhanced health of marigolds grown under P limitation. They also enhanced growth under optimal or slightly basic pH, but their efficacy was not improved by the inoculant supplements evaluated in this experiment. The native microbial community in peat-based soilless substrate was resilient to PSB inoculation.}, } @article {pmid41526937, year = {2026}, author = {Arı, M and Erdogan, MA and Erbaş, O}, title = {Mitigative effects of Otilonium Bromide on methotrexate-induced hepatic damage in rats.}, journal = {BMC research notes}, volume = {19}, number = {1}, pages = {15}, pmid = {41526937}, issn = {1756-0500}, abstract = {OBJECTIVE: Hepatotoxicity is a significant adverse effect associated with long-term methotrexate (MTX) treatment, limiting its clinical utility. This study aimed to comprehensively evaluate the potential hepatoprotective effects of Otilonium Bromide (OB) against MTX-induced liver injury in an experimental rat model by integrating biochemical, molecular, and histopathological assessments.

RESULTS: MTX administration resulted in significant structural and functional liver damage, as evidenced by elevated biochemical markers, alanine aminotransferase (ALT), transforming growth factor-beta (TGF-β), NOD-like receptor family pyrin domain-containing 3 (NLRP3), platelet-derived growth factor (PDGF), malondialdehyde (MDA) and worsened histopathological scores, including increased hepatocyte necrosis, fibrosis, and cellular infiltration. Treatment with OB significantly reduced these biochemical markers and improved histopathological changes compared to the MTX + saline group. Otilonium Bromide demonstrated hepatoprotective effects in the rat model of MTX-induced liver injury, likely through its anti-inflammatory and antifibrotic properties. These effects may be mediated by modulation of oxidative stress and the intestinal microbiome. Further studies are needed to explore its clinical applicability.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-025-07585-6.}, } @article {pmid41526934, year = {2026}, author = {Fallahzadeh, A and Mahmoodi, T and Kwon, S and Liu, M and Nolan, A}, title = {Multi-omics of oxidative stress and particulate matter exposure: a systematic review.}, journal = {Respiratory research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12931-025-03487-0}, pmid = {41526934}, issn = {1465-993X}, support = {U01 -OH012069; -OH011855; -OH011300//Centers for Disease Control and Prevention Foundation/ ; UL1TR001445; KL2TR001446/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Exposure to particulate matter (PM) is a significant public health concern associated with respiratory, cardiovascular, and metabolic diseases. Oxidative stress is a key biological mechanism mediating the harmful effects of PM exposure. However, a comprehensive review of relating PM exposure to omics layers of oxidative stress has been lacking. We aimed to systematically review the current evidence on the associations between PM exposure and the multi-omics signatures of oxidative stress.

METHODS: We conducted a systematic review of studies published between January 2021 and March 2024 in PubMed and Web of Science, following a registered protocol (PROSPERO ID: CRD42024617742). Eligible studies assessed the impact of PM exposure on oxidative stress-related omics in adult human populations. Data on exposure assessment, study characteristics, and omics outcomes were extracted, and the risk of bias was evaluated using the Newcastle-Ottawa Scale and Cochrane's.

RESULTS: Seventy-seven studies were included. PM exposure was consistently associated with oxidative stress markers across multiple omics platforms. Studies on the analytes showed that PM was associated with an increase in oxidative markers. Metabolomics studies revealed alterations in pro-oxidant metabolites (e.g., eicosanoids, ceramides) and disruptions in antioxidant pathways (e.g., glutathione, vitamin C, and E metabolism). PM exposure was also linked to changes in energy metabolism, fatty acid oxidation, and detoxification pathways. Genomics studies reported differential methylation in genes involved in oxidative stress and inflammation. Microbiome studies suggest that PM exposure alters the composition of gut and nasal microbiota, favoring a pro-oxidative profile. However, some studies reported no significant associations, highlighting heterogeneity in findings.

CONCLUSION: Our systematic review demonstrates that PM exposure affects multiple molecular pathways related to oxidative stress across diverse omics platforms. These findings highlight the complex responses to PM, underscoring the need for integrative multi-omics approaches to fully understand the health impacts of air pollution.}, } @article {pmid41526899, year = {2026}, author = {Jia, K and Chen, Y and Dai, D and Xie, Y and Peng, H and Cao, Y and Zou, H and Qiu, C and Tan, Y and Zhang, X and Lu, Z and Yin, X and Peng, Z and Li, J and Shen, L}, title = {Impact of Helicobacter pylori infection on gut and intratumoral microbiome and its association with immunotherapy response in gastrointestinal cancer.}, journal = {BMC medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12916-025-04575-0}, pmid = {41526899}, issn = {1741-7015}, support = {823B2069//National Natural Science Foundation of China/ ; 82203881//National Natural Science Foundation of China/ ; U22A20327//National Natural Science Foundation of China/ ; 7222021//Beijing Natural Science Foundation/ ; QMS20201102//Beijing Hospitals Authority Youth Programme/ ; }, abstract = {BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with enhanced efficacy of immunotherapy in gastric cancer (GC). However, the mechanisms underlying this enhancement are not fully understood.

METHODS: We recruited 218 GC patients, 134 esophageal squamous cell carcinoma (ESCC) patients, and 86 dMMR/MSI-H colorectal cancer (CC) patients and collected their stool and tumor samples to analyze the gut and intratumoral microbiome. We assessed microbial diversity and composition and correlated these findings with clinical outcomes to evaluate the relationship between H. pylori status, microbiome alterations, and immunotherapy efficacy.

RESULTS: H. pylori-positive patients showed higher alpha diversity and unique microbial signatures, which were associated with increased immune-related progression-free survival (irPFS) and overall survival (irOS). In addition, we found that the abundance of 45 gut microbiome species was significantly different between the two groups. The gut microbiome of the H. pylori-positive GC group was enriched with species such as Clostridium leptum, Oscillibacter sp. ER4, and Ruminococcus bromii, which were associated with improved treatment response. However, they predicted poor prognosis in patients with esophageal squamous cell carcinoma and colorectal cancer patients with dMMR/MSI-H. Microbial co-occurrence network revealed significantly distinct interaction patterns among the groups. In addition, we found enhanced L-arginine biosynthesis in the gut microbiome of H. pylori-positive GC. In terms of intratumoral bacteria, we identified two genera, Streptococcus and Granulicatella, that were mutually exclusive with H. pylori infection in GC. Enhanced L-lysine fermentation to acetate and butanoate was observed among intratumoral bacteria, suggesting potential metabolic shifts in the tumor microenvironment. Incorporating H. pylori infection status into the microbiome-based prediction model further improved the accuracy of predicting immunotherapy outcomes in GC.

CONCLUSION: These findings suggest that H. pylori had significant effects on the structure and functional activity of gut and intratumoral microbiome, some of which may affect the efficacy of immunotherapy. The clinical value of H. pylori infection status should be considered when establishing a prediction model for immunotherapy efficacy based on gut microbiome.}, } @article {pmid41526636, year = {2026}, author = {Neff, HA and Yıldız-Altay, Ü and Salam, N and Ward, DV and Shepard, D and Ramirez-Ortiz, ZG and Richmond, JM}, title = {Gut dysbiosis in a murine model of cutaneous lupus erythematosus correlates with antigen-specific T cells and antigen-presenting cells in skin.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-34741-6}, pmid = {41526636}, issn = {2045-2322}, support = {Mechanisms & Targets Award//Lupus Research Alliance/ ; Mechanisms & Targets Award//Lupus Research Alliance/ ; }, abstract = {The commensal organisms constituting the human microbiome are increasingly appreciated to fortify epithelial barriers and modulate host immunity. Dysbiosis of both single strains and communities can contribute to inflammatory conditions. Here, we sought to characterize potential dysbiosis in our inducible mouse model of cutaneous lupus erythematosus (CLE). We hypothesized that gut dysbiosis would occur based on several studies that found lower Firmicutes/Bacteroidetes (F/B) ratios and decreased diversity in systemic lupus erythematosus (SLE) cohorts compared to healthy counterparts, a mouse study that identified Ro60 commensal orthologs that can trigger onset of lupus-like disease, and a study of CLE that identified outgrowth of Staphylococcus aureus in the skin. Using whole genome shotgun sequencing, we identified differences in pre- and post-irradiation cohorts, particularly an increase in Duncaniella, a decrease in Prevotella, and a reduction in alpha diversity following irradiation. Baseline alterations in CLE mice gut bacteria compared to littermate controls were also extant, including trends toward increased Parabacterides distasonis and Bacteroides acidifaciens in CLE mice. Importantly, we noted an increase in Phocaeicola sartorii in CLE mice compared to littermate controls post-disease induction. We examined the mycobiome in our mice and noted a reduction of Colletotrichum tofieldiae specifically in CLE mice post-disease induction, and a trend towards increased Periglandula ipomoeae. Last, we correlated abundance of genera and species with flow cytometry data obtained from the skin, lymph node and spleen, and identified specific strains that correlated with presence of antigen-specific T cells and different antigen presenting cell populations. Thus, our model exhibits similar changes to other models of lupus-like disease, and our data identify potential novel strains/species that could be modified for CLE and/or SLE treatment such as through generation of probiotics or specific antimicrobial agents.}, } @article {pmid41526566, year = {2026}, author = {Swarte, JC and Zhang, S and Bakker, SJL and Björk, JR and Weersma, RK}, title = {The gut microbiome in solid-organ and haematopoietic-stem-cell transplantation.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {41526566}, issn = {1740-1534}, abstract = {Solid-organ transplantation (for example, kidney or liver) and haematopoietic-stem-cell transplantation have revolutionized treatment of end-stage organ failure and haematological malignancies. However, long-term outcomes are often undermined by complications such as allograft rejection, graft-versus-host disease in haematopoietic-stem-cell recipients, opportunistic infections, adverse effects of drugs and decreased quality of life. Emerging evidence now highlights the gut microbiome and its metabolites (such as short-chain fatty acids) as a potentially modifiable factor influencing transplantation outcomes. Transplantation recipients frequently exhibit gut dysbiosis, which has been linked to graft function, risk of infection (for example, vulnerability to multidrug-resistant bacteria), immune-mediated complications and patient survival. Furthermore, pharmacomicrobiomics studies indicate that microorganisms can metabolize immunosuppressive drugs into less active forms (such as the conversion of the immunosuppressive drug tacrolimus into less active or toxic forms through keto-reduction, glucuronidation or deconjugation) or can activate prodrugs (such as the conversion of mycophenolate mofetil into mycophenolic acid), thereby modulating drug efficacy and safety. Here, we discuss how the intestinal ecosystem is altered and persistently shaped by transplantation-related factors and immunosuppression and how these changes correlate with clinical outcomes. We provide a perspective on leveraging microbiome insights, through biomarkers or microbiome-targeted interventions, to improve outcomes in solid-organ and stem-cell transplantation.}, } @article {pmid41526497, year = {2026}, author = {Iktilat, K and Levin, G and Isacson, M and Turjeman, S and Tzemah-Shahar, R and Gamliel, G and Louzoun, Y and Koren, O and Agmon, M}, title = {Integrating gut microbiota and violence exposure metrics to classify psychological distress in middle-aged adults.}, journal = {Communications medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s43856-025-01319-2}, pmid = {41526497}, issn = {2730-664X}, abstract = {BACKGROUND: Exposure to violence and psychological distress are positively correlated across populations. Microbiota-gut-brain crosstalk research supports that the microbiota is affected by environmental stressors and may influence mental state. Accordingly, we explored how the microbiota relates to exposure to violence and distress in midlife, a pivotal yet underexplored period. This life stage is marked by emerging vulnerability to chronic stress and mental health decline yet offers opportunities for early identification and intervention.

METHODS: We characterized the fecal microbiota of a previosly snowball-recruited Israeli-Muslim cohort (n = 305, 40-65 yrs) exposed to ongoing and increasing violence (during adulthood) and examined correlations with subjective reports of exposure to violence and psychological distress. We then used machine learning to leverage microbiota profiles and exposure to violence, classifying individuals into high- and low-distress categories.

RESULTS: We identify unique microbial signatures associated with increasing exposure to violence and distress. Some associated bacteria were previously identified in the literature, while others were not yet described in the context of the gut-brain axis. Microbial profiles associated with violence and distress are largely non-overlapping, yet we are able to classify participants into high- and low distress categories using a combination of microbiota and violence variables. This combined model outperforms those using only microbiota or demographics, but its classification accuracy remains modest (with a median area-under-the-curve of 0.595 (IQR 0.045).

CONCLUSIONS: This research sheds light on the microbiota-gut-brain axis, highlighting that psychological distress and exposure to violence are differentially associated with microbiota composition in midlife. These cross-sectional findings, together with moderate classification into distress classes based on the microbiome, suggest that holistic, context-aware approaches would benefit proactive mental health interventions.}, } @article {pmid41526493, year = {2026}, author = {Smith, DR and Haq, S and Niu, M and Malla, S and Saha, R and Peer, A and Bianco, P and Romanova, S and Samuelson, DR and Knoell, DL}, title = {ZIP8 loss impairs macrophage-mediated phagolysosomal removal of bacteria and is overcome by butyrate supplementation.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-025-09504-8}, pmid = {41526493}, issn = {2399-3642}, support = {5R35GM143009//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {Zinc deficiency impacts billions of people and contributes significantly to the increased incidence of community-acquired pneumonia worldwide. Myeloid cells require the zinc transporter ZIP8 for proper host defense. Previously, we observed that infection with S.pneumoniae in myeloid-specific Zip8 knockout mice (Zip8KO) results in increased bacterial burden and mortality despite increased recruitment of macrophages into the lung. Here, we reveal that the lungs of infected Zip8KO mice generate a unique population of dysfunctional macrophages with defects in phagolysosomal function and cell survival. In particular, Zip8KO bone marrow-derived macrophages have increased bacterial accumulation due to deficits in lysosomal number and function via defective mTORC1/TFEB signaling. Knowing that labile Zn cannot enter the cytosol through ZIP8 and that ZIP8 loss impairs butanoate synthesis by the gut microbiome, both previously reported by our group, we reveal an alternative treatment strategy via extended oral phenylbutyrate supplementation. Despite ongoing ZIP8-mediated impairment of lung host defense, phenylbutyrate restored macrophage-mediated bacterial clearance and improved host outcomes. Given the high incidence of diet-induced Zn deficiency and the rs13107325 ZIP8 defective variant allele in humans, future investigations that foster preventive, patient-centered treatment strategies that counter immune dysfunction due to Zn dyshomeostasis are warranted.}, } @article {pmid41526416, year = {2026}, author = {Hasan, R and Shaikh, MTM and Rawat, S and Singh, V and Tamang, R and Choudhury, S}, title = {Intratumoral microbiome signatures in a North Central Indian colorectal cancer cohort: identification of novel prognostic biomarkers and functional pathways.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1815}, pmid = {41526416}, issn = {2045-2322}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/pathology/mortality ; India/epidemiology ; Female ; Male ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/genetics ; RNA, Ribosomal, 16S/genetics ; Aged ; *Gastrointestinal Microbiome ; Adult ; Cohort Studies ; *Microbiota ; Bacteria/genetics/classification ; }, abstract = {Colorectal cancer (CRC) remains a major global health burden, with emerging evidence implicating gut and oral microbiome dysbiosis in its pathogenesis. This comparative observational study aimed to investigate intratumoral microbial signatures in early-onset CRC (EOCRC) and their association with clinical outcomes. In fact, till date there is no comprehensive study yet that directly compares the microbiome of EOCRC patients in North Central India to other EOCRC groups globally. We analysed 50 matched tumor and adjacent normal tissues (obtained from the same patient) using 16S rRNA amplicon sequencing. Taxonomic and functional analyses were conducted using DESeq2, LEfSe, and KEGG pathway prediction (via PICRUSt2). Our findings revealed distinct intratumoral enrichment of oral pathobionts such as Leptotrichia buccalis and Filifactor alocis, which showed significant correlation with mortality risk. Caldilinea aerophila was detected for the first time in human tumor tissue and was strongly associated with advanced TNM stages (p = 0.01; 83% specificity) in North Central Indian population. LEfSe analysis identified an overrepresentation of Actinomycetales. KEGG pathway analysis revealed enrichment of MAPK signaling, styrene, and aminobenzoate degradation pathways. Depletion of Lactobacillus plantarum and presence of dietary-linked microbes suggest microbial modulation by lifestyle. These findings highlight novel microbial biomarkers and immune-related pathways with potential prognostic implications in this regional CRC cohort.}, } @article {pmid41526369, year = {2026}, author = {Fu, W and Sun, C and Sun, B and Li, P and Ding, X and Guo, Q and Yuan, J and Lai, H}, title = {Flavonoid-mediated bacterial spermidine biosynthesis enhances vitamin accumulation in tomato fruits.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-68244-9}, pmid = {41526369}, issn = {2041-1723}, abstract = {Rhizosphere microbes benefit plant growth and health. How plant-microbe interactions regulate fruit quality remains poorly understood. Here, we elucidate the multi-level modulation of vitamin accumulation in tomato by flavonoid-mediated crosstalk between host plants and rhizosphere microbes. SlMYB12-overexpressing plants with up-regulated flavonoid biosynthesis accumulate higher levels of vitamins C and B6 in fruits compared to wild-type plants grown in natural soil. Flavonoid-mediated improvement of fruit quality depends on the presence of soil microbiomes and relates to rhizosphere enrichment of key taxa (e.g. Lysobacter). Multi-omics analyses reveal that flavonoids attract Lysobacter soli by stimulating its twitching motility and spermidine biosynthesis, which in turn boosts vitamin accumulation in fruits across tomato cultivars and soil types. RpoN acts as a dual regulator in L. soli that is responsive to flavonoids, controlling bacterial motility and spermidine production. Our study provides insight into flavonoid-mediated rhizosphere signalling and underscores plant-microbiome orchestration for improved tomato fruit quality.}, } @article {pmid41526362, year = {2026}, author = {Ascandari, A and Aminu, S and Benhida, R and Daoud, R}, title = {Cross-cohort resistome and virulome gradients structure the colorectal cancer microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00905-5}, pmid = {41526362}, issn = {2055-5008}, abstract = {The gut microbiome is increasingly implicated in colorectal cancer (CRC), yet the functional signatures associated with disease progression remain poorly resolved across populations. We performed an assembly-based metagenomic analysis of more than 500 samples from three geographically distinct cohorts to characterize resistome and virulome patterns associated with CRC. Using a cross-validated modeling framework based on Partial Least Squares (PLS) regression, we identified two reproducible latent functional gradients that structured variation in antimicrobial-resistance and virulence-factor profiles. One gradient was enriched for adhesion, efflux, and biofilm-associated functions, while the second reflected immunomodulatory and barrier-related pathways. These components were statistically robust, directionally stable across cohorts, and consistent with functional themes frequently reported in CRC microbiome studies. To summarize variation along these gradients, we derived an exploratory Dual-Axis Index (DAI) based on the two stable PLS components. Although its discriminative performance was moderate, the DAI provided an interpretable low-dimensional representation of how resistome-virulome patterns differed across healthy, adenoma, and carcinoma states. These results suggest that functional gene profiles in CRC are organized along reproducible statistical axes, and highlight functional modules, such as adhesion-, iron-associated, and immune-interaction pathways that may complement taxonomic or metabolic biomarkers in future multimodal approaches. Our work provides a reproducible, assembly-based framework for examining the functional organization of CRC-associated microbiomes across diverse populations.}, } @article {pmid41526019, year = {2026}, author = {Donaubauer, AJ and Frey, B and Agaimy, A and Lange, F and Mogge, L and Fietkau, R and Iro, H and Munoz, LE and Weber, M and Kesting, M and Gaipl, US and Haderlein, M and Müller, S}, title = {Definition of predictive and prognostic immune biomarkers for salivary gland cancer from the intratumoural and systemic immune status: detailed protocol of the prospective, observatory ImmoGlandula study.}, journal = {BMJ open}, volume = {16}, number = {1}, pages = {e100021}, doi = {10.1136/bmjopen-2025-100021}, pmid = {41526019}, issn = {2044-6055}, mesh = {Humans ; *Salivary Gland Neoplasms/immunology/therapy/pathology ; Prospective Studies ; Prognosis ; *Biomarkers, Tumor/immunology ; Immunotherapy ; Observational Studies as Topic ; Female ; }, abstract = {INTRODUCTION: Salivary gland carcinomas (SGC) are rare tumours. The term SGC is not more than an umbrella for a variety of histogenetically, morphologically and biologically distinct entities. Accordingly, SGCs have not been sufficiently investigated to date. Their rarity makes it difficult to reach high patient numbers for individual entities in clinical studies, leading to pooling patients with different histological subtypes to attain sufficient participants. The different histological subtypes of SGC differ significantly in their clinicopathological features, such as their grading, their occurrence and their outcome. SGCs are usually stratified into low-grade, intermediate-grade or high-grade tumours. In most kinds of SGC, specific targetable molecular markers are lacking. The inclusion of immunotherapy (IT), however, might improve the outcome of patients suffering from high-grade SGCs. In order to integrate IT as a therapeutic option for SGC and to facilitate therapeutic decisions based on tumour (immune) biology, predictive and prognostic immunological biomarkers are indispensable.

METHODS AND ANALYSIS: In this prospective study, 500 patients will be enrolled, who are distributed in three arms. The observational cohort includes patients with malignant salivary gland tumours, whereas patients with benign tumours of a salivary gland are grouped in the control group 1. In the control cohort, 2 patients do not have a salivary gland tumour but have a planned functional surgery of the nose or ear or a maxillofacial surgery. The local immune status from the tumour tissue and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analysed before and after surgery and after the adjuvant and definitive chemoradiotherapy, if applicable. Clinical baseline characteristics and outcome parameters will additionally be collected. Data mining and modelling approaches will finally be applied to identify interactions of local and systemic immune parameters and to define predictive and prognostic immune signatures based on the evaluated immune markers.

ETHICS AND DISSEMINATION: Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in September 2023 (application number 23-292-B). The results will be disseminated to the scientific audience and the general public via presentations at conferences and publication in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT06047236.}, } @article {pmid41525802, year = {2026}, author = {Cheng, C and Xu, S and Liu, Z and Zhang, H and Yang, Y and Zhang, Y and Ge, E and Xu, J and Zhu, Q and Li, X and Yu, B and Liu, M and Guo, Y}, title = {Microbial community differences between healthy and Ustilago-infected oats.}, journal = {Genomics}, volume = {}, number = {}, pages = {111202}, doi = {10.1016/j.ygeno.2026.111202}, pmid = {41525802}, issn = {1089-8646}, abstract = {Ustilago, a pathogenic fungus, poses a serious threat to oat growth and yield. However, the species composition, abundance, and distribution of microbial communities in Ustilago-infected oats remain poorly characterized. In this study, we conducted 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing and biochemical assays to compare microbial profiles and physiological traits between healthy (n = 60) and Ustilago-infected oats (n = 60). Our analyses revealed higher bacterial diversity in healthy oats, particularly in the spikes and stems. Significant shifts in microbial community structure were observed across all tissues in diseased plants. While the microbiome of healthy oats predominantly comprised beneficial bacteria, including Exiguobacterium indicum, infected plants were largely colonized by pathogens, including Ustilago hordei, Pyrenophora chaetomioides, and Curtobacterium flaccumfaciens pv. flaccumfaciens, suggesting the occurrence of disease-driven microbial restructuring. Functional predictions indicated that enriched pathways were primarily associated with metabolism, followed by genetic information processing and environmental signal transduction. Malondialdehyde content was significantly lower in most healthy oat tissues compared to Ustilago-infected oats, whereas the activities of the antioxidant enzymes superoxide dismutase and peroxidase were markedly higher. These results implied that Ustilago infection induced severe oxidative damage to membrane systems, likely compromising the plant's ability to scavenge superoxide ions and hydrogen peroxide, thereby reducing overall plant health.}, } @article {pmid41525776, year = {2026}, author = {, and Proctor, LM}, title = {Integrating microbiomes into One Health: insights from the 2025 One Health World Microbiome Partnership Summit.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {101319}, doi = {10.1016/j.lanmic.2025.101319}, pmid = {41525776}, issn = {2666-5247}, } @article {pmid41525625, year = {2026}, author = {Weng, Q and Hu, M and Peng, G and Lu, W and Wang, H and Zhu, J}, title = {Variational Bayesian Multi-Output Gaussian Process Regression for Metabolic Profiles Prediction with Microbiome Data.}, journal = {IEEE transactions on computational biology and bioinformatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TCBBIO.2026.3653067}, pmid = {41525625}, issn = {2998-4165}, abstract = {Understanding the pivotal role of the human microbiome in health necessitates accurate metabolite prediction, which is crucial for unraveling the intricate interplay between the gut microbiome and human health. This study introduces an innovative approach, Variational Bayesian Multi-Output Gaussian Process Regression (VBMOGPR), to address the challenges posed by the complex, high-dimensional nature of microbiome data. VBMOGPR predicts microbial metabolites, quantifies the model confidence, and incorporates uncertainty estimates. Employing a Bayesian framework with Automatic Relevance Determination (ARD) for feature selection enhances interpretability and performance. Comparative analysis across 14 datasets within a meta-database demonstrated the superiority of VBMOGPR, marking a significant advancement in metabolite prediction and its implications for microbiome impact on human health. In addition, we confirmed that VBMOGPR could tap the potential microbial metabolic association.}, } @article {pmid41525344, year = {2026}, author = {van der Ploeg, GR and White, FTG and Jakobsen, RR and Westerhuis, JA and Heintz-Buschart, A and Smilde, AK}, title = {ACMTF-R: Supervised multi-omics data integration uncovering shared and distinct outcome-associated variation.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0339650}, pmid = {41525344}, issn = {1932-6203}, mesh = {Female ; Humans ; Pregnancy ; Algorithms ; Metabolomics/methods ; Milk, Human/microbiology/metabolism ; *Multiomics ; Feces/microbiology ; Infant ; }, abstract = {The rapid growth of high-dimensional biological data has necessitated advanced data fusion techniques to integrate and interpret complex multi-omics and longitudinal datasets. Shared and unshared structure across such datasets can be identified in an unsupervised manner with Advanced Coupled Matrix and Tensor Factorization (ACMTF), but this cannot be related to an outcome. Conversely, N-way Partial Least Squares (NPLS) is supervised and captures outcome-associated variation but cannot identify shared and unshared structure. To bridge the gap between data exploration and prediction, we introduce ACMTF-Regression (ACMTF-R), an extension of ACMTF that incorporates a regression step, allowing for the simultaneous decomposition of multi-way data while explicitly capturing variation associated with a dependent variable. We present a detailed mathematical formulation of ACMTF-R, including its optimisation algorithm and implementation. Through extensive simulations, we systematically evaluate its ability to recover a small [Formula: see text]-related component shared between multiple blocks, its robustness to noise, and the impact of the tuning parameter ([Formula: see text]) which controls the balance between data exploration and outcome prediction. Our results demonstrate that ACMTF-R can robustly identify the [Formula: see text]-related component, correctly identifying outcome-associated shared and distinct variation, distinguishing it from existing approaches such as NPLS and ACMTF. The development of ACMTF-R was motivated by a real-world dataset investigating how maternal pre-pregnancy BMI affects the human milk microbiome, human milk metabolome, and infant faecal microbiome. Emerging evidence suggests that inter-generational transfer of maternal obesity may affect multiple omics layers, highlighting the need to identify outcome-associated variation. The applicability of ACMTF-R is therefore validated by applying it to this multi-omics dataset. ACMTF-R successfully identifies novel mother-infant relationships associated with maternal pre-pregnancy BMI, underscoring its utility in multi-omics research. Our findings establish ACMTF-R as a versatile tool for multi-way data fusion, offering new insights into complex biological systems by integrating common, local, and distinct variation in the context of a dependent variable.}, } @article {pmid41525336, year = {2026}, author = {Li, X and Smart, CE and Millard, K and Bell, KJ}, title = {Nutrition and healthy lifestyles for children and adolescents with early-stage type 1 diabetes.}, journal = {Hormone research in paediatrics}, volume = {}, number = {}, pages = {1-20}, doi = {10.1159/000550434}, pmid = {41525336}, issn = {1663-2826}, abstract = {Increasingly children and adolescents are being identified in early-stage type 1 diabetes (T1D), defined as two or more islet autoantibodies without hyperglycemia (above diagnostic threshold) or reliance on intensive insulin therapy. They require clinical monitoring and care. Healthy lifestyle education is recommended in guidelines, however evidence synthesis to inform clinical practice is lacking. Therefore, this review summarizes current evidence on nutrition, lifestyle to delay progression to stage 3 T1D; and proposes lifestyle strategies for children and adolescents with early-stage T1D. Specifically, we suggest a key focus on reducing beta-cell stress, promoting a healthy gut microbiome and establishing healthy lifestyles and relationships with food, prior to the introduction of intensive insulin therapy. As secondary prevention of T1D is an emerging research area and randomized controlled trials are scarce, evidence has been largely drawn from prospective cohort studies and routine clinical care for stage 3 T1D. A balanced and varied diet, limiting intake of foods containing high amounts of saturated fat and added sugar, and moderate levels of physical activity, are likely beneficial for overall health in children and adolescents with early-stage T1D. Low glycemic index (GI) diets may be protective against progression to stage 3 T1D.}, } @article {pmid41525322, year = {2026}, author = {Karagiannis, TT and Chen, Y and Bald, S and Tai, A and Reed, ER and Milman, S and Andersen, SL and Perls, TT and Segrè, D and Sebastiani, P and Short, MI}, title = {Integrative analysis across metagenomic taxonomic classifiers: A case study of the gut microbiome in aging and longevity in the Integrative Longevity Omics Study.}, journal = {PLoS computational biology}, volume = {22}, number = {1}, pages = {e1013883}, doi = {10.1371/journal.pcbi.1013883}, pmid = {41525322}, issn = {1553-7358}, abstract = {There are various well-validated taxonomic classifiers for profiling shotgun metagenomics data, with two popular methods, MetaPhlAn (marker-gene-based) and Kraken (k-mer-based), at the forefront of many studies. Despite differences between classification approaches and calls for the development of consensus methods, most analyses of shotgun metagenomics data for microbiome studies use a single taxonomic classifier. In this study, we compare inferences from two broadly used classifiers, MetaPhlAn4 and Kraken2, applied to stool metagenomic samples from participants in the Integrative Longevity Omics study to measure associations of taxonomic diversity and relative abundance with age, replicating analyses in an independent cohort. We also introduce consensus and meta-analytic approaches to compare and integrate results from multiple classifiers. While many results are consistent across the two classifiers, we find classifier-specific inferences that would be lost when using one classifier alone. Both classifiers captured similar age-associated changes in diversity across cohorts, with variability in species alpha diversity driven by differences by classifier. When using a correlated meta-analysis approach (AdjMaxP) across classifiers, differential abundance analysis captures more age-associated taxa, including 17 taxa robustly age-associated across cohorts. This study emphasizes the value of employing multiple classifiers and recommends novel approaches that facilitate the integration of results from multiple methodologies.}, } @article {pmid41525151, year = {2026}, author = {Walsh, SK and Armet, AM and Nikolaeva, DD and Mota, JF and Lucey, AJ and Oliero, M and Walter, J}, title = {Optimizing Dietary Fiber Intake: Strategies for Human Nutrition and Food Science.}, journal = {Annual review of food science and technology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-food-052824-044842}, pmid = {41525151}, issn = {1941-1421}, abstract = {Adequate dietary fiber intake from plant foods is critical for the prevention of noncommunicable chronic diseases (NCDs). However, across industrialized nations, consumption remains insufficient to meet established intake recommendations. This gap provides a strong rationale to include functional fibers into processed foods or use them as supplements, although their effectiveness in reducing NCD risk is inconclusive . In this review, we examine current nutritional strategies to optimize fiber intake, spanning whole-plant foods, processed foods made or enriched with fiber-containing ingredients, and fiber supplements. We examine the structure and physicochemical properties of the fiber types represented in these strategies and explore the mechanisms by which they influence the gut microbiome and NCD risk markers. Drawing on evidence from human intervention studies, we critically assess the strengths and limitations of each strategy to improve health outcomes and propose a framework for the effective and systematic integration of fiber into nutrition and food science.}, } @article {pmid41525137, year = {2026}, author = {Jackson, SA and Hrab, P and Zdouc, MM and Clarke, DJ and Dobson, ADW}, title = {New insights into the microbiome of the deep-sea sponge Inflatella pellicula and the secondary metabolic potential of metagenome-assembled genomes and the wider microbiome.}, journal = {Microbial genomics}, volume = {12}, number = {1}, pages = {}, pmid = {41525137}, issn = {2057-5858}, mesh = {*Porifera/microbiology ; Animals ; *Metagenome ; *Microbiota/genetics ; Secondary Metabolism/genetics ; Phylogeny ; *Bacteria/genetics/classification/metabolism/isolation & purification ; Multigene Family ; Genome, Bacterial ; Sequence Analysis, DNA ; }, abstract = {Marine sponges are found in all of the world's oceans, from the surface waters to the deepest abyssal zones. The marine sponge holobiont is a rich source of microbial and chemical diversity. Up to 63 bacterial phyla have been observed to be associated with sponges, and thousands of unique natural products have been extracted from sponges or their microbial symbionts. However, sponges from the deep sea and their associated microbial communities are relatively understudied, largely due to sampling-associated difficulties. Secondary metabolism biosynthetic gene clusters are phylogenetically distinct and hold the potential to produce novel chemistry with potential pharmacological or industrial utility. In order to gain further insights into the microbiome of the deep-sea sponge Inflatella pellicula, the metagenome of this sponge, sampled from a depth of 2,900 m, was sequenced. A large fraction of the sequence reads appeared to be 'biological dark matter' and could not be taxonomically classified. Further, unlike similar studies from different marine ecosystems, relatively few metagenome-assembled genomes (MAGs) could be assembled, and relatively few secondary metabolism biosynthetic gene clusters were identified. The identified clusters were, however, very dissimilar to known characterized clusters, but some shared similarities with clusters annotated in MAGs assembled from sponge metagenomes from disparate geographic locations. Therefore, renewed efforts to cultivate the hosts of these gene clusters may yield valuable small-molecule natural products.}, } @article {pmid41525049, year = {2026}, author = {Nishu, and Verma, K and Noor, SA and Mathur, V}, title = {Aboveground insect herbivory shapes plant-soil feedback and ecosystem resilience.}, journal = {Biologia futura}, volume = {}, number = {}, pages = {}, pmid = {41525049}, issn = {2676-8607}, abstract = {The interaction between plants and their surrounding soil ecosystems is complex, with plant-soil feedback acting as legacy effects from previous plants, influencing subsequent plant growth and insect interactions. Recent studies have shown that experiments focusing on individual factors in isolation do not accurately predict the outcomes of these complex interactions. Aboveground herbivores impact the development of root exudates and their surrounding microbiome, suggesting that herbivory indirectly shapes belowground biotic communities. Such impact of insect herbivory on plant-soil feedback is a crucial area of ecological research. Most studies focus on root-associated organisms and their influence on foliar herbivorous insects, and little attention has been given to the reverse interaction-how foliar herbivory affects the soil environment and PSF. This study explores the bidirectional influence of herbivory and PSF, revealing that aboveground insect herbivory can significantly alter plant-soil feedback mechanisms, influencing not only plant performance but also the broader community structure. A holistic approach that integrates soil microbial complexity with insect herbivory is needed to better predict community-level outcomes and enhance plant protection strategies. Our study thus highlighted the need for a community-based perspective when studying interactions among plants, insects and soil microorganisms.}, } @article {pmid41525005, year = {2026}, author = {Mir, PA and Kumar, N and Bhutia, GT and Chaudhary, P and Kaur, G and Gupta, SK}, title = {The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {41525005}, issn = {2509-2723}, abstract = {Alzheimer's disease (AD), the most common cause of dementia in the aging population, is marked by amyloid-beta (Aβ) plaques, tau tangles, and progressive neuronal degeneration, placing heavy clinical and socioeconomic burdens on healthcare worldwide. Aging remains the strongest risk factor, with chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and impaired proteostasis creating a vulnerable brain environment that accelerates AD onset and progression. Recent evidence highlights the gut-glia-immune axis as a critical pathway linking age-related microbiome changes to glial dysfunction. Microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, regulate microglial maturation, astrocytic activity, and neuroimmune signaling. However, age-associated dysbiosis disrupts glial homeostasis, amplifies neuroinflammation, and impairs amyloid clearance, thereby worsening neurodegeneration. Preclinical models including germ-free mice and fecal microbiota transplantation along with clinical studies of elderly AD patients, provide compelling evidence of microbiome-driven modulation of disease. From a therapeutic perspective, microbiome-targeted interventions including probiotics, prebiotics, synbiotics, and microbiota-directed small molecules offer promising strategies to restore glial balance, reduce inflammation, and protect cognitive function. This review highlights the therapeutic potential of probiotics, synbiotics, and fecal microbiota transplantation for mitigating neuroinflammation and cognitive decline in Alzheimer's disease. However, given the multifactorial nature of neurodegenerative disorders, these strategies are unlikely to be universally effective and must be tailored to individual patient profiles.}, } @article {pmid41524878, year = {2026}, author = {Ohsawa, M and Nishi, H and Hamai, Y and Emi, M and Ibuki, Y and Komatsuzawa, H and Kawaguchi, H and Okada, M}, title = {Relationship Between the Oral Microbiome and Treatment Efficacy in Esophageal Squamous Cell Carcinoma.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41524878}, issn = {1534-4681}, abstract = {BACKGROUND: As the relationship between oral microbiota and treatment efficacy in esophageal cancer remains unexplored, we aimed to clarify it using metagenomic analysis.

PATIENTS AND METHODS: Of the 140 consecutive patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy with R0 resection at Hiroshima University Hospital between April 2020 and May 2024, 74 who received neoadjuvant therapy were included in this study. 16S rRNA gene from oral tongue coating samples was amplified using polymerase chain reaction and subjected to next-generation sequencing. The oral microbiome data were analyzed using QIIME2 and linear discriminant analysis effect size, and the relationship between the oral microbiota and treatment efficacy and prognosis was assessed.

RESULTS: Alpha diversity of the oral microbiota was significantly correlated with the pathological response. Univariate and multivariate analyses showed that the alpha diversity of the oral microbiome (high versus low) was a significant predictor of a good pathological response. Patients with high alpha diversity had significantly improved recurrence-free survival and overall survival compared with those with low alpha diversity. Furthermore, eight bacterial groups (Lactobacillales, Peptostreptococcales-Tissierellales, Bifidobacteriaceae, Erysipelotrichaceae, Lactobacillaceae, Anaerovoracaceae, Staphylococcaceae, and Aerococcaceae) were significantly more abundant in individuals who responded well to neoadjuvant therapy and two bacterial groups (Streptococcaceae and Corynebacteriaceae) were significantly more abundant in poor responders.

CONCLUSIONS: Our results demonstrate a correlation between the oral microbiome and ESCC treatment efficacy, suggesting that it is a significant prognostic factor. Our findings may also help predict the efficacy of esophageal cancer treatment.}, } @article {pmid41461908, year = {2025}, author = {, and Alberts, T and Albritton, CF and Alcazar, R and Aljabri, Z and Alvarez, M and Aradhey, A and Ayalew, M and Azizian, N and Balayah, Y and Ball, DD and Barragan, E and Beshoar, C and Best, L and Biggane, E and Biggane, J and Blick, J and Blosser, M and Brown, AK and Campbell, MC and Canizares, Z and Chanhuhwa, FN and Chen, Y and Chin, DR and Chowdhury, K and Collins, T and Compton, B and Da Silva, J and Davis, NR and DeCaro, N and Delgadillo, F and Deng, Y and Duncan, J and Egwu, AC and Ekalle, GD and Elnawam, N and Enke, R and Ewhe, N and Ferrel, MA and Fierst, J and Freymiller, G and Fuller, K and Fulton-Wright, L and Gaysinskaya, V and Gill, T and Gillespie, E and Gonzalez Moreno, P and Goodwin, S and Graham, N and Graham, ME and Graves, JL and Grob, E and Gutierrez, R and Hager, A and Hakim, ST and Harris, A and Hoffman, AM and Hoffmann, T and Horton, AM and Hughes, A and Humphries, EM and Ikechi-Konkwo, JS and Ishtiaq, A and Jackson, R and James, JR and James, K and Jamison, SA and Jimenez, A and Johnson, R and Kauffman, A and Kaur, H and Kc, K and Keeton, A and Kelly, OE and Kerr, J and Kucher, N and Kuehu, DL and Larson, WA and Lee, J and Lee, A and Leek, JT and Lemaic, D and Liburd, LE and Lopez, AF and Mahmanzar, M and Mamae, K and Manjikian, R and Marone, M and Marquez, K and Martinson, A and Mavruk Eskipehlivan, S and Medrano, A and Melendrez-Vallard, M and Meller, R and Méndez, LB and Mendez Gonzalez, MP and Mesquita, N and Miller, CM and Mohd-Ibrahim, I and Mortensen, P and Mosher, S and Muja, A and Nasrin, N and Nasu, M and Nguyen, MH and Nguyen, BT and Nishiguchi, M and O'Connor, LM and Okie, D and Olowookorun, T and Ostrovsky, A and Ozuna, K and Pandey, A and Patel, SB and Paul, G and Pawar, S and Pearson, A and Petrik, D and Platero, J and Pontino, C and Pratap, AP and Pratap, S and Qin, Y and Rai, SK and Ray, N and Repesh, E and Rhinehardt, K and Roche, B and Rodriguez, A and Roy, S and Roy, S and Sawa, A and Schatz, MC and Sen, SK and Serikawa, R and Smith, T and Smith, L and Sniezek, J and Stewart, RD and Suarez-Martinez, EB and Taganna, J and Tan, FJ and Tsotakos, N and Udolisa, N and Ulbricht, K and Veo, T and Vessio, J and Walker, L and Wang, O and Wang, Q and Wappel, R and Wesby, K and Whitford, M and Wild, N and Xie, X and Yang, H and York, S and Zirkle, L}, title = {Unearthing soil biodiversity through collaborative genomic research and education.}, journal = {Nature genetics}, volume = {}, number = {}, pages = {}, pmid = {41461908}, issn = {1546-1718}, support = {2011934//National Science Foundation (NSF)/ ; U24 HG013013/HG/NHGRI NIH HHS/United States ; 75N92022P00232//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 5T34GM151403//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 2221924//National Science Foundation (NSF)/ ; 1839895//National Science Foundation (NSF)/ ; 2000157//National Science Foundation (NSF)/ ; U24HG013013//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 75N92023P00302//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, abstract = {The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.}, } @article {pmid40045571, year = {2026}, author = {Kim, DS and Kim, EH and Kim, JY and Kim, DH and Choi, YJ and Jeong, J and Sung, YH and Woo, DC and Kim, CJ and Lee, JC and Yun, M and Jeong, JY and Rho, JK}, title = {The Profile of Gut Microbiota in Carcinogenesis Driven by Mutant EGFR in Non-Small Cell Lung Cancer.}, journal = {Cancer research and treatment}, volume = {58}, number = {1}, pages = {115-127}, doi = {10.4143/crt.2024.1177}, pmid = {40045571}, issn = {2005-9256}, support = {2022IP0029//Asan Institute for Life Science/ ; RS-2023-00261982//Korea Health Industry Development Institute/Republic of Korea ; HR21C0198//Ministry of Health and Welfare/ ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Animals ; ErbB Receptors/genetics ; *Lung Neoplasms/genetics/pathology/microbiology ; Humans ; Mice ; *Carcinoma, Non-Small-Cell Lung/genetics/pathology/microbiology ; Mutation ; *Carcinogenesis/genetics ; Mice, Transgenic ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Phylogeny ; Feces/microbiology ; Female ; }, abstract = {PURPOSE: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)-induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis.

MATERIALS AND METHODS: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point.

RESULTS: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage.

CONCLUSION: Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.}, } @article {pmid41524843, year = {2026}, author = {Haysom-McDowell, A and Paudel, KR and Mehndiratta, S and Singh, M and Malik, MZ and Kokkinis, S and Pakan, PD and Williams, FE and Singh, SK and Dua, K and De Rubis, G}, title = {Fisetin-loaded Nanoemulsion and Fecal Microbiome Extract Enhance In Vitro Inhibition of Non-Small Cell Lung Cancer Progression.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {41524843}, issn = {1559-0283}, } @article {pmid41524809, year = {2026}, author = {Singh, G and Aran, KR}, title = {Rethinking on bile acid-brain axis: decoding neurotoxic and neuroprotective landscape in aging and Alzheimer's disease.}, journal = {Biogerontology}, volume = {27}, number = {1}, pages = {37}, pmid = {41524809}, issn = {1573-6768}, mesh = {Humans ; *Alzheimer Disease/metabolism/drug therapy/pathology ; *Bile Acids and Salts/metabolism ; *Aging/metabolism ; *Brain/metabolism/pathology ; Animals ; Gastrointestinal Microbiome ; Neuroprotective Agents ; Neuroprotection ; }, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative condition in which aging serves as the predominant risk factor. Emerging research underscores the importance of bile acids (BAs), traditionally recognized for their role in digestion, as key signaling mediators involved in both systemic metabolism and neural communication. Disruption of bile acid (BA) metabolism during aging arises from altered hepatic synthesis, gut microbial imbalance, and defective receptor signaling. These changes have been implicated in several neurodegenerative processes, including Aβ accumulation, tau protein abnormalities, mitochondrial impairment, and disturbances in immune regulation. Aging induces a shift in BA composition toward more cytotoxic species, contributing to blood-brain barrier disruption and enhanced neuronal damage. Multi-omics analyses have identified distinct BA signatures in plasma and cerebrospinal fluid of individuals with mild cognitive impairment and AD. These alterations show strong correlations with brain atrophy and progressive cognitive decline. Experimental and early clinical findings suggest potential neuroprotective effects of hydrophilic BAs such as ursodeoxycholic acid and tauroursodeoxycholic acid, along with therapeutic opportunities through modulation of BA receptors and microbiome-driven BA regulation. In the current era of AD research, the gut-liver-brain BA axis emerges as a novel mechanistic framework linking systemic metabolic aging to neurodegeneration. This review examines the molecular pathways through which BA dysregulation influences aging and AD, emphasizing its therapeutic relevance and supporting the development of biomarker-based and precision medicine approaches for neurodegenerative disorders.}, } @article {pmid41524665, year = {2026}, author = {Pibaque, P and Porporato, G and Cescutti, S and Cruz-Flores, A and Busche, T and Winker, A and Rapp, TM and Bergkamp, P and Doneva, A and Chakarov, N}, title = {Domination Versus Sisterhoods in the Blood Microbiota of Migrating Birds: Patterns of Within- and Between-Individual Blood Parasite Diversity Revealed Through Metabarcoding.}, journal = {Integrative zoology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1749-4877.70056}, pmid = {41524665}, issn = {1749-4877}, abstract = {Avian blood parasites of the genera Plasmodium, Haemoproteus, and Leucocytozoon are typically identified through Sanger sequencing of a partial cytochrome b fragment, the MalAvi barcoding region. This approach limits the detection of mixed infections and the relative frequencies of co-infecting parasites. In contrast, next-generation sequencing (NGS) can resolve these problems but has been underused for haemosporidian lineage identification in samples from the wild. We used an improved PCR protocol and sequencing with Illumina MiSeq to determine haemosporidian assemblages in wild birds captured at a migration stopover site in Bulgaria, Europe. From 406 samples obtained from 52 bird species, we detected 81 haemosporidian lineages in 131 infected samples from 32 species (32% prevalence). On average, individuals were infected with 2.4 lineages, with 59 birds infected by a single lineage, and 21 birds infected with 5-9 lineages. A subset of samples was Illumina- and Sanger-sequenced in parallel, finding mixed infections in 72 samples and 8× higher detection rate of mixed and co-infections through high-throughput sequencing. Both methods identified the same dominant (co-infecting) lineage (91%). Metabarcoding identified common mixed infections of sister lineage groups ("sisterhoods") known for prevalent lineages and morphospecies, including Plasmodium relictum p_SGS1, Haemoproteus motacillae h_YWT2, and Haemoproteus parabelopolskyi h_SYAT01. Some other lineages appeared consistently more dominant. Our study shows that in some host communities, metabarcoding can reveal a great diversity of mixed infections. This opens new horizons to the study of assemblages of haemosporidian parasites, their interactions within individual hosts, and co-evolution with other members of the blood microbiome and the hosts.}, } @article {pmid41524491, year = {2026}, author = {}, title = {Correction to "The Microbiome in Hidradenitis Suppurativa Tunnels: A Systematic Review".}, journal = {International journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ijd.70241}, pmid = {41524491}, issn = {1365-4632}, } @article {pmid41524460, year = {2026}, author = {Li, X and Yang, M and Jones, DL and Du, X and Liu, J and Guo, X and Tang, Z}, title = {Rhizosphere Metabolites and Microbial Communities Shape Lettuce Responses to Oxytetracycline Stress.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c10653}, pmid = {41524460}, issn = {1520-5118}, abstract = {Oxytetracycline (OTC), a persistent antibiotic frequently detected in agricultural soils, can influence plant growth and rhizosphere ecology. Using lettuce (Lactuca sativa L.) as a model, this study compared the effects of OTC under hydroponic and soil cultivation systems and integrated physiological, metabolomic, and microbiome analyses. Hydroponic exposure consistently inhibited growth, whereas soil culture showed a biphasic, dose-dependent pattern─low OTC doses stimulated growth while high doses suppressed it. In soil systems, OTC exposure reprogrammed rhizosphere metabolites and reshaped microbial networks, enriching taxa associated with OTC degradation and plant growth promotion (Chryseolinea, Nitrospira, Devosia, Haliangium). Structural equation modeling indicated that rhizosphere diversity and metabolite profiles mediate plant biomass responses. These findings reveal that rhizosphere metabolite-microbe networks play a key role in modulating plant hormetic responses to antibiotic stress, providing mechanistic insight into antibiotic-plant-microbe interactions in agroecosystems.}, } @article {pmid41524424, year = {2026}, author = {Grundmann, CO and Tomo, CJ and Hershelman, JL and Wolfe, BE and Sanchez, LM}, title = {Spatial metabolomics reveals the role of penicillic acid in cheese-rind microbiome disruption by a spoilage fungus.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0130525}, doi = {10.1128/msystems.01305-25}, pmid = {41524424}, issn = {2379-5077}, abstract = {Microbial interactions in cheese rinds influence community structure, food safety, and product quality. But the chemical mechanisms that mediate microbial interactions in cheeses and other fermented foods are generally not known. Here, we investigate how the spoilage mold Aspergillus westerdijkiae chemically inhibits beneficial cheese-rind bacteria using a combination of omics technologies. In cheese-rind community and co-culture experiments, A. westerdijkiae strongly inhibited most cheese-rind community members. In co-culture with Staphylococcus equorum, A. westerdijkiae strongly affected bacterial gene expression, including upregulation of a putative bceAB gene cluster that is associated with resistance to antimicrobial compounds in other bacteria. Mass spectrometry imaging revealed spatially localized production of secondary metabolites, including penicillic acid and ochratoxin B at the fungal-bacterial interface with Brachybacterium alimentarium. Integration of liquid chromatography-tandem mass spectrometry and genome annotations confirmed the presence of additional bioactive metabolites, such as notoamides and circumdatins. Fungal metabolic responses varied by bacterial partner, suggesting species-specific chemical strategies. Notably, penicillic acid levels increased 2.5-fold during interaction with B. alimentarium, and experiments with purified penicillic acid showed inhibition in a dose-dependent manner against this rind bacterium. These findings show that A. westerdijkiae deploys a context-dependent suite of mycotoxins and other metabolites, disrupting microbial community assembly in cheese rinds.IMPORTANCEThis study identifies the chemical mechanisms underlying the negative impacts of Aspergillus westerdijkiae on cheese-rind development, revealing how specialized metabolites like penicillic acid and ochratoxin B influence rind bacterial communities. By integrating biosynthetic gene cluster analyses with mass spectrometry, we demonstrate how chemical communication shapes microbial interactions, with possible implications for food safety and cheese quality. Understanding these interactions is essential for assessing the risks of fungal-driven spoilage and mycotoxin production in cheese-rind maturation. Beyond cheese, these findings contribute to broader microbiome ecology, emphasizing how secondary metabolites mediate microbial competition in natural and fermented food environments.}, } @article {pmid41524423, year = {2026}, author = {Benedict, EE and Agee, W and Hink, T and Parrish, KL and Reske, KA and Peacock, K and Bosserman, RE and Valencia, A and Saluja, A and Ovchiyan, E and Arter, O and Jolani, K and Dubberke, ER and Dantas, G and Kwon, JH}, title = {Community-associated quinolone-resistant and extended-spectrum beta-lactamase-producing Escherichia coli isolates are similar to clinical infection isolates by sequence type and resistome.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0159125}, doi = {10.1128/msystems.01591-25}, pmid = {41524423}, issn = {2379-5077}, abstract = {Escherichia coli is a public health threat capable of causing multiple types of infection, carrying a variety of antimicrobial resistance genes (ARGs), and disseminating ARGs to other microbes. Since ARG-carrying E. coli can exist as a commensal gut microbe, intestinal E. coli in community-associated (CA) members presents an under-appreciated reservoir of ARGs. We cultured 75 CA E. coli isolates from stool of 64 patients lacking inpatient healthcare exposures >24 hours in the previous 12 weeks. Remnant stool submitted to the Barnes-Jewish Hospital (BJH) microbiology laboratory for Clostridioides difficile testing was plated to MacConkey agar with ciprofloxacin and extended-spectrum beta-lactamase (ESBL) Chrome Agar to isolate resistant E. coli colonies, which were whole-genome sequenced. Isolates were compared to ESBL E. coli genomes published by Mahmud et al. (B. Mahmud, M. A. Wallace, K. A. Reske, K. Alvarado, et al., mSystems 7:e00519-22, 2022, https://doi.org/10.1128/msystems.00519-22), which were collected from bloodstream and urinary tract infections. We identified ESBL genes and quinolone resistance elements in E. coli isolates from all patients, 32 (50%) of whom had no recent antibiotic exposure. Sequence type (ST) 131 isolates carried more quinolone resistance elements but fewer ESBL genes than other STs. Eleven patients carried two distinct E. coli lineages simultaneously. CA ESBL E. coli displayed a lower diversity of beta-lactamase genes but similar rates of antibiotic resistance genes compared to ESBL E. coli reported by Mahmud et al. (https://doi.org/10.1128/msystems.00519-22). Carriage of resistance elements without recent antimicrobial exposure suggests the presence of circulating, resistant E. coli. Our results show the continually evolving resistance profile of CA E. coli, demonstrating the importance of characterizing antimicrobial resistance in the community.IMPORTANCEAntimicrobial-resistant Escherichia coli presents a substantial threat to public health, limiting treatment options and potentially horizontally transferring its resistance to other members of the gut microbiome. Resistance to quinolones and beta-lactams, specifically, hinders treatment of urinary tract and gastrointestinal infections, both commonly caused by E. coli. Tracking successful lineages, such as ST131, within the healthcare setting can inform clinicians about resistance patterns among their patients, but this work shows that other STs present an even higher antimicrobial resistance burden than ST131. In addition to monitoring multiple lineages of antimicrobial-resistant E. coli, it is necessary to identify and understand community-associated carriage of this organism, as evidenced by the increasing prevalence of community-associated ESBL E. coli carriage and our specific results showing similar resistance burdens within the clinic and community. This work presents insight into antimicrobial-resistant E. coli among those without significant healthcare exposures, providing important community-focused surveillance that is currently lacking.}, } @article {pmid41524397, year = {2026}, author = {Kozik, AJ}, title = {Out of the box: toward new frameworks for understanding human microbiomes.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0100024}, doi = {10.1128/msphere.01000-24}, pmid = {41524397}, issn = {2379-5042}, abstract = {The study of the human microbiome (mirroring broader practice across biomedical science), has historically defaulted to the use of simplified, socially constructed "boxes," such as racial and ethnic labels, that fail to accurately capture human variation and fundamentally misdirect the search for mechanisms to explain differences in health outcomes. Five years ago, I proposed a "frameshift," a fundamental conceptual shift away from relying on these categories and toward a more nuanced, careful approach to the complexity of human variation. Moving "out of the box" means tackling the difficult but essential work of analyzing microbial variation through a systems lens, connecting large-scale ecosocial drivers to individual mechanisms and outcomes. In this Full Circle review, I discuss rapid progress in the field toward this new framework and argue that by adopting transdisciplinary methods, we can generate more accurate, actionable, and equitable solutions for human health.}, } @article {pmid41524293, year = {2026}, author = {Sassun, R and Brucchi, F and Sileo, A and Vignati, B and Crippa, J and Achilli, P and Maggioni, D and Spinelli, A and Montroni, I and Hawkins, AT and Mari, G}, title = {Recurrent left-sided diverticulitis after surgery: A systematic review and single arm meta-analysis.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {28}, number = {1}, pages = {e70368}, doi = {10.1111/codi.70368}, pmid = {41524293}, issn = {1463-1318}, mesh = {Humans ; Recurrence ; *Diverticulitis, Colonic/surgery ; Elective Surgical Procedures/adverse effects/statistics & numerical data ; Male ; Female ; *Colectomy/adverse effects ; Middle Aged ; *Postoperative Complications/etiology ; Aged ; Surgical Stomas/statistics & numerical data ; }, abstract = {INTRODUCTION: Recurrent diverticulitis after resection remains a key concern despite advances in minimally invasive surgery. These recurrences may result from incomplete resection of the diseased segment, unrecognized synchronous diverticulosis or ongoing alterations in colonic motility and microbiome composition. This systematic review and single-arm meta-analysis aimed to estimate long-term recurrence and stoma rates following elective surgery for left-sided diverticulitis.

METHODS: Following PRISMA guidelines and PROSPERO registration, PubMed, Cochrane and Scopus databases were searched (2000-2025) for studies reporting recurrence after elective resection. Single-arm meta-analysis of proportions was performed using random-effects models. Quality was assessed using the JBI Checklist, while subgroup and sensitivity analyses explored heterogeneity. A comparative meta-analysis with medical treatment was not performed due to selection bias, crossover and lack of standardized non-operative protocols.

RESULTS: Twenty-four studies (7,525 patients; mean follow-up 53 months) were included. Pooled recurrence rate was 6.2% (95% CI: 4.8-8.0%; I[2] = 80.6%), with no difference between RCTs (6.3%) and observational studies (6.1%) or complicated vs. uncomplicated disease. Stoma rate (16 studies, 6,400 patients) was 17.1% (95% CI: 8.4-31.9%; I[2] = 99.3%), significantly higher in complicated (31.0%) than uncomplicated (5.5%) cases (p = 0.009) and significantly lower post-2020 (8.0% vs. 31.2%; p = 0.003). Quality was high in 92% of studies, while sensitivity analyses confirmed robustness.

CONCLUSIONS: Surgical resection achieves durable control with low recurrence and stoma rates. Research priorities include standardized definitions of recurrence, assessing long-term QOL and exploring microbiome influences to refine patient selection and minimize residual risk.}, } @article {pmid41524247, year = {2026}, author = {Mir, HD and Giorgini, G and Santos-García, I and Dumais, E and Rodríguez-Cueto, C and de Lago, E and Silvestri, C and Flamand, N and Fernández-Ruiz, J and Di Marzo, V}, title = {Defining the Intestinal eCBome and Oxylipin Signaling Systems in a TDP-43 Mouse Model of Frontotemporal Dementia.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {2}, pages = {e71306}, pmid = {41524247}, issn = {1530-6860}, support = {RTI-2018-098885-B-100//Federación Española de Enfermedades Raras (FEDER)/ ; PID2021-128906OB-I00//Federación Española de Enfermedades Raras (FEDER)/ ; //Canada Excellence Research Chairs, Government of Canada (CERC)/ ; CFREF-2014-00001//UL|Sentinelle Nord, Université Laval (Sentinel North)/ ; }, mesh = {Animals ; Mice ; *Endocannabinoids/metabolism ; Disease Models, Animal ; *Oxylipins/metabolism ; Gastrointestinal Microbiome ; *Frontotemporal Dementia/metabolism/genetics/pathology ; *Signal Transduction ; *DNA-Binding Proteins/genetics/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; }, abstract = {Frontotemporal dementia (FTD) is a group of early onset and progressive disorders, characterized by degeneration in the frontal and temporal lobes, and subsequent deterioration in cognition, personality, social behavior, and language, with aggregates of the RNA-binding protein TDP-43 being present in ~45% of the cases. We reported alterations of the endocannabinoidome (eCBome) in the brain of a TDP-43 mouse model of FTD. Here we investigated the small intestinal eCBome, oxylipins, and, preliminarily, the gut microbiome. The duodenum, jejunum, and ileum of TDP-43 overexpressing versus wildtype mice were investigated. Lipid mediators were measured by HPLC-MS/MS, and mRNA expression of genes involved in eCBome mediator action and metabolism, or intestinal permeability and inflammation, was analyzed by qPCR. Intestinal content microbiota composition and fecal short-chain fatty acids were studied by 16S DNA sequencing and GC-FID, respectively. Alterations were observed in TDP-43 mice for polyunsaturated fatty acids, N-acyl-ethanolamines, and oxylipins in the duodenum and the jejunum, and for oxylipins and 2-monoacylglycerols in the ileum. Regarding the receptors, mRNA expression of Cnr1 and Gpr119 was increased in the ileum, and that of Pparg in the duodenum, where Gpr55 was instead down-regulated. Regarding the enzymes, Faah and Napepld expression was increased in the ileum. Preliminary gut microbiota data suggest increases of Paraprevotella and Monoglobus in the feces, of DNF00809 in the ileum, and of Butyricicoccus, Candidatus_Arthromitus, and Oscillospira in the cecum, where Paraprevotella, Mucispirillum, and Akkermansia were instead decreased. Fecal acetic, butyric, and isobutyric acid were reduced. We suggest the existence of lipid signal-mediated gut-brain interactions in FTD.}, } @article {pmid41524133, year = {2026}, author = {Santos, YR and Andréo-Filho, N and Lopes, PS and Leite-Silva, VR}, title = {A review of skin microbiome and new challenges to cosmetic microbiome-friendly formulations.}, journal = {International journal of cosmetic science}, volume = {}, number = {}, pages = {}, doi = {10.1111/ics.70073}, pmid = {41524133}, issn = {1468-2494}, abstract = {Human skin is a complex ecosystem that hosts diverse species of microorganisms. Unbalanced conditions caused by intrinsic and/or extrinsic factors can lead to dysbiosis, presenting symptoms, such as dryness, high transepidermal water loss, reduced barrier protection, premature ageing, and in severe cases, inflammatory dermatoses. Strategies to maintain the skin microbiome balance are becoming increasingly suggested, with prebiotic, probiotic, or postbiotic ingredients promoting the diversity and relative abundance of important microorganisms. Topical products directly influence this balance, both traditional ingredients and specific active ingredients. The concentration and combination of these ingredients, as well as the pH of the final product, are extrinsic characteristics that can affect homeostatic skin condition. Focused on repairing or preserving the skin microbiota, microbiome-friendly cosmetics are gaining prominence in the cosmetics industry, with a focus on reducing or replacing ingredients with adverse effects on skin microbiota or adding positive compounds for the microbiota. This review approaches the main characteristics of the skin microbiome, in symbiosis and dysbiosis, elucidates strategies for skin microbiota rebalance, and addresses the challenges of developing microbiome-friendly products through studies of the interaction between skin microbiome and substantial classes of cosmetic ingredients, such as surfactants, lipophilic compounds, preservatives, fragrances, vitamins, and UV filters. The presented findings elucidate the relationship between the host, the skin microbiome, and the use of cosmetics, which could serve as a tool for the development of microbiome-friendly cosmetics. Given the growing popularity of this topic, we also highlight the need for further research focused on the dynamics between the skin microbiome and cosmetic ingredients.}, } @article {pmid41524110, year = {2026}, author = {Ogawa, M and Isobe, Y and Uchino, H and Hirayama, M and Kato, T and Negishi, K and Arita, M}, title = {The Microbiome Modulates Corneal Wound Healing via the Induction of Cholesterol Sulfotransferase Pathway.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {2}, pages = {e71429}, pmid = {41524110}, issn = {1530-6860}, support = {JPMJER2101//MEXT, Japan Science and Technology Agency (JST)/ ; 22zf0127007//Japan Agency for Medical Research and Development (AMED)/ ; 21ae0121036//Japan Agency for Medical Research and Development (AMED)/ ; 22KJ3143//MEXT, Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Animals ; *Sulfotransferases/metabolism/genetics ; Mice ; *Wound Healing/physiology/drug effects ; Mice, Knockout ; Humans ; *Microbiota/physiology ; Mice, Inbred C57BL ; *Corneal Injuries/microbiology/metabolism/pathology/drug therapy ; Cholesterol Esters/metabolism ; *Cornea/metabolism/microbiology ; Anti-Bacterial Agents/pharmacology ; Cholesterol/metabolism ; Male ; }, abstract = {The ocular surface is in direct contact with the external environment and is susceptible to injury from dust, dryness, or other foreign objects. Once corneal injury occurs, a local inflammatory response is triggered, followed by effective repair of the epithelial layer. In this study, we demonstrated that antibiotic treatment delayed corneal wound healing in mice. LC-MS/MS-based untargeted lipidomics and qPCR analyses revealed that the levels of cholesterol sulfate (CS) and the CS-synthesizing enzyme SULT2B1 were significantly upregulated by antibiotic treatment, and SULT2B1 knockout mice exhibited accelerated corneal wound healing along with increased recruitment of neutrophils and eosinophils. Topical application of CS delayed corneal wound healing. In vitro scratch assays revealed that CS delayed the wound healing of human corneal epithelial cells, potentially by inhibiting the DOCK2-Rac pathway. These results highlight the role of commensal bacteria in controlling corneal wound healing via the cholesterol-sulfotransferase pathway.}, } @article {pmid41523970, year = {2025}, author = {Xu, C and Kong, L and Mou, T and Tang, A and Hu, S and Lai, J}, title = {Vitamin B12 and Affective Disorders: A Focus on the Gut-Brain Axis.}, journal = {Alpha psychiatry}, volume = {26}, number = {6}, pages = {49138}, pmid = {41523970}, issn = {2757-8038}, abstract = {Accumulating evidence highlights the role of Vitamin B12 (VitB12) in the pathophysiology of affective disorders. However, its influence on brain function and the underlying mechanisms remain incompletely understood. In humans, VitB12 is obtained solely from dietary sources, primarily animal-based foods. VitB12 deficiency leads to the accumulation of homocysteine, a known contributor to emotional and behavioral dysregulation. VitB12 plays a critical role in maintaining neuron stability, synapsis plasticity, and regulating neuroinflammation by modulating key bioactive factors. These processes help to alleviate hippocampal damage, mitigate blood-brain barrier disruption, reduce oxidative stress, and enhance both structural and functional connectivity-collectively contributing to resilience against affective disorders. VitB12 from both diet and microbial sources is essential to gut homeostasis. Within the gut lumen, it stabilizes gut microbial communities, promotes short-chain fatty acid (SCFA) production, and supports neurotransmitter metabolism (e.g., serotonin and dopamine) via its role in S-adenosyl-l-methionine biosynthesis. Crucially, VitB12, gut microbiota, SCFAs, intestinal mucosa, and vagal nerve signaling interact synergistically within the gut-brain axis (GBA) to maintain gut microenvironment stability, protect the gut-blood barrier, and suppress neuroinflammatory cascades, eventually reducing the susceptibility to affective disorders. This review synthesizes current evidence on the involvement of VitB12 in the GBA, its association with mood regulation, and its potential as a nutritional adjunct in managing affective disorders. By elucidating this integrative mechanism, we provide new insights into targeting the GBA to improve clinical outcomes in affective disorders.}, } @article {pmid41523930, year = {2025}, author = {Kanaya, A and Luković, E and Emala, C and Mikami, M}, title = {Effects of chronic allergic lung inflammation on gut microbiota and depression-like behavior in mice.}, journal = {Exploration of asthma & allergy}, volume = {3}, number = {}, pages = {}, pmid = {41523930}, issn = {2837-5076}, support = {K08 HL143052/HL/NHLBI NIH HHS/United States ; }, abstract = {AIM: Emerging epidemiological studies have reported a link between allergic diseases, including asthma, and depression. Evidently, the gut microbiota is involved in the pathogenesis of asthma and depression. Therefore, we investigated whether allergic lung inflammation in mice causes gut microbial dysbiosis, via the gut-brain axis, which is potentially associated with depression.

METHODS: Wild-type C57BL/6J female mice were sensitized with intranasal house dust mite (HDM) antigen or phosphate-buffered saline (PBS) for 6 weeks to induce chronic allergic lung inflammation. Sucrose preference tests were performed for assessing depression. Fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between the HDM and PBS groups. The distance calculation, clustering of operational taxonomic units, rarefaction analysis, and estimator calculation (α- and β-diversity) were performed.

RESULTS: There was a significant difference in β-diversity (Bray-Curtis dissimilarity, F-statistics = 6.16, p = 0.001) of the gut microbiota between HDM and PBS groups. However, there was no difference in the α-diversity. We observed multiple differentially abundant bacteria in the HDM and PBS groups. The order class Clostridia (p = 0.0036) and genus Faecalibaculum (p = 0.028) were more abundant in the HDM group, whereas the phylum Firmicutes (p = 0.037) and genera Dubosiella (p = 0.00024) and Turicibacter (p = 0.037) were more abundant in the PBS group. Notably, the relative abundance of some bacteria was correlated with the sucrose preference test results.

CONCLUSIONS: Six weeks of intranasal HDM administration to mimic the chronic status of lung inflammation in asthma changed the gut microbiome in mice and was associated with depression-like behavioral changes.}, } @article {pmid41523773, year = {2025}, author = {Martín Giménez, VM and García Menéndez, S and Sanz, RL and Schiavone, M and Ferder, L and Inserra, F and Manucha, W}, title = {Potential role of nanopharmacology in reducing neuroinflammation associated with hypertension and metabolic disorders.}, journal = {World journal of experimental medicine}, volume = {15}, number = {3}, pages = {106743}, pmid = {41523773}, issn = {2220-315X}, abstract = {Hypertension disrupts cerebral blood flow, leading to endothelial dysfunction, breakdown of the blood-brain barrier (BBB), and inflammatory cell infiltration. This cascade triggers glial cell activation, increases oxidative stress, and causes pro-inflammatory cytokine release, creating a neurotoxic environment. In this context, we explore the intricate connection between hypertension, neuroinflammation, and neurodegeneration, as well as how hypertension interacts with other metabolic disorders, such as obesity and diabetes, to further worsen neuroinflammation. Additionally, we discuss the role of the renin-angiotensin-aldosterone system, the impact of the microbiome, and the potential contribution of chronic infections in exacerbating neuroinflammation. It is essential to emphasize the potential of nanotechnology to transform therapeutic approaches. Nanoparticle-based drug delivery systems can enhance the bioavailability and selectivity of antihypertensive drugs, antioxidants, and neuroprotective compounds, enabling targeted delivery across the BBB. By combining effective blood pressure management with nanotechnology-enabled therapies that modulate inflammation, oxidative stress, and protein aggregation, we can explore new avenues for preventing and treating hypertension and metabolic disorder-associated neurodegenerative conditions. Ultimately, hypertension significantly contributes to neuroinflammation and neurodegeneration by promoting neuronal cell death, primarily through impaired cerebral blood flow and disruption of the BBB. The interaction of hypertension with metabolic disorders exacerbates these effects. However, advancements in our understanding and new technologies reveal promising nanopharmacological approaches for targeted drug delivery to the brain, thereby improving treatment outcomes, enhancing adherence, and reducing side effects.}, } @article {pmid41523758, year = {2025}, author = {Khan, AS and Kamthan, M and Ali, A}, title = {Understanding the intricate interactions between microbiota and host.}, journal = {World journal of experimental medicine}, volume = {15}, number = {3}, pages = {101277}, pmid = {41523758}, issn = {2220-315X}, abstract = {The review examines the intricate relationship between the microbiota and its host, highlighting how these microbial communities influence various physiological functions beyond simple coexistence. The microbiota plays a crucial role in regulating the immune system, metabolism, and overall health. We explore the diverse microbial populations inhabiting different body regions and their essential contributions to maintaining balance within the host. Recent research has uncovered molecular mechanisms that govern microbiota-host interactions, offering new insights into how these microbes support health and, conversely, how imbalances known as dysbiosis can increase susceptibility to diseases. While much attention has been given to the gut microbiota, this review also explores the influence of microbes in other parts of the body, including their effects on various organs and tissues. Additionally, we discuss emerging evidence on the gut-brain axis, illustrating how the microbiota can impact brain function and behavior. Understanding this connection could open new possibilities for treating neurological and psychological disorders. Finally, we evaluate microbiota-based therapies such as probiotics and fecal microbiota transplantation, emphasizing the importance of personalized approaches. By integrating findings from multiple disciplines, this review provides a comprehensive perspective on the microbiota's vital role in human health and its potential as a therapeutic target.}, } @article {pmid41523692, year = {2026}, author = {Nosal, BM and Aksenov, A and Andersen, C and Lee, EC and Zhou, Y and Chun, OK}, title = {The gut-bone axis: potential influence of anthocyanins and implications for postmenopausal osteoporosis.}, journal = {Food science and biotechnology}, volume = {35}, number = {1}, pages = {13-25}, pmid = {41523692}, issn = {2092-6456}, abstract = {With the aging population worldwide and increased life expectancy, the risk of postmenopausal osteoporosis (PMO) is an increased public health concern. Current treatments for PMO have declined in use over the past decade which has led to an increased focus on finding dietary agents that possess antioxidant and anti-inflammatory properties for prophylaxis and treatment of osteoporosis. Anthocyanins (ACNs) have been shown to exert therapeutic effects in chronic diseases due to their antioxidant and anti-inflammatory properties. ACNs are also thought to be involved in modulating the gut microbiome owing to their prebiotic properties. The gut microbiome has been implicated as a potential target for osteoporosis prevention and treatment since it can modulate immune and endocrine systems, which influence bone metabolism. This review summarizes findings related to ACNs' influence on the gut-bone axis, with a focus on the immune and endocrine systems and potential implications for PMO prevention.}, } @article {pmid41523651, year = {2026}, author = {Sitohang, IBS and Legiawati, L and Widaty, S and Nilasari, H and Agustin, T and Chairunnisa, S and Manurung, THP}, title = {Comparative Profile of Microbiome in Normal Skin and Acne Vulgaris Skin Patients.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {19}, number = {}, pages = {1-7}, pmid = {41523651}, issn = {1178-7015}, abstract = {INTRODUCTION: Changes in the skin microbiome are associated with acne vulgaris (AV), a condition characterized by comedones, papules, and pustules. While some bacteria have been studied, many others remain unexplored, highlighting the need to understand the microbiome differences between acne-prone and normal skin. This study aimed to compare skin microbiome profiles between AV patients and healthy individuals and to explore associations with microbial diversity and specific bacterial populations involved in AV pathogenesis.

METHODS: A total of 144 participants were recruited, comprising 36 AV patients and 108 healthy controls. Skin samples were collected from the left cheek after standardized preconditioning. DNA was extracted using the DNeasy PowerSoil Kit™, and the V3-V4 region of 16S rRNA was amplified and sequenced. Microbial diversity was assessed by the Shannon index, and correlations with sebum levels were analyzed.

RESULTS: The results revealed significant differences in microbial diversity, with AV patients exhibiting a markedly lower Shannon index compared to controls, indicating decreased microbial diversity and potential dysbiosis. While the relative abundance of Cutibacterium acnes, a bacterium commonly associated with AV, showed no significant differences between the two groups, the prevalence of Staphylococcus epidermidis was notably higher in AV patients. This suggests that S. epidermidis may play a complex role in the inflammatory processes associated with AV. Moreover, the study identified a negative correlation between microbial diversity and sebum levels, suggesting that increased sebum production may favor the growth of S. epidermidis, potentially exacerbating the condition.

CONCLUSION: These findings highlight the interaction between host factors and microbial composition. This study emphasizes the role of skin microbiome dysbiosis in acne vulgaris and provides insights for future microbiome-based therapeutic strategies. Further research is needed to clarify microbial mechanisms and potential interventions targeting the microbiome in the management of acne vulgaris.}, } @article {pmid41523287, year = {2026}, author = {Fang, S and Wang, S and Liu, Y and Zhu, C and Wang, S and Xu, F}, title = {Clinical Safety and Tolerability of Bifidobacterium bifidum BBi32: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial With Genomic and In Vitro Corroboration.}, journal = {Food science & nutrition}, volume = {14}, number = {1}, pages = {e71420}, pmid = {41523287}, issn = {2048-7177}, abstract = {Bifidobacterium bifidum BBi32, isolated from a healthy infant, underwent a multi-tiered safety assessment to evaluate its genetic features, in vitro properties, and effects on gut microbiota and host biomarkers. Whole-genome sequencing (WGS) and functional annotation were performed alongside in vitro assays assessing acid and bile tolerance, mucin degradation, hemolysis, Caco-2 cytotoxicity, and antibiotic susceptibility. Acute oral toxicity was tested in mice. A randomized, double-blind, placebo-controlled clinical trial (n = 40, 8 weeks) evaluated tolerability and exploratory endpoints, including hematology, liver and renal function, LL-37 levels, gastrointestinal symptom scores, and 16S rRNA-based microbiome profiling. The BBi32 genome comprised a 2.2 Mbp circular chromosome with 99.99% average nucleotide identity to the type strain, no plasmids, and no acquired antimicrobial resistance or virulence genes. Functional categories were enriched for ABC transporters, purine metabolism, and defense mechanisms. BBi32 demonstrated tolerance to acid and bile, lacked mucin-degrading, or hemolytic activity, showed no cytotoxicity to Caco-2 cells, and was susceptible to most antibiotics. Acute toxicity test yielded an LD50 > 2 × 10[10] CFU/kg with no adverse effects. In the clinical trial, daily BBi32 administration (3 × 10[10] CFU) was well tolerated, with no hematological or hepatic abnormalities. Compared with placebo, BBi32 reduced uric acid, urea, and creatinine levels, increased LL-37, and improved gastrointestinal symptom scores. Microbiome analysis revealed higher alpha diversity, distinct community clustering, enrichment of Romboutsia, and predicted functional shifts toward amino acid biosynthesis and peptidase activity. Genomic, in vitro, toxicological, and clinical data collectively indicate that BBi32 meets key safety criteria and favorably modulates host and microbiome biomarkers, supporting its probiotic potential.}, } @article {pmid41523278, year = {2026}, author = {Ji, G and Li, C and Yao, Z and Li, Z and Yang, B and Hu, L and Yu, H and Jiang, T and Wang, S and Wang, H}, title = {Therapeutic Potential of Irpex lacteus Polysaccharides in Lupus Nephritis: Insights From Gut Microbiota and Metabolomics Analysis in MRL/Lpr Mice.}, journal = {Food science & nutrition}, volume = {14}, number = {1}, pages = {e71446}, pmid = {41523278}, issn = {2048-7177}, abstract = {Polysaccharides from Irpex lacteus (PCP) were evaluated for their therapeutic effects on lupus nephritis (LN) in MRL/lpr mice. After 8-week interventions with low- and high-dose PCP, we systematically evaluated the therapeutic efficacy by measuring the levels of autoantibodies, the expression of inflammatory cytokines, and renal function-related parameters. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PCP intervention in LN. PCP could reverse the phenotype of MRL/lpr mice, reduce autoantibody levels, alleviate inflammatory responses, and improve renal function. Gut microbiome analysis found that PCP can improve gut microbiota composition and abundance of two phyla (Firmicutes, Bacteroidota) and five genera (Lachnospiraceae NK4A136 group, Alistipes, Butyricicoccus, Bacteroides, Lactobacillus), which play an important role in the process of PCP intervention on metabolism in MRL/lpr mice. UHPLC-MS untargeted metabolomics showed that PCP significantly affects multiple key differential metabolites, including Linoleic acid, L-Phenylalanine, L-Tyrosine, and 56 other metabolites. These metabolites are primarily involved in metabolic pathways such as tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, linoleic acid metabolism, and arachidonic acid metabolism. Correlation analysis between gut microbiota and differential metabolites reveals a close relationship, suggesting that gut microbiota promoting host metabolism may be one of the mechanisms by which PCP treats LN. PCP alleviates LN by modulating the "microbiota-metabolism axis," reducing autoantibodies, inflammation, and renal damage, while reshaping gut microbiota and regulating key metabolic pathways.}, } @article {pmid41523242, year = {2025}, author = {Qi, W and Tian, L and Li, Z and Xu, J and Wang, T}, title = {Pathogen spectrum and management strategies for opportunistic infections in lung cancer in the immunotherapy era: recent advances from fungi to mycobacteria.}, journal = {American journal of cancer research}, volume = {15}, number = {12}, pages = {5140-5167}, pmid = {41523242}, issn = {2156-6976}, abstract = {Lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Opportunistic infections (OI) are increasingly recognized in this population due to disease-related immune dysfunction and treatment-induced immunosuppression. Compared with the chemotherapy era, the use of immune checkpoint inhibitors and targeted agents has shifted the OI profile. Pneumocystis jirovecii pneumonia (PJP) and invasive pulmonary aspergillosis (IPA) are reported more often in older adults and patients with lymphopenia, while tuberculosis (TB) and nontuberculous mycobacteria (NTM) cluster in those with structural lung disease (e.g., bronchiectasis, cavities) and prolonged immunosuppression. High-risk features include absolute lymphocyte count <500/µL, corticosteroids ≥20 mg prednisone-equivalent for ≥4 weeks, airway obstruction, prior TB, chronic obstructive pulmonary disease/interstitial lung disease (ILD), and recent broad-spectrum antibiotics. Diagnosis should integrate high-resolution computed tomography (HRCT) patterns (e.g., diffuse ground-glass for PJP; nodules with halo sign for IPA), microbiology [bronchoalveolar lavage fluid (BALF) culture/microscopy, galactomannan (GM)/β-D-glucan (BDG)], and metagenomic next-generation sequencing, interpreted against host factors and treatment timeline, while carefully distinguishing immune-related pneumonitis and TKI-associated ILD. Prophylaxis with TMP-SMX is recommended for high-risk patients; voriconazole (or isavuconazole) is first-line for IPA with attention to drug-drug interactions; TB/NTM regimens require coordination with anticancer therapy, especially where rifamycins interact with TKIs. Vaccination (influenza, pneumococcus, zoster) and antimicrobial stewardship are essential. Future work should validate risk scores prospectively and clarify microbiome-immunotherapy-infection relationships.}, } @article {pmid41523241, year = {2025}, author = {Wang, Y and Sun, W and Li, H and Xu, F and Cui, W}, title = {Decoding the metastatic nexus: how chronic stress reprograms neuroendocrine-metabolic-microbiome circuits to fuel tumor metastasis.}, journal = {American journal of cancer research}, volume = {15}, number = {12}, pages = {5058-5083}, pmid = {41523241}, issn = {2156-6976}, abstract = {Metastasis, the leading cause of death in patients with solid tumors, involves the spread of cancer cells to distant organs. While genetic and environmental factors contribute, chronic stress is a crucial factor in metastatic progression by disrupting neuroendocrine, immune, metabolic, and microbial homeostasis. This review synthesizes evidence linking chronic stress to tumor metastasis through three pathways: (1) direct effects on tumor cell metabolism, (2) remodeling of the tumor microenvironment, and (3) dysregulation of the gut microbiota. Describe how activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system influence epithelial-mesenchymal transition, immune evasion, and angiogenesis via β-adrenergic and glucocorticoid receptor signaling. Explore how microbial metabolites and barrier dysfunction influence immune and neuroendocrine circuits, creating a pro-metastatic loop. Finally, we highlight therapeutic strategies, including psychological interventions and pharmacologic approaches, to alleviate chronic stress. This review proposes a mechanistic framework linking neuroendocrine signaling, metabolic reprogramming, and the microbiome-immune axis.}, } @article {pmid41523132, year = {2025}, author = {Arita, R}, title = {Targeted therapies for meibomian gland dysfunction - The role of antibiotics in meibomian gland dysfunction management.}, journal = {Taiwan journal of ophthalmology}, volume = {15}, number = {4}, pages = {516-525}, pmid = {41523132}, issn = {2211-5072}, abstract = {Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye, significantly impairing the quality of life. Bacterial proliferation and inflammation play central roles in the pathogenesis of MGD, creating a vicious cycle of gland obstruction and ocular surface instability. Antibiotics, particularly tetracyclines (e.g. doxycycline and minocycline), and macrolides (e.g. azithromycin and erythromycin), are widely used as adjunctive therapy for moderate-to-severe or refractory MGD. This review conducted a comprehensive literature search of PubMed, focusing on original peer-reviewed articles published in English that reported on the efficacy and/or safety of oral or topical antibiotics for MGD or blepharitis. Eligible studies were identified using the specific search terms, screened by title and abstract, and selected based on predefined inclusion and exclusion criteria. Relevant data were extracted and synthesized, with an emphasis on randomized controlled trials and comparative studies. The review indicates that both oral and topical antibiotics improve subjective symptoms, tear film stability, ocular surface staining, meibum quality, and lid margin abnormalities in the short term. Oral azithromycin may be at least as effective as doxycycline, with a shorter treatment course and fewer adverse events, while topical azithromycin offers similar or superior efficacy to systemic regimens with reduced systemic exposure. However, benefits are usually limited to active treatment periods, and optimal dosing and duration remain uncertain. Long-term efficacy, safety, risk of resistance, and effects on the ocular microbiome require further investigation. Antibiotics should be used judiciously as part of a comprehensive, individualized management strategy for MGD.}, } @article {pmid41523060, year = {2025}, author = {Agrawal, R and Shah, M and Srivastava, V and Naik, SR and Patel, NR and Dwivedy, S and Mehta, M and Patel, BJ and Makkad, RS}, title = {An In vitro Study of the Isolation of Candidal Strains in Patients at Increased Risk of Oral Squamous Cell Carcinoma.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {17}, number = {Suppl 4}, pages = {S2870-S2872}, pmid = {41523060}, issn = {0976-4879}, abstract = {BACKGROUND: OSCC stands as a prominent oral malignancy that develops because of lifestyle behavior and microbial activity. The pathogenesis of OSCC receives attention through modern research since Candida species reportedly contribute to the development of OSCC through inflammatory responses and nitrosamine generation and epithelial tissue malformation.

MATERIALS AND METHODS: Sixty subjects participated in this in vitro study, which was separated into two distinct groups: Group A with 30 patients who had high OSCC risk oral lesions (leukoplakia and erythroplakia) and Group B which included 30 healthy subjects. A laboratory research involved collecting samples through swabs from saliva and mucosa, which were subsequently cultured on Sabouraud Dextrose Agar (SDA) alongside CHROMagar for fungal detection. The researchers identified isolated colonies by checking their ability to form germ tubes combined with carbohydrate assimilation tests.

RESULTS: Out of the 30 Group A samples, 80% (24/30) demonstrated candidal growth where Candida albicans constituted 70.8% of strains and Candida tropicalis made up 16.7% alongside Candida glabrata counting for 12.5%. The overall candidal growth among participants in Group B was limited to 30% (9/30) as C. albicans constituted 88.9%, whereas C. glabrata accounted for 11.1%. The incidence of candidal colonization proved markedly higher among the high-risk group compared to controls according to statistical analysis (P = 0.002).

CONCLUSION: The numbers of Candida species, particularly C. albicans, rise substantially within the oral environments of patients dealing with potentially malignant disorders. The obtained data support the possibility that oral cancer development may be related to candidal colonization, thus demanding additional studies on this association.}, } @article {pmid41523026, year = {2025}, author = {Sahu, M and Agarwal, G and Jain, G and Saad, T and Qureshi, MA and Mishra, S}, title = {Determination of Gut Microbiome Patterns Associated with Developing Active Tuberculosis in a Case-Control Study.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {17}, number = {Suppl 4}, pages = {S3069-S3071}, pmid = {41523026}, issn = {0976-4879}, abstract = {BACKGROUND: The gut microbiome plays a critical role in modulating systemic immunity and may influence susceptibility to infectious diseases, such as tuberculosis (TB). This study aimed to compare gut microbial profiles between individuals with active pulmonary TB and healthy controls to identify potential microbial signatures associated with disease development.

METHODS: A hospital-based case-control study was conducted with 90 participants: 45 treatment-naïve TB patients and 45 healthy controls. Stool samples were collected and analyzed using 16S rRNA sequencing. Microbial diversity was assessed using the Shannon index, and relative abundances of key bacterial phyla were compared. Statistical analysis included Mann-Whitney U tests and LEfSe for differential taxa identification.

RESULTS: TB patients showed significantly lower alpha diversity (Shannon index: 2.91 ± 0.37) compared to controls (3.81 ± 0.28, P < 0.001). The relative abundance of Proteobacteria was significantly higher in TB cases, while Firmicutes and Bacteroidetes were more abundant in controls. These findings indicate a pro-inflammatory gut microbiota shift in active TB.

CONCLUSION: Active tuberculosis is associated with gut microbial dysbiosis, marked by reduced diversity and altered bacterial composition. These microbial signatures could aid in early diagnosis and serve as future targets for microbiome-based interventions.}, } @article {pmid41522762, year = {2025}, author = {Yang, H and Liu, X and Yuan, D and Li, H and Mu, X}, title = {A prognostic nomogram for colorectal cancer: integrating blood microbiome and clinical factors.}, journal = {Journal of gastrointestinal oncology}, volume = {16}, number = {6}, pages = {2651-2663}, pmid = {41522762}, issn = {2078-6891}, abstract = {BACKGROUND: The microbiota is pivotal in colorectal cancer (CRC), yet the prognostic value of the blood microbiome and its utility in clinical prediction models remain poorly explored. This study aims to develop a blood microbiome-associated prognostic score (MAPS) that integrates blood microbiome data with clinical factors to improve the accuracy of CRC prognosis prediction and enhance our understanding of the tumor microenvironment (TME).

METHODS: We analyzed whole-genome and transcriptomic sequencing data of CRC patients from The Cancer Genome Atlas (TCGA). A MAPS was developed from blood microbiome data using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. A nomogram integrating MAPS and key clinical factors was constructed to predict overall survival (OS). Its predictive accuracy was validated via time-dependent receiver operating characteristic (ROC) analysis, yielding area under the curve (AUC) values for 1-, 3-, and 5-year OS. Underlying mechanisms were investigated through gene set enrichment analysis (GSEA) and immune cell infiltration estimation from matched RNA sequencing (RNA-seq) data.

RESULTS: The MAPS, comprising seven key blood microbes, was an independent prognostic factor. The integrative nomogram demonstrated robust predictive performance, with AUCs of 0.800, 0.805, and 0.755 for predicting 1-, 3-, and 5-year OS, respectively. Mechanistically, the high-MAPS subgroup exhibited enriched pro-tumorigenic pathways (e.g., inflammatory response, hypoxia) and an immunosuppressive TME characterized by increased Treg cell infiltration. We further identified S100A8 and PROK2 as potential therapeutic targets.

CONCLUSIONS: Our study delivers a validated prognostic nomogram based on the blood microbiome and elucidates its link to an immunosuppressive TME, highlighting its dual utility in patient stratification and target discovery.}, } @article {pmid41522496, year = {2026}, author = {Gedam, PA and Khandagale, K and Barvkar, VT and Bhandari, S and Patil, S and Wayal, S and Bhangare, I and Bhagat, KP and Landage, K and Kale, R and Bhoite, V and More, S and Mahajan, V and Gawande, S}, title = {Microbial allies: shaping growth, physiology, and rhizosphere dynamics of onion (Allium cepa L.).}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20566}, pmid = {41522496}, issn = {2167-8359}, mesh = {*Rhizosphere ; *Onions/microbiology/growth & development/physiology ; *Soil Microbiology ; Fertilizers ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics/classification ; }, abstract = {The present study investigates the dual impact of microbial biofertilizers on the phenotypic performance and rhizosphere microbiome composition in an onion crop. A pot experiment was conducted with seven treatments of microbial inoculants, such as Azotobacter, Azospirillum, Piriformospora indica, phosphate solubilizing bacteria (PSB), and control treatments with and without chemical fertilizers. The growth, physiological, and biochemical traits of onion were assessed alongside rhizospheric soil microbiome profiling using 16S rRNA metagenomic sequencing. Significant enhancement in plant height, leaf number, leaf area, chlorophyll content, photosynthetic rate, and antioxidant enzyme activity with low leaf temperature was observed in plants inoculated with Azotobacter and Azospirillum. Notably, the Azotobacter treatment yielded a significant enhancement in the bulb phenol content. Rhizosphere metagenomic analysis revealed 17 dominant phyla, with Actinobacteria (25.3%), Proteobacteria (22.2%), Firmicutes (12.8%), and Chloroflexi (11.02%) comprising over 70% of the total microbiome. Alpha and beta diversity metrics indicated that microbial inoculation, especially with Azospirillum and PSB, enriched the soil microbial community structure. Distinct clustering and correlations with specific microbial taxa such as Candidatus Nitrososphaera and Pseudomonas were observed in response to individual biofertilizer treatments. This study highlights the potential of biofertilizers not only in enhancing onion growth and development but also in modulating beneficial rhizosphere microbial communities. Integrating biofertilizers into onion production systems could reduce the dependency on chemical fertilizers and promote sustainable crop management.}, } @article {pmid41522492, year = {2026}, author = {Arredondo, A and Àlvarez, G and Isabal, S and Teughels, W and Laleman, I and Contreras, MJ and Isbej, L and Huapaya, E and Mendoza, G and Mor, C and Nart, J and Blanc, V and León, R}, title = {Cross-sectional comparative shotgun metagenomic analysis of the subgingival resistome in healthy subjects and patients with periodontitis from four countries.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2610588}, pmid = {41522492}, issn = {2000-2297}, abstract = {BACKGROUND: The oral cavity is a known reservoir of antibiotic resistance genes (ARGs), but little is known about their subgingival distribution across health states and regions.

OBJECTIVE: This study aimed to characterize and compare the subgingival resistome and mobile genetic elements (MGEs) in healthy subjects (HS) and periodontitis patients (PP) from Belgium, Chile, Peru and Spain.

DESIGN: Subgingival samples pooled from the deepest site of each quadrant of 40 HS and 40 PP were analyzed via shotgun metagenomic sequencing. After human DNA depletion, the microbial composition was assessed with MetaPhlAn 4.0; ARGs were identified using MEGAHIT and AMRFinderPlus; and MGEs with MGEfinder.

RESULTS: ARG richness was significantly higher in PP (mean 3.98) than in HS (2.15). PP from Peru showed more ARGs than HS from Chile and Spain. In total, 28 ARGs were found, conferring resistance to eight antibiotic classes. β-lactam, tetracycline and aminoglycoside resistance were more abundant in PP. Macrolide resistance was lower in Chilean samples than in Peruvian and Spanish ones. Additionally, 99 MGE-associated genes were detected, with 16 differing by diagnosis and 78 by country.

CONCLUSIONS: Subgingival resistome profiles vary significantly by periodontal status and geography, underscoring the influence of clinical and regional factors on antimicrobial resistance in the oral microbiome.}, } @article {pmid41522487, year = {2026}, author = {Al Qassab, M and Chaarani, N and Hamou, A and Harb, R and Jradi, A and Zeineddine, M and Ghadieh, HE and Khattar, ZA and Azar, S and Kanaan, A and Harb, F}, title = {The Gut Microbiota-Insulin Resistance Axis: Mechanisms, Clinical Implications, and Therapeutic Potential.}, journal = {FASEB bioAdvances}, volume = {8}, number = {1}, pages = {e70080}, pmid = {41522487}, issn = {2573-9832}, abstract = {Emerging evidence highlights the pivotal role of the gut microbiota (GM) in regulating host metabolism and contributing to the development of insulin resistance (IR). Gut dysbiosis alters the production of critical metabolites, including short-chain fatty acids (SCFAs), bile acids, indole derivatives, and trimethylamine N-oxide (TMAO), which influence intestinal barrier integrity, inflammatory pathways, and glucose homeostasis. Recent clinical and translational studies indicate that SCFAs can improve fasting insulin and HOMA-IR, although the magnitude of benefit varies substantially across individuals, highlighting ongoing controversy surrounding their metabolic effects. Altered microbial regulation of bile-acid metabolism has also been implicated in impaired lipid and glucose signaling, reinforcing the relevance of FXR- and TGR5-mediated pathways in IR. Elevated TMAO levels have further been associated with adverse metabolic outcomes, though debate persists regarding its causal role versus its function as a diet-dependent biomarker. Microbiota-targeted strategies, including dietary fiber, probiotics, and fecal microbiota transplantation (FMT), show potential to modulate these metabolic pathways, yet clinical results remain inconsistent. This narrative review synthesizes recent mechanistic discoveries and clinical findings on microbiota-derived metabolites in IR, highlights key controversies, and outlines future priorities for translating microbiome science into effective and personalized interventions for metabolic disease prevention and management.}, } @article {pmid41522466, year = {2026}, author = {Jain, V}, title = {Gut microbiome in biliary atresia.}, journal = {World journal of pediatric surgery}, volume = {9}, number = {1}, pages = {e001068}, pmid = {41522466}, issn = {2516-5410}, abstract = {Biliary atresia (BA) is a progressive cholangiopathy of infancy and the leading cause of pediatric liver transplantation. Despite surgical intervention with the Kasai portoenterostomy, long-term outcomes remain poor, with many patients progressing to cirrhosis. Emerging evidence implicates the gut microbiota-a dynamic ecosystem crucial to immune development and liver homeostasis-in BA pathogenesis and clinical progression. This review synthesizes current literature on gut microbiota composition in BA before and after the Kasai procedure, highlighting consistent patterns of dysbiosis, including pathobiont expansion and depletion of beneficial microbes such as Bifidobacterium. The review explores associations between microbial profiles and clinical outcomes-highlighting potential mechanisms involving bile acid metabolism, microbial translocation, and immune modulation. Further understanding of gut-liver-microbiota interactions in BA may inform microbiome-targeted therapies to improve native liver survival.}, } @article {pmid41522445, year = {2025}, author = {Glazunova, E and Molodtsova, P and Grabarnik, I and Kurnosov, A and Bikaeva, I and Shipulin, G and Zlobovskaya, O}, title = {Healthy human gut microbiome: Towards standardized research.}, journal = {AIMS microbiology}, volume = {11}, number = {4}, pages = {786-820}, pmid = {41522445}, issn = {2471-1888}, abstract = {OBJECTIVE: An increasing number of international researchers are focusing on the taxonomic composition of fecal microbiota and its correlation with disorders. Thousands of researchers compare conditionally healthy cohorts to those with specific diseases to identify potential markers. However, clinical application requires assessing the feasibility of synthesizing these findings and establishing reference intervals for normal gut flora, at least at higher taxonomic levels.

DESIGN: This study involves a systematic review and meta-analysis of human gut microbiota research based on 16S rRNA gene next-generation sequencing (NGS). Relevant research was sourced following the PRISMA guidelines. Descriptive statistics, linear regression analysis by weighted least squares method, Mann-Whitney test, and Benjamini-Hochberg procedure adjustments were employed. The study has been registered with PROSPERO (CRD42023431467).

RESULTS: Of the 4,346 studies initially identified, 86 publications involving 20,748 unique participants met the quality criteria and were included in the analysis of the impact of fecal sample preparation on taxonomic composition. The phylotype composition, in relation to preprocessing methods and cohort locations, are presented as relative abundances (%): Bacillota (median 49.5-59.6%), Bacteroidota (28.0-33.4%), Pseudomonadota (3.4-5.9%), Actinomycetota (2.3-3.7%), Verrucomicrobiota (0.5-1.0%), Fusobacteriota (maximum 4.6%), and Euryarchaeota (maximum 2.11%). The content of 27 key family-level representatives was also evaluated. The well-known hypothesis regarding the influence of the homogenization stage on taxonomic composition was examined using generalized results.

CONCLUSION: While supported by a strong theoretical basis and evidence from individual practical cases, none of the phyla showed a statistically significant association and consistent relationship with sample preparation or cohort location when generalizing across studies after the two exceptionally large cohorts exclusion, both originating from a single research group. These findings underscore the need for strict methodological standardization in microbiome studies. Key features of the 16S NGS process accounting for these results are outlined, along with proposed optimizations for microbiome research.}, } @article {pmid41522435, year = {2025}, author = {Zalila-Kolsi, I}, title = {Engineered bacteria as living therapeutics: Next-generation precision tools for health, industry, environment, and agriculture.}, journal = {AIMS microbiology}, volume = {11}, number = {4}, pages = {946-962}, pmid = {41522435}, issn = {2471-1888}, abstract = {Synthetic biology has revolutionized precision medicine by enabling the development of engineered bacteria as living therapeutics, dynamic biological systems capable of sensing, responding to, and functioning within complex physiological environments. These microbial platforms offer unprecedented adaptability, allowing for real-time detection of disease signals and targeted therapeutic delivery. This review explores recent innovations in microbial engineering across medical, industrial, environmental, and agricultural domains. Key advances include CRISPR-Cas systems, synthetic gene circuits, and modular plasmid architectures that provide fine-tuned control over microbial behavior and therapeutic output. The integration of computational modeling and machine learning has further accelerated design, optimization, and scalability. Despite these breakthroughs, challenges persist in maintaining genetic stability, ensuring biosafety, and achieving reproducibility in clinical and industrial settings. Ethical and regulatory frameworks are evolving to address dual-use concerns, public perception, and global policy disparities. Looking forward, the convergence of synthetic biology with nanotechnology, materials science, and personalized medicine is paving the way for intelligent, responsive, and sustainable solutions to global health and environmental challenges. Engineered bacteria are poised to become transformative tools not only in disease treatment but also in diagnostics, biomanufacturing, pollution mitigation, and sustainable agriculture.}, } @article {pmid41522308, year = {2025}, author = {Henry, GD and Diaz, N and Phillips, CD and Lentz, AC and Perito, P and Natale, R and Bennett, N and Stuart, AR and Henry, CJ and Chung, PH}, title = {Methods and early findings from a study comparing next-generation sequencing versus traditional cultures for penile implants concerning for low-grade infection.}, journal = {Translational andrology and urology}, volume = {14}, number = {12}, pages = {3945-3951}, pmid = {41522308}, issn = {2223-4691}, abstract = {Microbial culture is the current standard of care to choose therapeutic antibiotics for infection occurring with inflatable penile prostheses (IPPs). However, next-generation sequencing (NGS) of DNA has proven beneficial for analysis of biofilm composition and relative abundance of specific microorganisms. The main goal of this study is to evaluate whether NGS compared to microbial culture can better guide the management and antibiotic selection and device survival rates. We hypothesize that identifying microbial composition with NGS, as compared with traditional culture, will lead to better therapeutic strategies resulting in improved patient outcomes and device survival. In this present manuscript, we describe the overall study methodology and analyze device survival rates, classify clinical presentations of IPP infections, and determine infected implant microbial composition and antibiotic resistance among an early patient cohort. These early results included 18- to 80-year-old consecutive male patients who received antimicrobial treatment without surgical replacement for at least 7 days since identification of infected IPPs. Subjects were randomized into two analytic arms: traditional culture and NGS. Throughout the study, investigators and patients completed questionnaires to provide data for comparison. To date, of the 9 patients enrolled in the study, 6 eventually underwent device removal due to worsening infection within 7 days of initiating empiric antibiotic treatment. Six patients were seen in a clinic setting, while 3 were seen in the hospital/emergency department: 7 implants were primary, while 2 were secondary. All subjects received a Coloplast IPP but had differing reservoirs and reservoir locations. In cases where penile shaft tenderness was present, the implanted IPP was more often removed within 7 days. In contrast, when no tenderness was reported, the device remained viable for at least 10 days. As of this report, 11 active sites have participated in the study, with ongoing patient enrollment aimed at reaching sufficient sample sizes for statistical comparison. Penile shaft tenderness was a common presentation among patients whose early antibiotic treatment for IPP infection failed. Recruitment of additional patients to this prospective, randomized controlled trial will help to identify favorable presentations of IPP infection. Additional data will allow comparison of implantation outcomes between NGS and traditional culture.}, } @article {pmid41521788, year = {2026}, author = {Hernandez-Rovira, B and Villamaria, E and Oh, J and Ozarslan, B and Wyles, S}, title = {Topical Carboxytherapy Modulates the Skin Microbiome Following CO2 Laser Resurfacing: A Pilot Study.}, journal = {Journal of cosmetic dermatology}, volume = {25}, number = {1}, pages = {e70668}, doi = {10.1111/jocd.70668}, pmid = {41521788}, issn = {1473-2165}, support = {//Lumisque Skincare, LLC/ ; }, } @article {pmid41521690, year = {2026}, author = {Bailey, AM and Hofseth, LJ}, title = {Microplastics in Early Onset Carcinogenesis.}, journal = {Carcinogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgaf093}, pmid = {41521690}, issn = {1460-2180}, abstract = {Plastics have become integral to modern life, but their persistence has generated vast quantities of microplastics (MPs, <5 mm) and nanoplastics (NPs, <1 µm) that now contaminate food, water, air, and human tissues. Although not yet classified as carcinogens by the International Agency for Research on Cancer, accumulating experimental and epidemiologic evidence raises concern that MPs may contribute to cancer development. Global plastic production has risen from 2 megatons in 1950 to more than 450 megatons annually in 2022, leaving behind pervasive waste that fragments into MPs and NPs. These particles act as xenobiotics, carrying toxic additives and adsorbed pollutants, provoking oxidative stress, chronic inflammation, DNA damage, and microbiome disruption; all processes central to carcinogenesis. MPs have been detected in human cancers, and animal studies show tissue accumulation, fibrosis, and genomic instability following exposure. Importantly, the proliferation of plastics parallels a global rise in early-onset cancers (diagnosed before age 50), suggesting a possible, though unproven, temporal association. Individuals born after the 1950s plastic boom have experienced continuous MP exposure beginning in utero, potentially predisposing them to carcinogenic pathways later in life. In this review, we integrate human biomonitoring data, experimental findings, and clinical observations to evaluate the emerging hypothesis that chronic MP exposure contributes to cancer risk. While causality has not been established, the biological plausibility and mounting evidence underscore the urgent need for mechanistic and epidemiologic studies to clarify the role of MPs and NPs in cancer development. It also underscores an urgent need for research into causal pathways and preventive mechanisms.}, } @article {pmid41521588, year = {2026}, author = {Alolod, GAL and Guzman, JPMD and Bermeo-Capunong, MRA and Konishi, K and Koiwai, K and Kondo, H and Hirono, I}, title = {Metagenomic Insights on the Progression of White Muscle Disease in Kuruma Shrimp (Penaeus japonicus) Caused by Photobacterium damselae subsp. damselae.}, journal = {Journal of fish diseases}, volume = {}, number = {}, pages = {e70117}, doi = {10.1111/jfd.70117}, pmid = {41521588}, issn = {1365-2761}, support = {22H00379//Japan Society for the Promotion of Science/ ; JPMJSA1806//Japan Science and Technology Agency/ ; }, abstract = {Kuruma shrimp (Penaeus japonicus) is an economically important shrimp perennially affected by diseases. In 2022, White Muscle Disease (WMD) was first characterised in this Penaeid species, caused by Photobacterium damselae subsp. damselae (Pdd). In this study, muscular and gut microbiome dynamics and their function in the disease progression are investigated by 16S rRNA metagenome sequencing using Illumina sequencing technologies. Alpha diversity indices showed that Pdd infection in the muscle, stomach, and intestine did not significantly change bacterial diversity between control and infected groups at all time points observed (Days 0, 1, 3, 5, 7 and 10). In the infected samples, the Shannon and Simpson indices increased starting Day 5 (D5), in congruence with the first observation of muscle whitening. Bacterial composition for the infected group at the genus level revealed that Photobacterium and Vibrio have increased their relative abundance in the muscle at Day 5 (D5) until Day 7 (D7), but declined at Day 10 (D10). As for stomach samples, Photobacterium declined in abundance and later increased significantly at Day 7 (D7). Photobacterium in the intestinal samples from the infected group increased at Day 5 (D5) but later decreased at Day 7 (D7). Meanwhile, linear discriminant analysis Effect Size (LEfSe) identified that most taxa belong to phylum Pseudomonadota, which can be potential markers for WMD. Moreover, the temporal dynamics of the amplicon sequencing variant ASV2, confirmed to be 100% homologous to the WMD-P3 strain used in this study, were characterised. For all tissues, the logarithmic relative abundance is considered high and very apparent in infected samples collected at Day 7 (D7). Overall, our study provides an understanding of the muscle and gut microbial community, specifically at the genus level, distinguished between WMD-infected and healthy Kuruma shrimps.}, } @article {pmid41521409, year = {2025}, author = {Lindsay, J and Yeoh, D and Teh, BW and Reynolds, GK and Henden, A and McQuilten, Z and Wheeler, M and Hamilton, A and Nelson, A and Nakagaki, M and Sandhu, S and Slavin, MA and , }, title = {Consensus guidelines for antibacterial prophylaxis in patients with neutropenia.}, journal = {Internal medicine journal}, volume = {55 Suppl 7}, number = {}, pages = {115-135}, doi = {10.1111/imj.70250}, pmid = {41521409}, issn = {1445-5994}, mesh = {Humans ; *Antibiotic Prophylaxis/standards/methods ; *Neutropenia/drug therapy/chemically induced ; *Anti-Bacterial Agents/therapeutic use ; *Consensus ; Australia/epidemiology ; Neoplasms/drug therapy ; *Practice Guidelines as Topic/standards ; }, abstract = {Since the publication of the Australian consensus guidelines in 2011, the routine use of prophylactic antibiotics in patients with neutropenia has remained controversial, because of concern that the risks of promoting antimicrobial resistance outweighed the level of evidence that their use reduced mortality. Populations at risk have changed over this period and now include a multitude of new cancer therapies, such as targeted cancer therapies and immunotherapies. Emerging understanding about the importance and role of the microbiome in defining treatment response and patterns of antibiotic resistance has also expanded. In addition, the management of neutropenic fever has improved significantly through the development and routine implementation of sepsis pathways. These updated consensus guidelines review recent evidence for the use of antibacterial prophylaxis in adults and children receiving cancer therapies associated with neutropenia. Recommendations presented in these guidelines were based on evaluating current evidence for the benefits and harms of antibacterial prophylaxis while considering the current Australian and New Zealand healthcare setting. In most circumstances, the potential harm of antibiotic resistance, adverse effects of antibiotics and disruption to the microbiome, outweighed the benefit of reducing the incidence of infection, without a benefit in mortality.}, } @article {pmid41521406, year = {2025}, author = {Douglas, AP and Cooley, L and McMullan, B and Kinsella, P and Laundy, N and Yap, N and Bupha-Intr, O and Alcorn, K and Bajel, A and Weinkove, R and Legg, A and Roberts, JA and Trubiano, JA and Conyers, R and Thursky, KA and , }, title = {Consensus guidelines for initial management of neutropenic fever.}, journal = {Internal medicine journal}, volume = {55 Suppl 7}, number = {}, pages = {43-67}, doi = {10.1111/imj.70248}, pmid = {41521406}, issn = {1445-5994}, mesh = {Humans ; *Consensus ; *Neutropenia/therapy/diagnosis ; *Anti-Bacterial Agents/therapeutic use ; *Fever/diagnosis/therapy/etiology/drug therapy ; *Disease Management ; *Practice Guidelines as Topic/standards ; Adult ; }, abstract = {This update of the Australasian consensus guidelines for the initial empiric management of neutropenic fever occurs in the context of major changes in cancer treatment paradigms, as well as advances in the management of sepsis and new models of care for infections since the last version of these guidelines in 2011. Acknowledging the important role of antimicrobials in the disruption of the gut microbiome and emerging antimicrobial resistance, as well as the changing epidemiology of antimicrobial resistance more broadly, these guidelines address current evidence for optimal empiric neutropenic fever therapy. A writing group - including adult and paediatric representatives across infectious diseases, microbiology, haematology, transplant and oncology, as well as across craft groups, including medicine, nursing and pharmacy - was developed to produce and address key management questions. This was overseen by a steering committee, which included consumer representation. Using an extensive review of the literature, these guidelines provide consensus recommendations with evidence grading for initial empiric management of neutropenic fever in adults and children, including recommended investigations, antimicrobial therapy and approach to patients with beta-lactam allergy or risk factors for multidrug-resistant infection. Management beyond the first 72 h is discussed in separate chapters of this issue: the Subsequent Management (for high-risk neutropenic fever) and Ambulatory Management (for low-risk neutropenic fever) chapters.}, } @article {pmid41521300, year = {2026}, author = {Deng, W and Chen, D and Wei, Y and Chen, W and Chen, K and Zhong, H and He, X}, title = {Washed microbiota transplantation relieves atopic dermatitis via gut-skin microbiome rebalancing.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04717-1}, pmid = {41521300}, issn = {1471-2180}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; 82300440//National Natural Science Foundation of China Youth Program/ ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which dysbiosis of gut and skin microbiota contributes to pathogenesis and severity. Washed microbiota transplantation (WMT)-an improved form of fecal microbiota transplantation with enhanced safety and microbiota quality control-has shown efficacy in a single reported adolescent case. However, clinical data on WMT in AD and its effects on the skin and gut microbiota remain limited.

METHODS: Twenty-three patients with moderate-to-severe AD received at least two courses of WMT between January 2022 and December 2023. Disease activity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index, the Eczema Area and Severity Index (EASI), the Numeric Rating Scale (NRS) for itch, and the Dermatology Life Quality Index (DLQI). Peripheral blood counts, cytokine profiles, lymphocyte subsets, and gut and skin microbiota were assessed before and after treatment.

RESULTS: WMT was well tolerated (58 sessions; 5.2% mild adverse events) and significantly improved SCORAD, EASI, DLQI, and NRS scores, with greater EASI reductions in adults than in children. Absolute basophil counts decreased significantly after treatment, whereas other hematologic and cytokine parameters remained stable. Gut microbiota showed an increased Gut Microbiome Health Index, a decreased Microbial Dysbiosis Index, and enrichment of short-chain fatty acid-producing taxa, including the Eubacterium coprostanoligenes group, Lachnospiraceae, and Coprococcus. Skin microbiota shifted from Staphylococcus dominance to higher abundances of Acinetobacter, Perlucidibaca, and other potentially protective genera, inversely correlating with disease severity and systemic inflammation.

CONCLUSIONS: WMT appears safe and effective in alleviating clinical manifestations of AD while reshaping both gut and skin microbiota. These parallel microbial shifts support the gut-skin axis as a therapeutic target and highlight WMT as a promising microbiota-centered intervention for immune-mediated skin diseases.}, } @article {pmid41521238, year = {2026}, author = {Zhoua, J and Leia, K and Zhang, P and Wang, Z and Wang, W}, title = {Probiotics regulate the intestinal microbiome to promote growth in juvenile Salmo trutta fario.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35054-y}, pmid = {41521238}, issn = {2045-2322}, support = {CARS-46//China Agriculture Research System of Specialty Freshwater Fish/ ; }, } @article {pmid41521228, year = {2026}, author = {Sharma, S and Seekatz, A and Alizadeh, M and Hassan, H and Yitabrek, A and Pratt, S and Abdelaziz, K}, title = {Early-life supplementation of poultry-derived lactobacilli drives microbial succession and gut immune modulation in broiler chickens.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35177-2}, pmid = {41521228}, issn = {2045-2322}, support = {SC-1700628//USDA National Institute of Food and Agriculture Hatch Project/ ; 2016204//South Carolina Department of Agriculture (ACRE CGP)/ ; }, abstract = {While probiotic supplementation via feed or drinking water is well known to improve poultry gut health by modulating the microbiota and enhancing immune function, the effects of in ovo supplementation remain largely unexplored. In this study, we investigated the effects of administering a lactobacilli cocktail in ovo (embryonic day 18), post-hatch, and in combination on gut immunity and the succession of the cecal microbiota in broilers over 5 weeks. 16S rRNA gene-based sequencing of cecal contents revealed a steady increase in Shannon diversity during the first 2 weeks (PERMANOVA, p < 0.005), with community structure stabilizing by week 3 across all groups. In ovo administration of lactobacilli improved early hatch rates and modulated microbial composition during early succession, including reductions in Klebsiella and Enterococcus, and enrichment of Lactobacillus, during the first two weeks (MaAsLin2, q < 0.25). These microbiome shifts were accompanied by a reduction in the expression of the pro-inflammatory cytokines, including interferon gamma (IFN-γ), interleukin-1β (IL-1β), and IL-8 in the cecal tonsils. These findings highlight the transient yet critical role of early-life probiotic interventions in shaping gut microbial colonization and immune response in broiler chickens. More importantly, a single in ovo lactobacilli dose yielded effects comparable to weekly oral or combined administration.}, } @article {pmid41521189, year = {2026}, author = {Vardeman, ET and Cheng, HP and Vandebroek, I and Kennelly, EJ}, title = {The effects of the Caribbean medicinal plant Argemone mexicana on Gardnerella vaginalis using a co-culture method with vaginal Lactobacillus spp.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-26731-5}, pmid = {41521189}, issn = {2045-2322}, support = {F31AT011471//National Institutes of Health, NCCIH/ ; }, abstract = {Bacterial vaginosis (BV) is caused by vaginal microbiome dysbiosis, when beneficial Lactobacillus species are no longer dominant and are replaced by harmful anaerobic bacteria such as Gardnerella vaginalis. In Caribbean cultures, women use plants topically, such as Argemone mexicana, to treat several vaginal infections, including BV. There has been little research into how traditional botanical extracts affect the vaginal microbiota, especially as these extracts are often prepared in different ways for the same condition. This study aims to evaluate the effect of botanical preparations using an in vitro co-culture assay with beneficial Lactobacillus species and BV-causing Gardnerella vaginalis. This is an application of an in vitro co-culture assay to assess the effect of botanical preparations on the vaginal microbiota. We hypothesized that variations in the chemical composition of these preparations would affect the composition of vaginal microbiota. Argemone mexicana extractions were tested using an in vitro co-culture method with Gardnerella vaginalis and one of three vaginal Lactobacillus species and evaluated by UPLC-qToF-MS for metabolomic chemical analysis. Aqueous extractions that did not have significant antibacterial effect compared to the control in monoculture suppressed the growth of Gardnerella vaginalis in co-culture with Lactobacillus, supporting the traditional Dominican use of this plant. These results are likely related to the presence of berberine and polysaccharides in the aqueous extractions.}, } @article {pmid41521071, year = {2026}, author = {Kwon, ES}, title = {Integrating Perspectives on Aging: From Mechanistic Causes to Therapeutic Interventions.}, journal = {BMB reports}, volume = {}, number = {}, pages = {}, pmid = {41521071}, issn = {1976-670X}, abstract = {Aging poses one of the most urgent biomedical challenges of the 21st century, increasing vulnerability to chronic diseases and limiting healthspan in aging populations. Recent advances in aging research are transforming our understanding of aging from an inevitable decline to a multidimensional and potentially modifiable biological process. This special issue presents five invited reviews that collectively illustrate the recent progress in aging research. These articles introduce emerging concepts that shed light on the fundamental causes of aging, including the genetic architecture underlying human aging, senescence-driven fibrotic scarring arising from imperfect tissue repair, and the progressive erosion of epigenetic information in the brain. They further highlight promising avenues for intervention-such as epigenetic rejuvenation, the bidirectional interplay between the aging gut microbiome and host physiology, and the emergence of precision geronutrition. By integrating genetic, molecular, cellular, microbial, and nutritional perspectives, this collection emphasizes a future where extending human healthspan is both realistic and scientifically attainable.}, } @article {pmid41520913, year = {2026}, author = {Yang, X and Liu, Y and Miao, K}, title = {Microbiome-Modulated Immunotherapy in Oncology: Current Applications and Future Prospects.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2026.01.001}, pmid = {41520913}, issn = {1096-3650}, abstract = {Cancer immunotherapy has transformed oncology, yet therapeutic efficacy remains heterogeneous and frequently limited by primary or acquired resistance. Increasing evidence demonstrates that both intra- and extratumoral microbiota critically modulate antitumor immunity, influencing clinical responses of immunotherapy and immune-related adverse events (irAEs). Microbial communities regulate the tumor immune microenvironment through multiple mechanisms, including microbe-associated molecular patterns, microbial metabolites, and outer membrane vesicles, acting on tumor or immune cells. These insights have fostered the development of microbiome-based applications in oncology, ranging from predictive biomarkers to therapeutic interventions such as engineered bacteria, fecal microbiota transplantation, probiotics, prebiotics, outer membrane vesicles, bacteriophages, and dietary modulation. Early-phase clinical studies indicate that microbiota-targeted strategies can enhance immunotherapy efficacy or mitigate irAEs, although strain specificity, interindividual variability, and safety remain significant challenges. Future progress will require mechanistic elucidation, integration of multi-omics analyses, standardization of methodologies, and personalized intervention frameworks to translate microbiome modulation into clinically actionable, precision immunotherapy.}, } @article {pmid41520880, year = {2026}, author = {Tham, TN and Huong, NTL and Kim, QN and Kieu, NTD and Huy, NT}, title = {The Role of the Gut Microbiome in Childhood Obesity: Mechanistic Insights and Community-Based Interventions.}, journal = {Clinical nutrition ESPEN}, volume = {}, number = {}, pages = {102911}, doi = {10.1016/j.clnesp.2026.102911}, pmid = {41520880}, issn = {2405-4577}, abstract = {Childhood obesity remains a critical issue, yet traditional efforts focusing on diet and exercise have failed. This review proposes that gut microbiota dysbiosis is not an association, but rather a potentially causal and actionable mechanism underlying childhood obesity. An altered gut microbiome, defined by diminished diversity and specific changes, such as a higher Firmicutes/Bacteroidetes ratio, is a primary contributor to excess weight because of its ability to enhance energy overconsumption, dysregulate production of short-chain fatty acids, regulate appetite, and induce chronic low-grade inflammation. This overview seeks to provide a synthesis of mechanistic evidence and controversies of the gut microbiome as a targetable leverage point, by assessing the microbial signatures of obesity and reflect on the evidence to date and what it implies about the effort: A quest for a singular "obesity microbe" is unlikely to provide success. The unexplained complexity of the host and environment, the lack of a high-quality standard, and evidence of functional microbial pathways and metabolites provide a more fruitful focus. Among other things, this article suggests using high-fiber, whole food dietary strategies to modify the microbiome, the targeted use of evidence-based multi-strain probiotics, and designing school and public health policies to create protective microbiome public health policies. The childhood obesity demands that future efforts focus on the integration of large, multi-omic, longitudinal studies, and the implementation of high-fidelity long-term randomized controlled trial designs that establish the causative relationships, uniform structure to the protocols and enable the implementation of high-impact, equity-based, scalable precision nutrition methodologies.}, } @article {pmid41520868, year = {2026}, author = {Bajinka, O and Jallow, L and Ozdemir, G}, title = {A multi-target therapeutic framework for Alzheimer's disease: an integrative mechanistic review.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2026.01.010}, pmid = {41520868}, issn = {1873-7544}, abstract = {BACKGROUND: Alzheimer's disease (AD) is increasingly recognized as a multifactorial network disorder in which amyloid and tau pathology interact with mitochondrial dysfunction, neuroinflammation, metabolic impairment, vascular dysregulation, and synaptic failure. This review provides an integrative, systems-level synthesis of these mechanisms with emphasis on diagnostic and therapeutic implications.

METHODS: A structured narrative review was conducted using PubMed, Scopus, Web of Science, and Embase (2010-2025). Eligible studies included clinical trials, biomarker validation studies, cohort analyses, and mechanistic investigations. Evidence was synthesized by mechanistic domain with focus on cross-system interactions and translational relevance.

FINDINGS: Convergent data indicate that soluble Aβ species, tau propagation, glial dysregulation, insulin resistance, mitochondrial bioenergetic failure, lipid imbalance, and BBB dysfunction form a self-reinforcing neurodegenerative network. Diagnostic advances-including plasma p-tau181/217, Aβ42/40 ratio, GFAP, sTREM2, neuronal exosomes, and multimodal machine-learning models-enable earlier staging and refinement of therapeutic selection. Therapeutic development is shifting from linear amyloid removal to multi-target strategies incorporating anti-tau agents, glial-modulating compounds, metabolic and microbiome interventions, medical nutrition, and multidomain lifestyle programs. Across trials, combined strategies targeting interacting mechanisms demonstrate stronger biomarker and cognitive effects than single-axis approaches.

CONCLUSIONS: AD management requires a systems-oriented therapeutic architecture in which interventions are selected based on mechanistic dominance, biomarker stage, and potential synergy. We outline a multi-target strategy integrating amyloid/tau modulation, neuroimmune regulation, metabolic-vascular stabilization, and synaptic support. Future work should prioritize biomarker-guided stratification, treatment sequencing, and prevention-oriented combination designs.}, } @article {pmid41520514, year = {2026}, author = {Kharb, A and Zhu, X}, title = {Unlocking therapeutic impacts of the gut microbiota with computational tools.}, journal = {Current opinion in biotechnology}, volume = {97}, number = {}, pages = {103431}, doi = {10.1016/j.copbio.2025.103431}, pmid = {41520514}, issn = {1879-0429}, abstract = {The human gut microbiota, particularly the intestinal microbiota, shapes host physiology, disease risk, and therapeutic outcomes through complex metabolic and enzymatic activities. Recent advances in molecular omics, metabolomics, enzyme bioinformatics, and artificial intelligence (AI) have created unprecedented opportunities to elucidate its therapeutic roles to further enable precision microbiome medicine for personalized prevention, diagnosis, and treatment. In this review, we highlight emerging applications that leverage molecular omics and metabolomics technologies to dissect gut microbial functions, along with developments in enzyme bioinformatics and AI tools that reveal gut microbial species, enzymes, and metabolic pathways impacting human health. Finally, we discuss perspectives on data standardization, functional annotation, and interpretability, and how emerging tools are accelerating translational microbiome research.}, } @article {pmid41520466, year = {2026}, author = {Rapaka, D and Saniotis, A and Thatayaone, M and Bitra, VR}, title = {Neuroendocrine signaling as a pathological seed for the female bias of Alzheimer's disease and the concept of estrobolome.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {195}, number = {}, pages = {118999}, doi = {10.1016/j.biopha.2026.118999}, pmid = {41520466}, issn = {1950-6007}, abstract = {The prevalence of Alzheimer's disease (AD) is anticipated to escalate with the global increase in life expectancy. Although sex-based differences in AD have been previously documented, doubts persist regarding the relationship between sex and pathophysiological pathways. Sex hormones may contribute to these disparities, with a heightened risk of AD-related dementia associated with oophorectomy before menopause. We cannot ascertain if estrogens alone are solely accountable for this accelerated pathological progression of the disease. Estrogens are regulated by the gut microbiota. Thus, the gut-estrogen-brain axis appears to be implicated as a potential new influencer in the pathophysiology of AD, as the female microbiome differs from the male gut microbiome. This suggests it could be a risk factor for the higher prevalence of AD in women. This review speculates on the possible mechanisms for AD prevalence in women, including both anatomical and neuroendocrinological perspectives.}, } @article {pmid41520335, year = {2026}, author = {Sang, J and Li, S and Xu, C and Pan, X and Zhu, Y and Li, Y and Ma, C and Zhang, Y and Chen, S and Qiu, Q and Si, H and Huang, Z and Wang, J and Jiao, J and Li, Z}, title = {Rumen microbiome biogeography and ventral epithelial architecture in three ruminant species.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116779}, doi = {10.1016/j.celrep.2025.116779}, pmid = {41520335}, issn = {2211-1247}, abstract = {Ruminants thrive in diverse ecosystems by leveraging their rumen microbiome to ferment fibrous plants. However, the spatial biogeography of rumen microbiome and the genetic diversity of the ventral rumen epithelium remain unknown. Here, we present a multi-omics study in roe deer, sika deer, and sheep, integrating region-resolved microbiome and metabolome across 11 ruminal sacs, as well as single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing (RNA-seq) of ventral epithelium. We reveal species-specific microbial compositions and metabolic capacities contributing to differences in short-chain fatty acid and vitamin B production. We uncover functional divergence, genomic specialization, and metabolic changes across the microbiome of distinct ruminal sacs. Single-cell profiling reveals changes of immune responses and structural remodeling of the ruminal ventral epithelium. We demonstrate that vitamin B12 promotes epithelial growth and we identify genes enhancing stem cell differentiation. Our results highlight variation in microbial ecology and epithelial architecture among three ruminant species, offering insights to improve livestock productivity.}, } @article {pmid41520334, year = {2026}, author = {Peng, Z and Zhang, H and Ding, Y and Liu, Z and Xie, M}, title = {Prior high fiber intake impinges on the cellular responses of mesenteric adipose and intestinal tissues to subsequent high fat feeding.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116801}, doi = {10.1016/j.celrep.2025.116801}, pmid = {41520334}, issn = {2211-1247}, abstract = {While high-fiber diets (HfiDs) promote weight loss, their long-term efficacy is limited by rapid weight regain upon returning to high-fat diets (HFDs). Using C57BL/6J mice in diet-switching paradigms, we characterized tissue-specific responses to HfiD-to-HFD transitions through single-nucleus and spatial transcriptomics. HfiD pre-feeding enhanced mesenteric white adipose tissue progenitor/adipocyte sensitivity to subsequent HFD exposure. In the intestine, HfiD prevented HFD-induced immune-enterocyte expansion in the duodenum and reversed the enterocyte-to-goblet cell shift in the colon while maintaining persistent epigenetic reprogramming. Although HfiD-induced microbiome changes were largely reversed by HFD, we identified sexually dimorphic remodeling of adipose cell populations during diet transitions. Our findings demonstrate that prior HfiD feeding fundamentally reprograms adipose and intestinal responses to subsequent HFD challenge, providing mechanistic insights into dietary intervention outcomes. This work establishes a spatiotemporal resource for understanding tissue plasticity during dietary changes, offering new perspectives for obesity management strategies.}, } @article {pmid41520313, year = {2026}, author = {Chai, Y and Zhou, Y and Peng, H and Jiang, Y and Dai, J and Liu, J}, title = {Comparative efficacy of hyperthermic chemotherapy and BCG instillation in non-muscle invasive bladder cancer: a systematic review and meta-analysis.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, pmid = {41520313}, issn = {1573-2584}, support = {2023YFS0257//Science & Technology Department of Sichuan Province/ ; }, abstract = {OBJECTIVE: To systematically evaluate the comparative efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) versus bacillus Calmette-Guérin (BCG) instillation in patients with non-muscle-invasive bladder cancer (NMIBC).

METHODS: A systematic literature search was conducted across PubMed, Embase, the Cochrane Library, and CBM from inception to June 30, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251075299. Randomized controlled trials and cohort studies comparing HIVEC with BCG in NMIBC patients were included. Primary outcomes were 24-month recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse events. Risk ratios (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models.

RESULTS: Seven studies involving 820 patients were included. The meta-analysis showed no significant differences between HIVEC and BCG in 24-month RFS (RR = 1.01, 95% CI: 0.90-1.12), PFS (RR = 1.00, 95% CI: 0.95-1.05), or OS (RR = 0.99, 95% CI: 0.91-1.09). However, BCG was associated with a significantly higher incidence of dysuria (RR = 1.38, 95% CI: 0.57-3.37). No significant differences were observed in other adverse events such as urinary tract infection, hematuria, or pain.

CONCLUSION: HIVEC demonstrates comparable oncological efficacy to BCG in terms of 24-month RFS, PFS, and OS for NMIBC patients, while offering a better tolerability profile with a significantly lower risk of dysuria. These findings support HIVEC as a valuable alternative treatment option, particularly in the context of BCG shortages or for BCG-intolerant patients.}, } @article {pmid41520283, year = {2026}, author = {Duquesnoy, M and Chassaing, B}, title = {MBRA 3.0: integrating the mucus environment for advanced high-throughput in vitro intestinal microbiome modeling.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612804}, doi = {10.1080/19490976.2026.2612804}, pmid = {41520283}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mucus/microbiology/metabolism ; *Intestinal Mucosa/microbiology/metabolism ; *Bacteria/classification/genetics/isolation & purification/metabolism ; Feces/microbiology ; Fatty Acids, Volatile/metabolism ; Models, Biological ; Colon/microbiology ; High-Throughput Screening Assays/methods ; }, abstract = {The colonic mucus layer is a dynamic barrier that plays central roles in intestinal health, and recent studies highlight that it harbors a distinct and functionally critical microbial community. However, most in vitro gut models fail to recapitulate this mucosal niche, limiting mechanistic investigation of microbiota-mucus interactions. Here, we developed the MBRA 3.0 system, a next-generation chemostat engineered to integrate mucus-coated carriers and enable high-throughput dissection of spatial microbiome dynamics. Using fecal microbiota from eight human donors, we report that mucus addition does not impact total bacterial density but selectively shapes microbial community structure, metabolic output, and pro-inflammatory potential in a donor-dependent manner. Notably, MBRA 3.0 resolves stable, compositionally distinct mucus-associated and luminal communities, mirroring in vivo spatial heterogeneity. Integration of this mucosal niche also modulates short-chain fatty acid (SCFA) profiles and inflammatory signatures, highlighting the relevance of the spatial context for intestinal microbiota research. Hence, MBRA 3.0 offers a scalable and customizable platform to model mucus-microbiota interactions, advancing our understanding of gut ecology and supporting translational discovery in gastrointestinal health and disease.}, } @article {pmid41520282, year = {2026}, author = {Yin, Q and Gupta, S and Muller, E and Almeida, A}, title = {The human gut microbiome in enteric infections: from association to translation.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612836}, doi = {10.1080/19490976.2026.2612836}, pmid = {41520282}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Bacteria/genetics/classification/isolation & purification ; Host-Pathogen Interactions ; Animals ; }, abstract = {Enteric infections remain a leading global cause of morbidity, mortality and economic loss, increasingly compounded by the rise of antimicrobial resistance. The gut microbiome - spanning bacteria, archaea, fungi, protists and viruses - is now recognized as an important mediator that shapes susceptibility to infection, pathogen expansion and disease severity through mechanisms such as colonization resistance, resource competition and immune modulation. Conversely, the gut microbial community can facilitate enteric infection through other processes such as cross-feeding and horizontal gene transfer. In this review, we synthesize correlative and mechanistic evidence currently available on microbiome-pathogen interactions; outline host, environmental and socioeconomic modifiers that affect disease risk across the life course; and evaluate current clinical applications. We highlight key limitations in the field and identify priority areas for future research to refine causal models of microbiome-pathogen ecology and enable targeted diagnostics and therapeutics for preventing and managing enteric infections.}, } @article {pmid41520281, year = {2026}, author = {Tang, TWH and Ullah, K and Lee, JJ and Chen, HC and Hsieh, PCH}, title = {Comparative insights into the gut-heart axis: cross-species and cross-population perspectives.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2611617}, doi = {10.1080/19490976.2025.2611617}, pmid = {41520281}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Cardiovascular Diseases/microbiology ; *Heart/physiology ; Swine ; Bacteria/classification/metabolism/genetics/isolation & purification ; Host Microbial Interactions ; Species Specificity ; *Gastrointestinal Tract/microbiology ; Disease Models, Animal ; }, abstract = {Gut microbiota research has rapidly expanded our understanding of host-microbe interactions in cardiovascular diseases, yet translation of these insights remains challenged by species-specific differences and substantial population heterogeneity. In this review, we synthesize current evidence across rodents, swine, non-human primates, and multi-ethnic human cohorts to delineate conserved versus context-dependent features of the gut-heart axis. Rodent models remain indispensable for mechanistic discovery, enabling causal testing through germ-free, antibiotic-treated, and humanized microbiota platforms, whereas large-animal models better replicate human cardiac anatomy, physiology, and microbial ecology. Human studies provide essential clinical relevance, demonstrating that patients with myocardial infarction, coronary artery disease, atrial fibrillation, and heart failure harbor distinct microbial and metabolite signatures. However, these findings vary across populations due to differences in diet, lifestyle, host genetics, medication exposure, and environmental transitions. Despite taxonomic variability, several functional pathways, most notably short-chain fatty acid production, bile acid biotransformation, and aromatic amino acid metabolism generating molecules such as trimethylamine-N-oxide and phenylacetylglutamine, consistently associate with cardiovascular risk. At the same time, population-specific features, including glycan-microbe interactions shaped by ABO and FUT2 genotypes, diet-responsive metabolite profiles, and variable drug-microbiome interactions, highlight the importance of genetic and environmental context. By integrating cross-species and cross-population evidence, this review outlines a framework for identifying robust microbial pathways, clarifying their translational boundaries, and guiding the development of microbiota-informed diagnostics and interventions that account for biological, cultural, and environmental diversity.}, } @article {pmid41520196, year = {2026}, author = {Verburgt, CM and Dunn, KA and Bielawski, JP and Otley, AR and Heyman, MB and Sunseri, W and Shouval, DS and Boneh, RS and de Meij, T and Hyams, JS and Denson, LA and Kugathasan, S and Benninga, MA and de Jonge, WJ and Van Limbergen, JE}, title = {Timing is Everything: Lessons Learned for Building Microbiome-Based Models in Pediatric Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf313}, pmid = {41520196}, issn = {1536-4844}, support = {//CIHR-SPOR-Chronic Diseases/ ; //Canadian Institutes of Health Research [CIHR]-Canadian Association of Gastroenterology-Crohn's Colitis Canada New Investigator Award [2015-2019] Crohn/ ; 585718//Colitis Foundation of America, Pro-Kiids/ ; TKI-LSH-ADT-2021-AMC-26344//Health Holland TKI grant/ ; }, } @article {pmid41520073, year = {2026}, author = {Alam, N and Yaseen, G and Chandio, MA and Khan, RA and Nasir, MF and Shenawa, E}, title = {Discordance between preoperative urine culture and intraoperative stone/pelvis culture as a predictor of post-PCNL sepsis: a single-center retrospective analysis for targeted antibiotic stewardship.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, pmid = {41520073}, issn = {1573-2584}, abstract = {PURPOSE: To evaluate the diagnostic accuracy of preoperative midstream urine culture (PMUC) against intraoperative stone and pelvic urine cultures, and to determine if culture discordance independently predicts sepsis following percutaneous nephrolithotomy (PCNL).

METHODS: This retrospective cohort study analyzed 250 adult patients undergoing PCNL between January 2023 and October 2025. All participants had both PMUC and intraoperative stone/pelvic urine cultures. The primary outcome was post-PCNL sepsis defined by Sepsis-3 criteria. Diagnostic performance metrics were calculated, and the association between discordance and sepsis was assessed using multivariable logistic regression, LASSO penalization, and propensity-score matching to adjust for confounders.

RESULTS: Culture discordance was observed in 30% (75/250) of patients. The sensitivity of PMUC for detecting upper urinary tract colonization was only 48%. Sepsis occurred in 6.8% of the total cohort but was significantly more frequent in the discordant group (17.3 vs 2.3%, p < 0.0001). In multivariable analysis, discordance remained the strongest independent predictor of sepsis (adjusted OR 6.23, 95% CI 2.20-17.62, p < 0.001), displacing stone burden and operative time. Notably, patients with sterile preoperative urine but positive intraoperative cultures accounted for 92.3% of sepsis events within the discordant group.

CONCLUSION: PMUC is an unreliable surrogate for the upper tract microbiome, failing to detect colonization in over half of cases. Culture discordance is a robust predictor of post-PCNL sepsis, driven by untreated bacterial biofilms within stones. Routine intraoperative culturing is essential for targeted antibiotic stewardship to mitigate septic complications.}, } @article {pmid41519984, year = {2026}, author = {Cronin, B and Kandel, S and McElroy, T and Syed, S and Swinton, C and Corley, C and Sridharan, V and Robeson, MS and Allen, AR}, title = {Changes in gut, microbiome, and cognition after doxorubicin, cyclophosphamide, and paclitaxel chemotherapy treatment.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-33903-w}, pmid = {41519984}, issn = {2045-2322}, support = {1R01CA258673/GF/NIH HHS/United States ; }, abstract = {Over 317,000 new cases of breast cancer will be diagnosed in 2025, making it the most diagnosed cancer among women in the United States. Advancements in treatment options such as chemotherapy and radiation have resulted in a 5-year survival rate of 91%. Upwards of 78% of the 4.1 million breast cancer survivors currently living in the United States report chemotherapy induced cognitive impairment (CICI), or "chemobrain". CICI defined as an impairment in memory, learning, executive function, and attention following chemotherapy treatment. There is a need for a better understanding of the long-term side effects of these treatments and the impact these may have on the quality of life for these survivors. In this study, we used a translational mouse model to study cognitive decline via intraperitoneal injections of the combination chemotherapy AC-T: Doxorubicin (DOX), Cyclophosphamide (CYP), and Paclitaxel (PTX). Mice underwent behavior tests to assess social memory and anxiety 30 days after the last AC-T injection. AC-T treated mice revealed behavioral deficits in social memory and an increase in anxiety-like behavior. RNA-sequencing and western blot analysis revealed negatively altered expression of transcripts associated with neurogenesis, axonal guidance, neurotransmission, and protein IEGs such as Arc, c-Fos, and Egr-1, respectively. Proteomics indicated increases in inflammatory markers in intestinal tissue, which also coincided with changes in intestinal morphology of AC-T treated mice. The gut microbiota of AC-T treated mice showed became dysbiotic. This study provides a multi-omic overview of the effects of AC-T treatment on cognition and intestinal inflammation and morphology.}, } @article {pmid41519975, year = {2026}, author = {Christoffersen, SN and Østergaard, SK and de Jonge, N and Pertoldi, C and Sørensen, JG and Noer, NK and Kristensen, TN and Nielsen, JL and Bahrndorff, S}, title = {Arctic Insects Show a Highly Dynamic Microbiome Shaped by Abiotic and Biotic Variables.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-025-02685-z}, pmid = {41519975}, issn = {1432-184X}, abstract = {Arctic regions are inhabited by terrestrial ectotherms that have adapted to an extreme environment where food resources are limited. The host associated microbiome may partly explain their ability to live under these conditions, but very little is known about the microbiome of Arctic ectotherms. We investigate how the bacterial community of the Greenlandic seed bug (Nysius groenlandicus) and damsel bug (Nabis flavomarginatus) is affected by different abiotic and biotic factors (time, acclimation temperature, humidity, and diet) under both field and laboratory conditions. We found large differences in the bacterial composition and diversity between the two species including species-specific presence of potentially symbiotic bacteria. The bacterial community of both species changed across the season, which may be explained by the changing climatic conditions, such as temperature and humidity. This was further supported by results from the laboratory experiments. We also found that diet changed the bacterial composition in both species and that bacteria could be transferred from prey to predator. Together, these results show that the bacterial community of some Arctic insects are highly dynamic and modulated by different abiotic and biotic factors, suggesting that the microbiome plays an important role for these organisms to persist in an extreme and resource-limited Arctic environment.}, } @article {pmid41519950, year = {2026}, author = {Ye, X and Zhang, T and Zhou, J and Zhao, C and Wu, J}, title = {The gut microbial profile and circulating metabolism are associated with functional constipation in children.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {41519950}, issn = {1530-0447}, abstract = {BACKGROUND: A growing body of evidence highlights the link between gut microbiome imbalances and constipation. However, the role of gut microbiota and its metabolic interactions in pediatric functional constipation (FC) remains incompletely understood.

METHODS: We recruited a total of 40 children with FC and 40 healthy children (CONT). 16SrRNA and metagenomic sequencing were used to evaluate the changes in the gut microbiota structure and gene function in FC patients. Differences in serum metabolite levels were analyzed via targeted metabolomic sequencing.

RESULTS: The FC group exhibited a decrease in gut microbiota diversity, an increase in Bacteroides and Prevotella abundances, depletion of genera such as Lactobacillus and Bifidobacterium and an imbalance of related metabolic activities. Metabolomic analysis revealed that the levels of several metabolites, including taurine and glycochenodeoxycholic acid, which are involved in bile acid (BA) metabolic pathways, differed between the FC and CONT groups. Differences in metabolite levels were associated with changes in the abundances of specific bacteria and with intestinal dysfunction in FC patients.

CONCLUSION: FC in children is associated with distinct gut microbiota alterations and dysregulated BA metabolism. These findings provide potential therapeutic targets for modulating the gut microbiome and metabolic pathways in FC management.

IMPACT: This study offers a comprehensive perspective on the intricate relationship between microbial composition and metabolic pathways in the context of functional constipation in children. This study focuses on children, highlighting how disruptions in bile acid metabolism due to gut microbiota disorders are linked to the occurrence of functional constipation. These findings suggest that disturbances in bile acid metabolism may play a role in the mechanisms underlying functional constipation by impairing intestinal secretion and transport functions. This study offers a new way to study the effects of the gut microbiota, bile acid metabolism, and the gut‒brain axis.}, } @article {pmid41519893, year = {2026}, author = {Schaefer-Dreyer, P and Behrens, W and Winkel, A and Pott, PC and Paulsen, M and Stanislawski, N and Tanisik, F and Melk, A and Schmidt, BMW and Lucas, H and Heiden, S and Klopp, N and Illig, T and Blume, H and Blume, C and Yang, I and Stiesch, M}, title = {Effects of cigarette smoking on the oral microbiome in adolescents.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1348}, pmid = {41519893}, issn = {2045-2322}, mesh = {Humans ; Adolescent ; *Microbiota ; Male ; Female ; *Mouth/microbiology ; *Cigarette Smoking/adverse effects ; *Bacteria/genetics/classification ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Smoking, a risk factor for periodontitis and peri-implantitis, is associated with shifts in the oral microbiome (OM) composition. Although smoking habits are almost always established before adulthood, data on effects of smoking on the OM in adolescents is rare. The aim of this study was to investigate the early impact of smoking on the OM composition in pupils. The adolescent cohort, aged 14-20, comprised 98 smokers and 98 non-smokers matched for several physiological co-variates. Buccal swabs were analysed for OM composition using high-throughput sequencing of the full-length 16 S rRNA gene targeting species-level resolution. Parameters of bacterial diversity and abundance of individual bacterial taxa were related to information on smoking. The microbiome dataset contained 733 species-level taxa. Streptococcus, Rothia, and Haemophilus dominated both groups, smokers and non-smokers. Smoking exerted a discernible influence on the overall microbial composition as measured by weighted UniFrac distances. The number of species-level bacterial taxa was significantly higher in individual smokers compared to non-smokers. Furthermore, several taxa, including known pathogens, exhibited significant differences in abundance between the two groups. The genera Veillonella, and Actinomyces, as well as and multiple Actinomyces species, Dialister invisus, Atopobium parvulum, Streptococcus mutans and Prevotella melaninogenica were significantly more abundant in smokers. Our findings indicated an early onset of smoking-related changes already in the oral microbiome of adolescents.}, } @article {pmid41519453, year = {2026}, author = {Combs, MP and Shaver, CM}, title = {Emerging from the shadows: reading between the lines to illuminate the microbiome's role in CLAD.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.healun.2026.01.001}, pmid = {41519453}, issn = {1557-3117}, } @article {pmid41519378, year = {2026}, author = {Jeong, H and Eppel, PS and Kaelber, DC and Singh, RP and Talcott, KE}, title = {Malabsorption Syndromes and Risk of Age-Related Macular Degeneration: Evidence from Real-World Data.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.002}, pmid = {41519378}, issn = {2468-6530}, abstract = {PURPOSE: Despite mechanistic links connecting malnutrition and gut microbiome with retinal health, clinical research exploring the relationship between malabsorption syndromes and age-related macular degeneration (AMD) remains limited. This study compared the risks of AMD diagnosis in patients with and without various malabsorption syndrome diagnoses.

DESIGN: Retrospective cohort study of aggregated, de-identified patient data from multiple healthcare organizations across the United States using the TriNetX U.S. Collaborative Research Network in 11/2025.

PARTICIPANTS: Adults with a cataract-related International Classification of Diseases (ICD) encounter diagnosis codes and no baseline AMD ICD encounter diagnosis codes were divided into groups based on the presence of ICD encounter diagnosis codes for celiac disease (CeD), ulcerative colitis (UC), Crohn's disease (CrD), chronic pancreatitis (CP), and short bowel syndrome (SBS). Within the CP cohort, patients with pancreatic enzyme replacement therapy (PERT) prescription orders were subanalysis. For each cohort, a corresponding control cohort of patients without the respective ICD encounter diagnosis codes was created.

METHODS: The study and control cohorts were propensity-matched 1:1 on demographic factors, comorbidities, and disease-related conditions and prescription orders. The matched cohorts were compared on the risk of having AMD ICD encounter diagnoses.

MAIN OUTCOME MEASURE: Risk ratios (RR) and 95% confidence intervals (CI) of having an AMD ICD encounter diagnosis code with an accompanying retinal optical coherence tomography Common Procedural Terminology code. Significance was defined as CI ≤0.9 or ≥1.1.

RESULTS: Compared to controls without IBD, the CrD cohort (n=9,537, RR=1.42, CI=1.16-1.74), but not the UC cohort (n=15,039, RR=1.28, CI=1.09-1.51), had a higher risk of having early/intermediate AMD. CP was associated with an increased risk of AMD (n=12,856, RR=1.82, CI=1.53-2.16), even in the PERT subset (n=3,812, RR=1.83, CI=1.35-2.48). SBS (n=3,747) was associated with an increased risk of advanced/exudative AMD (RR=1.98, CI=1.31-2.98), but not early/intermediate AMD (RR=1.28, CI=0.96-1.71). CeD was not associated with increased AMD risk (n=9,315, RR=1.09, CI=0.88-1.35).

CONCLUSIONS: Chronic non-infectious causes of malabsorption syndromes-CrD, CP, and SBS-may represent underrecognized risk factors of AMD. This explorative study adds clinical evidence for a potential role of the gut-retina axis in the pathogenesis of AMD.}, } @article {pmid41519280, year = {2026}, author = {Yan, T and Rong, L and Wang, S and Song, X and Hu, B and Wang, Z and Wang, X and Ding, X and Guan, R and Yu, H and Niu, D and Zhang, Y}, title = {Alterations in cardiovascular biomarkers and gut microbiome associated with night shift work: Insights from the Chinese Platform Workers Study.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123735}, doi = {10.1016/j.envres.2026.123735}, pmid = {41519280}, issn = {1096-0953}, abstract = {The expansion of the gig economy has been marked by an increase in platform workers, including ride-hailing drivers, who typically work non-standard schedules, with night shifts being common. Although night shift work was known to disrupt circadian rhythms and elevate cardiovascular risks, the interplay between early alteration in cardiovascular biomarkers and gut microbiome remain unclear. To investigate these associations in the platform worker groups, we conducted a cross-sectional study comparing 66 night shift and 175 day shift ride-hailing drivers in Beijing, China. All participants underwent health examinations, provided blood tests for the assessment of four key cardiovascular biomarkers (hs-cTnI, ET-1, NT-pro-BNP, and FABP-3), and submitted fecal samples for gut microbiome profiling via 16S rDNA sequencing. Bioinformatics, linear regression, and mediation analyses were conducted to evaluate the associations between night shift work, biomarkers, and microbial taxa, with adjustments for key sociodemographic and lifestyle factors. Night shift drivers exhibited significantly higher levels of NT-pro-BNP (median 49.8 vs. 41.3 pg/ml, P = 0.044), an association that remained significant after adjustment for covariates (β = 0.195, P = 0.004). Twenty differentially abundant taxa were identified, four of which were significantly associated with hs-cTnI. No significant mediation effect was observed. This study found that night shift work in ride-hailing drivers was significantly associated with adverse cardiovascular biomarker profiles and distinct gut microbiome alterations. Correlation analysis further suggested that gut microbial changes were linked to the observed cardiovascular risk. This study reported associations between night-shift work and alterations in early cardiovascular injury biomarkers as well as the gut microbiota, suggesting a potential link between gut microbiota and night-shift-related cardiovascular injury.}, } @article {pmid41519271, year = {2026}, author = {Nicholas, JC and Alkis, T and Bis, JC and Boerwinkle, E and Brody, JA and Clish, CB and de Vries, PS and Gao, Y and Gerzsten, RE and Guo, X and Johnson, AD and Larson, MG and Lemaitre, RN and Psaty, BM and Ramachandran, V and Reiner, AP and Rich, SS and Rodriguez, B and Rong, J and Rotter, JI and Simino, J and Smith, NL and Wilson, J and Yao, J and Morrison, AC and Yu, B and Raffield, LM}, title = {Fibrinogen-Associated Plasma Metabolites and Implications for Coagulation, Inflammation, and Vascular Diseases.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2025.12.016}, pmid = {41519271}, issn = {1538-7836}, abstract = {BACKGROUND: Fibrinogen is a critical coagulation factor that plays an essential role in thrombosis and is elevated in individuals with chronic inflammation. Here, we used fibrinogen as a representative quantitative measure of pro-coagulant risk and evaluated metabolites associated with fibrinogen levels through non-targeted plasma metabolomic profiling (Broad and Metabolon platforms).

METHODS: Our analysis included 10,533 individuals across six U.S. based cohorts representing diverse population groups. The cross-sectional relationship between each of 789 tested metabolites and plasma fibrinogen concentration was assessed with adjustment for relevant covariates such as age, sex, body mass index, and circulating lipoprotein levels.

RESULTS: Meta-analysis of per-cohort results revealed 270 metabolites significantly associated with fibrinogen level (FDR adjusted p-value < 0.05). Lipid species such as glycerophospholipids, sphingolipids, and fatty acyls were prevalent among significantly associated metabolites; some of these may capture effects of inflammation, as supported by sensitivity analyses adjusted for C-reactive protein. Significant associations between fibrinogen levels and serotonin, thyroxine, and sex-hormone derivatives may capture endogenous influences on fibrinogen levels. Exogenous compounds and microbial co-metabolites significantly associated with fibrinogen also implicate lifestyle and microbiome risk-factors. Only a portion of fibrinogen-associated metabolites (30%) have been associated with a cardiovascular disease outcome in a prior study, suggesting the associations discovered here may provide insights on vascular biology which case-control studies may not yet be powered to detect.

CONCLUSIONS: These findings contribute to a growing list of metabolite biomarkers that may influence coagulation and inflammation pathways and may thereby contribute to vascular risk.}, } @article {pmid41519234, year = {2026}, author = {Holdaway, CM and Vo, A and Leonard, KA and Nelson, R and Thiesen, A and Fan, Y and Marcolla, CS and Clugston, RD and Willing, BP and Jacobs, RL}, title = {Dietary Ethanolamine Increases Hepatic Lipid Accumulation in Mice Fed a High Fat Diet.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101348}, doi = {10.1016/j.tjnut.2025.101348}, pmid = {41519234}, issn = {1541-6100}, abstract = {BACKGROUND: Ethanolamine (Etn), a precursor of phosphatidylethanolamine (PE), may alter hepatic lipid homeostasis and gut health; its dietary effects remain undefined.

OBJECTIVE: To determine the effects of dietary Etn on lipid and glucose metabolism and liver/gut health in high-fat diet (HFD)-fed mice, complemented by in vitro hepatocyte assays.

METHODS: Ten-week-old C57BL/6 mice (20 male, 18 female) were fed ad libitum HFD (45% energy from fat) with (ES) or without (CON) Etn (8 g/kg diet) for 10 weeks. Outcomes included body/liver weight, glucose tolerance (GTT), plasma PC/CE/TG, hepatic TG/PC/PE, hepatic ER-stress and inflammation markers, jejunal morphology/barrier/inflammation genes, and fecal microbiota (α/β diversity). HuH7 cells received 20 μM or 5 mM Etn to assess TG/PC/PE synthesis.

STATISTICS: repeated-measures ANOVA (GTT), t-test or Wilcoxon (other endpoints), PERMANOVA (β diversity); α=0.05.

RESULTS: ES increased hepatic TG in females by 230% vs CON (p = 0.001), and trended higher in males (p = 0.054); hepatic PC and PE masses were unchanged. In ES-males, GTT AUC decreased by 22.6% (p = 0.037), and plasma PC, CE, and TG were reduced by: PC - 16.6%, CE - 24.5%, TG - 25.9% (all p < 0.05). ES males showed higher hepatic Tnf and Cd68 and increased CHOP protein (all p < 0.05). In vitro, Etn did not alter hepatocellular TG, PC, or PE synthesis (all p > 0.05). Female ES mice exhibited altered fecal β-diversity (PERMANOVA p = 0.006) with early jejunal inflammatory signals (Tnf ↑; p = 0.055).

CONCLUSIONS: Dietary Etn modifies hepatic lipid storage and gut microbiota in a sex-dependent manner and improves glucose tolerance in males, whereas in vitro data indicate no direct effect on hepatocyte lipid synthesis.}, } @article {pmid41519187, year = {2026}, author = {Zhang, Z and Tao, H and Mao, K and Meng, F and Jiang, S and Chen, J and He, X and Tian, X}, title = {The Central Qi Theory in Traditional Chinese Medicine: Gut Microbiota Modulation as a Strategic Target for Hepatocellular Carcinoma Therapy.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121147}, doi = {10.1016/j.jep.2025.121147}, pmid = {41519187}, issn = {1872-7573}, abstract = {Patients with intermediate and advanced hepatocellular carcinoma (HCC) often derive limited benefit from systemic therapy and experience a substantial symptom burden with deterioration in quality of life. These challenges underscore the need for safe, effective adjunctive or alternative therapies. The traditional Chinese medicine concept of Central Qi shows conceptual contemporary with contemporary understanding of the gut-liver axis and microbiome biology. Chinese herbal medicines centered on tonifying the central and replenishing qi (Buzhong Yiqi) are considered adjunctive or alternative therapeutic options for alleviating symptoms, improving quality of life, and enhancing tolerance and adherence to standard treatments.

AIM OF THIS REVIEW: To delineate links among the interrelations among Central Qi, the gut microbiota, and HCC, to synthesize evidence on how Buzhong Yiqi medicines modulate the gut microbiota, and to elucidate the proposed mechanistic bases for their potential adjunctive effects in HCC. This review aims to provide a biologically plausible framework to inform microbiome-based mechanistic research and clinical translation.

METHODS: Databases including PubMed, Web of Science, Elsevier ScienceDirect, CNKI, and Google Scholar were searched using predefined terms related to hepatocellular carcinoma, gut microbiota, and the gut-liver axis, nutrient absorption, metabolic regulation, immune modulation, and Buzhong Yiqi medicines, as well as their representative herbs. In vivo, in vitro, and clinical studies published from 2000 to October 2025 were included.

RESULTS: Dysbiosis disrupts the metabolic pathways of bile acid, short-chain fatty acid, and tryptophan metabolic pathways, while compromising the intestinal barrier. This disruption can worsen appetite regulation and energy imbalance, as well as weaken antitumor immunity. Buzhong Yiqi medicines have been reported to enrich beneficial taxa, reduce pathogens and pathobionts, and improve microbial metabolite profiles, restoration of barrier integrity, improvements in nutrient intake and energy homeostasis. These findings are heterogeneous and largely derived from non-HCC models, but collectively suggest potential support of metabolic and immune homeostasis, with possible influence on the tumor immune microenvironment. Early exploratory data also indicate a potential interaction with immune checkpoint inhibitors, although its clinical significance remains uncertain.

CONCLUSION: Central Qi deficiency provides a biologically plausible conceptual framework linking impaired digestion, disrupted energy metabolism, microbial dysbiosis, and reduced immune responsiveness in HCC. Modulation of the GM through Buzhong Yiqi medicines may offer supportive metabolic and immunological benefits, but current evidence is preliminary, based mainly on associative findings, and requires cautious interpretation. Key uncertainties remain regarding causal relationships, HCC-specific mechanisms, and the consistency of clinical effects. Future research should prioritize standardized preparations, mechanistic validation, biomarker-guided stratification, and rigorously designed clinical trials to clarify the clinical relevance of these proposed pathways and to advance global acceptance of integrative therapy.}, } @article {pmid41519162, year = {2026}, author = {Olmstead, M and Van Nest, K and Swistek, S and Cohnstaedt, LW and Oppert, B and Shults, P}, title = {Microbial communities in filth flies collected from dairy and poultry farms for supplemental animal feed.}, journal = {Journal of economic entomology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jee/toaf283}, pmid = {41519162}, issn = {1938-291X}, support = {NP104- 3020-32000-20-00D//USDA/ ; }, abstract = {Alternative protein sources are needed due to the rising demand and increasing cost of protein ingredients in livestock diets. Mass collection of wild-caught flies from locations with high insect pressure may be an economical and environmentally sustainable approach to supplement livestock feed, but there may be feed safety issues from microbes found in field-caught insects. Therefore, we evaluated a sequencing-based approach to accurately identify potential pathogens in wild-caught flies captured on 2 different livestock farms. In this study, we combined whole-genome shotgun metagenomic sequencing with total RNA-seq to identify a broad range of microbial taxa present in and on wild-caught flies. We describe several databases tailored to the host insect, host animals, and pathogens associated with livestock and humans. Sequences were identified from potentially pathogenic bacteria including Escherichia coli, Gallibacterium anatis, Helicobacterium pullorum, Morganella morganii, Proteus mirabilis, and Providencia alcalifaciens. In addition, sequences from the pathogenic fungi Aspergillus fumigatus and viruses such as the fly pathogen Musca hytrosavirus were found. Despite the limitations of current database curation, a combination of metagenomics and total RNA-seq approaches to taxa identification can provide insight into a broad spectrum of potential pathogens in insects used as supplemental livestock feed.}, } @article {pmid41519109, year = {2026}, author = {Hoedt, EC and Talley, NJ}, title = {Toward a personalized diet-microbiome strategy in inflammatory bowel disease: Matching donor, diet, and patient.}, journal = {Med (New York, N.Y.)}, volume = {7}, number = {1}, pages = {100918}, doi = {10.1016/j.medj.2025.100918}, pmid = {41519109}, issn = {2666-6340}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diet therapy ; *Fecal Microbiota Transplantation/methods ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; *Diet ; }, abstract = {Fecal microbiota transplant plus dietary change to restore the imbalance of an individual's microbiome to relieve disorders such as inflammatory bowel disease has not been established but has promise. In this commentary, we suggest the need to embrace a more nuanced, personalized approach, one that considers microbial functionality, dietary context, and host compatibility.}, } @article {pmid41518932, year = {2026}, author = {Du, B and Yang, Y and He, L and Tang, Y}, title = {Microbiota and infertility: a translational review of mechanisms and clinical applications in assisted reproduction.}, journal = {European journal of obstetrics, gynecology, and reproductive biology}, volume = {318}, number = {}, pages = {114941}, doi = {10.1016/j.ejogrb.2026.114941}, pmid = {41518932}, issn = {1872-7654}, abstract = {Infertility constitutes a major global health concern, affecting approximately 17.5% of couples of reproductive age. Although advances in assisted reproductive technologies (ART) have expanded treatment options, success rates remain highly variable due to host-specific and biological determinants. This review synthesizes current evidence on the reproductive impact of the human microbiota and its translational relevance to ART outcomes. Vaginal microbial communities dominated by Lactobacillus, particularly L. crispatus, are associated with improved conception and implantation, whereas genital or intestinal dysbiosis correlates with infertility and suboptimal treatment responses. The microbiota modulates reproductive competence through intertwined immune, endocrine-metabolic, and mucosal barrier pathways that regulate inflammation, hormonal balance, and epithelial integrity. Emerging findings indicate that gut microbial alterations linked to polycystic ovary syndrome (PCOS) and endometriosis are accompanied by insulin resistance and chronic inflammation, impairing ovulation, endometrial receptivity, and embryo viability. Interventions such as probiotics and synbiotics yield heterogeneous efficacy; individualized antimicrobial strategies, metabolic modulation, and lifestyle optimization may offer complementary benefit, while microbiota reconstruction remains experimental. Methodological limitations, including contamination in low biomass samples, variations in sequencing workflows, and population heterogeneity, still hinder data comparability and mechanistic interpretation. Future research should prioritize adequately powered randomized controlled trials using standardized microbiome metrics and live birth as a primary endpoint. Integrating microbiome profiling into ART workflows may refine patient stratification and inform precision adjuvant therapies. However, clinical implementation requires stronger causal evidence, validated biomarkers, and harmonized methodological frameworks to translate microbiome discoveries into reproducible reproductive gains.}, } @article {pmid41518832, year = {2025}, author = {Hellwig, P and Seick, I and Meinusch, N and Benndorf, D and Wiese, J and Reichl, U and Heyer, R}, title = {Molecular community data meets anaerobic digestion Model 1 (ADM1) - a study about the correlation between metagenome-centric metaproteomics data of a two-step full-scale anaerobic digester and its corresponding mathematical model.}, journal = {Water research}, volume = {292}, number = {}, pages = {125272}, doi = {10.1016/j.watres.2025.125272}, pmid = {41518832}, issn = {1879-2448}, abstract = {Advanced models, such as the Anaerobic Digestion Model No 1 (ADM1), are essential for operating, planning, and optimizing renewable energy production in anaerobic digester plants (AD-P)s. In this study, the ADM1da model was employed to simulate a two-step AD-P in an industrial setting. The ADM1da model is an extended ADM1 model for mixed substrates, accounting for substrate-specific disintegration, temperature effects, biogas-related mass reduction, and mineral solids content. ADM1 models can represent the anaerobic digestion processes, although the biological assumptions are coarse and reflect the knowledge and available tools for microbial communities at the time of development. Meanwhile, metagenome-centric metaproteomics provides deeper insight into the metabolic activities of microbial communities in AD-Ps. Until now, this data has not been integrated with ADM1 models. The objective of this study is to assess the feasibility of incorporating metagenome-centric metaproteome data into the ADM1 model. In a novel approach, 49 high-quality metagenome-assembled genomes (MAGs) with associated protein abundances were systematically classified into the trophic groups defined by the ADM1 model using specifically developed grouping rules. Abundances of MAGs were more variable than the process parameter-dependent dynamics of ADM1. Depending on the grouping rules, 32%-78% of all high-quality MAGs were successfully categorized into ADM1 trophic groups. However, some MAGs, e.g., Methanotrix, were multifunctional (acetoclastic and hydrogenotrophic methanogenesis) and required assignment to multiple groups. Unfortunately, more precise grouping rules resulted in greater discrepancies between metaproteomics data and the model. Additionally, 22% of the MAGs could not be assigned. The metagenome-centric metaproteome data imply that ADM1 probably needs extension to cover the observed microbial function of syntrophic acetate oxidizers, hydrolytic bacteria, lactate- and ethanol-fermenting bacteria, and mortality by phages. It was also observed that changes in process parameters, such as those caused by seasonal feeding, led to significant changes in the protein abundance Integrating metagenome-centric metaproteomic data into ADM1 trophic groups was shown to be feasible.Some trophic groups detected in protein data but not implemented in ADM1 imply the need for data-driven model enhancement and approval. In the future, more accurate models considering molecular data could support a deeper understanding of microbial community dynamics in AD-Ps.}, } @article {pmid41518828, year = {2025}, author = {Wu, Z and Liang, F and Zhu, N and Han, C and Wang, Z and Wang, W and Wang, L and Guo, Y and Luo, W and Wang, Y}, title = {Codonopsis pilosula regulates pathogen defense mechanisms through collaboration of root volatile compounds and microbial interactions.}, journal = {Plant physiology and biochemistry : PPB}, volume = {231}, number = {}, pages = {110974}, doi = {10.1016/j.plaphy.2025.110974}, pmid = {41518828}, issn = {1873-2690}, abstract = {Codonopsis pilosula responds to pathogen infection by modulating root volatile organic compounds (VOCs) and reshaping the rhizosphere microbiome. GC-IMS analysis linked root VOCs with microbial community composition, showing positive correlations with Bradyrhizobium and beneficial fungi, and negative associations with Alternaria pathogens. Representative VOCs-benzothiazole, linalool, and (E,E)-2,4-heptadienal-showed significant antifungal activity against Fusarium oxysporum. Molecular docking and qPCR analyses indicate that these compounds may interact with stress-related proteins and potentially influence autophagy-associated pathways, suggesting stress responses that could contribute to fungal growth inhibition or cell death. Although autophagy was not directly demonstrated, these findings highlight VOCs as important mediators of plant defense signaling and may support the development of eco-friendly VOC-based antifungal strategies.}, } @article {pmid41518802, year = {2026}, author = {Yang, X and Ji, XH and Li, C and Lai, JL and Luo, XG}, title = {Multi-omics assessment of synthetic microbiome-mediated remediation of cyclotetramethylene tetranitroamine (HMX) contaminated water.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141026}, doi = {10.1016/j.jhazmat.2026.141026}, pmid = {41518802}, issn = {1873-3336}, abstract = {Cyclotetramethylene tetranitroamine (HMX) is a typical high-energy nitramine pollutant with an environmental persistence and toxic effects that pose serious ecological risks. In this study, a synthetic microbiome with complementary functions is built that enables the integration of multigroup technology to conduct a systematic analysis of the mechanism of remediation of HMX-contaminated water bodies. Four core bacterial strains (Bacillus altitudinis, B. cereus, B. subtilis, and Pseudomonas stutzeri) were directionally domesticated and screened from HMX-contaminated water. Through functional verification, they were confirmed to express key enzymes NfsA, YdhA, FdhA, and NirS, respectively, to form a complete HMX deep degradation-level connection path. The synthetic microbiome achieved 100 % removal of HMX and its intermediates within 60 days, and isotope tracing (δ[15]N enrichment +2.7 ‰) confirmed its complete mineralization ability. Multiomic analysis showed that the restoration process is accompanied by a systematic reshaping of the water microecology and chemical environment, so that the microbial community structure is optimized and the synthetic microbiome is successfully colonized and becomes the core node. Meanwhile, the energy metabolic network (glycolysis, TCA cycle, oxidative phosphorylation) is significantly enhanced; metagenomic data also revealed reduced viral abundance. Ionomics revealed that key nutrient elements, such as P and S, are efficiently assimilated and utilized. These findings identify an efficient HMX bioremediation strategy that utilizes the multiple dimensions of "community structure-metabolic function-environmental effects" through a multigroup integration framework. More importantly, this study provides a theoretical basis and practical paradigm for the rational design of functional microbial communities.}, } @article {pmid41518158, year = {2026}, author = {Barberá, A and Ortolá, R and Sotos-Prieto, M and Rodríguez-Artalejo, F and Moya, A and Ruiz-Ruiz, S}, title = {The Role of the Gut Microbiome in the Complex Network of Frailty Syndrome and Associated Comorbidities in Aging.}, journal = {Aging cell}, volume = {25}, number = {2}, pages = {e70365}, pmid = {41518158}, issn = {1474-9726}, support = {PID2019-105969GB-I00//Spanish Ministry of Science, Innovation and Universities/ ; PMPTA22/00107//Carlos III Health Institute (ISCIII)/ ; PMPTA22/00037//Carlos III Health Institute (ISCIII)/ ; PMPTA23/00001//Carlos III Health Institute (ISCIII)/ ; INVEST/2022/309//Next Generation-EU/ ; 22/1111//ISCIII/ ; //The Secretary of R + D + I/ ; //ERDF/ESF/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Frailty/microbiology ; Male ; Female ; Aged ; *Aging ; Comorbidity ; Aged, 80 and over ; RNA, Ribosomal, 16S/genetics ; Metagenomics ; }, abstract = {The gut microbiota changes throughout life, potentially influencing health and triggering physiological disorders. Frailty syndrome (FS) is an age-related condition that reduces quality of life and increases hospitalization and mortality risks, making early detection and prevention essential in older populations. This study analyzed 16S rRNA gene and metagenomics sequencing of fecal samples from 203 older adults (FS: n = 64, non-FS (NFS): n = 139) to assess the role of gut microbiota in FS and related comorbidities, such as sarcopenia and impaired lower extremity function (ILEF) or anthropometric variables. Consistent taxonomic patterns were observed: Eggerthella, Parabacteroides, and Erysipelatoclostridium were significantly abundant in FS, while Christensenellaceae R-7 group, Erysipelotrichaceae UCG-003, and Hungatella were enriched in NFS. Christensenellaceae R-7 group was also associated with better mobility. Metagenomics analysis identified 680 KEGG functions differing between groups, categorized into 28 metabolic pathways. FS individuals had overrepresented biotin metabolism, antimicrobial resistance, and energy production, but underrepresented ribosomal and protein synthesis and sporulation pathways. Resistome analysis found the tetM/tetO (K18220) gene most abundant, alongside tetracycline, β-lactam, and macrolide resistance, primarily mediated by antibiotic efflux and transporters. These findings highlight distinct microbial and functional signatures associated with FS, underscoring the complex interplay between the gut microbiota and host physiology in aging. Adjusting for covariates, age and diabetes acted as confounding factors in FS for both 16S gene and metagenomics sequencing. This study offers new insights into fundamental questions in the biology of aging and opens avenues for microbiota-targeted strategies to improve the quality of life in older adults.}, } @article {pmid41517910, year = {2026}, author = {Gewirtzman, J}, title = {The Global Woody Surface: A Planetary Interface for Biodiversity, Ecosystem Function, and Climate.}, journal = {Global change biology}, volume = {32}, number = {1}, pages = {e70699}, doi = {10.1111/gcb.70699}, pmid = {41517910}, issn = {1365-2486}, support = {DGE-2139841//National Science Foundation/ ; //Institute for Biospheric Studies, Yale University/ ; 80NSSC25M7127//NASA CT Space Grant/ ; }, } @article {pmid41517814, year = {2026}, author = {Jacob, SM and Son, B and Bagheri, S and Lee, S and Leckie, J and Chohan, B and Belway, C and Mascarenhas, J and Mobach, T and Korngut, LW and Sharkey, KA and Park, J and Nguyen, MD and Kim, SH and Pfeffer, G}, title = {The Oral Microbiome in Amyotrophic Lateral Sclerosis Shows Differentially Abundant Organisms in Limb Versus Bulbar Onset Disease: A Binational Study.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {22}, number = {1}, pages = {66-75}, doi = {10.3988/jcn.2025.0219}, pmid = {41517814}, issn = {1738-6586}, support = {//ALS Canada Discovery Grant/Canada ; //Barry Barrett Foundation/Canada ; /CAPMC/CIHR/Canada ; //International Development Research Council/Canada ; //Rose Family Foundation/Canada ; //Fondation Brain Canada/Canada ; /MOHW/Ministry of Health and Welfare/Korea ; RS-2024-00348451/MSIT/Ministry of Science and ICT, South Korea/Korea ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons leading to progressive disability and death. Approximately 10% of cases are caused by single-gene disorders with the remaining 90% of cases presumed to be caused by a combination of environmental and genetic factors. The microbiome (the ensemble of microorganisms that colonize body surfaces and organs) was recently identified for its importance in the pathogenesis of ALS.

METHODS: In this study, we recruited 100 participants from two ethnically and geographically distinct sites (71 from Calgary, Canada, and 29 from Seoul, Republic of Korea) which included 59 ALS participants and 41 controls. All participants provided saliva samples for oral microbial analysis using 16S rRNA sequencing. Basic demographic information was collected from all participants, and ALS participants provided additional clinical information including site of disease onset, disease duration, and ALS Functional Rating Scale - Revised score.

RESULTS: Significant differences in beta diversity of the oral microbiomes were seen between limb- and bulbar-onset ALS participants. Two bacterial genera were differentially abundant between these groups, Bifidobacteriaceae Bifidobacterium was enriched in bulbar-onset cases, while Pasteurellaceae Haemophilus was enriched in limb-onset cases. No significant differences were found between ALS participants and controls, but there were significant differences when comparing participants from different sites of recruitment. Amongst household pairs (n=35 pairs), ALS participants differed from control participants at the Seoul site.

CONCLUSIONS: Despite the cohort and household effects, our study identified differentially abundant organisms that may be important to the phenotypic variability of ALS and should be considered for future study. Our study provides novel insights into design for future multi-site microbiome research in ALS.}, } @article {pmid41517622, year = {2026}, author = {Bicknell, B and Liebert, A and McLachlan, C and Kiat, H}, title = {Five-Year Follow-Up of Photobiomodulation in Parkinson's Disease: A Case Series Exploring Clinical Stability and Microbiome Modulation.}, journal = {Journal of clinical medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41517622}, issn = {2077-0383}, support = {NA//private donor/ ; }, abstract = {Background: Parkinson's disease (PD) involves progressive neurodegeneration with clinical or subclinical disturbance of the gut-brain axis, including altered gastrointestinal motility and enteric nervous system involvement. Clinical studies have reported gut microbiome alterations in PD, with shifts in taxa associated with inflammatory signalling and short-chain fatty acid (SCFA) metabolism. Photobiomodulation (PBM), a non-invasive light therapy, has been investigated as a potential adjunctive treatment for PD, with proposed effects on neural, metabolic, and immune pathways. We previously reported the five-year clinical outcomes in a PBM-treated Parkinson's disease case series. Here we report the five-year gut microbiome outcomes based on longitudinal samples collected from the same participants. This was an exploratory, open-label longitudinal study without a control group. Objective: Our objective was to assess whether long-term PBM was associated with changes in gut microbiome diversity and composition in the same Parkinson's disease cohort as previously assessed for changes in Parkinson's symptoms. Methods: Six participants from the earlier PBM proof-of-concept study who had been diagnosed with idiopathic PD and who had continued treatment (transcranial light emitting diode [LED] plus abdominal and neck laser) for five years had their faecal samples analysed by 16S rDNA sequencing to assess microbiome diversity and taxonomic composition. Results: Microbiome analysis revealed significantly reduced evenness (α-diversity) and significant shifts in β-diversity over five years, as assessed by Permutational Multivariate Analysis of Variance (PERMANOVA). At the phylum level, Pseudomonadota and Methanobacteriota decreased in four of the six participants. Both of these phyla are often increased in the Parkinson's microbiome compared with the microbiomes of healthy controls. Family-level changes included increased acetate-producing Bifidobacteriaceae (five of the six participants); decreased pro-inflammatory, lipopolysaccharide (LPS)-producing Enterobacteriaceae (two of the three participants who have this bacterial family present); and decreased LPS- and H2S-producing Desulfovibrionaceae (five of six). At the genus level, Faecalibacterium, a key butyrate producer, increased in four of the six participants, potentially leading to more SCFA availability, although other SCFA-producing bacteria were decreased. This was accompanied by reductions in pro-inflammatory LPS and H2S-producing genera that are often increased in the Parkinson's microbiome. Conclusions: This five-year case series represents the longest follow-up of microbiome changes in Parkinson's disease, although the interpretation of results is limited by very small numbers, the lack of a control group, and the inability to control for lifestyle influences such as dietary changes. While causal relationships cannot be inferred, the parallel changes in improvements in mobility and non-motor Parkinson's symptoms observed in this cohort, raises the hypothesis that PBM may interact with the gut-brain axis via the microbiome. Controlled studies incorporating functional multi-omics are needed to clarify potential mechanistic links between microbial function, host metabolism, and clinical outcomes.}, } @article {pmid41517479, year = {2025}, author = {Wu, B and He, Z and Xu, T}, title = {A Vanished Association Between Proton Pump Inhibitors and Clostridioides Difficile Infection After Minimizing Bias.}, journal = {Journal of clinical medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41517479}, issn = {2077-0383}, abstract = {Background: The gut microbiome might be affected by proton-pump inhibitors (PPIs), increasing the risk of Clostridioides difficile infection (CDI); however, the association between PPIs and Clostridioides difficile infection (CDI) remains controversial. Aim: The aim of this study is to reevaluate the association between PPIs and CDI based on pharmacovigilance data, taking competition bias into account. Methods: PPI-related CDI adverse event reports, based on the Food and Drug Administration adverse event reporting system database from 2004 to 2023, were analyzed. Included PPI cases were stratified into CDI and non-CDI groups. Disproportionality analysis was performed using the reporting odds ratio (ROR) and information component (IC). The effect of competition bias on signal detection was quantitatively investigated. Age-stratified analyses were conducted to assess residual confounding. Results: A total of 238,470 PPI reports were included, with 1268 cases in the CDI group and 237,202 cases in the non-CDI group. Initial analysis revealed a significant PPI-CDI association (ROR = 2.36, 95% confidence interval (95%CI) 2.19 to 2.53; IC = 1.21, 95%CI 0.97 to 1.45), with CDI signals detected for five PPI agents, including pantoprazole, omeprazole, lansoprazole, rabeprazole, and dexlansoprazole. After excluding competition from antibacterial drugs, CDI signal strength decreased substantially (ROR = 1.47, 95%CI 1.34 to 1.62; IC = 0.55, 95%CI 0.23 to 0.87), retaining a significant CDI signal only for rabeprazole and pantoprazole. Upon further exclusion of antibacterial or immunosuppressive drug users and renal injury event cases, CDI signal strength decreased (ROR = 1.48, 95%CI 1.32 to 1.66; IC = 0.56, 95%CI 0.18 to 0.94), with pantoprazole as the sole CDI signal drug. Age-stratified analyses demonstrated complete signal loss after antibacterial drug adjustment across all age groups. Conclusions: The current large-scale pharmacovigilance study indicated that the observed PPI-CDI association may be mediated predominantly by antibacterial drug co-exposure rather than PPI direct causation.}, } @article {pmid41517247, year = {2026}, author = {Shah, SMH and Volpe, S and Colonna, F and Valentino, V and De Filippis, F and Torrieri, E and Cavella, S}, title = {Combined Effect of Plasma-Activated Water, Edible Coating, and Active Packaging on Cherry Tomato Shelf-Life: Kinetics and Microbiome Approach.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517247}, issn = {2304-8158}, support = {817936//European Commission/ ; }, abstract = {Cherry tomatoes are highly appreciated for their nutritional value but remain highly perishable due to rapid respiration and senescence. This study evaluated a multi-hurdle strategy combining plasma-activated water (PAW), sodium caseinate-based edible coating, and antioxidant active packaging to preserve minimally processed (MP) cherry tomatoes stored at 1 °C, 4 °C, and 8 °C for 15 days. Quality evolution was monitored through physical, chemical, nutritional, and microbiological parameters and described using pseudo-zero- and first-order kinetic models, with temperature dependence expressed by the Arrhenius equation. The combined treatment (prototype) slowed the degradation rates of pH, titratable acidity, total polyphenols, and antioxidant capacity, as reflected by consistently lower kinetic rate constants across all temperatures. Prototype samples showed better retention of polyphenols and antioxidant capacity, particularly at 1 °C and 4 °C, without detrimental effects on visual appearance. Metagenomic analysis revealed that the multi-hurdle treatment reshaped the microbial community, reducing the relative abundance of potentially problematic taxa such as Acinetobacter johnsonii and limiting the occurrence of antimicrobial resistance (AMR) genes at the end of storage. This study provides the first integrated assessment of PAW, edible coating, and antioxidant active packaging as a synergistic multi-hurdle strategy, demonstrating their combined ability to extend shelf life while modulating the microbiome and resistome of minimally processed cherry tomatoes.}, } @article {pmid41517237, year = {2026}, author = {Yao, Y and Wu, X and Wu, H and Su, W and Li, P}, title = {Multi-Omics Analyses Unveil the Effects of a Long-Term High-Salt, High-Fat, and High-Fructose Diet on Rats.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517237}, issn = {2304-8158}, abstract = {BACKGROUND: Unhealthy diets characterized by high salt, fat, and fructose content are established risk factors for metabolic and cardiovascular disorders and may have indirect effects on cognitive function. However, the combined impact of a high-salt, high-fat, and high-fructose diet (HSHFHFD) on systemic physiology and brain health remains to be fully elucidated.

METHODS: Sprague-Dawley (SD) rats received a customized high-salt, high-fat diet supplemented with 30% fructose water for 18 weeks. Physiological and brain parameters were assessed, in combination with multi-omics analyses including brain proteomics and metabolomics, serum metabolomics, and gut microbiota profiling.

RESULTS: HSHFHFD significantly elevated blood glucose, blood pressure, and serum levels of TG, TC, and LDL in rats. Serum metabolomic profiling identified over 100 differentially abundant metabolites in the Model group. Proteomics, metabolomics, and gut microbiome integration revealed pronounced alterations in both brain proteomic and metabolomic profiles, with 155 differentially expressed proteins associated with glial cell proliferation and 65 differential metabolites linked to fatty acid and amino acid metabolism, among others. Experimental validation confirmed marked upregulation of GFAP and Bax protein, concomitant with downregulation of ZO-1 and occludin. Furthermore, HSHFHFD perturbed the CREB signaling pathway, leading to diminished BDNF expression. The levels of inflammatory factors, including IL-6, IL-10, IL-1β and TNFα, were significantly elevated in the brain. Oxidative stress was evident, as indicated by elevated malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and altered NAD[+]/NADH ratio. Additionally, HSHFHFD significantly reduced the abundance of beneficial gut bacteria, including Lactobacillus, Romboutsia, and Monoglobus.

CONCLUSIONS: HSHFHFD-induced depletion of gut Lactobacillus spp. may disrupt the linoleic acid metabolic pathway and gut-brain axis homeostasis, leading to the impairment of neuroprotective function, blood-brain barrier dysfunction, and exacerbated neuroinflammation and oxidative stress in the brain. These effects potentially increase the susceptibility of rats to neurodegenerative disorders.}, } @article {pmid41517189, year = {2026}, author = {Grigore-Gurgu, L and Leuștean-Bucur, FI and Bahrim, GE}, title = {Genetic Engineering and Encapsulation Strategies for Lacticaseibacillus rhamnosus Enhanced Functionalities and Delivery: Recent Advances and Future Approaches.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517189}, issn = {2304-8158}, support = {GI 7960/2025//"Dunarea de Jos" University of Galati/ ; }, abstract = {This review addresses the recent advances made through various genetic engineering techniques to improve the properties of Lacticaseibacillus rhamnosus, not only for industrial applications, but also for the health-related benefits. However, due to the strict regulations on microorganisms intended for human consumption, concerning the insufficient characterization degree of the newly isolated strains and the lack of data regarding the safety of the genetically modified (GM) variants, the feasibility of bringing such L. rhamnosus strains to the market and their safety prospects were evaluated. Given their multiple in vivo functions in the contexts of synbiotic and symbiotic functionality, L. rhamnosus strains are more than classic probiotics and need furthermore attention. In the functional food context, this review highlights the impact of L. rhamnosus derived bioactives on the human gut-organ axis, pointing out recently demonstrated molecular mechanisms of action with the host's gut microbiome to reduce the negative effects of obesity and its related metabolic disorders, as well as depression and Parkinson's disease, as the major challenges confronting humans today. Beyond that, considering L. rhamnosus delivery and its postbiotics accessibility to consumers via functional foods, notable progress was made to enhance their stability by developing various encapsulation systems, which are also emphasized.}, } @article {pmid41517135, year = {2025}, author = {Liao, L and Yu, Z and Lu, Y and Hu, Y and Zhu, Y and Zhang, Y and Yu, D}, title = {Integrative Analysis of Nutritional Components, Differential Metabolites, and Endophytic Microbiota Reveals Flavor Determinants of Lushan Russet Potato.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517135}, issn = {2304-8158}, support = {32160075//National Natural Science Foundation of China/ ; jjsbsq2020026//"Double Hundred and Double Thousand" Talent Project of Jiujiang City/ ; JXXTCiX202205//Jiangxi Modern Agriculture Research Collaborative Innovation Special Project/ ; S2024ZDYFN0025//the Key R&D Program Project of Jiujiang City/ ; S2024ZDYFN00151//the Key R&D Program Project of Jiujiang City/ ; 2020ZWZX03//Scientific Planning Project of Lushan Botanical Garden/ ; 2020ZWZX05//Scientific Planning Project of Lushan Botanical Garden/ ; jxsq2020104003//Double Thousand Plan of Jiangxi Province (PR China)/ ; }, abstract = {The Lushan Russet potato, cultivated in Lushan Mountain (China), is renowned for its unique flavor, which deteriorates when cultivated at low altitudes. To unravel its flavor determinants, we compared high/low-altitude-cultivated Lushan Russet potato (LsM/LS) and reference Zhongshu5 (Zs) via nutritional, metabolomic, and endophytic microbiota analyses. LsM/LS had higher dry matter, potassium, and other flavor-related components than Zs. Non-targeted LC-MS metabolomics identified 461 metabolites. Pairwise comparisons revealed 263 significant differential metabolites (SDMs) between LsM and Zs (205 more abundant in LsM), 240 between LS and Zs, and 237 between LsM and LS. KEGG enrichment showed that SDMs were mainly involved in metabolic pathways. High-throughput sequencing of endophytic microbiota showed clear beta diversity separation, which correlated with metabolomic changes. These results indicate that Lushan Russet potato's unique flavor is jointly determined by nutrient/metabolite accumulation and endophytic microbiome diversity, providing a basis for optimizing its quality and mitigating flavor deterioration in low-altitude cultivation.}, } @article {pmid41517088, year = {2025}, author = {Xue, R and Zong, X and Jiang, X and You, G and Wei, Y and Guo, B}, title = {Artificial Intelligence-Driven Food Safety: Decoding Gut Microbiota-Mediated Health Effects of Non-Microbial Contaminants.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517088}, issn = {2304-8158}, support = {7244451//Beijing Natural Science Foundation/ ; }, abstract = {A wide range of non-microbial contaminants-such as heavy metals, pesticide residues, antibiotics, as well emerging foodborne contaminants like micro- and nanoplastics and persistent organic pollutants-can enter the human body through daily diet and exert subtle yet chronic effects that are increasingly recognized to be gut microbiota-dependent. However, the relationships among multi-contaminant exposure profiles, dynamic microbial community structures, microbial metabolites, and diverse clinical or subclinical phenotypes are highly non-linear and multidimensional, posing major challenges to traditional analytical approaches. Artificial intelligence (AI) is emerging as a powerful tool to untangle the complex interactions between foodborne non-microbial contaminants, the gut microbiota, and host health. This review synthesizes current knowledge on how key classes of non-microbial food contaminants modulate gut microbial composition and function, and how these alterations, in turn, influence intestinal barrier integrity, immune homeostasis, metabolic regulation, and systemic disease risk. We then highlight recent advances in the application of AI techniques, including machine learning (ML), deep learning (DL), and network-based methods, to integrate multi-omics and exposure data, identify microbiota and metabolite signatures of specific contaminants, and infer potential causal pathways within "contaminant-microbiota-host" axes. Finally, we discuss current limitations, such as data heterogeneity, small-sample bias, and interpretability gaps, and propose future directions for building standardized datasets, explainable AI frameworks, and human-relevant experimental validation pipelines. Overall, AI-enabled analysis offers a promising avenue to refine food safety risk assessment, support precision nutrition strategies, and develop microbiota-targeted interventions against non-microbial food contaminants.}, } @article {pmid41516959, year = {2025}, author = {Huang, CH and Lu, MC and Koo, M}, title = {Global Research on Hemodialysis Nutrition and Patient-Centered Priorities: A Bibliometric Analysis (2006-2025).}, journal = {Healthcare (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {41516959}, issn = {2227-9032}, abstract = {Background: Optimal nutritional care is essential to improving outcomes in hemodialysis, yet translation of evidence into routine practice remains uneven across settings. To inform health system planning and implementation priorities, we mapped global research on hemodialysis-related nutrition. Methods: We searched the Web of Science Core Collection for English-language original articles on nutrition and hemodialysis from 1 January 2006 to 13 October 2025. Publication trends, productivity by country and institution, influential journals and authors, citation impact, and conceptual structure via Keyword Plus co-occurrence, trend, and thematic evolution analyses were assessed using the bibliometrix package (version 5.0) in R. Results: A total of 332 articles from 115 journals were identified, with substantial growth and multidisciplinary authorship, though international collaboration remains limited. The United States contributed 21.4% of publications and achieved the highest citation impact, while China, Japan, Iran, and Brazil formed the next tier of contributors. The Journal of Renal Nutrition accounted for 16.6% of papers. Highly cited studies established links between dietary intake, mineral and electrolyte management, and survival, while supporting the use of intradialytic oral nutritional supplements. Thematic evolution showed a shift from biochemical markers toward patient-centered priorities, including diet quality, adherence, body composition, mental health, and quality of life. Emerging directions point to whole-diet approaches and microbiome-modulating strategies. Conclusions: Global research on diet and hemodialysis has progressed from foundational nutrient studies to multidimensional, patient-focused approaches. Our findings suggest opportunities for health systems to strengthen dietitian-led models of care, integrate patient-reported outcomes, and prioritize scalable nutrition interventions within routine dialysis services.}, } @article {pmid41516317, year = {2025}, author = {Dubiński, P and Odzimek-Rajska, M and Podlewski, S and Brola, W}, title = {Emerging Insights into the Role of the Microbiome in Brain Gliomas: A Systematic Review of Recent Evidence.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516317}, issn = {1422-0067}, support = {SUPB.RN.25.016//The Jan Kochanowski University in Kielce, Poland/ ; }, mesh = {Humans ; *Glioma/microbiology/pathology ; *Gastrointestinal Microbiome ; *Brain Neoplasms/microbiology/pathology ; Animals ; Dysbiosis/microbiology ; }, abstract = {Gliomas, particularly glioblastoma multiforme, remain among the most lethal brain tumours despite multimodal therapy. Increasing evidence indicates that systemic factors, including the gut microbiota, may influence glioma progression through immune, metabolic, and neurochemical pathways. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to synthesize recent evidence on the role of gut and intratumoral microbiota in glioma biology. Peer-reviewed studies published within the last five years were identified through structured searches of major biomedical databases, and original studies using human cohorts, animal models, or Mendelian randomization approaches were included. The 17 studies met the eligibility criteria. Glioma was consistently associated with gut dysbiosis characterized by a reduced Firmicutes:Bacteroidetes ratio and enrichment of Verrucomicrobia, particularly Akkermansia, alongside decreased short-chain fatty acids and altered neurotransmitter profiles, contributing to neuroinflammation, immune suppression, and blood-brain barrier dysfunction. Antigenic mimicry by Bacteroidetes-derived peptides may impair antitumour T-cell responses, while intratumoral Fusobacteriota and Proteobacteria appear to promote angiogenesis and pro-inflammatory chemokine expression. In contrast, SCFA-producing taxa such as Ruminococcaceae and probiotic genera including Lactobacillus and Bifidobacterium show protective associations. Evidence is limited by small cohorts and methodological heterogeneity. Standardized humanized models and integrated multi-omics approaches are required to clarify causal mechanisms and support microbiome-targeted therapies in glioma.}, } @article {pmid41516296, year = {2025}, author = {Nikolova, R and Donchev, D and Vaseva, K and Ivanov, IN}, title = {Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Insights into Disease Mechanisms.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516296}, issn = {1422-0067}, support = {project № BG-RRP-2.004-0007-С03//European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/microbiology/etiology/immunology ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Animals ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling clinical condition, whose hallmark characteristic is post-exertional malaise (PEM). It can affect many organs and systems, leading to severe impairment of patients' quality of life. Although numerous post-infectious, immunological, neurological, metabolic, and endocrine alterations have been documented, neither a definitive diagnostic marker nor approved treatments are available. The etiology and pathophysiology remain incompletely understood; however, emerging evidence suggests that the gut microbiome plays a role in immune responses and the development of ME/CFS. It is hypothesized that specific disturbances in gut microbiome composition, known as dysbiosis, may compromise the integrity of the intestinal barrier. This consequently leads to translocation of microbial components, which further triggers an immune response and systemic inflammation complicating the clinical presentation of ME/CFS. Furthermore, in terms of the so-called gut-brain axis, microbiome changes may lead to distinct neurocognitive impairments observed in ME/CFS patients. This review offers the readers a broad perspective on the topic on ME/CFS, with a particular emphasis on the interplay between the gut microbiome and disease mechanisms. Last but not least, recent data on potential treatment strategies for intestinal dysbiosis in ME/CFS patients have been included.}, } @article {pmid41516244, year = {2025}, author = {Tassibekova, G and Zholdassova, M and Novosolova, N and Malm, T and Giniatullin, R and Kustubayeva, A}, title = {More than Dysbiosis: Imbalance in Humoral and Neuronal Bidirectional Crosstalk Between Gut and Brain in Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516244}, issn = {1422-0067}, support = {BR27198099//This research has been funded by the Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/microbiology/pathology/etiology ; *Dysbiosis/metabolism/microbiology ; *Gastrointestinal Microbiome ; *Brain/metabolism ; Animals ; Neurons/metabolism ; Brain-Gut Axis ; }, abstract = {The intestinal microbiota, a diverse community of microorganisms residing in the human gut, recently attracted considerable attention as a contributing factor to various neurological disorders, including Alzheimer's Disease (AD). Within the established framework of the gut-brain axis (GBA) concept, it is commonly suggested that dysbiosis, through microbial metabolites entering the brain, affect the cognitive functions in patients with AD. However, evidence for such a role of dysbiosis remains largely associative, and the complexity of the communication channels between the gut and the brain is not fully understood. Moreover, the new players of the GBA are emerging and the AD concept is constantly evolving. The objective of this narrative review is to synthesize the current evidence on the humoral, endocrine, immune, and neural communication mechanisms linking the gut and brain in AD and highlight newly discovered GBA messengers such as microRNAs, extracellular vesicles, T-cells, and the intestinal hormones, including emerging neuroprotective role for glucagon-like peptide-1 (GLP-1). Based on this knowledge, we aimed to develop a conceptual understanding of the GBA function in health and AD. We specify that, in AD, the GBA goes beyond a disrupted microbiome, but operates in conjunction with impaired intestinal secretion, motility, barrier permeability, and neuroinflammatory signaling. These factors are associated with the dysfunction of the hypothalamic-pituitary axis, altered somatic and autonomic neuronal gut regulation, and abnormal, due to memory problems, behavioral aspects of food intake. Identifying the individual profile of key molecular and cellular players contributing to an unbalanced GBA should optimize existing approaches or propose new approaches for the complex therapy of AD.}, } @article {pmid41516240, year = {2025}, author = {Micu, AE and Popescu, IA and Halip, IA and Mocanu, M and Vâță, D and Hulubencu, AL and Gheucă-Solovăstru, DF and Gheucă-Solovăstru, L}, title = {From Gut Dysbiosis to Skin Inflammation in Atopic Dermatitis: Probiotics and the Gut-Skin Axis-Clinical Outcomes and Microbiome Implications.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516240}, issn = {1422-0067}, mesh = {Humans ; *Dermatitis, Atopic/microbiology/therapy ; *Probiotics/therapeutic use ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Skin/microbiology/pathology/immunology ; Inflammation/microbiology ; }, abstract = {Atopic dermatitis (AD) is a chronic inflammatory skin disease in which barrier impairment, immune dysregulation, and gut-skin dysbiosis intersect, prompting growing interest in probiotics as microbiota-modulating adjuncts. We conducted a narrative review of peer-reviewed articles indexed in PubMed, Scopus, and Google Scholar, restricted to publications from 1 January 2018 to 31 October 2025 (searches last run in December 2025). Eligible evidence included randomized controlled trials (RCTs), observational studies, and mechanistic or conceptual reviews addressing microbiome alterations and microbiota-modulating interventions in AD. Most pediatric RCTs using multistrain, Lactobacillus-dominant formulations (often combined with Bifidobacterium) reported modest improvements in AD severity and pruritus and in selected barrier- and inflammation-related biomarkers. However, direct cutaneous microbiome "restoration" outcomes were reported in a minority of studies, and most clinical evidence relies on clinical endpoints and gut-skin axis plausibility rather than longitudinal skin microbiome readouts. Single-strain regimens showed inconsistent effects, and evidence in adolescents and adults remained heterogeneous. Mechanistically, probiotics may enhance short-chain fatty acid (SCFA) signaling, dampen toll-like receptor 2/4 (TLR2/4)-nuclear factor kappa B (NF-κB) activation, and promote interleukin-10 (IL-10)- and transforming growth factor-β (TGF-β)-driven tolerance. Probiotics are a biologically plausible adjunct targeting the gut-skin axis in AD and are generally well tolerated; however, heterogeneity across trials, limited follow-up, inconsistent adverse-event reporting, and scarce skin microbiome endpoints preclude firm clinical recommendations.}, } @article {pmid41516219, year = {2025}, author = {Duman, H and Avcı, İ and Salih, B and Kayılı, HM and Bechelany, M and Karav, S}, title = {Exploring the Activity of a Novel N-Glycosidase (EndoBI-2): Recombinant Production to Release Bioactive Glycans.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516219}, issn = {1422-0067}, mesh = {*Polysaccharides/metabolism/chemistry ; Recombinant Proteins/metabolism/genetics ; *Glycoside Hydrolases/metabolism/genetics ; Ribonucleases/metabolism ; Tandem Mass Spectrometry ; *Bifidobacterium/enzymology ; Glycoproteins/metabolism ; *Bacterial Proteins/metabolism/genetics ; *Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase/metabolism/genetics ; }, abstract = {The gut microbiome evolves in response to host development, health state, lifestyle, nutrition, and microbial interactions. The survival of gut microbiota depends on its ability to utilize its host-indigestible complex oligosaccharides. Certain gut microbes produce glycosidases that cleave N-glycoproteins to release N-glycans that are then used as a carbon source. However, commercial glycosidases are inefficient and, thus, require improved deglycosylation strategies to study their functions and scale up their production. Therefore, the main objective of this study was to recombinantly produce and characterize the novel endo-β-N-acetylglucosaminidase 2 (EndoBI-2) from Bifidobacterium longum subsp. infantis (B. infantis) and to evaluate its enzymatic performance for controlled N-glycan release. Furthermore, the optimum reaction conditions for EndoBI-2 were investigated on model glycoprotein RNAse B using model glycoprotein. The released N-glycans were profiled by hydrophilic interaction liquid chromatography-fluorescence detection-quadrupole time-of-flight tandem mass spectrometry (HILIC-FLD-QTOF-MS/MS). We demonstrated that EndoBI-2 possesses a strong temperature tolerance and efficiently cleaves N-glycans under mild reaction conditions, exhibiting high activity at pH 5. These findings highlight EndoBI-2 as a robust and efficient biocatalyst for the production of bioactive N-glycans from diverse N-glycoproteins, with potential applications in glycobiotechnology.}, } @article {pmid41516169, year = {2025}, author = {Uvarova, YE and Khlebodarova, TM and Vasilieva, AR and Shipova, AA and Babenko, VN and Zadorozhny, AV and Slynko, NM and Bogacheva, NV and Bukatich, EY and Shlyakhtun, VN and Korzhuk, AV and Pavlova, EY and Chesnokov, DO and Peltek, SE}, title = {Genetic Characterisation of Closely Related Lactococcus lactis Strains Used in Dairy Starter Cultures.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516169}, issn = {1422-0067}, support = {075-15-2025-516//Ministry of Science and Higher Education of the Russian Federation (the Federal Scientific-technical program for genetic technologies development for 2019-2030)/ ; FWNR- 2022-0022//Ministry of Science and Higher Education project "Study of metabolic control networks in living systems under environmental interaction, including in genetically modified organisms."/ ; }, mesh = {*Lactococcus lactis/genetics/classification/isolation & purification/metabolism ; *Cheese/microbiology ; Food Microbiology ; Phylogeny ; Genome, Bacterial ; Fermentation ; Microbiota/genetics ; }, abstract = {The complex microbiota of cheese starters plays a key role in determining the structure and flavour of the final product, primarily through their acid-forming capacity, protease activity, and exopolysaccharide synthesis. However, the specific microbial communities underlying the unique qualities of artisanal cheeses remain poorly understood. This study presents the microbiological and molecular genetic characterisation of the microbiome isolated from an artisanal cheese starter in Kosh-Agach, Altai, Russia. Metagenomic analysis of this starter revealed the presence of three bacterial genomes corresponding to those of Lactococcus lactis. Pure cultures from this starter were obtained by sequential subculture, and seventeen colonies displaying distinct characteristics on differential media were selected. Genome sequencing was performed for each colony. Bioinformatic analysis based on the rpoB gene grouped the isolates into three clusters, each corresponding to a distinct strain of Lactococcus lactis subsp. diacetilactis. This classification was further confirmed by microbiological and microscopic analyses. A notable finding was that none of the strains produced the characteristic aroma compounds of L. l. subsp. diacetilactis, namely, diacetyl and CO2. The functional properties and metabolic characteristics of this starter consortium are discussed.}, } @article {pmid41522201, year = {2023}, author = {Kim, E}, title = {Effects of natural mono- and di-saccharide as alternative sweeteners on inflammatory bowel disease: a narrative review.}, journal = {Korean journal of community nutrition}, volume = {28}, number = {3}, pages = {181-191}, pmid = {41522201}, issn = {2951-3146}, abstract = {OBJECTIVES: The incidence of inflammatory bowel disease (IBD) is increasing globally, and excessive added sugar consumption has been identified as one of the contributing factors. In the context of IBD, it is essential to explore functional sweeteners that can improve metabolic health and minimize the risk of IBD-related symptoms. This review article aims to shed light on the effects of natural mono- and di-saccharides as alternative sweeteners, specifically focusing on potential benefits for IBD.

METHODS: A comprehensive literature review was performed using PubMed and Google Scholar databases with articles published after the year 2000. The search terms 'IBD', 'added sugar', 'sweeteners', 'mono-saccharide', and 'di-saccharide' were combined to retrieve relevant articles. A total of 21 manuscripts, aligning with the objectives of the study, were selected. Papers focusing on artificial or high-intensity sweeteners were excluded to ensure relevant literature selection.

RESULTS: Multiple studies have emphasized the association between the high consumption of added sugars such as simple sugars and the increased risk of developing IBD. This is suggested to be attributed to the induction of pro-inflammatory cytokine productions and dysbiosis of the gut microbiota. Consequently, there is a growing demand for safe and functional sweeteners, in particular mono- and di-saccharides, that can serve as alternatives for IBD patients. Those functional sweeteners regulate inflammation, oxidative stress, and Intestinal barrier protection, and restore microbiome profiles in various IBD models including cells, animals, and humans.

CONCLUSIONS: Understanding these mechanisms resolves the link between how sugar consumption and IBD, and highlights the beneficial effects of natural alternative sweeteners on IBD when they were administered by itself or as a replacement for simple sugar. Further, exploration of this relationship leads us to recognize the necessity of natural alternative sweeteners in dietary planning. This knowledge could potentially lead to more effective dietary strategies for individuals with IBD.}, } @article {pmid41516078, year = {2025}, author = {Lupusoru, R and Moleriu, LC and Mare, R and Sporea, I and Popescu, A and Sirli, R and Goldis, A and Nica, C and Moga, TV and Miutescu, B and Ratiu, I and Belei, O and Olariu, L and Dumitrascu, V and Dragomir, RD}, title = {AI-Guided Multi-Omic Microbiome Modulation Improves Clinical and Inflammatory Outcomes in Refractory IBD: A Real-World Study.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516078}, issn = {1422-0067}, support = {without a Grant Number.//"Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania;/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Adult ; Female ; Male ; *Inflammatory Bowel Diseases/microbiology/therapy ; Middle Aged ; Biomarkers/blood ; *Artificial Intelligence ; Feces/microbiology ; Inflammation/microbiology ; Metagenomics/methods ; Treatment Outcome ; Young Adult ; Multiomics ; }, abstract = {Inflammatory bowel disease (IBD) remains difficult to manage in patients who fail multiple therapeutic lines, and growing evidence suggests that alterations in the gut microbiome contribute to persistent symptoms and inflammatory activity. This study evaluated a three-month, AI-guided, multi-omic personalized microbiome modulation program in adults with treatment-refractory IBD. Baseline stool metagenomic sequencing, blood biomarkers, micronutrient panels, and clinical data were integrated through an artificial intelligence platform to generate individualized plans combining dietary adjustments, targeted synbiotics, selective antimicrobials, and micronutrient correction. Clinical outcomes, inflammatory markers, and microbial signatures were reassessed after three months. Across 358 participants, stool frequency decreased substantially, urgency and rectal bleeding resolved in most patients, and over 70% reported a "much improved" overall condition. Inflammatory biomarkers showed marked normalization, with reductions in hs-CRP and fecal calprotectin observed in over 85% of cases. Micronutrient deficiencies, particularly iron and zinc, also improved, and beneficial microbial taxa such as Faecalibacterium prausnitzii, Bifidobacterium longum, and Akkermansia muciniphila increased significantly. These findings suggest that personalized, multi-omic microbiome modulation may support clinically meaningful improvements by targeting microbial, metabolic, and immune imbalances rather than symptoms alone. While encouraging, these results require confirmation in randomized controlled studies.}, } @article {pmid41515997, year = {2025}, author = {Ahmed, I and Nijs, J and Vanroose, M and Vandeputte, D and Kindt, S and Elma, Ö and Hendrix, J and Huysmans, E and Lahousse, A}, title = {Oral and Gut Health, (Neuro) Inflammation, and Central Sensitization in Chronic Pain: A Narrative Review of Mechanisms, Treatment Opportunities, and Research Agenda.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41515997}, issn = {1422-0067}, mesh = {Humans ; *Chronic Pain/therapy/microbiology/etiology/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Central Nervous System Sensitization ; *Oral Health ; *Neuroinflammatory Diseases ; Dysbiosis ; }, abstract = {Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood-brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain.}, } @article {pmid41515464, year = {2026}, author = {Mendóza, R and Santos, JM and Liu, X and Elmassry, MM and Ji, G and Kiritoshi, T and Neugebauer, V and Shen, CL}, title = {Gingerol-Enriched Ginger Extract Effects on Anxiety-like Behavior in a Neuropathic Pain Model via Colonic Microbiome-Neuroimmune Modulation.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {1}, pages = {}, pmid = {41515464}, issn = {1420-3049}, support = {GRANT2020-04545//United States Department of Agriculture-NIFA/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Zingiber officinale/chemistry ; Male ; *Neuralgia/drug therapy/microbiology ; *Anxiety/drug therapy ; Disease Models, Animal ; *Plant Extracts/pharmacology/chemistry ; Rats, Sprague-Dawley ; Behavior, Animal/drug effects ; Colon/microbiology ; Catechols ; Fatty Alcohols ; }, abstract = {Growing evidence has revealed that gut dysbiosis is associated with the development of anxio-depressive disorders through mechanisms that involve neuroimmune signaling, neurotransmitter changes, and neuroplasticity in the brain. This study investigated the effects of gingerol-enriched ginger (GEG) on specifically anxiety-related neuroinflammation-, neuroimmunity-, neuroplasticity-, neurotransmission-, and neurotoxicity-associated genes in different brain regions, as well as on alterations linked to colonic microflora-driven dysbiosis, in the spinal nerve ligation (SNL) rat model of neuropathic pain (NP). Twenty-seven male rats were assigned to 3 groups: sham, SNL, and SNL-treated with GEG at 200 mg/kg body weight (SNL+200GEG) via oral gavage for 5 weeks. Anxiety-like behavior was assessed on the elevated plus maze (EPM). mRNA expression was assessed by qRT-PCR using respective primers. Correlation between behavioral parameters and colonic microbiome composition was analyzed using the Spearman rank correlation. The SNL+200GEG group demonstrated decreased anxiety-like behavior in the SNL model. Compared to the SNL group, the SNL+200GEG group had increased mRNA expression of NRF2 (amygdala: left), LXRα (amygdala: both sides), and CX3CR1 (amygdala: both sides, hippocampus: right). GEG modulated neuroplasticity as shown by increased gene expression of PGK1 (amygdala: right, hippocampus: both sides), MEK1 (frontal cortex: both sides), LDHA (frontal cortex: both sides), GPM6A (frontal cortex: both sides, amygdala: right, hippocampus: right, and hypothalamus), and GLUT1 (amygdala: right) as well by decreased gene expression of HIF1α (in all brain regions except for the hypothalamus). GEG modulated neurotransmission via clearance of excessive glutamate release as suggested by increased gene expression of SLC1A3 (frontal cortex: both sides, hippocampus: right) and via augmenting mGluR5 signaling as shown by increased gene expression of GRM5 (hippocampus: both sides, hypothalamus) as well as downregulation of KMO, HAAO, GRIN2B, and GRIN2C influencing downstream serotonergic neurotransmission and NMDA receptor-mediated glutamatergic pathways in different brain regions. GEG further alleviated neurotoxicity through downregulated gene expression of SIRT1, KMO, IDO1, and HAAO in different brain regions. Moreover, the increased relative abundance of Bilophila spp., accompanied by decreased time spent in the EPM open arms, suggests that increased Bilophila abundance increases anxiety-like behavior. GEG supplementation mitigated anxiety-like behavior in male rats with NP, at least in part, by reducing SNL-induced inflammatory sequelae-related mRNA gene expression in different brain regions. In addition, there is a positive correlation between the abundance of Bilophila wadsworthia and the degree of anxiety-like behavior.}, } @article {pmid41515410, year = {2025}, author = {Zykova, MV and Trofimova, ES and Azarkina, LA and Lasukova, TV and Mihalyov, DA and Drygunova, LA and Danilets, MG and Ligacheva, AA and Tsupko, AV and Bashirov, SR and Belousov, MV}, title = {Pharmacological Effects of Humic Substances and Their Signaling Mechanisms.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {1}, pages = {}, pmid = {41515410}, issn = {1420-3049}, support = {056-00065-24-02//The research was supported by the State Task of the Ministry of Health of the Russian Federation/ ; }, mesh = {*Humic Substances/analysis ; Humans ; *Signal Transduction/drug effects ; Animals ; Gastrointestinal Microbiome/drug effects ; Antioxidants/pharmacology/chemistry ; }, abstract = {This comprehensive review presents the results of an in-depth analytical literature search on the biological activity of humic substances and their possible pharmacological mechanisms of action. The unique chemical structure of humic substances has determined their widespread use in many economic sectors, including medicine. Thanks to modern advances in pharmaceuticals, pharmacology, and toxicology, it has been possible to demonstrate the multifaceted biological activity of humic substances and, consequently, the possibility of using them to treat and prevent many infectious and non-infectious pathologies, including diseases considered incurable. The article presents data on their immunotropic, antibacterial, antiviral (including HIV), antitumor, antioxidant and antiradical, cardiotropic, hepatoprotective, regenerative, detoxifying, and adaptogenic effects; their influence on the intestinal microbiome; studies of the toxic properties of humic substances and the safety of their use in medicine; and the current trend of using humic substances as unique matrices for creating next-generation bionanomaterials. An analysis of data on the intracellular mechanisms that play a key role in the implementation of the effects of humic substances is conducted. Thus, the natural genesis of humic substances, their multifaceted biological activity, and the absence of toxic and allergenic properties explain the growing interest of scientists from all over the world in their study.}, } @article {pmid41515284, year = {2026}, author = {Curca, FR and Luchian, I and Bida, FC and Virvescu, DI and Rotundu, G and Butnaru, OM and Balan, G and Surlari, Z and Georgescu, A and Pasarin, L and Budala, DG}, title = {From Diet to Oral and Periodontal Health: Exploring the Crucial Role of Nutrition-A Narrative Review.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515284}, issn = {2072-6643}, mesh = {Humans ; *Oral Health ; *Periodontal Diseases/prevention & control/etiology ; *Diet/adverse effects ; *Nutritional Status ; Microbiota ; Dental Caries/etiology ; Feeding Behavior ; Dysbiosis ; Inflammation ; }, abstract = {Background: The growing body of evidence linking dietary factors to oral and periodontal health is characterized by substantial heterogeneity in study design, dietary assessment methods, and reported outcomes, warranting a comprehensive narrative synthesis. Diet is a key determinant of oral and periodontal health, influencing inflammation, oxidative stress, salivary composition, and the oral microbiome. Objectives: This narrative review aims to synthesize current clinical, epidemiological, and mechanistic evidence on how dietary patterns and specific nutrients affect oral and periodontal health, focusing on inflammatory pathways, microbiome modulation, nutrient-dependent tissue mechanisms, and clinical outcomes. Methods: A structured narrative search was conducted in PubMed, Scopus, Web of Science, and Google Scholar (2000-2025). Studies examining diet, nutrients, the oral microbiome, caries, gingival inflammation, or periodontal disease were screened through a multistep process, resulting in 98 included articles. Results: High-sugar and ultra-processed diets trigger inflammation and oral dysbiosis, increasing caries and periodontal susceptibility. In contrast, nutrient-rich and anti-inflammatory diets improve immune regulation, support microbial balance, and are associated with better periodontal parameters. Conclusions: Dietary habits significantly shape oral and periodontal outcomes through interconnected metabolic, microbial, and immunological pathways. Integrating targeted nutritional counseling into dental care may strengthen prevention strategies and improve long-term oral health.}, } @article {pmid41515276, year = {2026}, author = {Kowalczewski, PŁ and Gumienna, M and Jeżowski, P and Świątek, M and Górna-Szweda, B and Rybicka, I and Ruszkowska, M and Kluz, MI and Bordiga, M}, title = {Potato Protein-Based Vegan Burgers: Discovering the Health-Promoting Benefits and Impact on the Intestinal Microbiome.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515276}, issn = {2072-6643}, support = {LIDER/27/0105/L-11/19/NCBR/2020//National Centre for Research and Development/ ; }, mesh = {Humans ; *Solanum tuberosum/chemistry ; *Gastrointestinal Microbiome/drug effects ; Caco-2 Cells ; HT29 Cells ; *Plant Proteins/pharmacology ; *Diet, Vegan ; Dietary Fiber/analysis ; Nutritive Value ; Glucuronidase/metabolism ; Digestion ; }, abstract = {INTRODUCTION: The increasing global interest in plant-based diets has led to the development of innovative meat analogs that not only mimic the sensory properties of traditional products but may also offer potential health benefits. In this study, we investigated the nutritional characteristics and biological activity of potato protein-based vegan burgers (PBBs) enriched with plant-derived iron and fiber sources.

METHODS: The burgers were subjected to in vitro gastrointestinal digestion, followed by evaluation of their cytotoxic potential against human intestinal cancer cell lines (Caco-2 and HT-29) and normal colon epithelial cells (CCD 841 CoN). Additionally, their influence on the intestinal microbiota composition and enzymatic activity of β-glucosidase and β-glucuronidase was assessed.

RESULTS: PBBs demonstrated favorable nutritional profiles, high protein and fiber contents, and a balanced fatty acid ratio (n-6/n-3). After digestion, bioaccessible fractions showed selective cytotoxicity toward cancer cells, while maintaining safety for normal intestinal cells. Furthermore, PBBs modulated the gut microbiota by promoting the growth of beneficial genera (Lactobacillus, Bifidobacterium) and reducing potentially harmful Enterobacteriaceae, accompanied by decreased β-glucuronidase activity.

CONCLUSIONS: These findings suggest that potato protein-based burgers could represent a functional plant-based alternative to conventional meat products, contributing to intestinal health and potentially reducing colorectal cancer risk.}, } @article {pmid41515254, year = {2026}, author = {Sujani, S and Czerwinski, KJ and Savaiano, DA}, title = {A Narrative Review: A1 and A2 Milk Beta Caseins Effect on Gut Microbiota.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515254}, issn = {2072-6643}, support = {F.90029218.06.002//a2 milk company/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Milk/chemistry ; Animals ; *Caseins/pharmacology ; Dysbiosis ; }, abstract = {Background/Objectives: The composition and function of gut microbiome is significantly influenced by dietary factors. Growing evidence suggests that A1-type and A2-type beta casein (β-CN) may exert distinct effects on the gut environment, with implications for digestive discomfort and broader health outcomes. This review summarizes current evidence on how milk-derived A1 and A2 β-CN affect the gut microbiota. Methods: We conducted a literature search using PubMed, Web of Science, and Scopus to identify studies examining effects of milk β-CN on gut microbiota. Results: A total of eight studies were included. Results show inconsistencies within the limited number of studies. However, compared to A2, A1 β-CN was more frequently associated with dysbiosis and an increased abundance of potentially pathogenic species. Conversely, A2 β-CN promoted microbial diversity, which is linked to improved gut integrity and metabolic health. Conclusions: These findings suggest that β-CN variants distinctly influence the gut microbiota composition, and results were more significant in immunosuppressed subjects or those with other underlying health conditions, indicating that dairy products rich in A2 β-CN may offer advantages in personalized dietary management. However, well-designed human studies are essential to translate findings from rodent models to clinically relevant outcomes and future research should focus on mechanistic exploration and population-specific responses.}, } @article {pmid41515240, year = {2025}, author = {Dong, X and Lin, L and Miao, W and Zhai, Z and Hao, Y and Zhang, M and Wang, R and Ge, S and Zhang, H and Ai, L and Zhao, L}, title = {Subcellular Localization Dictates Therapeutic Function: Spatially Targeted Delivery of Amuc_1100 by Engineered Lacticaseibacillus paracasei L9 Enhances Intestinal Barrier in Colitis.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515240}, issn = {2072-6643}, mesh = {Animals ; *Colitis/chemically induced/therapy/microbiology/drug therapy ; Mice ; *Probiotics/administration & dosage ; *Intestinal Mucosa/metabolism/microbiology ; *Lacticaseibacillus paracasei/genetics/metabolism ; Disease Models, Animal ; Macrophages/metabolism ; Mice, Inbred C57BL ; Cytokines/metabolism ; Dextran Sulfate ; Akkermansia ; }, abstract = {Background/Objectives: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). Akkermansia muciniphila and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic Lacticaseibacillus paracasei L9 for targeted Amuc_1100 delivery. Methods: We engineered Lc. paracasei L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrity, and mucosal repair. Results: The secretory (pUA-L9) and surface-display (pUPA-L9) strains most effectively suppressed pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in macrophages. In mice, both strains alleviated colitis and outperformed native A. muciniphila in improving disease activity. Crucially, they exhibited distinct, specialized functions: pUA-L9 acted as a systemic immunomodulator, reducing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), elevating anti-inflammatory mediators (IL-4 and IL-10), and promoting goblet cell differentiation; notably, the inhibitory effect of pUA-L9 on IL-6 expression was approximately 2-fold greater than that of pUPA-L9. In contrast, pUPA-L9 excelled in local barrier repair, uniquely restoring mucus layer integrity (Muc1, Muc2, and Tff3) and reinforcing tight junctions (ZO-1, Occludin, Claudin1, Claudin3, and Claudin4). In particular, pUPA-L9 increased Muc2 expression by approximately 3.6-fold compared with pUA-L9. Conclusions: We demonstrate that the subcellular localization of Amuc_1100 within an engineered probiotic dictates its therapeutic mode of action. The complementary effects of secretory and surface-displayed Amuc_1100 offer a novel, spatially targeted strategy for precision microbiome therapy in IBD.}, } @article {pmid41515223, year = {2025}, author = {Liu, Q and Gu, W and Ma, J and Wang, J and Yu, M and Xu, M and Wang, S}, title = {A Pilot Randomized Controlled Trial and Multi-Omics Analysis of Electrolysed Alkaline Water: Impacts on Gut Microbiota and Metabolic Signatures in Hyperuricemia.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515223}, issn = {2072-6643}, support = {NA//Shanghai Kangshi Food Technology Co., Ltd., Shanghai 201103, China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Adult ; Female ; Middle Aged ; *Hyperuricemia/therapy/microbiology/metabolism/blood ; Pilot Projects ; Aged ; Quality of Life ; Young Adult ; Uric Acid/blood ; *Drinking Water/chemistry ; Adolescent ; Metabolomics ; China ; *Metabolome ; Multiomics ; }, abstract = {Background/Objectives: Hyperuricemia (HUA) is the second most common metabolic disease in China (24.5% in males, 3.6% in females), which can induce multiple complications such as gout and diabetes. Existing urate-lowering drugs have significant hepatorenal toxicity, necessitating safe lifestyle interventions. Electrolyzed alkaline water (EAW) as daily drinking water has shown preliminary effectiveness, but it lacks randomized controlled evidence and mechanistic studies at the microbiome-metabolome interface. Methods: We conducted a 12-week randomized controlled trial in 40 adults aged 18-65 years with elevated serum uric acid (SUA). Participants consumed either 1.5 L/day of EAW (pH 8.5-9.5) or purified water (pH 7.0). Clinical indicators, quality of life (SF-36), gut microbiota, and gut metabolomics were comprehensively assessed to evaluate intervention efficacy and explore potential mechanisms. Results: After 12 weeks, the EAW group exhibited a larger reduction in serum uric acid than the control group, along with improvements in selected physical health-related quality-of-life measures. Modest differences in gut microbial composition were observed between groups. Metabolomic analyses identified group-level differences in metabolites enriched in pathways related to purine metabolism and other urate-associated metabolic processes. Conclusions: This pilot randomized controlled trial suggests that consumption of EAW is associated with a modest reduction in serum uric acid. Exploratory multi-omics analyses indicate concurrent changes in gut microbiota and metabolic profiles. These findings support further investigation of electrolyzed alkaline water as a potential adjunctive, non-pharmacological option for hyperuricemia in larger and longer-term studies. Ethics: This trial was registered with the Chinese Clinical Trial Registry under the identifier ChiCTR2500100190. Ethical approval for the present study was granted by the Nankai University Institutional Review Board (NKUIRB2025001, 23 January 2025).}, } @article {pmid41515213, year = {2025}, author = {Marano, G and Traversi, G and Mazza, O and Caroppo, E and Capristo, E and Gaetani, E and Mazza, M}, title = {The Immune Mind: Linking Dietary Patterns, Microbiota, and Psychological Health.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515213}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Diet, Mediterranean/psychology ; *Depression/immunology ; *Mental Health ; Probiotics/administration & dosage ; Anxiety/immunology ; Prebiotics/administration & dosage ; Adult ; *Diet ; }, abstract = {Background/Objectives: Nutritional patterns influence the gut-brain axis and immune signaling with potential consequences for depression and anxiety. We conducted a review focused on clinically meaningful psychiatric outcomes (symptom severity/diagnosis) to synthesize recent evidence (2020-2025) on Mediterranean-style dietary interventions; ultra-processed food (UPF) exposure; and psychobiotic/prebiotic strategies, integrating mechanistic insights relevant to practice. Methods: Searches in PubMed/MEDLINE, Scopus, and Web of Science (January 2020-October 2025) combined terms for diet, Mediterranean diet (MD), UPF, microbiota, probiotics, psychobiotics, depression, and anxiety. Eligible designs were randomized/controlled trials (RCTs), prospective cohorts, and systematic reviews/meta-analyses reporting clinical psychiatric outcomes in adults. We prioritized high-quality quantitative syntheses and recent RCTs; data were extracted into a prespecified matrix and synthesized narratively. Results: Recent systematic reviews/meta-analyses support that MD interventions reduce depressive symptoms in adults with major or subthreshold depression, although large, long-term, multicenter RCTs remain a gap. Exposure to UPF is consistently associated with higher risk of common mental disorders and depressive outcomes in large prospective cohorts. Psychobiotics (specific probiotic strains and prebiotics) show small-to-moderate benefits on depressive symptoms across clinical and nonclinical samples, with heterogeneity in strains, dosing, and duration. Mechanistic reviews implicate microbiota-derived metabolites (short-chain fatty acids) and immune-inflammatory signaling (including tryptophan-kynurenine pathways) as plausible mediators. Conclusions: Clinically, emphasizing Mediterranean-style dietary patterns, reducing UPF intake, and considering targeted psychobiotics may complement standard psychiatric care for depression. Future work should prioritize adequately powered, longer RCTs with standardized dietary protocols and microbiome-informed stratification to clarify responders and mechanisms.}, } @article {pmid41515205, year = {2025}, author = {Nikolaidis, CG and Gyriki, D and Stavropoulou, E and Karlafti, E and Didangelos, T and Tsigalou, C and Thanopoulou, A}, title = {Modulating the Gut Microbiome in Type 2 Diabetes: Nutritional and Therapeutic Strategies.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515205}, issn = {2072-6643}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/therapy/diet therapy ; *Gastrointestinal Microbiome/physiology ; Probiotics/administration & dosage/therapeutic use ; Prebiotics/administration & dosage ; Dysbiosis/therapy/microbiology ; Animals ; Synbiotics/administration & dosage ; Blood Glucose/metabolism ; }, abstract = {Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder influenced not only by genetics, diet, and lifestyle but also by the gut microbiota. Dysbiosis (imbalances in microbial composition) can disrupt gut barrier integrity, alter microbial metabolites, and trigger low-grade inflammation, contributing to insulin resistance and β-cell dysfunction. Nutritional interventions, such as probiotics, prebiotics, synbiotics, postbiotics, and bioactive food components, represent potential therapeutic approaches for ameliorating gut eubiosis and advancing glycemic regulation. This narrative review incorporates evidence from selected studies identified by searches in PubMed, Scopus, and Google Scholar for studies published up to November 2025. The methodology included a structured literature search of in vitro, animal, and human studies, with a focus on intervention trials and mechanistic research. There are many positive signals from randomized controlled trials (RCTs), but heterogeneity and short follow-up limit definitive recommendations. Evidence from clinical and experimental studies indicates a beneficial effect on fasting glucose, hemoglobin A1c, and inflammatory markers, though heterogeneity of the individual and the variability in study designs limit generalization. There is insufficient evidence to recommend microbiota modulation as standard therapy in any disease. Key knowledge gaps include standardized interventions, stratified analyses by medication use (e.g., metformin), clinically meaningful endpoints, and long-term safety data. This review summarizes current knowledge on gut microbiota-driven mechanisms in T2DM and evaluates emerging microbiota-targeted therapies as adjunctive strategies for metabolic improvement.}, } @article {pmid41515177, year = {2025}, author = {Odriozola, A and González, A and Odriozola, I and Corbi, F and Álvarez-Herms, J}, title = {Thyroid-Microbiome Allostasis and Mitochondrial Performance: An Integrative Perspective in Exercise Physiology.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515177}, issn = {2072-6643}, mesh = {Humans ; *Exercise/physiology ; *Thyroid Gland/physiology/metabolism ; *Mitochondria/physiology/metabolism ; *Allostasis/physiology ; *Microbiota/physiology ; Thyroid Hormones/metabolism ; }, abstract = {Exercise acts as a physiological stimulus, requiring precise coordination among endocrine, microbial, and mitochondrial systems to maintain metabolic stability through allostatic regulation. The goal of the article is to integrate multidisciplinary evidence to characterize the thyroid-microbiome-mitochondrial axis as a key regulator of the allostatic state in athletic physiological response. During acute, chronic, and overload training phases, the thyroid-microbiome-mitochondrial axis operates bidirectionally, coupling microbial signaling with endocrine and mitochondrial networks to mediate metabolic response to exercise. This response shows interindividual variability driven by sex, age, genetics, and nutritional status, shaping the boundaries between adaptive efficiency and allostatic overload. Microbial metabolites, such as short-chain fatty acids (SCFA) and secondary bile acids, modulate deiodinase activity, bile acid recycling, and mitochondrial biogenesis through AMPK-SIRT1-PGC1α signaling, optimizing substrate use and thermogenic capacity. Thyroid hormones reciprocally regulate gut motility, luminal pH, and bile secretion, maintaining microbial diversity and mineral absorption. Under excessive training load, caloric restriction, or inadequate recovery, this network becomes transiently unbalanced: SCFA synthesis decreases, D3 activity increases, and a reversible low-T3/high-rT3 pattern emerges, resembling early Hashimoto- or Graves-like responses. Selenium-, zinc-, and iron-dependent enzymes form the redox link between microbial metabolism, thyroid control, and mitochondrial defense. In conclusion, the thyroid-microbiome-mitochondrial axis provides the physiological basis for the allostatic state, a reversible phase of dynamic recalibration that integrates training, nutrition, environmental stress, and circadian cues to sustain thyroid activity, mitochondrial efficiency, and microbial balance. This integrative perspective supports precision interventions to optimize recovery and performance in athletes.}, } @article {pmid41515166, year = {2025}, author = {Stavrou, G and Menni, AE and Kotzampassi, K}, title = {Probiotics at the Frontline: Redefining Therapeutic Possibilities.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515166}, issn = {2072-6643}, mesh = {*Probiotics/therapeutic use ; Humans ; *Gastrointestinal Microbiome ; }, abstract = {Recently, advances in microbiome research have emphasized the fundamental role of probiotics-in addition to their inanimate form, postbiotics, and psychobiotics, a rapidly expanding group of probiotics with psychotropic potential [...].}, } @article {pmid41515159, year = {2025}, author = {Robert, M and Saha, S and Dizman, N and Rohlfs, M and Sirmans, E and Simon, J and Amaria, RN and Glitza Oliva, IC and Tawbi, HA and Davies, MA and Ikeguchi, A and Basen-Engquist, K and Schadler, K and Roth, ME and Song, W and Zhang, X and Ajami, NJ and Cohen, L and Wargo, JA and Peterson, CB and McQuade, JL and Daniel, CR}, title = {Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes and the Microbiome in Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515159}, issn = {2072-6643}, support = {na/MRA/Melanoma Research Alliance/United States ; na//Andrew Sabin Family Fellowship/ ; na//MD Anderson Melanoma Moon Shot/ ; 1P30CA016672/NH/NIH HHS/United States ; 1R01CA291965/NH/NIH HHS/United States ; 1P50CA221703/NH/NIH HHS/United States ; 1R01HL158796/NH/NIH HHS/United States ; }, mesh = {Humans ; *Melanoma/therapy/drug therapy/psychology ; Male ; Female ; Middle Aged ; *Gastrointestinal Microbiome ; *Patient Reported Outcome Measures ; *Cancer Survivors/psychology ; *Diet ; Aged ; Adult ; *Immunotherapy/adverse effects ; Quality of Life ; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use ; Depression ; Anxiety ; Prospective Studies ; Exercise ; }, abstract = {Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma. Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening questionnaires for depression, anxiety, diet and physical activity. The gut microbiome was characterized via metagenomic sequencing in a subsample (n = 39). Patients' clinicopathological characteristics and experience of irAEs (during treatment) and CT (persisting >6 months after completion of therapy) were extracted retrospectively from the medical record. Results: In the overall cohort, 60% were experiencing CT, while 16% and 20% reported clinically relevant levels of depression and anxiety symptoms, respectively. We observed significant differences in overall gut microbiome composition between survivors with and without CT (p = 0.02). Consumption of fruit and vegetables was inversely associated with anxiety (ρ = 0.3, p = 0.038). Added sugar consumption was correlated with the severity of experienced symptoms (ρ = 0.4, p = 0.003), with pronounced associations across the spectrum of symptoms, including pain, fatigue and shortness of breath (p < 0.05). Conclusions: These results suggest that CT is experienced by a substantial proportion of ICB-treated metastatic melanoma survivors. Patients experiencing CT also showed distinct microbiome features. However, additional research in prospective settings is needed to confirm these hypotheses.}, } @article {pmid41515150, year = {2025}, author = {Tonacci, A and Gorini, F}, title = {Sensory Characteristics of Probiotic-Containing Foods: A Multidisciplinary Perspective on Enhancing Acceptability and Consumer Adherence.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515150}, issn = {2072-6643}, mesh = {*Probiotics ; Humans ; *Consumer Behavior ; *Taste ; Gastrointestinal Microbiome ; *Food Preferences ; }, abstract = {Globally, the consumption of foods containing probiotics has increased significantly due to their well-recognized health benefits, including the modulation of gut microbiota and immune function. However, despite strong scientific support, daily massive adherence to probiotic food remains limited, mainly because of their suboptimal sensory appeal and the huge variability in consumer expectations. Sensory attributes-flavor, aroma, texture, and appearance-strongly influence liking, purchase, and the habitual consumption necessary for probiotics to exert the physiological effects for which they are consumed. The present narrative review explores the complex, multidimensional interplay between sensory features, consumer perception, and probiotic efficacy. By integrating evidence from nutritional science, microbiology, sensory science, and behavioral psychology, we outline how technological innovation and sensory optimization can improve both product acceptability and adherence. We also discuss how cross-modal perception, the cultural framework, and labeling influence hedonic responses. Finally, we highlight emerging directions, such as sensory-driven strain selection, omics-based flavor profiling, and personalized sensory nutrition, as tools to bridge the gap between scientific efficacy and consumer satisfaction. Improving the sensory design of probiotic foods is pivotal to translate microbiome science into meaningful, sustainable dietary behaviors that support the nutrition-gut-immunity axis.}, } @article {pmid41515148, year = {2025}, author = {Kowalcze, K and Dyńka, D and Klus, W and Dudzińska, M and Paziewska, A}, title = {Modulation of Gut Microbiome and Metabolome as One of the Potential Mechanisms of Ketogenic Diet Effect in the Treatment of Epilepsy.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515148}, issn = {2072-6643}, support = {xxx//University of Siedlce/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Diet, Ketogenic ; Humans ; *Epilepsy/diet therapy/microbiology/metabolism ; *Metabolome ; Animals ; Fatty Acids, Volatile/metabolism ; Dysbiosis ; }, abstract = {BACKGROUND/OBJECTIVES: The over 100-year-old practice of using ketogenic diet (KD) in the treatment of epilepsy has consolidated its position as an effective therapeutic tool. The available publications suggest a significant influence of KD on gut microbiome and metabolome and, on the other hand, a correlation between microbiome and metabolome changes and the course of epilepsy. The conclusion is therefore justified that KD can exert a therapeutic effect in epilepsy through the mechanism of gut microbiome and metabolome modulation.

METHODS: This article is a narrative review aimed at a comprehensive analysis of the literature to gather existing evidence on the relationship between ketogenic diet, its antiepileptic effects and modulation of gut microbiome and metabolome.

RESULTS: It has been demonstrated that a ketogenic diet exerts a significant effect on intestinal bacteria and their metabolites, among other actions, increasing the Bacteroides to Firmicutes (B/F) ratio, alleviating dysbiosis, reducing the inflammatory condition in the gut and whole body, increasing the number of specific strains associated with antiepileptic effect, mediating the production of neurotransmitters (GABA, serotonin), exerting influence on the dopaminergic system, on a number of metabolic pathways, on inhibition of genotoxicity and production of short-chain fatty acids (SCFA) in the intestine.

CONCLUSIONS: Further studies are needed, since the effect of KD on gut microbiome and metabolome modulation in the treatment of epilepsy is an extremely promising and trendsetting direction of research.}, } @article {pmid41515128, year = {2025}, author = {Juhl, AE and Westfall, M and Hebbelstrup Jensen, B and Mirsepasi-Lauridsen, HC}, title = {Gut Microbiota in IBD: The Beneficial and Adverse Effects of Diet and Medication.}, journal = {Nutrients}, volume = {18}, number = {1}, pages = {}, pmid = {41515128}, issn = {2072-6643}, support = {4289-00312B//Innovation fonden/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/microbiology/drug therapy/diet therapy/therapy ; *Diet/adverse effects ; Probiotics/therapeutic use ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; Crohn Disease/microbiology/drug therapy ; Diet, Western/adverse effects ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a global disease with a considerable increase in prevalence and the impact on the health and well-being of patients suffering from this condition is vast. Diet has been suspected of being a contributor to IBD severity as well as intake of antibiotics.

METHODS: A literary search was conducted on the most recent studies on the subject of IBD, diet, and medical treatment to identify high-quality research findings within this area of research. Research published within the last decade was prioritized. Studies in English language were included in the search, and the knowledge gained was synthesized in the review.

RESULTS: Dietary patterns, specifically intake of Westernized diets, were associated with increased inflammation and increased disease severity in patients suffering from IBD, specifically patients suffering from Crohn's disease (CD). A co-administration of pre- and probiotics was found to contribute to disease remission in ulcerative colitis patients, however, to a lesser extent in patients with CD. A bidirectional effect on the intestinal microbiome was seen as a result of intake of the medicines used for the treatment of IBD patients, which affects both bioavailability of the drug and efficacy of the treatment. The baseline composition of the intestinal microbiome in IBD patients dictates their response to the different treatments.

CONCLUSIONS: Diet and medical treatment both have a large impact on the architecture of the intestinal Microbiome in IBD patients and are, as such, both essential to understand to enable individualized and optimized treatment.}, } @article {pmid41515107, year = {2026}, author = {Thomaidis, G and Boutzikas, G and Alexopoulos, A and Zamioudis, C}, title = {Phylogenetic Divergence and Domestication Jointly Shape the Tomato Root Microbiome.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41515107}, issn = {2223-7747}, support = {3082//Hellenic Foundation for Research and Innovation (H.F.R.I.) under the "2nd Call for H.F.R.I. Research Projects to support Faculty Members & Researchers"/ ; }, abstract = {Domestication reduced the genetic diversity in modern crops, often resulting in reduced resilience to biotic and abiotic stress. Evidence is now accumulating that domestication also altered the structure and function of root-associated microbiomes, creating new opportunities to harness beneficial microbes for breeding and crop improvement. Using multi-region 16S rRNA sequencing, we compared the rhizosphere and endosphere bacterial communities of cultivated tomato (Solanum lycopersicum cv. Moneymaker) with six wild relatives (S. pimpinellifolium, S. huaylasense, S. peruvianum, S. chilense, S. habrochaites, and S. pennellii) spanning the main wild lineages within Solanum sect. Lycopersicon. Bacterial community structure in the rhizosphere was broadly conserved across all seven hosts, and diversity remained comparable among genotypes. Despite this overall stability, the rhizosphere microbiomes were ordered along a gradient consistent with host phylogeny, with Moneymaker clustering near S. pimpinellifolium, the four green-fruited Eriopersicon species forming a cohesive block, and S. pennellii occupying the most distinct position. Within this hierarchy, individual hosts showed specific recruitment preferences, including enrichment of Streptomycetaceae in S. pimpinellifolium, Bacillaceae in S. chilense, and contrasting patterns of nitrifiers among Eriopersicon species and S. pennellii. Differential abundance testing in the endosphere revealed consistent reductions in several bacterial families in wild accessions, alongside the enrichment of Streptomycetaceae and Rhodobiaceae in multiple wild species. Overall, our study suggests that domestication exerted a modest effect on tomato root microbiomes, while wild relatives retained microbial association traits that could be harnessed in microbiome-informed breeding to improve resilience in cultivated tomato.}, } @article {pmid41515088, year = {2026}, author = {Durán-Sequeda, DE and Soto-Valera, ZE and Pizarro Castañeda, R and Torres, MJ and Tobias, LS and Vergel, C and Quintero Linero, AP and Bolívar-Anillo, HJ and Amils, R and Iglesias-Navas, MA}, title = {Increased Drought Stress Tolerance in Maize Seeds by Bacillus paralicheniformis Halotolerant Endophytes Isolated from Avicennia germinans.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41515088}, issn = {2223-7747}, support = {BPIN 2022000100074//Sistema General de Regalias (SGR) de Colombia/ ; }, abstract = {Avicennia germinans, a representative of the marine coastal mangrove ecosystem, vital in the Colombian Caribbean, harbors a unique microbial diversity that could contain microorganisms with the potential to promote plant growth of agricultural species such as maize. The objective of this research was to evaluate A. germinans endophytes at different sampling sites and in diverse plant organs in order to identify the growth-promoting role of the most sodium chloride-tolerant endophyte found. These were then inoculated in maize seeds under drought stress conditions simulated by polyethylene glycol (PEG) in vitro. To this end, samples of adult A. germinans plants were collected from four mangrove ecosystems in the Colombian Caribbean. Several isolates were able to tolerate up to 15% NaCl (w/v), produce indole-3-acetic acid (IAA), show proteolytic activity, and inhibit phytopathogenic fungi. The best-performing strain, C1T-KM1901-B, was genomically identified as Bacillus paralicheniformis and evaluated as a bioinoculant in maize seeds under PEG-induced drought stress. Inoculation with B. paralicheniformis significantly increased germination potential and germination index of drought-resistant seeds compared to non-inoculated controls under severe drought stress conditions (40% PEG). In addition, inoculated seedlings exhibited significantly higher roots and shoot fresh and dry biomass at moderate to severe drought stress levels (15% and 20% PEG). These results are position B. paralicheniformis C1T-KM1901-B, isolated from Avicennia germinans, as a promising bioinoculant to enhance maize establishment under drought conditions.}, } @article {pmid41515076, year = {2026}, author = {Cano-Serrano, S and Castelán-Sánchez, HG and Oyaregui-Cabrera, H and Hernández, LG and Pérez-Pérez, MC and Santoyo, G and Orozco-Mosqueda, MDC}, title = {Assessment of Bacterial Diversity and Rhizospheric Community Shifts in Maize (Zea mays L.) Grown in Soils with Contrasting Productivity Levels.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/plants15010130}, pmid = {41515076}, issn = {2223-7747}, support = {2024-2025//CIC-UMSNH/ ; }, abstract = {The resident microbiota in agricultural soils strongly influences crop health and productivity. In this study, we evaluated the prokaryotic diversity of two clay soils with similar physicochemical characteristics but contrasting levels of maize (Zea mays L.) and wheat (Triticum aestivum L.) production using 16S rRNA gene sequencing. Yield records showed significant differences in grain production over five consecutive years. When comparing prokaryotic alpha diversity between the "non-productive" and "productive" soils, no major differences were found, and the abundance of ammonia-oxidizing archaea (AOA) and bacterial genera such as Arthrobacter, Neobacillus, and Microvirga remained consistent across soils. Analysis of the top 20 genera showing the greatest abundance shifts by compartment (bulk soil vs. rhizosphere) revealed that genera such as Priestia, Neobacillus, Sporosarcina, and Pontibacter decreased in the rhizosphere of the non-productive soil, while in the productive soil, these genera remained unchanged. In the non-productive soil, genera such as Flavisobacter decreased in abundance in the rhizosphere, whereas Arthrobacter increased. Principal coordinates analysis (PCoA) showed no clear clustering by compartment (bulk vs. rhizosphere), but two distinct clusters emerged when grouping by soil type (productive vs. non-productive). Interaction networks varied by soil type: non-productive soils showed positive Candidatus-Bacillus and negative Massilia links, while productive soils were dominated by Flavisolibacter and negative Pontibacter. Across soils, Rhizobium-Bradyrhizobium associations were positive, whereas Neobacillus and Priestia were negative. These findings highlight that a few potential beneficial microbiota and their interactions may be key drivers of soil productivity, representing targets for microbiome-based agricultural management.}, } @article {pmid41515075, year = {2026}, author = {Seemakram, W and Suebrasri, T and Chankaew, S and Boonlue, S}, title = {Influence of Arbuscular Mycorrhizal Fungi on Soybean Growth and Yield: A Metabarcoding Approach.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/plants15010131}, pmid = {41515075}, issn = {2223-7747}, support = {grant number B13F680065//the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation/ ; }, abstract = {This study evaluated the efficiency of arbuscular mycorrhizal fungi (AMF) in promoting the growth, yield, protein, and phytochemical contents of Glycine max cv. Morkhor 60. A completely randomized pot experiment was conducted for 90 days in non-sterile soil with nine replications. Three AMF species were tested and compared with two non-mycorrhizal controls, with and without NPK fertilizer. All AMF treatments enhanced plant growth, photosynthetic rate, and water-use efficiency compared with the unfertilized control. Inoculation with Acaulospora dilatata KKU-SK202 produced the highest pod number and increased 100-seed weight by 27.00% and 4.13% over the non-inoculated and NPK treatments, respectively. Gigaspora margarita KKU-SK210 yielded the highest total protein and phenolic contents, while A. dilatata KKU-SK401 showed the highest antioxidant activity (72.09%). Metabarcoding analysis revealed that AMF inoculation reduced root colonization by pathogenic fungi, with G. margarita KKU-SK210 and A. dilatata KKU-SK202 being the most effective. These results suggest that AMF inoculation can enhance soybean productivity and seed quality while reducing chemical fertilizer dependency and pathogenic fungal incidence.}, } @article {pmid41515021, year = {2025}, author = {Teng, Y and Yin, C and Xu, F and Chen, J and Wu, Q and Ye, M and Liu, Y and Zhu, K}, title = {Citrus Genotype Modulates Rhizosphere Microbiome Structure and Function Under Drought Stress.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/plants15010077}, pmid = {41515021}, issn = {2223-7747}, support = {KJQN202303518//Science and Technology Research of Chongqing Municipal Education Commission/ ; sxzybs-202201//Research Initiation Project for Doctor Recruitment of Chongqing Three Gorges Vocational College/ ; 32201766//National Natural Science Foundation of China/ ; }, abstract = {Drought stress substantially impairs citrus growth and alters the rhizosphere microbial composition; however, the role of these microbial communities in plant drought tolerance remains poorly understood. This study investigated the rhizosphere microbial structure, soil enzymatic activities, and physicochemical properties of drought-tolerant (DR) and drought-sensitive (DS) citrus varieties under drought stress conditions. High-throughput sequencing revealed that drought significantly altered microbial community composition, reducing the bacterial Shannon diversity by about 15% and enriching Gram-negative, stress-tolerant, and potentially pathogenic bacteria, as well as plant pathogenic fungi (upregulated 25.4% in DS), while reducing undefined saprotrophs (downregulated from 76.2 to 54.0% in DS). Notably, the DR variety exhibited a more stable and complex bacterial network, with 23.5% more edges and a higher proportion of positive correlations (54.3%), higher enrichment of beneficial fungi like Penicillium and Trichoderma, and unique recruitment of mycorrhizal fungi (up to 10.2%), which were nearly absent in DS. Furthermore, soil catalase and urease activities decreased under drought stress conditions. In contrast, acid phosphatase activity increased by up to 40% in DR. Correlation analyses indicated that these microbial shifts were closely associated with changes in soil nutrient availability. Our findings demonstrated that the drought-tolerant citrus variety modulates its rhizosphere microbiome towards a more cooperative and resilient state, highlighting the critical role of host-specific microbial recruitment in enhancing plant adaptation to drought stress for sustainable agriculture.}, } @article {pmid41514971, year = {2025}, author = {Wang, Q and Huang, J and Zhang, Y and Li, Z and Wei, L and Yin, X and Zhang, X and Zhou, Y}, title = {Long-Term Excess Nitrogen Fertilizer Reduces Sorghum Yield by Affecting Soil Bacterial Community.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/plants15010025}, pmid = {41514971}, issn = {2223-7747}, support = {the Natural Science Foundation of Chongqing (CSTB2024NSCQ-MSX0836) the Chongqing Research Institute Performance Incentive Guide Project (cstc2022jxjl80016, cqaas2020jxjl03) the Chongqing Technology Innovation and Application Development Project (cstc2019j//The research was supported by the Natural Science Foundation of Chongqing (CSTB2024NSCQ-MSX0836), the Chongqing Research Institute Performance Incentive Guide Project (cstc2022jxjl80016, cqaas2020jxjl03), and the Chongqing Technology Innovation and Ap-pli/ ; }, abstract = {The application of nitrogen (N) fertilizer is one of the most important measures to affect crop yield and soil bacterial communities. In this study, the four rates of N (namely N0F 0 kg N ha[-1], N1F 90 kg N ha[-1], N2F 180 kg N ha[-1], and N3F 270 kg N ha[-1]) along with a control (no fertilization, CK) were evaluated for their influence on sorghum yield, soil chemical properties, bacterial community, and diversity. The results showed that the yield-increasing effect was reduced by the higher dose of N input. Compared with N0F, sorghum yield increased by 58.8% in N1F and 68.2% in N2F but decreased by 8.1% in N3F relative to N2F. The soil pH decreased significantly with increasing N application. Compared with CK or N0F, N3F treatment increased the available P content by up to 18.6% or 32.2% but decreased the alkaline hydrolysis N, available K, organic matter, and total N contents by 8.4% or 23.8%, 5.5% or 10.6%, 8.4% or 28.8%, and 11.1% or 39.6%, respectively. In addition, different fertilization treatments altered the soil bacterial communities. Excess N fertilizer led to a decrease in bacterial abundance, and compared with N0F, the absolute abundance of bacteria increased by 18.7% in N1F, while it decreased by 31.8% in N3F. The predominant phyla, including Acidobacteria, Proteobacteria, and Chloroflexi, in the microbiome shift under different N application levels. The redundancy analysis (RDA) and Pearson's correlation analyses indicated that the soil properties, especially soil pH, available P, total P, total N, and organic matter, were the key environmental factors that defined the bacterial community in the ecosystem. Within the scope of the present experiment, N application at 90 kg N ha[-1] (N1F) optimized soil bacterial community abundance in sorghum-cultivated soil, while N2F (180 kg N ha[-1]) achieved the highest sorghum yield, suggesting a trade-off between optimizing the soil microbiome and maximizing crop yield under long-term fertilization.}, } @article {pmid41514963, year = {2025}, author = {Yoshioka, H and Morota, G and Iwata, H}, title = {Reciprocal BLUP: A Predictability-Guided Multi-Omics Framework for Plant Phenotype Prediction.}, journal = {Plants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/plants15010017}, pmid = {41514963}, issn = {2223-7747}, support = {JP23KJ0506//Japan Society for the Promotion of Science/ ; JP22K21352//Japan Society for the Promotion of Science/ ; JPMJCR16O2//Japan Science and Technology Agency/ ; JPMJAN23D1//Japan Science and Technology Agency/ ; }, abstract = {Sustainable improvement of crop performance requires integrative approaches that link genomic variation to phenotypic expression through intermediate molecular pathways. Here, we present Reciprocal Best Linear Unbiased Prediction (Reciprocal BLUP), a predictability-guided multi-omics framework that quantifies the cross-layer relationships among the genome, metabolome, and microbiome to enhance phenotype prediction. Using a panel of 198 soybean accessions grown under well-watered and drought conditions, we first evaluated four direction-specific prediction models (genome → microbiome, genome → metabolome, metabolome → microbiome, and microbiome → metabolome) to estimate the predictability of individual omics features. We evaluated whether subsets of features with high cross-omics predictability improved phenotype prediction. These cross-layer models identify features that play physiologically meaningful roles within multi-omics systems, enabling the prioritization of variables that capture coherent biological signals enriched with phenotype-relevant information. Consequently, metabolome features were highly predictable from microbiome data, whereas microbiome predictability from metabolomic data was weaker and more environmentally dependent, revealing an asymmetric relationship between these layers. In the subsequent phenotype prediction analysis, the model incorporating predictability-based feature selection substantially outperformed models using randomly selected features and achieved prediction accuracies comparable to those of the full-feature model. Under drought conditions, the phenotype prediction models based on metabolomic or microbiomic kernels (MetBLUP or MicroBLUP) outperformed the genomic baseline (GBLUP) for several biomass-related traits, indicating that the environment-responsive omics layers captured phenotypic variations that were not explained by additive genetic effects. Our results highlight the hierarchical interactions among genomic, metabolic, and microbial systems, with the metabolome functioning as an integrative mediator linking the genotype, environment, and microbiome composition. The Reciprocal BLUP framework provides a biologically interpretable and practical approach for integrating multi-omics data, improving phenotype prediction, and guiding omics-based feature selection in plant breeding.}, } @article {pmid41514871, year = {2025}, author = {Brajdic, L and Reed, EK and Pearson, HB and Brown, HL}, title = {Cutibacterium acnes: An Emerging Prostate Cancer Pathogen.}, journal = {Biology}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/biology15010030}, pmid = {41514871}, issn = {2079-7737}, support = {A27894/CRUK_/Cancer Research UK/United Kingdom ; 02-456679//Applied Microbiology International/ ; }, abstract = {Cutibacterium acnes (C. acnes) has emerged as a potential contributor to prostate cancer (PCa) pathogenesis, yet the mechanistic basis remains unclear. This review explores the prevalence, persistence and mechanistic impact of C. acnes within the prostate to help decipher the functional consequence and diagnostic value of a C. acnes infection in this setting. We examine the evidence supporting C. acnes colonisation of both premalignant and malignant tissue, and critically evaluate how prostate tumour physiology, particularly hypoxia and low pH, may facilitate microbial persistence. Emerging data suggest that C. acnes modulates inflammatory and immune pathways, influencing macrophage activation, cytokine production, and the regulation of immune checkpoints. Additionally, we discuss studies demonstrating its involvement in DNA damage, host cell metabolism, and extracellular matrix remodelling. The identification of C. acnes in urinary and gut microbiomes, alongside the presence of its genomic DNA in extracellular vesicles in circulation indicate broad diagnostic potential. While discrepancies in methodology have hampered a consensus, recent genomic and functional studies provide new avenues to distinguish contamination from true pathogenicity. Ultimately, future research exploring whether C. acnes is a biomarker, bystander, or bona fide driver of PCa, and its potential role in personalised diagnostics are crucial to advance the field and unravel the predictive and therapeutic value of C. acnes. Clarifying this relationship will advance our understanding of microbiome-cancer dynamics and could help inform innovative early detection and screening strategies that improve patient care.}, } @article {pmid41514803, year = {2025}, author = {Zhu, Y and Chai, Y and Chen, S and Qian, W and Si, H and Li, Z}, title = {Distinct Rumen Microbial Features and Host Metabolic Responses in Three Cervid Species.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/ani16010116}, pmid = {41514803}, issn = {2076-2615}, support = {2023YFD1302000//National Key Research and Development Program of China/ ; U24A20434//National Natural Science Foundation of China/ ; 20240101012JJ//Natural Science Foundation of Jilin Province/ ; }, abstract = {Rumen microbiota is pivotal for nutrient metabolism and physiological adaptation in ruminants. This study investigated the rumen microbial community, fermentation parameters, and serum biochemistry of three Cervid species-Sika deer (Cervus nippon), Reindeer (Rangifer tarandus), and Milu deer (Elaphurus davidianus) (n = 5/group)-fed an identical diet. Using 16S rRNA sequencing and biochemical analyses, we found that while Bacteroidota, Firmicutes, and Proteobacteria were dominant phyla across species. Sika deer and Milu deer exhibited significantly higher microbial diversity and abundance of carbohydrate-digesting genera (e.g., Butyrivibrio, Saccharofermentans), and pathways of carbohydrate digestion and absorption, starch and sucrose metabolism compared to Reindeer. Conversely, Reindeer showed increased abundances of Lachnospiraceae ND3007 and butyrate metabolism pathway, and significantly elevated rumen volatile fatty acid concentrations, particularly acetate and butyrate. Serum profiling revealed that Milu deer had significantly higher lipid levels (CHO, TG, LDL-C) but lower total protein and AST levels compared to other species. Notably, WGCNA linked these blood lipid traits to host genes enriched in PI3K-Akt, MAPK, and bile secretion pathways. These findings demonstrate distinct species-specific rumen fermentation patterns and host metabolic adaptations, suggesting a coordinated regulation between the rumen microbiome and host genetics in Cervid.}, } @article {pmid41514762, year = {2025}, author = {Wei, M and Wang, S and Lin, F and Han, S and Zhang, T and Kuang, Y and Tong, G}, title = {A Hypothesis of Gut-Liver Mediated Heterosis: Multi-Omics Insights into Hybrid Taimen Immunometabolism (Hucho taimen ♀ × Brachymystax lenok ♂).}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/ani16010074}, pmid = {41514762}, issn = {2076-2615}, support = {2023YFD2400405//the National Key Research and Development Program of China/ ; NO.HSY2024Q09//the Central Public-interest Scientific Institution Basal Research Fund (HIRFRI)/ ; NO. 2023TD59//the Central Public-interest Scientific Institution Basal Research Fund (HIRFRI)/ ; }, abstract = {This study investigated the molecular and microbial factors behind the higher disease resistance of hybrid taimen by combining gut microbiome profiling with host transcriptomic analysis of intestinal and liver tissues. Both hybrid taimen and H. taimen were raised under the same recirculating aquaculture system (RAS) conditions. After recording survival rates following three enteritis outbreaks, samples of intestinal contents and tissues were collected from both groups. The gut microbiota was analyzed using full-length 16S rRNA sequencing in PacBio, and host gene expression was assessed with Illumina RNA-seq. Functional predictions were made using PICRUSt2 and Gene Set Enrichment Analysis (GSEA). Results showed that hybrids had significantly higher survival rates after enteritis (p < 0.05). Although microbial alpha diversity was similar, beta diversity revealed slight compositional differences. Hybrids showed higher levels of Hapalosiphon and Tepidimicrobium, microbes associated with antimicrobial compounds and the metabolism of short-chain fatty acids (SCFAs). Functional predictions indicated enrichment in selenocompound metabolism and ansamycin biosynthesis in hybrids. Transcriptomic analysis identified 4233 differentially expressed genes (DEGs) in the intestine and 3980 in the liver. In hybrids, intestinal tissues exhibited increased expression of immune pathways, including complement activation, lysosomal activity, and the transforming growth factor-beta (TGF-β) signaling pathway. Liver tissues demonstrated higher expression of genes related to cholesterol synthesis, fatty acid degradation, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. qRT-PCR validated the expression patterns of 20 selected DEGs. These findings tentatively suggest that the elevated disease resistance of hybrid taimen may be linked, at least in part, to a combination of microbial taxa inferred to produce antimicrobial metabolites and short-chain fatty acids, as well as an apparent intensification of intestinal immune and barrier-related gene expression, and hepatic pathways that possibly support energy supply and steroid-based immunity. However, this multi-omics data set is only correlational. We still do not know whether a single strain or a few host genes are enough to produce the resistant phenotype. Gnotobiotic trials, microbiota transplants, and targeted metabolomics will be necessary to turn these interesting associations into solid evidence.}, } @article {pmid41514732, year = {2025}, author = {Zhou, Y and Wu, Y and Ma, C and Ruan, X and Cha, M and Zhou, Y and Li, T and Sun, W and Liu, H}, title = {Comparative Profiling of the Fecal Bacteriome, Mycobiome, and Protist Community in Wild Versus Captive (Cervus canadensis).}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/ani16010044}, pmid = {41514732}, issn = {2076-2615}, support = {2022YFDZ0072//The 2022 Inner Mongolia Autonomous Region Key R&D and Achievement Transformation Project (Science and Technology Support for Northeast Revitalization), titled "Innovation and Promotion of Application of Deer Source Probiotic Preparation"/ ; 2023RC-Industry-Research-Institute-7//The Hohhot Science and Technology Innovation Project/ ; }, abstract = {Diet and living environments exert a profound influence on gut microbiota composition. This study presents the first comprehensive characterization of fecal bacteria, fungi, and protozoa in wild (WA) (n = 10) and captive (DA) (n = 11) wapiti (Cervus canadensis) in China. Results reveal distinct microbial profiles between the two groups. In wild wapiti, Escherichia-Shigella and UCG-005 were the dominant bacterial genera, while Succinivibrio and Treponema predominated in captive individuals. Among fungi, Agaricus and Preussia were most abundant in wild wapiti, whereas Xeromyces was identified in captive ones. For protozoa, Heteromita was the primary genus in wild wapiti, while Heteromita, Entamoeba, and Eimeria were the main genera in captive wapiti. Functional predictions further underscored these differences. In wild wapiti, bacterial and fungal functions were primarily associated with carbon metabolism and the pyruvate cycle, with mutualistic interactions prevailing among bacteria, fungi, and protozoa. Conversely, captive wapiti exhibited functional profiles centered on lipopolysaccharide and amino acid metabolism, also characterized by mutualistic coexistence among microbial communities. These findings highlight the significant impact of dietary composition on the gut microbiome. In summary, wild wapiti appear to possess a superior capacity for plant fiber utilization. These findings provide valuable data for the health management of farmed wapiti and their adaptability in natural habitats.}, } @article {pmid41514731, year = {2025}, author = {Fu, D and Mao, K and Zang, Y and Qu, M and Qiu, Q and Zhao, X and Ouyang, K and Li, Y}, title = {Effects of Rumen-Protected β-Alanine on Growth Performance, Rumen Microbiome, and Serum Metabolome of Beef Cattle.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/ani16010043}, pmid = {41514731}, issn = {2076-2615}, support = {No. 3230810//National Natural Science Foundation of China/ ; 20232BCJ23016//the Young Talents Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province/ ; CARS-37//the China Agriculture Research System of MOF and MARA/ ; }, abstract = {β-alanine has been shown to significantly improve nitrogen utilization efficiency in beef cattle, but its impact on growth performance remains unclear. This study involved 36 healthy 18-month-old Simmental crossbred bulls with similar weights (627 ± 41 kg). The cattle were divided into two groups, with each group comprising six replicates of three animals. While the control group received the basal diet, the treatment group was administered an additional 96 g/d/cattle rumen-protected β-alanine (RP-β-Ala). The study was conducted over a 35-day period, which included an initial 7 days for adaptation. At the end of the trial, body weight was recorded, and samples were collected. Results show that RP-β-Ala enhanced average daily gain (p = 0.065) and crude protein (CP) digestibility (p = 0.065) and reduced gain-to-feed ratio (p = 0.078). Analysis of rumen microbiota revealed that RP-β-Ala positively modulated the rumen microbiota by enriching beneficial genera such as Prevotella, Treponema, and Selenomonas. This enrichment increased volatile fatty acid production and nitrogen utilization efficiency, as evidenced by elevated ruminal ammonia-N and microbial CP levels, along with decreased serum urea nitrogen. Metabolomics identified key alterations in arachidonic acid metabolism, specifically the upregulation of metabolites 14,15-DiHETrE and prostaglandin D2, and enhanced antioxidative capability indicated by increased serum total antioxidant capacity (T-AOC). Concurrently, RP-β-Ala reduced serum TNF-α levels. This reduction was achieved by suppressing harmful bacteria like Thermoactinomyces and Saccharopolyspora, along with inhibiting their polyamine synthesis, specifically spermine and spermidine. Collectively, these effects alleviated oxidative stress and inflammation. These findings demonstrate that RP-β-Ala enhances beef cattle growth through improved energy supply and antioxidant capacity.}, } @article {pmid41514654, year = {2025}, author = {Liu, KYP and Huang, A and Pepin, C and Shen, Y and Tsang, P and Poh, CF}, title = {Oral Microbiome in Oral Cancer Research from Sampling to Analysis: Strategies, Challenges, and Recommendations.}, journal = {Cancers}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/cancers18010145}, pmid = {41514654}, issn = {2072-6694}, abstract = {The oral microbiome has become an emerging focus of oral cancer research, with growing evidence linking microbial communities to disease development, progression, and prognosis. However, there is limited consensus on optimal sampling strategies, storage methods, and analytical approaches. This narrative review critically evaluates current strategies for sampling, preservation, DNA extraction, sequencing, and data analysis in oral microbiome research related to oral cancer. We compared commonly used sampling methods, including saliva, oral rinse, swab, brush, and tissue biopsy, and reviewed preservation conditions, extraction kits, sequencing platforms, and analytical pipelines reported in recent oral microbiome studies. Sampling approaches affect microbial yield and site specificity. Saliva and oral rinse samples are convenient and noninvasive but may dilute lesion-specific microbial signals, whereas lesion-directed swabbing or brushing yields greater microbial biomass and biological relevance. Preservation media and storage temperature significantly influence microbial stability, and DNA extraction methods vary in their ability to remove host DNA. Although 16S rRNA gene sequencing remains the most common approach, shotgun metagenomics offers higher resolution and function insights but is still limited by clinical applicability. Differences in data pre- and post-processing models and normalization strategies further contribute to inconsistent microbial profiles. Given that oral mucosal sites differ markedly in structure and microenvironment, careful consideration is required to ensure that collected samples accurately represent the biological question being addressed. Methodological consistency across all workflow stages-from collection to analysis-is essential to generate reproducible, high-quality data and to enable reliable translation of oral microbiome research into clinical applications for cancer detection and risk assessment. Together, these insights provide a framework to guide future study design and support the development of clinically applicable microbiome-based biomarkers.}, } @article {pmid41514614, year = {2025}, author = {Peddireddi, RSS and Kuchana, SK and Kode, R and Khammammettu, S and Koppanatham, A and Mattigiri, S and Gobburi, H and Alahari, SK}, title = {Role of Gut Microbiome in Oncogenesis and Oncotherapies.}, journal = {Cancers}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/cancers18010099}, pmid = {41514614}, issn = {2072-6694}, abstract = {The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care.}, } @article {pmid41514613, year = {2025}, author = {Leonov, G and Starodubova, A and Makhnach, O and Goldshtein, D and Salikhova, D}, title = {Intratumoral Microbiome: Impact on Cancer Progression and Cellular Immunotherapy.}, journal = {Cancers}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/cancers18010100}, pmid = {41514613}, issn = {2072-6694}, support = {КBК: 075 0110 47 2 U8 70440 621. Scientific topic code: FSSF-2025-0004.//This research was funded by Ministry of Education and Science, grant number КBК: 075 0110 47 2 U8 70440 621. Scientific topic code: FSSF-2025-0004./ ; }, abstract = {The intratumoral microbiota, comprising bacteria, fungi, and viruses within the tumor microenvironment, actively influences carcinogenesis. Key mechanisms include the induction of host DNA damage, modulation of critical oncogenic signaling pathways such as WNT-β-catenin, NF-κB, and PI3K, and the orchestration of inflammatory processes. The microbiome's interaction with the host immune system is complex and bidirectional. On one hand, specific microbes can foster a pro-tumorigenic niche by suppressing the activity of cytotoxic T cells and natural killer (NK) cells or by promoting the accumulation of immunosuppressive cell types like tumor-associated macrophages (TAMs). On the other hand, microbial components can serve as neoantigens for T cell recognition or produce metabolites that reprogram the immune landscape to enhance anti-tumor responses. The composition of this microbiome is emerging as a crucial factor influencing the outcomes of immunotherapies. Prospective investigations in cancer immunotherapy ought to prioritize mechanistic inquiry employing integrative multi-omics methodologies. The execution of meticulously designed clinical trials for the validation of microbial biomarkers, and the systematic, evidence-based development of microbiome-targeted therapeutic interventions aimed at enhancing antitumor immune responses.}, } @article {pmid41514460, year = {2026}, author = {Vander Elst, N}, title = {Clinical implementation of endolysins targeting gram-positive bacteria points toward a combination strategy with standard-of-care antibiotics: a selective review.}, journal = {European journal of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40001-025-03655-4}, pmid = {41514460}, issn = {2047-783X}, abstract = {Endolysins, which are peptidoglycan hydrolases derived from bacteriophages, are expected to innovate antimicrobial treatment. More specifically, several endolysins that target gram-positive bacteria are currently being evaluated in clinical trials, reflecting increasing interest in their therapeutic application. Research involving endolysins has expanded exponentially over the last 20 years, which has resulted in a substantial diversification. With most of the field having focused on endolysin discovery, biochemical characterization and applying protein engineering strategies, it remains unclear whether endolysins should eventually be implemented as stand-alone antimicrobials or alongside standard-of-care antibiotics, an ambiguity that is also reflected in the endolysins that are currently being evaluated in clinical trials. This selective review, inspired by a selection of preclinical studies in which endolysin monotherapy had inconsistent outcomes, concludes that endolysins hold their greatest therapeutic potential when used in combination with standard-of-care antibiotics, except in cases, where therapy is limited to a local or topical application only. In the latter, antibiotic supplementation can negatively impact the microbiome that is essential to maintain, for example, skin, ear, eye, nasopharyngeal, gut and vaginal homeostasis. By combining endolysins with antibiotics that preferably target the bacterial cell wall or membrane, such as β-lactams, as well as lipo- and glycopeptides, synergistic or additive effects can be exploited that substantially reduce minimal inhibitory concentrations, restoring antibiotic susceptibility in otherwise resistant bacteria. Overall, this selective review asserts that endolysins may be best implemented alongside standard-of-care antibiotics, as this may lead to more consistent and reliable clinical outcomes, particularly in systemic infections.}, } @article {pmid41514445, year = {2026}, author = {Li, M and Zhu, S and Sun, H and Huo, Y and Cao, Q and Deng, Z and Li, K and He, Y and Lu, X and Gao, J and Xu, C}, title = {Rumen microbiota modulates metabolic stress in high-yield dairy cows: insights from early to peak lactation.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02318-0}, pmid = {41514445}, issn = {2049-2618}, support = {32402957//National Natural Science Foundation of China/ ; 32125038//National Natural Science Foundation of China/ ; BX20240417//China National Postdoctoral Program for Innovative Talents/ ; 2024M753563//China Postdoctoral Science Foundation funded project/ ; 2023YFD1801100//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: Early lactation (EL) in high-yield dairy cows represents a critical lactation phase marked by significant metabolic stress, which often provokes health disorders and production losses. The rumen microbiome is instrumental in regulating host health and metabolism. However, its contribution to metabolic stress experienced by EL cows has been largely unexplored.

RESULTS: Metabolic stress was prominently observed during EL in the form of elevated oxidative stress (OS), inflammation, and lipolysis. This stress gradually decreased with the progression of lactation from day in milk (DIM) 21 to 90. To identify the underlying mechanisms, this study analyzed EL cows (DIM 32) and peak lactation (PL, DIM 72) using an integrative approach including rumen metagenomics, rumen metabolomics, host metabolomics, and their interactions. Metagenomic analysis revealed a higher abundance of methanogenic archaea (Methanobrevibacter and Methanosphaera) in EL cows, driving increased methane production and subsequent energy loss. This energy waste likely worsened the negative energy balance and caused excessive lipolysis in EL cows. In contrast, the rumen microbiota of PL cows was enriched with Prevotella species and anti-inflammatory bacterial genera (Bacteroides, Parabacteroides, and Alistipes), which are associated with the alleviation of host metabolic stress. Functional analysis of the rumen microbiota uncovered increased tryptophan biosynthesis in EL cows, driving kynurenine production. Conversely, PL cows exhibited a greater abundance of enzymes involved in tryptophan metabolism, thus facilitating the production of indole-3-acetic acid (IAA). Metabolomics analysis also identified the tryptophan metabolism pathway as a shared link between the rumen and serum. Specifically, the kynurenine pathway, associated with OS and inflammation, was upregulated in EL cows, while the indole pathway, particularly the production of IAA, was markedly elevated in PL cows, which attenuated OS and inflammation.

CONCLUSIONS: The study results indicate that the rumen microbiota is pivotal in mitigating metabolic stress in EL cows by modulating tryptophan metabolism. Specifically, the transition from EL to PL was characterized by an enhanced tryptophan-indole pathway and a suppressed tryptophan-kynurenine pathway. The results offer meaningful insights into the microbial mechanisms underlying metabolic stress and identify potential strategies for improving cow health and productivity during lactation. Video Abstract.}, } @article {pmid41514433, year = {2026}, author = {Yang, J and Feng, Y and Guo, T and Guo, S and Yang, M and Zhou, D and Lin, P and Wang, A and Jin, Y}, title = {The impact of rumen and hindgut microbiomes on the persistent productivity of long-lived dairy cows.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02309-1}, pmid = {41514433}, issn = {2049-2618}, support = {2023YFD1801100//National Key R&D Program of China/ ; 2022GD-TSLD-46//Shaanxi Livestock and Poultry Breeding Double-chain Fusion Key Project/ ; 2018BBF33001//The Key R&D Program of Ningxia Hui Autonomous Region/ ; }, abstract = {BACKGROUND: In high-producing dairy systems, the average productive lifespan of cows is around 2.5-4 years. Persistent productivity and longevity are key determinants of dairy cow production performance and herd profitability. Although gastrointestinal microbiota influences dairy cow productivity, the mechanisms by which host-microbiome interactions support sustained productivity in long-lived dairy cows remain unclear. Therefore, this study integrated the metagenomics and metabolomics of the rumen and rectum, along with serum and milk metabolomics, to elucidate the potential impact of the rumen and rectum microbiota on the productivity of long-lived dairy cows.

RESULTS: Serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), and high-density and low-density lipoprotein cholesterol (HDL-C and LDL-C) levels in long-lived dairy cows were positively correlated with milk yield (MY) and elevated in long-lived high-yielding (LH) dairy cows, whereas insulin (INS) and glucagon (GCG) were negatively correlated with MY and higher in long-lived low-yielding (LL) dairy cows. Rumen propionate level was elevated in LH group and positively correlated with MY. The rumen microbiome, in LH cows upregulated pathways involved in amino acid, cofactor, and vitamin metabolism. LH cows' rumen and rectum microbial networks had cohesion and vulnerability levels similar to those of LL cows and exhibited dependence on key nodes. The rumen and rectum MY-associated purine metabolites, guanosine and D-ribose-1-phosphate, mediated 65.56% and 67.55% of the significant positive effects of Acidaminococcaceae bacterium and Parabacteroides sp. on MY, respectively. Furthermore, the specific lipid metabolism-associated rumen microbiota module enhanced serum eicosapentaenoic acid (EPA) levels by modulating rumen α-linolenic acid metabolism, thereby promoting the synthesis of Pe(20:5/0:0) in milk, which positively contributed to MY.

CONCLUSIONS: This study revealed the potential contributions of the rumen and rectum microbiota to the productivity of long-lived dairy cows via purine metabolites, as well as the potential role of the rumen microbial network module in influencing productivity through α-linolenic acid metabolism, providing new insights for nutritional management strategies aimed at improving the persistent production capacity of dairy cows. Video Abstract.}, } @article {pmid41514203, year = {2026}, author = {You, S and Zou, Y and Xiao, Y and He, L and Liu, L and Sun, Y and Jia, Y and Ge, G and Du, S}, title = {Animal performance and gut microbiota of cattle as affected by the unfermented or fermented total mixed ration.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04678-x}, pmid = {41514203}, issn = {1471-2180}, abstract = {Diet regulates the gut microbiota, which in turn affects animal performance, but how diet shapes the animal performance and gut microbiota remains largely unknown. To fill this gap, the author conducted a comprehensive study of the influence of total mixed ration (TMR) or fermented TMR (FTMR) on the animal performance and gut microbiome. Sixteen Simmental male cattle were randomly allocated to two treatments (one cattle per pen). The animals were fed with the TMR and FTMR diets respectively. The results showed that the contents of ADF, NDF, cellulose and total cellulose in the FTMR were significantly decreased (p < 0.05), the average daily weight gain of the Simmental male cattle shows an increasing trend (TMR: 0.31 vs. FTMR: 0.62), while no significant (p = 0.2382) difference was found between the two treatments. The metagenomics analysis showed significant (p < 0.05) difference in the α-diversity and β-diversity, and the dominant bacterial genera were Weissella, Lactiplantibacillus, Levilactobacillus and Companilactobacillus. The 16S rRNA sequencing indicated that a significant (p = 0.018) difference in the bacterial communities between the cattle fed with TMR or FTMR diet, while no significant (p < 0.05) differences were detected on the primary genus. It can be found that the FTMR diet increased the average daily gain of cattle by improving the chemical composition and microbial functional profile of the FTMR diet, and affected the growth performance of cattle.}, } @article {pmid41514163, year = {2026}, author = {Cullen, JT and Lawlor, PG and Cormican, P and Gardiner, GE}, title = {Profiling the bacteriome of a diet fed in meal or pelleted form, delivered as dry, wet/dry or liquid feed and its impact on the fecal and intestinal bacteriome of grow-finisher pigs.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skaf461}, pmid = {41514163}, issn = {1525-3163}, abstract = {Research is limited on how feed-associated microbes impact the intestinal bacteriome, growth and feed efficiency of pigs. The aims of this study were to; (1) profile the bacteriome of a meal or pelleted diet, delivered as dry, wet/dry or liquid feed using 16S rRNA gene sequencing; (2) determine its impact on the fecal and intestinal bacteriome of grow-finisher pigs; (3) investigate if differentially abundant bacterial taxa are correlated with growth parameters of these pigs. The experiment was a 2 x 3 factorial arrangement, with two factors for feed form (meal, pellets) and three factors for feed delivery (dry, liquid, wet/dry). It involved 216 Danavil Duroc x (Large White x Landrace) pigs penned in same sex pen groups of 6 pigs of similar weight (average ∼33.3 kg). Pen groups were blocked by sex and weight before being randomly assigned to 1 of 6 wheat-barley-soya-based dietary treatments in a completely randomised block design: (1) Dry meal; (2) Dry pellets; (3) Liquid meal; (4) Liquid pellets; (5) Wet/dry meal; (6) Wet/dry pellets. Diets were fed on an ad-libitum basis for 64 days. Liquid feed was prepared at a water: feed ratio of 2.5:1 (fresh matter basis). Dry feed was sampled from silos and bags and liquid feed from mixing tanks and troughs. Bacterial richness was lower in the dry pellets compared to meal (P ≤ 0.05). The liquid feed bacteriome was more diverse than that of dry feed (P ≤ 0.001). Weissella and Leuconostoc had higher relative abundance (RA) in residual-trough sampled liquid feed compared to mixing tank and fresh trough-sampled feed. The ileal bacteriome was more diverse (P ≤ 0.01) in meal-fed than pellet-fed pigs, with higher RA of Megasphaera and Mitsuokella, while Streptococcus and Escherichia-Shigella had greater RA in pellet-fed pigs (P ≤ 0.01). Lactobacillus was enriched in the intestinal digesta of liquid meal-fed pigs (P ≤ 0.05), corresponding with its predominance in this diet. Liquid meal-, liquid pellet- and wet/dry pellet-fed pigs had the highest average daily gain (P < 0.001). Feed conversion efficiency (FCE) was better in dry pellet-fed compared to liquid-fed pigs (P < 0.001). Leuconostoc (associated with feed fermentation) was most abundant in the feces and ileal digesta of liquid-fed pigs and correlated with poorer FCE (P ≤ 0.05). The same Leuconostoc found in liquid feed were also detected in the digesta and feces of liquid-fed pigs, implicating feed bacteria as a potential cause of the poorer FCE of liquid-fed pigs.}, } @article {pmid41514147, year = {2026}, author = {Guo, X and Dai, H and Jia, Z and Peng, Y and Lu, L and Su, Y and Li, J and Li, Q and Huang, Z and Wang, Y and Qi, F and Li, D and Lv, X and Liang, Y and Ma, B}, title = {Reactive oxygen species in the rhizosphere orchestrate the recruitment of beneficial bacteria.}, journal = {The EMBO journal}, volume = {}, number = {}, pages = {}, pmid = {41514147}, issn = {1460-2075}, support = {42090060,42277283//the National Natural Science Foundation of China/ ; 2024SSYS0104,2021C02064-7 and 2024ZD1000603//Key Research and Development Program of Zhejiang Province (Key R&D plan of Zhejiang Province)/ ; 2024M762854//| Postdoctoral Research Foundation of China (China Postdoctoral Research Foundation)/ ; }, abstract = {Respiratory burst oxidase homolog D (RBOHD)-dependent reactive oxygen species (ROS) in Arabidopsis are well known to suppress pathogen colonization, but their influence on beneficial microbes remains unclear. Here, we found that the beneficial rhizobacterium Pseudomonas anguilliseptica was significantly less enriched in the rhizosphere of rbohD mutants than in that of wild-type plants. Conversely, elevated rhizosphere ROS levels, either triggered by pretreatment with pathogenic Dickeya solani bacteria or caused by mutations in ROS scavenging genes (e.g., in apx1 and cat2 mutants), promoted the rhizosphere recruitment of P. anguilliseptica. This promoting effect was abolished by catalase treatment. In situ microfluidic chemotaxis assays further revealed that P. anguilliseptica exhibits a chemotactic response to low concentrations of hydrogen peroxide (≤ 500 nM), accompanied by upregulated expression of chemotaxis- and motility-related genes. Notably, inoculation of P. anguilliseptica effectively suppressed D. solani-induced disease symptoms, and this protective effect was attenuated by catalase treatment. Collectively, these findings reveal a previously unrecognized role of ROS in recruitment beneficial microbiota to enhance plant growth and suppress disease symptoms.}, } @article {pmid41513966, year = {2026}, author = {Grübbel, H and Ly-Sauerbrey, Y and Arndt, F and Pavletić, B and Leuko, S and Rinderknecht, F}, title = {Short-time thermal inactivation of surrogates of the public transport microbiome with a low-cost thermoresistometer.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-35087-3}, pmid = {41513966}, issn = {2045-2322}, abstract = {In this study, the thermal inactivation of the bacterial genera Staphylococcus, Enterococcus and Burkholderia, which can be found in public transportation environments, as well as the bacteriophage MS2 as a surrogate for potential viral pathogens are investigated. To quantify the thermal inactivation characteristic, an automated and inexpensive thermoresistometer is constructed and set up, which enables the microorganisms to be exposed to short-term thermal shocks. The time dependent temperature curves were measured to account for heat-up and cooling times. Afterwards, the microorganisms were exposed to temperatures in the range of [Formula: see text] to [Formula: see text] for durations of 2 s up to 10 s and the thermal inactivation of the respective microorganisms was measured by counting colony forming units (CFU) and plague forming units (PFU). The data was visualized and fitted to an analytical thermodynamic model based on a first-order reaction and the Arrhenius equation to predict thermal inactivation times. This study reports the first measured thermal inactivation values for E. viikkiensis and B. lata, which have not been studied before. The results for MS2 and S. capitis show significantly shorter inactivation times than previous experiments. After exposure to [Formula: see text] for 2 s there was no measurable survival of all tested microorganisms. The semi-automated test setup used allows for consistent measurements and can be adapted by other research groups.}, } @article {pmid41513795, year = {2026}, author = {Wadia, R}, title = {Microbiome signatures in cancer.}, journal = {British dental journal}, volume = {240}, number = {1}, pages = {42}, doi = {10.1038/s41415-025-9491-8}, pmid = {41513795}, issn = {1476-5373}, } @article {pmid41513699, year = {2026}, author = {Veerus, L and Subrahmanian, A and Blaser, MJ}, title = {The testobolome in microbial testosterone metabolism and human health.}, journal = {NPJ biofilms and microbiomes}, volume = {12}, number = {1}, pages = {9}, pmid = {41513699}, issn = {2055-5008}, support = {NIH U01AI22245/NH/NIH HHS/United States ; }, mesh = {*Testosterone/metabolism ; Humans ; *Gastrointestinal Microbiome/physiology ; *Bacteria/metabolism/classification/genetics ; }, abstract = {We propose the term testobolome, analogous to the estrobolome, to describe gut bacteria that metabolize testosterone. Testosterone undergoes microbial transformations similar to estrogens, potentially influencing host hormone homeostasis and health. This review defines the testobolome, identifies its known members, and explores mechanisms that are shared or distinct from the estrobolome. We outline a framework for future research into microbiome-mediated steroid metabolism, including its role in aging and hormone-driven diseases.}, } @article {pmid41513667, year = {2026}, author = {Azizan, N and Al-Maleki, AR and Rofiee, MS and Karajacob, AS and Loke, MF and Goh, JPE and Kallarakkal, TG and Wan Harun, WHA and Vaithilingam, RD and Teh, LK and Salleh, MZ and Tay, ST}, title = {Metabolomic profiling reveals alterations in Candida pathophysiology and host interactions during primary oral candidiasis and following antifungal treatment.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1089}, pmid = {41513667}, issn = {2045-2322}, support = {DP KPT FRGS/1/2019/SKK11/UM/01/1//Ministry of Higher Education, Malaysia/ ; }, mesh = {Humans ; *Antifungal Agents/therapeutic use/pharmacology ; *Candidiasis, Oral/drug therapy/metabolism/microbiology/physiopathology ; *Metabolomics/methods ; Female ; Male ; Middle Aged ; Adult ; *Metabolome ; Aged ; *Candida/drug effects/pathogenicity/metabolism ; *Host-Pathogen Interactions ; }, abstract = {Comparative metabolomics may shed light on host immunity and biology in oral candidiasis (oral thrush). Untargeted metabolomic analyses were performed on oral rinses collected from 26 primary oral candidiasis patients (OT), 12 patients after antifungal treatment (AT), and 12 unaffected individuals (C). Host immune modulation metabolites against oral candidiasis, Candida virulence and antifungal properties were identified. The upregulation of C17 sphinganine, L-leucine, monoacylglycerol, phosphatidylethanolamine, and spermine, in OT and AT groups, highlights the role of host immunity in Candida clearance. The altered sphingolipid levels suggest disrupted membrane integrity and immune function, while dysregulated amino acid, purine, and glutathione metabolism reflect oxidative stress and inflammation. Antifungal metabolites, specifically dichloroacetate, 1-monopalmitin, and undecane-2-one, were significantly upregulated in the OT group; conversely, fatty acids (palmitic amide, linoleamide, stearamide, and pentadecanal) were downregulated. Metabolomic similarities between oral candidiasis and xerostomia were evident, with shared markers such as L-valine, L-leucine, D-proline and 4-hydroxyphenylpyruvic acid. Increases in lipid metabolites, carboxylic acids, and amino acids, particularly L-leucine and hypoxanthine in patients upon resolution of oral candidiasis following antifungal treatment suggests fungal clearance, immune activation and recovery from oxidative stress. Some metabolites identified in oral candidiasis patients have reported roles in oral carcinogenesis, however, the findings remain observational and warrant further validation. Our results demonstrate that oral candidiasis is associated with distinct metabolomic alterations compared with healthy controls, and that antifungal therapy reshapes the oral metabolic profiles via complex host-microbiome-fungal metabolic pathways. The identification of oral candidiasis-associated metabolites also highlights their potential as non-invasive biomarkers and therapeutic targets for oral healthcare.}, } @article {pmid41513661, year = {2026}, author = {Meyer, AR and Tan, JP and Mihaila, MP and Neugebauer, M and Nyström, L and Bokulich, NA}, title = {Shipped and shifted: modeling collection-induced bias in microbiome multi-omics using a tractable fermentation system.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00909-1}, pmid = {41513661}, issn = {2055-5008}, support = {101060247//HORIZON EUROPE European Research Council/ ; 101060247//HORIZON EUROPE European Research Council/ ; 22.00210//Swiss State Secretariat for Education, Research and Innovation (SERI)/ ; 22.00210//Swiss State Secretariat for Education, Research and Innovation (SERI)/ ; }, abstract = {Large-scale, decentralized microbiome sampling surveys and citizen science initiatives often require periods of storage at ambient temperature, potentially altering sample composition during collection and transport. We developed a generalizable framework to quantify and model these biases using sourdough as a tractable fermentation system, with samples subjected to controlled storage conditions (4 °C, 17 °C, 30 °C, regularly sampled up to 28 days). Machine-learning models paired with multi-omics profiling-including microbiome, targeted and untargeted metabolome profiling, and cultivation-revealed temperature-dependent shifts in bacterial community structure and metabolic profiles, while fungal communities remained stable. Storage induced ecological restructuring, marked by reduced network modularity and increased centrality of dominant taxa at higher temperatures. Notably, storage duration and temperature were strongly encoded in the multi-omics data, with temperature exerting a more pronounced influence than time. 24 of the top 25 predictors of storage condition were metabolites, underscoring functional layers as both sensitive to and informative of environmental exposure. These findings demonstrate that even short-term ambient storage (<2 days) can substantially reshape microbiome, metabolome, and biochemical profiles, posing risks to data comparability in decentralized studies and emphasizing the need to recognize and address such biases. Critically, the high predictability of storage history offers a path toward bias detection and correction- particularly when standardized collection protocols are infeasible, as is common in decentralized sampling contexts. Our approach enables robust quantification and modeling of such storage effects across multi-omics datasets, unlocking more accurate interpretation of large-scale microbiome surveys.}, } @article {pmid41513603, year = {2026}, author = {Liu, P and Yang, Z and Yin, Q and Jin, X and Dong, Y and Luo, Y and Tao, B and Xu, X and Cheng, Y and Yang, B}, title = {A community screening tool for neuropsychiatric symptoms in the elderly: integrating cortisol, microbiome, and social factors with machine learning.}, journal = {Translational psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41398-025-03797-3}, pmid = {41513603}, issn = {2158-3188}, abstract = {Neuropsychiatric symptoms (NPS) are early indicators of cognitive decline due to neurodegenerative diseases, and their timely detection is of the utmost importance. We aimed to develop and validate methods for large-scale NPS screening among elderly individuals and explore underlying metabolic mechanisms. This observational, cross-section study involved 138 and 200 participants in the modeling and external validation cohorts, respectively, chosen from community healthcare centers in Chongqing, China. Data collection involved demographic questionnaires, saliva samples for oral microbiome analysis, and assays for other biomarkers (IL-6, IL-1β, TNF-α, Cath-B and cortisol). EXtreme gradient boosting(XGBoost), support vector machine(SVM), and logistic regression(LR) were developed with RFE and LASSO. The models were primarily evaluated using AUROC and F1 scores. The best model was interpreted using SHAP values, while the LR model was transformed into a nomogram. Additionally, BioCyc function pathway analysis was used to predict the functional shift of biomarkers. The genus-augmented XGBoost model achieved the highest performance, with an AUROC of 0.936 and an F1 score of 0.864, outperforming other models. The LR model was converted into a nomogram to facilitate NPS-risk assessment in community settings. The external validation confirmed the strong predictive power (AUROC = 0.986, F1 score = 0.944). Enrichment and correlation analyses revealed cortisol and microbial interactions with pathways such as the pentose phosphate pathway and enterobacterial common antigen biosynthesis. The XGBoost-augmented model and nomogram offer promising tools for community-based NPS screening, while enrichment analysis provides insights into biological mechanisms.}, } @article {pmid41513411, year = {2026}, author = {Cristoferi, L and D'Amato, D and Maino, C and Bernasconi, D and Dinelli, ME and Malandrin, SMI and Facciotti, F and Festa, MM and Gerussi, A and Rossi, E and Malinverno, F and Tettamanti, P and Cazzaniga, ME and Corso, R and Ippolito, D and Galimberti, S and Invernizzi, P and Carbone, M}, title = {Prospective, randomised, placebo-controlled, phase 2 clinical trial assessing the efficacy and safety of oral vancomycin in patients with primary sclerosing cholangitis with/out inflammatory bowel disease in Italy: study protocol of VanC-IT trial.}, journal = {BMJ open}, volume = {16}, number = {1}, pages = {e106630}, doi = {10.1136/bmjopen-2025-106630}, pmid = {41513411}, issn = {2044-6055}, mesh = {Humans ; *Cholangitis, Sclerosing/drug therapy/complications ; *Inflammatory Bowel Diseases/complications/drug therapy ; Italy ; Adult ; Adolescent ; Middle Aged ; Prospective Studies ; *Vancomycin/administration & dosage/therapeutic use/adverse effects ; Administration, Oral ; *Anti-Bacterial Agents/administration & dosage/therapeutic use/adverse effects ; Young Adult ; Aged ; Female ; Male ; Randomized Controlled Trials as Topic ; Clinical Trials, Phase II as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). No therapy currently halts disease progression. The strong gut-liver axis implicated in PSC pathogenesis supports the investigation of microbiome-targeted treatments. Oral vancomycin (OV), an antibiotic with potential immunomodulatory properties, has shown encouraging results in improving clinical symptoms and liver biochemistry in PSC. However, prospective data on its safety and efficacy remain limited.

METHODS AND ANALYSIS: Oral Vancomycin for primary sclerosing Cholangitis in ITaly (VanC-IT) is a phase II, dose-finding, randomised, placebo-controlled, trial designed to evaluate the efficacy and safety of OV in patients with PSC, with or without underlying IBD. Adults and adolescents aged 15-75 years will be enrolled following a 10-week screening and run-in period and randomised in a 1:1:1 ratio to receive either placebo, OV 750 mg/day or OV 1500 mg/day for 24 weeks. Randomisation will be stratified by baseline liver stiffness (< or ≥14.4 kPa). Participants will be followed at 4 and 12 weeks post-treatment. The primary efficacy outcome is the change in serum alkaline phosphatase at 24 weeks. Key secondary outcomes will assess the safety, the impact of OV on liver biochemistry, PSC risk scores, circulating and imaging markers of liver disease, IBD activity, quality of life and incidence of PSC-related clinical events. Key translational aims include sequencing of the faecal microbiota, metabolomic profiling of serum and stool samples and immunological profiling of serum associated with OV treatment.

ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee CE Brianza on 10 February 2023, number 4017. Trial registration number NCT05876182. Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION NUMBER: NCT05876182.}, } @article {pmid41513029, year = {2026}, author = {Cross, CB and Bowen, JM and Leifert, WR and Beale, DJ and Francois, M and Joshi, R and Fosh, BG and Coller, JK and Tuke, J and Bareham, M and Cosier, DJ and To, LH and Ryan, FJ and Wardill, HR}, title = {Pre-treatment Gut Microbiome and Salivary Metabolome Signatures Associate with Chemotherapy-Induced Cognitive Decline in Women with Breast Cancer: A Prospective Pilot Study.}, journal = {Cancer letters}, volume = {}, number = {}, pages = {218234}, doi = {10.1016/j.canlet.2025.218234}, pmid = {41513029}, issn = {1872-7980}, } @article {pmid41512948, year = {2026}, author = {Masso, ZF and Ebrahim Mullah, HB and Thiba, A and Dinat, S and Nweke Supervisor, EE and Norton, GR and Woodiwiss, AJ and Cromarty, AD and Candy, GP}, title = {Identification of multiple cardiotonic steroids in faecal material of untreated humans and rat strains.}, journal = {Steroids}, volume = {}, number = {}, pages = {109747}, doi = {10.1016/j.steroids.2026.109747}, pmid = {41512948}, issn = {1878-5867}, abstract = {UNLABELLED: Endogenous cardiotonic steroid (CTS) concentrations are raised in cardiovascular diseases. CTSs undergo gastro-hepatobiliary recirculation, with the gut being an important route of elimination, yet the presence of CTSs in faecal material is seldom reported. This study investigated methods to extract and identify the presence of CTSs in faecal material of rats and humans without prior treatment.

METHODS: Freeze-dried faecal material from different untreated rat strains was extracted using various solvents, with separation and identification of CTSs using HPLC/MS. Preliminary results were obtained from human faecal material.

RESULTS: Multiple CTSs were identified in faecal material, with marinobufagenin (MBG) predominant. Telocinobufagin was only detected in certain rat strains, whereas the extraction methods used did not recover ouabain. MBG and digoxin were elevated in Dahl salt sensitive rats fed supplementary salt. Bufalin was present in most spontaneously hypertensive rats (SHRs) but was not detectable in Wistar Kyoto rats (WKY). Conversely, digitoxin was detected in most WKYs but only few SHRs. Levels of digitoxin and bufalin remained relatively constant over 24 days in untreated rats. Solvent selection was critical in determining the CTSs extracted from human faecal material.

CONCLUSIONS: Multiple CTSs were detected in faecal material of untreated rats and humans Steroids varied between rat strains and aligned with phenotype. Extraction requires further solvent optimisation and the use of tandem MS/MS is essential to reliably detect the profile of CTSs present. Analysis of CTSs present in readily available faecal material will enable studies to determine relationships between CTSs, the microbiome and disease progression.}, } @article {pmid41512779, year = {2026}, author = {Sawangproh, W and Phaenark, C and Paejaroen, P}, title = {Microplastic pollution in annelids: A systematic review of species-specific impacts, toxicity pathways, and ecological risks.}, journal = {Ecotoxicology and environmental safety}, volume = {309}, number = {}, pages = {119686}, doi = {10.1016/j.ecoenv.2026.119686}, pmid = {41512779}, issn = {1090-2414}, abstract = {Microplastic (MP) pollution has emerged as a pervasive environmental stressor affecting terrestrial, freshwater, and marine ecosystems, with sediment-associated particles posing risks due to their persistence, bioavailability, and interactions with organisms and co-occurring contaminants. Annelids, including oligochaetes and polychaetes, are key ecosystem engineers that regulate sediment structure, nutrient cycling, and organic matter decomposition, making them highly relevant for evaluating the ecological risks of MP and nanoplastic (NP; <1 µm) contamination. Here, we synthesize peer-reviewed studies published up to 30 March 2025 to assess species-specific responses, toxicity pathways, and ecological implications of MP and NP exposure across terrestrial, freshwater, and marine annelids. By integrating evidence within a feeding-guild framework, we show that annelid responses are strongly trait-dependent rather than uniform. Deposit feeders and detritivores, such as Arenicola marina, Lumbriculus variegatus, Eisenia fetida, and Enchytraeus crypticus, frequently exhibit oxidative stress, altered energy allocation, gut microbiome disruption, and reproductive impairment. In contrast, filter feeders, including Sabella spallanzanii, often function as particle sinks with limited direct physiological effects, while carnivorous species, such as Hermodice carunculata, facilitate trophic transfer of MPs. Particle characteristics, particularly small size (<100 µm), irregular morphology, polymer type (notably polyethylene and polystyrene), and chemical aging, emerge as consistent determinants of adverse outcomes. Conversely, survival and population-level effects are often absent under short-term or environmentally realistic exposures, indicating compensatory physiological responses and limitations of standard toxicity endpoints. Overall, this review demonstrates that annelids act not only as sensitive sentinels of plastic contamination but also as active regulators of MP fate and ecological risk in sediment-based ecosystems.}, } @article {pmid41512666, year = {2026}, author = {Liu, JB and Li, S and Sun, GZ and Lin, ZX and Miao, ZM}, title = {Gut microbiota modulation by novel synbiotic improves production performance and ovarian function in aged laying hens via gut-ovary axis.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106394}, doi = {10.1016/j.psj.2026.106394}, pmid = {41512666}, issn = {1525-3171}, abstract = {The management of oxidative stress and ovarian dysfunction associated with aged laying hens, which is highly involved in gut microbiota, has been suggested as a feasible approach to improve production performance. Here, we investigated the effects of a novel synbiotic (Bacillus amyloliquefaciens + inulin, BAI), a gut microbiota regulator, on the improvement of production performance in aged laying hens, and dissected the underlying mechanisms using multi-omics analysis. Our findings showed that, compared to the control, high-dosage BAI supplementation significantly improved production performance; enhanced intestinal health, evidenced by the increase of villus height (p < 0.01), the expression of gut barrier-related genes (Claudin-1 and Claudin-2) (all p < 0.001), and immune levels (SIgA and IFN-γ) (all p < 0.01); meliorated ovarian function, confirmed by reduced oxidative stress (p < 0.001) and pathological lesions, as well as increased follicle numbers (p < 0.01 or p < 0.001), serum contents of reproductive hormone (estrogen, luteinizing hormone, and follicle-stimulating hormone) (p < 0.05 or p < 0.001), and the mRNA levels of yolk precursor synthesis-associated genes (APOVLDL-Ⅱ, VTG-Ⅱ, and VLDLR) (all p < 0.001). The 16S rRNA sequencing showed that BAI augmented the relative amount of Lactobacillus, Akkermansia, and Bacteroides and other short-chain fatty acids (SCFAs)-producers. Blood metabolome analysis demonstrated that the predominant metabolites changed by BAI were principally involved in SCFA metabolism, steroid hormone biosynthesis, steroid biosynthesis, and intestinal immune network for IgA production. Ovarian transcriptome analysis indicated that BAI significantly inhibited pathways of ferroptosis and peroxisome, confirmed by RT-qPCR. Furthermore, fecal microbiota transplantation (FMT) from BAI-treated aged hens improved production performance, ovarian function, and oxidative stress status in antibiotic-administrated hens. In sum, our study uncovers that BAI improves production performance and ovarian dysfunction via gut microbiota in aged laying hens. Thus, modulating gut microbiome is an effective approach to laying rate reduction of aged hens.}, } @article {pmid41512635, year = {2025}, author = {Li, N and Zhu, Z and Wu, S and Gong, D and Day, R and Vijayakumar, V and Yu, X and Chen, Q and Feng, Y and Wang, Q and Hu, Z and Li, J and Du, J and Xu, C and Li, W and Chen, L and Hu, J and Li, X}, title = {Effects of a novel synbiotic intervention on abdominal visceral fat reductions and gut microbiota in overweight and obese adults: A randomized, double-blind, placebo-controlled trial.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {57}, number = {}, pages = {106560}, doi = {10.1016/j.clnu.2025.106560}, pmid = {41512635}, issn = {1532-1983}, abstract = {BACKGROUND AND AIMS: Emerging evidence highlight the gut microbiome as an important regulator of metabolic health, with probiotics and prebiotics demonstrating exciting potential for their role in health promotion. This study aims to investigate a novel synbiotic formulation comprising four probiotic strains (Bifidobacterium animalis subsp. lactis CECT 8145, and three Lacticaseibacillus rhamnosus strains), prebiotics (inulin, fructooligosaccharides), and Chrysanthemum morifolium extract. We hypothesized that this intervention would improve metabolic health parameters, particularly visceral adiposity.

METHODS: In a 12-week, double-blind, randomized, placebo-controlled, parallel-group trial with a 6-week post-intervention follow-up, 112 participants (BMI: 24.0-34.9 kg/m[2]) received daily synbiotic or a matched placebo. Changes in visceral adipose tissue (VAT) area, serving as the primary endpoint, were quantified by dual-energy X-ray absorptiometry (DXA). Secondary outcomes included analysis of blood biochemical parameters, body composition, and fecal microbiota characterization.

RESULTS: Compared with placebo, synbiotic supplementation significantly reduced VAT area from baseline to week 12 (p = 0.048). In subgroup analyses by gender and BMI, the effect was more pronounced in men than in women (p = 0.051) and was highly significant in individuals with 24 ≤ BMI <28 (p = 0.003). However, subcutaneous adipose tissue (SAT) increased in the 24 ≤ BMI <28 subgroup (p = 0.027). Although no significant changes occurred in blood biochemistry, BMI, or waist circumference, the synbiotic group showed a trend toward greater total body fat reduction between weeks 12-18 (p = 0.077). Microbiota analysis revealed transient enrichment of B. animalis subsp. lactis (ASV110) and L. rhamnosus (ASV473), which dissipated by week 18.

CONCLUSIONS: This synbiotic formulation reduced visceral fat, a key driver of metabolic dysfunction, and modulated adipose distribution, particularly in men and overweight (24 ≤ BMI <28) individuals. These results support its use as a functional food for visceral adiposity management.

TRIAL REGISTRATION: This study was registered on the website of www.chictr.org.cn, number ChiCTR2400088457.}, } @article {pmid41512573, year = {2025}, author = {Henson, CC and Green, K and Slater, R and McLaughlin, J and Hann, M and Barraclough, L and Burden, S and Gillespie, L and Ward, T and Probert, C}, title = {Feasibility Study Exploring the Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome to Improve the Detection and Management of Gastrointestinal Toxicity.}, journal = {Clinical oncology (Royal College of Radiologists (Great Britain))}, volume = {50}, number = {}, pages = {103994}, doi = {10.1016/j.clon.2025.103994}, pmid = {41512573}, issn = {1433-2981}, abstract = {AIMS: Eighty percent patients develop gastrointestinal (GI) symptoms during pelvic radiotherapy. The triggering event is a known enabling identification of pathophysiological changes. The focus of this study was feasibility (identification, recruitment, and retention), however, exploratory microbiome and metabolome analyses were performed.

MATERIALS AND METHODS: Patients undergoing pelvic radiotherapy underwent faecal sampling (baseline, week 4, and 6 months), with assessment of GI toxicity using the Imflammatory Bowel Disease Questionnaire (IBDQ) bowel (IBDQB) subset. Participants were split into 2 groups based on IBDQB at week-4. Exploratory analysis was performed to identify differences in metabolome (gas chromatography-mass spectrometry) and microbiome (16s rRNA sequencing).

RESULTS: Two hundred twenty-seven patients were screened, 69 were approached, and 17 were recruited over 18 months (mean age: 61.6 ± 15.3 years; 14 female; 1 withdrawal). Metabolome analysis showed lower heptanal and octanal in baseline samples of patients with higher GI toxicity; lower (methyltrisulfanyl)methane in week-4 samples of patients with higher GI toxicity; and higher butanoic acid and benzaldehyde in month 6 samples in patients with higher GI toxicity. Whole-group microbiome analysis showed a trend towards decreased alpha diversity at 4 weeks; no differences in beta diversity; and a trend towards increase in Lachnoclostridium and decrease in Ruminococcaceae Incertae sedis at week 4. Microbiome analysis split by GI toxicity showed lower alpha diversity for the high GI toxicity group (each timepoint); no significant difference in beta diversity between groups; more genera differentially abundant between the GI toxicity groups at 4 weeks, than at other timepoints.

CONCLUSION: Recruitment was lower than anticipated. Attrition was low. Exploratory analysis suggests heptanal and octanal may have a role as a biomarker for GI toxicity, and lower alpha diversity may predict GI toxicity, with Lachnoclostridium and Ruminococcaceae Incertae sedis as bacteria of interest.}, } @article {pmid41512536, year = {2026}, author = {Xu, J and Fang, J and Wu, R and Wang, Y and Zhang, C and Wang, X and Qiu, T}, title = {Exploring the genomic features and plant growth-promoting properties of Enterobacter vonholyi Y16 isolated from maize rhizosphere.}, journal = {Microbiological research}, volume = {305}, number = {}, pages = {128437}, doi = {10.1016/j.micres.2026.128437}, pmid = {41512536}, issn = {1618-0623}, abstract = {Maize yields rely heavily on chemical fertilizers, yet over half of the applied nitrogen remains unutilized, and excessive use harms soil, highlighting the need for sustainable alternatives. Plant growth-promoting rhizobacteria (PGPR) enhance plant growth and stress resistance, providing sustainable agricultural solutions. Here, we isolated Enterobacter vonholyi Y16 from the maize rhizosphere, and demonstrated multiple plant growth-promoting traits, including phosphate solubilization, potassium solubilization, siderophore secretion, and indole-3-acetic acid biosynthesis. An integrated approach combining rhizosphere microbiome profiling with plant transcriptomics was employed to elucidate the mechanisms of gene expression changes underlying PGPR-induced maize growth promotion. Inoculation with Y16 significantly increased primary root length in Arabidopsis thaliana by 16.7 %, and enhanced maize plant height, stem diameter, fresh shoot weight, and fresh root weight by 18.41 %, 22.32 %, 48.41 %, and 62.31 %, respectively. Strain Y16 successfully colonized the rhizosphere and influenced bacterial community composition under sterile soil conditions. Transcriptomic analysis revealed Y16-mediated regulation of key pathways, including plant hormone signaling, mitogen-activated protein kinase signaling, phenylpropanoid biosynthesis, and starch and sucrose metabolism. Notably, auxin-responsive genes were upregulated, correlating with Y16 abundance. These findings provide theoretical evidence for the molecular mechanisms of plant growth promotion by PGPR and offer insights for advancing sustainable agricultural development.}, } @article {pmid41512232, year = {2025}, author = {Kang, JW and Vemuganti, V and Jonaitis, EM and Johnson, SC and Asthana, S and Carlsson, CM and Chin, NA and Engelman, CD and Ulland, TK and Rey, FE and Bendlin, BB}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e105650}, doi = {10.1002/alz70856_105650}, pmid = {41512232}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Biomarkers/blood ; Aged ; *Alzheimer Disease/diagnosis ; Neuropsychological Tests ; *Imidazoles/blood ; Executive Function/physiology ; Middle Aged ; Aged, 80 and over ; Gastrointestinal Microbiome/physiology ; }, abstract = {BACKGROUND: Among the various modifiable risk factors for AD development, the gut microbiome stands out as a potential therapeutic target, offering opportunities for intervention in the very early stages to potentially prevent disease onset. Notably, specific gut microbial metabolites may critically modulate metabolic and neuroimmune mechanisms shared with type 2 diabetes (T2D) and atherosclerosis-conditions that increase the risk of neurovascular and neurodegenerative disorders. Among these metabolites, imidazole propionate (ImP), a gut bacteria-derived metabolite of histidine, has garnered attention for its potential to cross the blood-brain barrier and exacerbate neurodegenerative processes.

METHOD: Participants included in the analysis were from Wisconsin ADRC and Wisconsin Registry for Alzheimer's Prevention (WRAP) studies. ImP was determined using the Metabolon platform. Three composite tests for measuring executive functions, along with assessments of two other cognitive domains-immediate learning and delayed recall-were used to compute the global composite scores for the three-test version of the Preclinical Alzheimer's Cognitive Composite (PACC3). The PACC3 scores were derived using three distinct measures of executive functions-Animal Naming Test (PACC3-AN, n = 859), Category Fluency Test (PACC3-CFL, n = 1118), and Trail-Making Test B (PACC3-TRLB, n = 1116)-and subsequently transformed into z-scores. Ordinary Least Squares (OLS) multiple linear regression approach was used to evaluate the relationship between levels of ImP and cognitive scores while accounting for covariates such as age and sex in the analysis.

RESULT: Lower cognitive performance was associated with higher levels of plasma ImP while controlling for age and sex, even in cognitively normal individuals before the onset of detectable cognitive symptoms.

CONCLUSION: Despite the modest associations, the significance of predictors suggests these factors warrant further exploration in understanding their combined contribution to ImP levels and broader neurodegenerative mechanisms.}, } @article {pmid41511994, year = {2026}, author = {Mullowney, MW and Moran, A and Hernandez, A and McMillin, M and Rose, AR and Moran, D and Little, J and Nguyen, AB and Patel, BK and Lehmann, CJ and Odenwald, MA and Pamer, EG and Yeo, KJ and Sidebottom, AM}, title = {Fecal butyrate and deoxycholic acid quantitation for rapid assessment of the gut microbiome.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0337727}, pmid = {41511994}, issn = {1932-6203}, mesh = {*Deoxycholic Acid/analysis ; Humans ; *Feces/chemistry/microbiology ; *Gastrointestinal Microbiome ; Chromatography, High Pressure Liquid ; *Butyrates/analysis ; Mass Spectrometry ; }, abstract = {The intestinal microbiome is composed of myriad microbial species with impacts on host health that are mediated by the production of metabolites. While loss of bacterial species and beneficial metabolites from the fecal microbiome is associated with development of a range of diseases and medical complications, there are currently no clinical diagnostic tests that rapidly identify individuals with microbiome deficiencies. This method aims to rapidly quantify fecal concentrations of butyrate and deoxycholic acid, as depletion of these two metabolites are associated with adverse clinical outcomes and result from the loss of a subset of health-associated bacterial species. We present a rapid diagnostic screen based on 3-nitrophenylhydrazine derivatization and ultrahigh-performance liquid chromatography-mass spectrometry that measures fecal butyrate and deoxycholic acid concentrations as markers of microbiome function. A matrix-matched calibration curve was developed using a simulated fecal mixture to optimize accuracy and facilitate adherence to clinical laboratory regulations. The assay resulted in an analytical measurement range from 4.30-3030 µM (LLOQ = 3.71 µM) for butyrate and from 0.9-64.9 µM (LLOQ = 0.7 µM) for deoxycholic acid. Precision evaluation demonstrated a coefficient of variation <15% at all quality control levels tested. The rapid liquid chromatography-mass spectrometry screen can be performed in under an hour from extraction to provision of quantitative results, enabling the rapid identification of patients with defective microbiome function.}, } @article {pmid41511948, year = {2026}, author = {Cazals, A and Gebhardt-Henrich, S and Berger, Q and Rossignol, MN and Jardet, D and Toscano, MJ and Zerjal, T}, title = {Exploring the relationships between the gut microbiome composition and movement patterns of laying hens in a multitier cage-free housing system.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0340059}, pmid = {41511948}, issn = {1932-6203}, mesh = {Animals ; *Chickens/microbiology/physiology ; *Gastrointestinal Microbiome ; Female ; RNA, Ribosomal, 16S/genetics ; *Housing, Animal ; Bacteria/genetics/classification ; Cecum/microbiology ; *Behavior, Animal ; }, abstract = {In this study we investigated the relation between caecal microbiota composition and movement patterns in laying hens. We used hens from Pure line matings of Hendrix Genetics to continuously monitor the movement of individuals in a connected three-tier aviary throughout the laying period, from 18 to 60 weeks of age. The aviary contained three vertical tiers: a top-level, mid-level, and lower-level. In addition, the aviary had a floor littered and an attached wintergarden which was accessible from approximately 21 WOA onwards. Differences in the hens' use of space were observed including: differences in the number of visits and time spent in the wintergarden and litter areas. Microbiota characterization, using 16S rRNA gene sequencing from 237 samples, revealed an association (P < 0.05) between microbiome composition and the number of visits to the litter. We observed differences (adjusted P-value < 0.05) between hens that frequently visited the litter (>30 times/day) and those that visited the litter less often (<10 times/day) in five bacterial families and seven genera. Notably, hens classified as visiting the litter less often, showed an increased abundance of Coriobacteriales, Peptococcales, Oribacterium and Lachnoclostridium taxa. Overall, this study offers new insights on the potential role of the microbiota in hen movement patterns.}, } @article {pmid41511880, year = {2026}, author = {Gawron, J and Czech, M and Rückert, T and Holzmüller, V and Andreev, G and Burk, AC and Hartmann, A and Chatterjee, S and Andrieux, G and Marquard, FE and Baur, AS and Stell, AV and Krausz, M and Braun, LM and Osswald, N and Melchinger, W and Wertheimer, T and Proano-Vasco, AI and Maas-Bauer, K and Schmitt-Graeff, A and Boerries, M and Köhler, N and Ayuk, FA and Schell, C and Quante, M and Zeiser, R}, title = {Gastrin for the treatment of acute graft-versus-host disease of the stomach.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2025031080}, pmid = {41511880}, issn = {1528-0020}, abstract = {Acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT) and patients with steroid-refractory aGVHD have a dismal prognosis. We have previously shown that the enteroendocrine hormone glucagon-like peptide-2 (GLP-2) has tissue regenerative activity in the lower GI in mice and patients with steroid-refractory aGVHD. Here we explored the tissue protective effect of the enteroendocrine hormone gastrin for aGVHD of the stomach. We observed that aGVHD caused a loss of gastrin-producing G-cells and parietal cells (PCs) and an increase of pH in the stomach, while allogeneic T cells infiltrated the stomach wall. Pentagastrin treatment of aGVHD mice rescued the loss of PCs, normalized the pH in the stomach, increased stomach stem cell marker expression and abundance of LGR5+ cells, and changes in the stomach microbiome. Gastrin also increased the viability of stomach and small intestine organoids in vitro. Gast-/- mice experienced more severe aGVHD in the intestine and liver compared to WT mice, which was rescued by pentagastrin-treatment. In patients developing aGVHD, low gastrin levels in stomach biopsies were connected to reduced survival. Moreover, gastrin expression in the stomach correlated with aGVHD severity and tissue damage scores in independent patient cohorts. This study delineates the protective role of gastrin in aGVHD of the stomach in mice and patients and provides a rationale for therapeutic use of pentagastrin in a clinical trial for patients with aGVHD.}, } @article {pmid41511735, year = {2026}, author = {Balkrishna, A and Agarwal, U and Saxena, S and Sharma, G and Arya, V}, title = {Toward an Integrated Therapeutic Approach for Familial Hypercholesterolemia.}, journal = {Current medical science}, volume = {}, number = {}, pages = {}, pmid = {41511735}, issn = {2523-899X}, support = {F. No. Ad-35013/4/2022-KPMG-NMCG//Ministry of AYUSH, Government of India/ ; }, abstract = {Familial hypercholesterolemia (FH) is a heritable condition that disrupts the body's ability to clear low-density lipoprotein cholesterol (LDL-C), commonly known as "bad cholesterol" from the bloodstream. This leads to persistently elevated LDL levels from birth, significantly increasing the risk of premature atherosclerosis and cardiovascular events, such as heart attack and stroke. This occurs due to variations in genes such as low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). The treatments that are available for FH include pharmacological interventions, microbiome-based treatments, molecular approaches, nanotechnology methods, surgical procedures, nutraceuticals, herbal therapy, yoga and physical fitness methods, along with lifestyle management. This review discusses the adverse effects associated with various conventional treatment methods for hypercholesterolemia and the need for a safe and effective approach for the treatment of this genetic condition. An integrated approach combining pharmacological, molecular, and lifestyle interventions has emerged as a pragmatic solution. Yoga and fitness-based therapies positively impact lipid profiles, offering non-pharmacological and holistic adjunctive options. This comprehensive approach addresses the multifaceted aspects of FH management, considering genetic factors, socioeconomic considerations, and individualized patient needs.}, } @article {pmid41511706, year = {2026}, author = {Shekar, P and Pradeep, S and Shivamallu, C and Prashant, A and Vishwanath, P}, title = {Immune-microbiota crosstalk in colorectal cancer: mechanistic pathways, biomarkers, and translational therapeutics.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {41511706}, issn = {1699-3055}, abstract = {Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.}, } @article {pmid41511412, year = {2026}, author = {Jeong, J and Baines, KJ and Maleki Vareki, S}, title = {Microbial-Derived Metabolites and Their Impact on Cancer Immunotherapy.}, journal = {Cancer immunology research}, volume = {}, number = {}, pages = {OF1-OF11}, doi = {10.1158/2326-6066.CIR-25-1018}, pmid = {41511412}, issn = {2326-6074}, support = {//Weston Family Foundation (WFF)/ ; //Lotte and John Hecht Memorial Foundation (LJHMF)/ ; //Ontario Institute for Cancer Research (OICR)/ ; }, abstract = {The gut microbiome has emerged as a modulator of both cancer progression and patient responses to therapies like immune checkpoint inhibitors (ICI). Recent evidence highlights microbially derived metabolites as key regulators of immune response and tumor microenvironment dynamics. This review explores the role of four prominent classes of bacterial metabolites-inosine, indole, bile acids, and short-chain fatty acids-in shaping antitumor immunity and modulating ICI efficacy. Each of these metabolites and their derivatives demonstrate complex and context-dependent effects on immune cells. The duality of exerting both pro- and anti-inflammatory effects underscores the therapeutic potential and challenges of metabolite-targeted interventions. By examining current preclinical findings and ongoing clinical trials, we identify promising avenues for enhancing immunotherapy through microbiome modulation and call for further mechanistic insights to inform precision treatment strategies.}, } @article {pmid41511307, year = {2025}, author = {Kang, S and Jeong, DY and Seo, J and Daily, JW and Park, S}, title = {Microbiota-Mediated Bile Acid Metabolism as a Mechanistic Framework for Precision Nutrition in Gastrointestinal and Metabolic Diseases.}, journal = {Cells}, volume = {15}, number = {1}, pages = {}, pmid = {41511307}, issn = {2073-4409}, support = {RS-2023-00208567//National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT/ ; }, mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/physiology ; *Metabolic Diseases/metabolism/microbiology ; *Gastrointestinal Diseases/microbiology/metabolism ; Animals ; *Precision Medicine ; }, abstract = {Gut microbiota play a central role in shaping bile acid (BA) metabolism through community-specific capacities for deconjugation, dehydroxylation, and other transformation reactions. Distinct microbiome compositional patterns-often referred to as enterotype-like clusters-correspond to reproducible functional profiles that generate unique BA metabolic signatures with relevance for metabolic and gastrointestinal health. This narrative review synthesizes current evidence describing the interplay between microbial composition, BA metabolism, and metabolic dysfunction. A structured literature search was conducted in PubMed, Web of Science, EMBASE, and Scopus using predefined keywords related to bile acids, microbiome composition, metabolic disorders, and enterotypes. Studies were screened for human clinical relevance and mechanistic insights into BA-microbiome interactions. Across the evidence base, Bacteroides-, Prevotella-, and Ruminococcus-associated community types consistently demonstrate different BA transformation capacities that influence secondary BA production and downstream host signaling through FXR and TGR5. These differences are linked to variation in metabolic dysfunction-associated steatotic liver disease, obesity, type 2 diabetes, inflammatory bowel disease, and colorectal cancer. Host genetic variations in BA synthesis, transport, and signaling further modify these microbiome-BA interactions, contributing to the heterogeneity of dietary intervention responses. Overall, the literature supports a model in which microbiome-derived BA profiles act as metabolic phenotypes that shape host lipid and glucose homeostasis, inflammation, and gut-liver axis integrity. Emerging clinical applications include microbiome-stratified dietary strategies, targeted probiotics with defined BA-modifying functions, and therapeutic approaches that align BA-modulating interventions with an individual's microbial metabolic capacity. Establishing integrated biomarker platforms combining microbiome clustering with BA profiling will be essential for advancing precision nutrition and personalized management of metabolic and gastrointestinal diseases.}, } @article {pmid41511192, year = {2026}, author = {Shi, C and Li, L and Sun, XL and Liu, S and Zhou, Y}, title = {Polystyrene Microplastics Disrupt Vertical Transmission of the Breast Milk Microbiome, Impairing Early-Life Gut Colonization and Immune Development in Offspring.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {1}, pages = {e71448}, doi = {10.1096/fj.202503819R}, pmid = {41511192}, issn = {1530-6860}, support = {2025GY068//Public Welfare Application Research Project of Huzhou Science and Technology Bureau (CN)/ ; 2025C02106//Key Research and Development Program of Zhejiang Province (Key R&D plan of Zhejiang Province)/ ; }, mesh = {Female ; Animals ; *Gastrointestinal Microbiome/drug effects ; *Microplastics/toxicity ; Pregnancy ; *Polystyrenes/toxicity ; Maternal Exposure/adverse effects ; Mice ; *Prenatal Exposure Delayed Effects ; *Milk/microbiology ; *Milk, Human/microbiology ; }, abstract = {Microplastics, as a class of emerging contaminants (ECs), have been found to accumulate in mammary tissue, and their potential transgenerational risks to offspring health have garnered widespread attention. Here, we investigated whether maternal microplastic exposure may alter the breast milk microbiome, thereby disrupting early intestinal microbiota colonization in offspring and affecting their immune development. Pregnant and lactating dams were exposed to two concentrations of polystyrene microplastics (PS-MPs, 10 and 40 mg/L) via drinking water. Our results showed that maternal PS-MPs exposure disrupted early gut microbiota colonization in offspring, manifested as imbalances in both maternal milk microbiota and offspring gut microbiota. Beneficial bacterial abundance decreased (e.g., Ligilactobacillus), while potentially harmful bacteria increased (e.g., Escherichia-Shigella). Concurrently, offspring from the exposed group exhibited excessive weight gain and impaired immune development, characterized by significantly reduced serum interleukin-6 (IL-6) levels, decreased splenic T-cell proportions, and compromised intestinal barrier integrity. Further analysis indicated that these outcomes were associated with alterations in milk microbiome structure and short-chain fatty acids (SCFAs) concentrations. Collectively, this study reveals the potential for maternal exposure to PS-MPs to impair offspring gut microbiota colonization and immune development by reshaping breast milk microbiota, suggesting the potential hazards of PS-MPs to maternal and infant health.}, } @article {pmid41511110, year = {2026}, author = {Gallardo Molina, P and Choi, BI and Vanek, M and Khan, MH and Tomasek, K and Kwant, AN and Dijkstra, P and de Vos, MGJ and Wolfe, AJ}, title = {SimUrine: a novel, fully defined artificial urinary medium for enhanced microbiological research of urinary bacteria.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0155925}, doi = {10.1128/aem.01559-25}, pmid = {41511110}, issn = {1098-5336}, abstract = {UNLABELLED: Urinary tract infections represent one of the most prevalent bacterial diseases, yet current diagnostic and research methodologies are hampered by inadequate culture media that fail to replicate the bladder biochemical environment. Conventional artificial urine formulations contain undefined components, lack essential nutrients, or inadequately support urinary microbiome (urobiome) growth. To address these limitations, we developed SimUrine, a fully defined synthetic urine medium that aims to replicate human bladder chemistry while supporting diverse microbial growth requirements. SimUrine was systematically developed through iterative optimization of multi-purpose artificial urine, incorporating defined concentrations of carbon sources, vitamins, trace elements, and amino acids within physiologically relevant ranges. The modular design enables component substitution without complete reformulation, facilitating customization for culturomics, antimicrobial susceptibility testing, and microbial ecology studies, while reducing batch-to-batch variability associated with authentic urine. Performance evaluation demonstrated SimUrine's capability to support the growth of fastidious urobiome members, including Lactobacillus species, Aerococcus urinae, and Corynebacterium riegelii, which fail to proliferate in conventional minimal media. Physicochemical characterization confirmed that SimUrine formulation exhibits properties within normal human urine ranges for density, conductivity, osmolarity, and viscosity, ensuring physiological relevance. Clinical applications revealed reduced antibiotic susceptibility compared to standard media, suggesting a more accurate representation of in vivo conditions. Co-culture experiments using Escherichia coli and Enterococcus faecalis demonstrated previously unobserved microbial interactions, highlighting SimUrine's utility for investigating urobiome dynamics. SimUrine represents a significant advancement in urobiome research methodology, providing a standardized, reproducible platform for investigating the urobiome under physiologically relevant conditions, potentially improving fundamental understanding and clinical diagnostic approaches.

IMPORTANCE: Urinary tract infections (UTIs) affect millions globally, yet current research and diagnostic methods rely on inadequate culture media that fail to replicate the bladder's unique biochemical environment. This fundamental limitation has hindered accurate UTI research and potentially compromised clinical treatment decisions. SimUrine addresses this critical gap as the first fully defined synthetic urine medium that mimics human bladder chemistry while supporting the growth of diverse urinary microbes. The breakthrough enables the cultivation of urobiome organisms in a minimal medium that resembles natural conditions, revealing novel microbial interactions that influence urinary health. Crucially, SimUrine demonstrates different antimicrobial susceptibility patterns compared to standard clinical media, suggesting current testing protocols may inaccurately predict treatment outcomes. This standardized, reproducible platform eliminates the variability of authentic urine samples while maintaining physiological relevance, potentially transforming urobiome research methodology and providing a new tool for the study of UTIs worldwide.}, } @article {pmid41511078, year = {2026}, author = {Bowerman, KL and Soo, RM and Chaumeil, PA and Blyton, MDJ and Sørensen, M and Gunbilig, D and Malig, M and Islam, M and Zaugg, J and Wood, DLA and Liachko, I and Auch, B and Morrison, M and Krause, L and Lindberg Møller, B and Neilson, EHJ and Hugenholtz, P}, title = {A molecular inventory of the faecal microbiomes of 23 marsupial species.}, journal = {Microbial genomics}, volume = {12}, number = {1}, pages = {}, pmid = {41511078}, issn = {2057-5858}, mesh = {*Feces/microbiology/virology ; Animals ; *Marsupialia/microbiology/virology/classification ; Phylogeny ; *Bacteria/genetics/classification/isolation & purification ; Metagenomics/methods ; Metagenome ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Viruses/genetics/classification ; }, abstract = {Despite the recent expansion of culture-independent analyses of animal faecal microbiomes, many lineages remain understudied. Marsupials represent one such group, where, despite their iconic status, direct sequencing-based analyses remain limited. Here, we present a metagenomic and metabolomic exploration of the faecal microbiomes of 23 Diprotodontia marsupials, producing a reference set of 3,868 prokaryotic and 12,142 viral metagenome-assembled genomes, the majority (>80 %) of which represent novel species. As with other animals, host phylogeny is the primary driver of microbiome composition, including distinct profiles for two eucalypt folivore specialists (koalas and southern greater gliders), suggesting independent solutions to this challenging diet. Expansion of several bacterial and viral lineages was observed in these and other marsupial hosts that may provide adaptive benefits. Antimicrobial resistance genes were significantly more prevalent in captive than wild animals, likely reflecting human interaction. This molecular dataset contributes to our ongoing understanding of animal faecal microbiomes.}, } @article {pmid41510789, year = {2026}, author = {Samy, A and Hassan, HMA and Elsherif, HMR}, title = {Synergistic roles of citric and formic acids and their salts on broiler health and performance.}, journal = {British poultry science}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/00071668.2025.2606833}, pmid = {41510789}, issn = {1466-1799}, abstract = {1. Organic acids have shown promise as safe and natural growth enhancers when added to broiler diets. 2. The current study aimed to assess how adding organic acids and their salts (OA+S) affected the intestinal microbiota, growth performance, antioxidant status and blood biochemical markers in broiler chickens.Four groups, each consisting of 90 chicks divided into six replicates (15 chicks per replicate), were randomly selected from 360 one-day-old chicks with similar initial body weights. 3. Birds fed a basal diet and received either: T1 (no addition; CTRL), T2 (1.5 g/kg feed formic acid + sodium formate, FFA), T3 (1.5 g/kg citric acid + sodium citrate, CCA) or T4 (0.75 g/kg each of FFA and CCA, MIX).Broilers fed MIX had the best BWG and FCR (p ≤ 0.05).4. All treatments significantly (p ≤ 0.05) improved performance compared to the control group. Antioxidant enzyme concentrations were higher in broiler chicks administered a combination of OA and their salts (FFA and CCA) relative to CTRL. 5. The levels of creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were not affected (p > 0.05) among all groups.6. The addition of FFA significantly elevated thyroid hormone levels (p ≤ 0.05); however, they remained within the normal range. 7. Feeding MIX enhanced immune responses to avian influenza H5, H9 and Newcastle disease ND titre compared to birds fed CTRL. 8. Lactobacillus spp. and total bacterial counts were higher in the FFA supplemented group than in CTRL.9. Broilers fed FFA had enhanced growth, better antioxidant status, improved gut microbiome and improved serum biochemical indicators, making it a safe and effective alternative to conventional antimicrobial growth promoters.}, } @article {pmid41510741, year = {2026}, author = {Xu, H and Huang, J and Guan, H and Wang, D and Yang, S}, title = {Citrus Flavanones as Neuroprotective Agents: Mechanisms and Dietary Relevance in Ischemic Stroke.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c14131}, pmid = {41510741}, issn = {1520-5118}, abstract = {Neuroprotection is pivotal in ischemic stroke management. Citrus flavanones, abundant in citrus fruits and their derived products, demonstrate significant neuroprotective potential, yet a comprehensive review of their roles in ischemic stroke is lacking. This review clarifies their mechanisms and applications for ischemic stroke prevention/treatment. Profiles of citrus flavanones in different dietary sources are summarized, and the dietary relevance of the concentrations used in preclinical studies is critically discussed. Citrus flavanones exert protection through diverse mechanisms, including antioxidation, anti-inflammation, mitochondrial protection, autophagy modulation, apoptosis inhibition, endoplasmic reticulum stress suppression, and blood-brain barrier (BBB) preservation, with angiogenesis promotion also suggested. They interact with the central nervous system either directly by crossing the BBB or indirectly via the microbiome-gut-brain axis. This review offers valuable insights to guide future research and the development of citrus-flavanone-based functional foods or therapeutics for ischemic stroke.}, } @article {pmid41510663, year = {2026}, author = {Gong, K and Wang, N and Chen, Y and Yu, J and Kuang, C and Xiong, X and Wan, R and Xing, F and Suzuki, M and Peng, L and Chun, C and Zuo, Y}, title = {Enhancing Iron Nutrition in Citrus: Synergistic Roles of Proline-2'-deoxymugineic Acid in Root Physiology and Microbiome.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c09250}, pmid = {41510663}, issn = {1520-5118}, abstract = {Iron (Fe) deficiency severely impairs plant growth and development in calcareous soils. Proline-2'-deoxymugineic acid (PDMA), a phytosiderophore analog that enhances Fe availability, alleviates Fe deficiency in field and vegetable crops but remains untested in perennial woody crops. Herein, we conducted pot and field trials on citrus, integrating physiological assays, RNA sequencing, 16S rRNA profiling, and metagenomics to evaluate PDMA/PDMA-Fe(III) effects on Fe nutrition, yield, root gene expression, and rhizosphere microbial dynamics. Results showed that PDMA/PDMA-Fe(III) significantly improved citrus Fe nutrition-outperforming traditional EDTA-Fe(III)- by increasing rhizosphere Fe availability, thereby increasing yield and downregulating Fe uptake- and stress response-related genes,with PDMA-Fe(III) had stronger suppression. PDMA-Fe(III) minimally disrupted the rhizosphere microbiome, while PDMA recruited plant growth-promoting rhizobacteria (e.g., Pseudomonas, Nitrospira); both treatments enriched microbial carbon fixation pathways. Collectively, PDMA/PDMA-Fe(III) represent eco-efficient Fe fertilizers for citrus orchards, providing sustainable remediation of Fe deficiency in calcareous soils.}, } @article {pmid41510046, year = {2025}, author = {Saiedi, E and Shapouri, R and Haghi, F and Zeighami, H}, title = {Comparative analysis of gut microbiota composition in the fecal samples from type 2 diabetes mellitus patients and healthy individuals: a case control study.}, journal = {Iranian journal of microbiology}, volume = {17}, number = {6}, pages = {875-884}, pmid = {41510046}, issn = {2008-3289}, abstract = {BACKGROUND AND OBJECTIVES: Insulin resistance and elevated blood glucose levels are the hallmarks of Type 2 Diabetes Mellitus (T2DM), a chronic metabolic condition. Emerging research suggests that gut microbiota may play a causal role in T2DM. This study compares T2DM patients' gut microbiota to healthy controls, focusing on Lactobacillus, Bifidobacterium, Akkermansia muciniphila, Prevotella, Bacteroidetes, and Firmicutes.

MATERIALS AND METHODS: This case-control research involved 50 T2DM patients and 50 healthy controls, aged 39-75. Quantitative real-time PCR (qPCR) employing 16S rRNA gene primers was used to detect and quantify bacterial diversity in fecal samples. Statistical analyses were performed to compare the microbiota composition between groups.

RESULTS: The gut microbiome of patients with Type 2 Diabetes Mellitus differed significantly from that of healthy controls. In T2DM patients, Lactobacillus spp. and the Firmicutes phylum had higher relative fold differences, while A. muciniphila had lower abundance. No substantial alterations were seen in Bifidobacterium spp., Prevotella, or Bacteroidetes. T2DM patients had more Lactobacillus spp. and Firmicutes and less A. muciniphila in their gut microbiome.

CONCLUSION: While gut microbiota is linked to T2DM, this study analyzes the bacterial composition to identify taxa that change significantly. Further research is essential to unravel the complex relationships between gut microbiota and T2DM pathogenesis, particularly through species-level analysis and genomic studies to identify the primary associated clades.}, } @article {pmid41510045, year = {2025}, author = {Maneesha, S and Arman, B and Kirti, D and Preethi, B and Rinku, C and Teenus, J and Raman, K and Raja, S and Anmol, K and Minal, BT}, title = {Preliminary investigation of changes in pathogen presence in the vaginal microbiome in association with age.}, journal = {Iranian journal of microbiology}, volume = {17}, number = {6}, pages = {901-911}, pmid = {41510045}, issn = {2008-3289}, abstract = {BACKGROUND AND OBJECTIVES: The vaginal microbiome represents a dynamic ecosystem that undergoes significant transformations throughout a woman's lifespan, influenced by hormonal fluctuations and physiological changes. Interpreting pathogen distribution and developing suitable therapeutic care techniques for women's reproductive health depends on an understanding of these age-related patterns. This study aims to thoroughly describe age-related changes in the makeup of the vaginal microbiome and the distribution of pathogenic species.

MATERIALS AND METHODS: Vaginal swab samples were collected from 29 subjects, categorized into different age groups (A: 15-30 years, B: 31-40 years, C: 41-50 years, and D: 51-60 years old females). Microbiome DNA was extracted from the collected vaginal swabs and shotgun next generation sequencing was performed. Post-sequencing, data was analysed using in-house pipeline followed by statistical analysis using R programming.

RESULTS: The results showed that microbial diversity varied significantly with age. Group C displayed the most severe pathogenic burden; Group A had the highest overall species diversity with 350 bacterial species. Group D displayed the greatest overall relative abundance levels of microorganisms, primarily due to Lactobacillus rhamnosus dominance.

CONCLUSION: This study shows that the composition of the vaginal microbiome changes fundamentally over the course of a woman's life, with each stage bringing with it its own set of microbial signatures, pathogenic risks, and therapeutic prospects.}, } @article {pmid41510033, year = {2025}, author = {Ghaderi, F and Hajebrahimi, Z and Fateh, A and Sotoodehnejadnematalahi, F and Ahmadi Badi, S and Vaezijoze, S and Siadat, SD}, title = {Tight junctions expression is affected by active, inactive, and derivatives of Akkermansia muciniphila.}, journal = {Iranian journal of microbiology}, volume = {17}, number = {6}, pages = {885-892}, pmid = {41510033}, issn = {2008-3289}, abstract = {BACKGROUND AND OBJECTIVES: Tight junctions (TJs) in the gastrointestinal tract are comprised of various junctional proteins including Occludin and Zonula Occludens (ZO-1) that have a critical role in epithelial barrier function. Gut microbiota and their derived metabolites can maintain and regulate gut epithelial barrier integrity.

MATERIALS AND METHODS: In the present study, the effects of active, heat-inactivated, cell-free supernatant, and outer membrane vesicles (OMVs) of Akkermansia muciniphila were evaluated on the expression of occludin and ZO-1 genes in Caco-2 cell line by quantitative real-time PCR.

RESULTS: Data have shown that both forms of the active (metabolically active, growing, and dividing state), and heat inactivated (by exposure to 56°C for 20 minutes) forms of the bacteria and the cell-free supernatant could affect the expression of occludin and ZO-1 genes (P < 0.05). OMVs significantly increased the expression of the occludin gene but had no effects on the expression of ZO-1.

CONCLUSION: Akkermansia muciniphila and its derived metabolites might have the potential to be used in the pharmaceutical and medicinal fields as probiotic, paraprobiotic and postbiotic agents to prevent metabolic and inflammatory diseases; Although, further research is needed to understand their interactions within the complex gut microbiome and to evaluate potential side effects or risks associated with their use.}, } @article {pmid41509984, year = {2026}, author = {Tenea, GN and Flores, C}, title = {Post-harvest microbiome dynamics and their impact on the safety and quality of Lupinus mutabilis sweet (Chocho).}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100536}, pmid = {41509984}, issn = {2666-5174}, abstract = {Chocho (Lupinus mutabilis Sweet), a traditional Andean legume, undergoes diverse post-harvest handling and processing steps that can influence its microbial composition and physicochemical properties. To understand how these factors shape food safety and consumer health, we characterized the chocho microbiome across the farm-to-table chain, including field-dried grains (Group C), open-market ready-to-eat products (Group A), and supermarket grains (Group K). Bacterial and fungal communities were profiled using 16S rRNA and ITS amplicon sequencing, and moisture, pH, titratable acidity, and total alkaloids were quantified and correlated with microbial patterns. High-depth 16S rRNA sequencing (60,000-140,000 reads/sample) showed the highest bacterial diversity in Group A (Shannon = 5.23), followed by Group K (4.69) and Group C (4.08). Richness and evenness differed significantly (p < 0.05) among groups, and beta-diversity analyses (Bray-Curtis, Jaccard, UniFrac) revealed clear clustering by grain source (PERMANOVA, p ≤ 0.005). Market grains were enriched in handling-associated genera such as Pseudomonas, Flavobacterium, and Enterococcus, whereas field grains contained soil-associated taxa including Paenibacillus and Arthrobacter. Fungal profiling showed the greatest richness and phylogenetic diversity in local-producer samples, with supermarket grains displaying lower but more even communities. Xerophilic Wallemia dominated dry grains, whereas moisture-exposed market grains were enriched in spoilage yeasts (Debaryomyces, Candida, Rhodotorula). Physicochemical traits varied widely: moisture (3.7-8.7%), titratable acidity (0.09-0.59%), pH (4.9-6.2), and alkaloids (<0.5% in processed grains vs. 5-7% in field samples). PCA explained 90.6% of the variance, with alkaloids strongly correlating with acidity (r = 0.94). Several processed samples exceeded national alkaloid limits (<0.02%), indicating incomplete debittering. These findings demonstrate that environmental exposure and handling strongly influence the microbial and toxicological safety of chocho along its supply chain.}, } @article {pmid41509630, year = {2026}, author = {Hill, K and LaFollette, A and Kirby, TO and Negrete, S and Babcock, D and Felton, K and Kohl, H and Sharma, K and Castillo, A and Roullet, JB and Gibson, KM and Ochoa-Repáraz, J}, title = {Impact of a GABA-Producing Lactococcus lactis on Microbiota and Mycobiota During CNS Inflammatory Demyelination.}, journal = {FASEB bioAdvances}, volume = {8}, number = {1}, pages = {e70085}, pmid = {41509630}, issn = {2573-9832}, abstract = {Gut microbes are key regulators of immune homeostasis. Their composition fluctuates over time and between individuals and is also influenced by disease. We and others have reported changes in gut bacterial composition following induction of experimental autoimmune encephalomyelitis (EAE), a well-established model for multiple sclerosis (MS). Specifically, we observed reductions in the abundance of bacteria capable of producing gamma-aminobutyric acid (GABA). Because GABA regulates immune cell function, we genetically engineered a Lactococcus lactis strain to overproduce GABA (P8s-GAD L. lactis) and hypothesized that this strain would have protective activity in EAE. To test this hypothesis, a suspension of P8s-GAD L. lactis was administered by gavage to C57BL/6 Envigo (Env) and Jackson Laboratories (Jax) mice at the time of EAE induction. Controls included mice treated with unmodified L. lactis (P-L. lactis) and mice treated with sterile bacterial medium. P8s-GAD L. lactis was clinically protective in Env mice but not in Jax mice. To understand the lack of protection in Jax mice, we examined the effects of treatments on intestinal micro- and mycobiota using 16S rRNA and IST sequencing, and samples were collected at disease induction, 14 days after, and at the end of the experiment (day 28). We also examined the impact of treatments on the brain, using whole-brain proteomics (day 28). Despite the lack of disease protection, P8s-GAD L. lactis significantly modified the gut microbiome by affecting broad taxonomic composition, as quantified by beta-diversity changes over time, and the CNS protein profile, including an increase in Gabra6 expression, the alpha-6 subunit of the GABA type A (GABARA) receptor. These changes, combined with reduced EAE severity observed in Env mice, suggest that GABA-producing bacteria could be considered for the treatment of neuroinflammatory conditions. The study also highlights the importance of controlling the mouse source in probiotic and microbiota research within experimental models of immune-mediated diseases.}, } @article {pmid41509585, year = {2026}, author = {Kang, NK and Kang, MJ and Keum, GB and An, C and Park, EJ and Bae, EK}, title = {Soil Chemistry and Microbial Community Patterns Across Tricholoma matsutake Fairy-Ring Developmental Stages in Yeongju, South Korea.}, journal = {Mycobiology}, volume = {54}, number = {1}, pages = {78-88}, pmid = {41509585}, issn = {1229-8093}, abstract = {This study investigates how shiro developmental stages, soil physicochemical properties, and seasonal variation shape fungal and bacterial communities associated with Tricholoma matsutake in a Pinus densiflora forest in Yeongju, South Korea. Seasonal soil samples from past, present, and future shiro zones were analyzed using ITS and 16S rRNA metabarcoding together with soil chemical measurements. Shiro-driven spatial heterogeneity, rather than seasonality, was the dominant factor structuring microbial communities. Fungal assemblages differed significantly among shiro stages, with exchangeable potassium (K[+]) emerging as the primary driver and a strong predictor of T. matsutake abundance. Elevated K[+] in active shiro zones corresponded to reduced fungal diversity, suggesting competitive exclusion by dominant ectomycorrhizal taxa. In contrast, bacterial communities were shaped mainly by water-soluble iron (Fe), shifting from Acidobacteria-rich assemblages in past zones to Proteobacteria in active zones. The enrichment of siderophore-associated taxa suggests a potential role of Fe acquisition processes, broadly consistent with mechanisms proposed in the mycorrhiza helper bacteria hypothesis, though not directly tested here. Overall, T. matsutake development generates nutrient-specific biogeochemical gradients-K[+] for fungi and Fe for bacteria-that reorganize soil microbial communities. These findings underscore tightly linked biotic-abiotic interactions in shiro ecology and highlight microbial and chemical features that may serve as indicators of shiro activity.}, } @article {pmid41509546, year = {2026}, author = {Steriade, C}, title = {The Gut Feeling Behind Autoimmune Encephalitis.}, journal = {Epilepsy currents}, volume = {}, number = {}, pages = {15357597251412104}, pmid = {41509546}, issn = {1535-7597}, abstract = {OBJECTIVE: Autoimmune encephalitis is a cause of brain inflammation characterized by auto-antibodies, which target cell surface neuronal proteins and lead to neuronal dysfunction. The most common form is associated with auto-antibodies to leucine-rich glioma-inactivated 1 (LGI1) protein, the presentation of which includes frequent focal seizures. The exact cause of these auto-antibodies remains unknown, but established predispositions include overrepresented human leukocyte antigen (HLA) alleles. Yet, these HLA alleles are themselves common in the healthy ancestry-matched population. One potential etiological hypothesis is that an environmental trigger, such as the gut microbiome, interacts with a genetically predisposed individual.

METHODS: To investigate this, we studied 42 patients with LGI1-antibody encephalitis (LGI1-Ab-E) and 27 familial/environmentally matched controls and performed metagenomic shotgun sequencing, to describe the compositional and functional differences in the gut microbiome.

RESULTS: We observed that LGI1-Ab-E gut microbiomes exhibited a significant reduction in the ratio of Firmicutes (or Bacillota) and Bacteroidetes phyla, which is associated with the dosage of HLA susceptibility allele count in patients with LGI1-Ab-E. Furthermore, we identified differences in functional gene profiles in the gut microbiome that led to a reduction of neuroinflammatory protective short-chain fatty acids (SCFAs) in LGI1-Ab-E patients.

SIGNIFICANCE: Taken together, our results suggest that a compositional shift in the gut microbiome of LGI1-Ab-E associates with a neuroinflammatory state, possibly through the reduction of SCFA production. Our study highlights the potential of the gut microbiome to explain some of the complex condition and unravel etiological questions. Validation studies with greater sample sizes are recommended.}, } @article {pmid41509542, year = {2025}, author = {Fang, Y and Cai, Y and Chen, X and Lin, Z}, title = {Exercise intervention regulates gut microbiota to improve type 2 diabetes: a narrative review of the mechanisms.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1698112}, pmid = {41509542}, issn = {2296-861X}, abstract = {BACKGROUND: The gut microbiota is increasingly recognized as a key factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Concurrently, exercise intervention has emerged as a promising non-pharmacological strategy for T2DM management, potentially mediated through gut microbiome modulation.

METHODS: This narrative review searched Web of Science, PubMed, and Embase for literature published from 1992 to the present, ultimately including 58 relevant publications. The focus was on elucidating the physiological mechanisms by which exercise modulates gut microbiota to ameliorate T2DM.

RESULTS: Our synthesis indicates that exercise training beneficially alters gut microbiota composition and function, which in turn enhances systemic insulin sensitivity and improves metabolic disturbances in T2DM. These improvements are mediated through multiple pathways, including bile acid metabolism, short-chain fatty acid production, lipopolysaccharide reduction, and branched chain amino acid catabolism. The effects of exercise on the gut microbiome are influenced by factors such as exercise intensity, duration, and type, suggesting the need for individualized regimens.

CONCLUSION: Exercise intervention improves T2DM by modulating gut microbiota via several mechanistic pathways. Future research should prioritize personalized exercise prescriptions, larger sample sizes, integrated multi-omics approaches, and exploration of combined interventions with diet or medication to optimize T2DM prevention and treatment.}, } @article {pmid41509497, year = {2025}, author = {Shen, Z and Eckert, J and Saffery, R and Allen, KJ and Walsh, A and , and Deming, C and Chen, Q and Laky, K and Li, JM and Chatman, L and , and Kong, HH and Perrett, KP and Segre, JA and Frischmeyer-Guerrerio, PA}, title = {Skin microbiome composition and function in the development of atopic diseases during infancy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.22.696050}, pmid = {41509497}, issn = {2692-8205}, abstract = {BACKGROUND: Atopic dermatitis (AD), food sensitization (FS), and food allergy (FA) frequently co-occur in infancy, but the factors driving distinct atopic phenotypes remain unclear. While FLG null mutations are major genetic risk factors for AD, they explain only a fraction of disease heritability, suggesting a potential role for the skin microbiome.

OBJECTIVE: To determine how early-life skin microbiome composition and its interaction with host genetics contribute to distinct atopic phenotypes in infancy.

METHODS: We analyzed >1,000 skin swabs from 429 infants in the VITALITY cohort using deep shotgun metagenomic sequencing at 2-3 months (pre-diagnosis) and 12 months (post-diagnosis). Differential abundance, strain-level, and microbial genome-wide association analyses were performed to identify taxonomic and functional features associated with AD, FS, FA, and their co-occurrence, as well as with FLG mutation status.

RESULTS: Within AD, microbial signatures differed by co-occurring FA or FS. At 12 months, Staphylococcus epidermidis was enriched in infants with AD alone, whereas infants with AD and FA exhibited decreased Staphylococcus hominis and Lactococcus species, along with increased Dermacoccus nishinomiyaensis and Malassezia slooffiae . At 2-3 months, early skin dysbiosis characterized by enrichment of Staphylococcus species was associated with subsequent development of AD with FS or FA, but not AD alone. Among infants with AD, FLG mutation carriers exhibited additional microbial shifts, including reduced Streptococcus species and increased Malassezia slooffiae . Strain-level analyses revealed mother-infant sharing of skin microbial taxa associated with AD, and microbial genome-wide association analyses identified species-specific genes linked to AD severity.

CONCLUSIONS: Infant atopic phenotypes are associated with distinct, phenotype-specific features of the skin microbiome that emerge both before and after clinical disease onset. By resolving microbial differences within AD according to allergic co-occurrence, host genetics, and early-life timing, this study highlights the infant skin microbiome as a potential target for early risk stratification.}, } @article {pmid41509494, year = {2025}, author = {Zhang, A and Horai, R and Jittayasothorn, Y and Badger, JH and Wu, Z and Gupta, A and Arunkumar, S and Murphy, CE and Shi, G and Nagarajan, V and McCulloch, JA and Kodati, S and Sen, HN and Lee, JW and Jacobs, JP and Xu, X and Mattapallil, MJ and Peng, Z and Xu, B and Palmer, RJ and Majdalani, N and Honda, K and O'hUigin, C and Caspi, RR}, title = {Gut microbial interaction networks control autoimmunity to neuroretina.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.04.691931}, pmid = {41509494}, issn = {2692-8205}, abstract = {The gut microbiome influences the development of immune-mediated inflammatory diseases. One such condition is autoimmune uveitis, a sight-threatening ocular inflammation driven by retina-specific T cells [1] . Using a model of spontaneous experimental autoimmune uveitis (sEAU) we showed that gut commensals provide innate and adaptive immune stimuli that trigger the disease [2] . Here we report that uveitis-promoting microbes are present in human gut flora and that colonization of germ-free (GF) mice with commensal flora from healthy human donors was sufficient to provoke disease. Severity of sEAU correlated with expansion of Akkermansia and contraction of short-chain fatty acid (SCFA)-producing Firmicutes, as well as decreased SCFA levels and a dominant gut Th1 effector response. Mechanistic gain-of-function experiments, enriching GF sEAU mice with Akkermansia, reproduced these microbiome, metabolite and immune phenotype shifts, and exacerbated disease. We propose that Akkermansia promotes autoimmunity by outcompeting SCFA-producers and enhancing Th1-type responses. Notably, an inverse correlation between Akkermansia (Verrucomicrobia) and Firmicutes was also present in fecal microbiome of patients with uveitis, multiple sclerosis and Crohn's disease. These findings reveal a stereotypic gut microbial interaction network that regulates systemic immune balance, and may represent an ecologically conserved mechanism through which the gut microbiome modulates autoimmune and inflammatory diseases.}, } @article {pmid41509481, year = {2026}, author = {Hallberg, ZF and Alvarez-Aponte, ZI and Gaudinier, AC and Taga, ME}, title = {Quenching corrinoid-based interactions in a model bacterial coculture.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41509481}, issn = {2692-8205}, abstract = {Microbial community structure is driven, in part, by the metabolic interdependencies of resident microbes. Thus, manipulating specific metabolic interactions represents one attractive way to both understand how microbial communities perform complex functions and alter them for therapeutic or environmental effects. However, it is not yet possible to control the availability of those metabolites produced by some members of the community that are required by others. Here, we report the development of a metabolite 'quenching' strategy that disrupts a specific metabolic interaction involving corrinoids, the vitamin B 12 family of cofactors, by applying a high-affinity corrinoid-binding protein, BtuG, to bacteria engaged corrinoid cross-feeding. Using a model coculture composed of Sinorhizobium meliloti , a bacterium that produces a corrinoid (cobalamin), and an Escherichia coli strain engineered to be corrinoid-dependent, we demonstrate corrinoid quenching by sequestration of extracellular corrinoid and show that BtuG specifically blocks corrinoid-dependent growth. We use this tool to calculate the amount of cobalamin released by S. meliloti cells and find that the cobalamin release rate is dependent on the growth phase of the producer, increasing to a maximum of approximately 40 cobalamin molecules per minute per cell in late exponential phase. This work establishes a strategy to selectively block microbial interactions that may be more broadly applied to dissecting community structure and function. We expect that applying high-affinity 'molecular sponges' to quench nutrient sharing will allow for the identification of key nutrients that structure microbial communities and empower precision microbiome manipulation strategies.}, } @article {pmid41509386, year = {2025}, author = {Balogun, IO and Mancuso, CP and Lieberman, TD}, title = {High Precision Binary Trait Association on Phylogenetic Trees.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.24.696407}, pmid = {41509386}, issn = {2692-8205}, abstract = {UNLABELLED: Traditional methods for identifying associations between genomic features and traits, or between pairs of genomic traits, struggle when applied to bacterial genomes. While several microbial GWAS (mGWAS) methods have been developed to account for the fact that genome-wide linkage in bacteria creates strong evolutionary-induced associations, these methods have high false discovery rates or lack statistical power, have poor performance on negative interactions, and face computational limits at the scale required for pangenome-wide study of gene-gene interactions. Here, we present SimPhyNI, a computationally optimized framework for efficient and rigorous mGWAS studies. SimPhyNI builds null co-occurrence distributions by independently simulating traits using phylogenetically-informed parameters, novelly including time to first event. The constrained variation in these simulations, combined with log odds ratio scoring for comparing across traits, robustly identifies both positive and negative associations. Using synthetic datasets mimicking both gene-gene and gene-trait associations, we demonstrate that SimPhyNI achieves high precision and recall for both positive and negative interactions. We demonstrate SimPhyNI's utility by detecting interactions between phage defense systems in E. coli and gene-gene interactions across the entire E. coli pangenome (>9 million tests). Though developed here for binary traits, SimPhyNI's design supports extension to multi-state and continuous traits using generalized models of stochastic simulation. SimPhyNI's performance and scalability enable genome-wide discovery of genetic interactions that drive microbial function, ecology, and disease.

DATA SUMMARY: SimPhyNI is publicly available at https://github.com/jpeyemi/SimPhyNI , and code for related benchmarking, validation, and biological analyses are available at doi.org/10.5061/dryad.9kd51c5xt. The neighbor-joining phylogenetic tree and phage defense system annotations used in this study were obtained from Wu et al. (2024). A representative set of Escherichia coli genomes and the corresponding maximum-likelihood phylogenetic tree were downloaded from the PanX database (https://pangenome.org/Escherichia_coli).

IMPACT STATEMENT: Understanding how bacterial genes associate with traits and with one another is essential for predicting disease outcomes, antibiotic resistance, and future evolution. However, identifying these interactions is challenging because shared ancestry creates false correlations. SimPhyNI overcomes this through an ancestry-informed statistical simulation process, achieving near-zero false positive rates while maintaining computational efficiency for large scale analyses. This efficiency enables systematic mapping of gene-gene interaction networks across large datasets containing thousands of genes and genomes. As microbial genomic datasets continue to expand, SimPhyNI's scalability and precision will accelerate discovery of the mechanistic principles underlying infectious disease, microbiome function, and microbial evolution and ecology.}, } @article {pmid41509298, year = {2025}, author = {Sharma, A and Panzetta, ME and Overly, M and Yang, H and Ernst, RK and Valdivia, RH}, title = {Multi-omic comparative analysis of members of the Akkermansia genus reveals species-specific adaptations to growth in mucin.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.30.696933}, pmid = {41509298}, issn = {2692-8205}, abstract = {Akkermansia muciniphila is a commensal, mucophilic anaerobic bacterium that influences human host physiology. Although additional prominent Akkermansia species have been identified in humans, their responses to mucin-rich environments remain poorly understood. We conducted a comparative analysis of four representative human isolates: A. muciniphila, A. biwaensis, A. massiliensis, and A. durhamii, focusing on proteins involved in mucin degradation, cell-surface components, and species-specific secreted metabolites during growth in mucin. Our results reveal unique adaptations of A. muciniphila to exploit mucin-rich environments, including higher expression of key mucin-degrading proteins during growth in mucin compared to other Akkermansia species. We also demonstrate that A. muciniphila expresses a significantly greater number of secreted PEPCTERM proteins, which contribute to host colonization. The expression of pili-associated proteins varied across species, with non- muciniphila species producing more predicted pili, suggesting the ability to colonize additional niches. Lastly, we find that small peptides previously linked to host and microbiome modulation in the GI tract are over-represented in the metabolomes of non- muciniphila species. Conversely, A. muciniphila produces more hydroxylated fatty acids, indicating potential mechanisms for modulating host health. These findings highlight genetic and regulatory mechanisms that may explain A. muciniphila 's dominance in the human gut.}, } @article {pmid41509238, year = {2025}, author = {Shrestha, A and Eline, Y and Sundstrom, K and Van Leuven, JT}, title = {Hive-associated bacteria improve honeybee survival during Paenibacillus larvae infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.24.696342}, pmid = {41509238}, issn = {2692-8205}, abstract = {Honeybees (Apis mellifera L.) are the most common pollinators of crops. Honeybee larvae are susceptible to Paenibacillus larvae , a spore-forming Gram-positive bacterium that causes American Foulbrood (AFB), one of the most destructive brood diseases worldwide. Existing antibiotic treatments are undesirable due to increasing pathogen resistance and their residual accumulation in bee products. Consequently, there is increasing interest in biological agents and natural strategies for AFB control. However, most studies remain limited to in vitro or in vivo experiments and rarely evaluate impacts on adult bees. In this study, we systematically investigated hive-associated bacteria for their potential to enhance larval survival during P. larvae infection. Bacteria isolated from AFB-infected combs were sequenced and screened for antagonistic activity. Several Bacillus species-including B. zhangzhouensis , B. subtilis , B. amyloliquefaciens , B. licheniformis , and B. mojavensis -inhibited one or more P. larvae strains. Notably, the lysate of B. licheniformis suppressed all tested strains; Further characterization revealed that its main antibacterial component consists of heat-stable proteins between 30-50 kDa. Two Bacillus strains were selected for larval infection assays using laboratory-reared honeybee larvae: both significantly improved survival by 42% and 71%, respectively. To evaluate potential effects on adult bees, newly emerged workers were caged and fed B. licheniformis ASx lysate. Their survival differed from that of untreated controls but remained comparable to the Terra-Pro-fed bees, a Terramycin-based AFB treatment, and their gut microbiome remained similar to that of untreated controls. Overall, our findings suggest that hive-associated Bacillus species offer promising, low-impact candidates for AFB disease management.}, } @article {pmid41509197, year = {2026}, author = {Ke, Z and Lin, L and Long, Y and Zhang, W and Guo, J and Yuan, L}, title = {Dihydroquercetin Attenuates Silica-Induced Pulmonary Fibrosis by Modulating the Gut Microbiota and the Serum Metabolites in Mice.}, journal = {Food science & nutrition}, volume = {14}, number = {1}, pages = {e71389}, pmid = {41509197}, issn = {2048-7177}, abstract = {Dihydroquercetin (DHQ), a crucial dihydroflavone found in nature, demonstrates notable antioxidant, anti-inflammatory, and antifibrotic effects. Nevertheless, the impact on the gut microbiome and metabolites associated with silicosis remains unclear. Hence, the objective of this research was to examine how DHQ impacts silicosis and the associated mechanisms through analyzing gut microbiota with 16S rRNA sequencing and conducting serum metabolomic analysis. The findings of our study showed that administering DHQ significantly attenuated the level of inflammation and fibrosis in the lung tissues of C57BL/6 mice exposed to silica. Furthermore, DHQ clearly raised the amount of Muribaculaceae, while diminishing the amount of Lactobacillus. DHQ treatment significantly decreased the sphingomyelin, arachidonic acid and its metabolites. Significantly, the correlation analysis showed that the influence of DHQ on the arachidonic acid metabolism, steroid hormone biosynthesis, and sphingolipid signaling pathways were linked to changes in the levels of Muribaculaceae and Lactobacillus in the gut microflora. In summary, our research demonstrated that DHQ can attenuated inflammation and lung fibrosis caused by silica exposure in the C57BL/6 mice, potentially by modulating the gut microbiota and serum metabolites.}, } @article {pmid41509044, year = {2026}, author = {El-Hadedy, DE and Chen, T and Cai, KQ and Klein-Szanto, AJ and Mu, A and Campbell, KS and Whelan, KA and Al-Hebshi, NN}, title = {Vendor-specific microbiomes influence oral cancer development and its response to Streptococcus mitis intervention in mice.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2611642}, pmid = {41509044}, issn = {2000-2297}, abstract = {BACKGROUND: We previously demonstrated that Streptococcus mitis exhibits anticancer properties in vitro. Here, we sought to validate these findings in vivo. Because mice from different vendors harbor distinct microbiomes that can influence disease susceptibility and experimental outcomes, we also examined whether vendor-specific oral and gut microbiomes affect oral carcinogenesis and response to S. mitis intervention.

MATERIALS AND METHODS: Oral carcinogenesis was induced using 4-NQO in C57BL/6 mice from Jackson Laboratory and Taconic Biosciences (n = 32 per vendor). Mice were randomized to biweekly oral swabbing with S. mitis or vehicle for 28 weeks. Oral and fecal microbiomes were profiled at baseline and week 8. At week 32, tongues were evaluated for tumor development.

RESULTS: Oral and gut microbiomes differed significantly between vendors. 4-NQO exposure induced marked microbial shifts and partial convergence of microbiome profiles. Jackson mice developed a significantly higher squamous cell carcinoma (SCC) burden. Several microbial taxa were associated with SCC, notably Clostridium, which was enriched in oral and fecal samples from Jackson mice. S. mitis reduced SCC burden in both cohorts and was accompanied by decreased Clostridium abundance.

CONCLUSIONS: These data support S. mitis as a potential anticancer agent and underscore the importance of microbiome context in preclinical cancer models.}, } @article {pmid41509043, year = {2026}, author = {Zhou, Z and Zhuang, Z and Ding, Y and Jiang, Y and Chen, S and Zhang, Q and Que, H and Lin, J and Deng, H and Wang, Y}, title = {Oral microbiome diversity and all-cause mortality in hypertensive adults: findings from a nationally representative cohort.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2609456}, pmid = {41509043}, issn = {2000-2297}, abstract = {BACKGROUND: Oral microbiome diversity has been associated with general health. However, its association with long-term outcomes in hypertensive individuals remains unclear.

OBJECTIVES: This study aimed to investigate whether oral microbiome diversity is associated with all-cause mortality in hypertensive individuals.

DESIGN: Data from 2,669 hypertensive individuals in the National Health and Nutrition Examination Survey (NHANES, 2009-2012) were analyzed. Oral microbiome diversity was assessed using four alpha-diversity metrics: the Simpson index, Shannon-Weiner index, Faith's Phylogenetic Diversity, and observed amplicon sequence variants (ASVs). Weighted multivariable Cox proportional hazards regression and interaction analyses were conducted.

RESULTS: During a mean follow-up of 8.61 years, 268 all-cause deaths occurred. Higher oral microbiome diversity assessed by the Simpson index (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.75; P trend < 0.01) and Shannon-Weiner index (HR = 0.47; 95% CI, 0.25-0.88; P trend < 0.05), was significantly associated with reduction in all-cause mortality risk. A potential interaction between sex and oral microbiome diversity on mortality risk was observed.

CONCLUSIONS: Higher oral microbiome diversity is an independent protective factor for survival in patients with hypertension, with potential sex-specific differences in this association. These findings suggest that enhancing oral microbiome diversity may potentially help promote overall health in individuals with hypertension.}, } @article {pmid41509038, year = {2026}, author = {Xu, T and Wei, Z and Zeng, Q and Feng, Q and Zhi, M}, title = {Unveiling potential driver taxa in subgingival plaque and their roles in mediating periodontitis progression.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2609452}, pmid = {41509038}, issn = {2000-2297}, abstract = {BACKGROUND: Periodontitis progression is accompanied by a succession of the oral microbiome. However, the dynamic microbial transitions that link different disease stages and contribute to disease progression remain incompletely understood.

OBJECTIVE: This study aims to identify microbial taxa that may serve as potential drivers underlying increasing severity of periodontitis.

DESIGN: Subgingival sample 16S rRNA gene sequencing data were reprocessed for quality control and taxonomic annotation. MaAsLin2 was used to identify microbial differences between groups, and co-occurrence networks were built based on the differential taxa. NetMoss algorithm was applied to identify key microbes driving the transition from health to periodontitis. Correlation and mediation analyses were used to assess the associations between these driver taxa and periodontal clinical indicators.

RESULTS: Putative novel pathogens (e.g. Filifactor alocis, Slackia exigua) were markedly enriched in periodontitis, whereas potential protective taxa (e.g. Haemophilus and Rothia) had higher relative abundance in the health group. The microbial co-occurrence networks in the periodontitis groups were progressively disrupted, characterized by reduced network robustness and heightened vulnerability in the Stage III and IV groups. The driver taxa probably influenced the severity of periodontitis through modulation of periodontal clinical indicators, with positive or negative correlations observed between these taxa and periodontal clinical indicators.

CONCLUSIONS: Capnocytophaga, Paludibacter, Dialister pneumosintes, Eubacterium minutum and Phocaeicola abscessus are proposed as key driver taxa across different periodontal health conditions, and exhibited significant correlations with periodontal clinical indicators.}, } @article {pmid41509037, year = {2026}, author = {Anshory, M and Strepis, N and Hays, JP and Rosandy, MG and Prawesti, AR and Iskandar, A and Wulanda, IA and Setyowatie, L and David, NI and Malem, NR and Kalim, H and Nijsten, TE and Nouwen, JL and Thio, HB}, title = {Transition of oral microbiome profile in HIV-infected Indonesian patients: the role of antiretroviral therapy.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2609445}, pmid = {41509037}, issn = {2000-2297}, abstract = {BACKGROUND: HIV infection alters host immunity, including the oral environment, leading to microbial imbalance and increased risk of opportunistic infections. Although antiretroviral therapy (ART) improves immune function, its effect on the oral microbiome remains unclear, particularly in Indonesia. This study investigated oral microbiome composition in people living with HIV and its associations with ART status, age, and sex.

METHODS: In this cross-sectional study, oral rinse samples from 245 adults (115 HIV-on-ART, 15 HIV-ART-naïve, and 115 HIV-negative controls) were analysed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance (ANCOM-BC2), and multivariable associations (PERMANOVA) were assessed.

RESULTS: The oral microbiome differed significantly between HIV-positive groups and controls (PERMANOVA p = 0.001, R² = 1.8%). HIV-ART-naïve individuals exhibited the highest alpha diversity and enrichment of pro-inflammatory genera, including Fusobacterium, Alloprevotella, and Staphylococcus. ART-treated individuals displayed a partial shift toward the control profile but retained persistent depletion of bacteria such as Filifactor and (Eubacterium) saphenum. Multivariate analysis identified HIV status, age, and sex as independent contributors to microbial variation.

CONCLUSION: HIV infection is associated with a distinct oral dysbiosis characterised by an increase in opportunistic pathogens and reduction in commensal bacteria. HIV-on-ART individuals show a transitional shift towards the HIV-negative oral microbiome profiles. Our findings suggest that biological and/or demographic factors coupled to oral microbiome profiles may facilitate targeted interventions in the personalised management of oral health for individuals living with HIV.}, } @article {pmid41508690, year = {2026}, author = {Jo, M and An, S and Kim, KT and Kim, DS and Kim, H and Kim, KH and Kim, S and Lee, YH and Chi, WJ and Park, SY}, title = {A multifunctional Streptomyces murinus bioinoculant integrates immune priming and microbiome restructuring for sustainable control of Sclerotinia minor in Brassica rapa.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.70544}, pmid = {41508690}, issn = {1526-4998}, support = {//National Institute of Biological Resources/ ; }, abstract = {BACKGROUND: Harnessing beneficial soil microbes provides an eco-friendly alternative to pesticides for sustainable crop protection. Members of the genus Streptomyces combine broad antagonistic activity with plant immune priming and growth promotion, yet their ecological roles and field reliability remain insufficiently understood. We investigated the soil actinobacterium Streptomyces murinus JS029 in the Brassica rapa-Sclerotinia minor pathosystem to elucidate its mechanisms of pathogen suppression, plant immune activation and rhizosphere microbiome modulation, and to develop a field-deployable formulation.

RESULTS: Streptomyces murinus JS029 secreted chitinase, cellulase and protease and produced the polyene macrolides pentamycin and filipin I, which are known to disrupt fungal cell walls and plasma membranes. Plants exposed to Streptomyces murinus JS029 exhibited strong activation of salicylic acid, jasmonic acid and ethylene signalling pathways and were associated with enhanced biomass and strong protection against Sclerotinia minor. A barley-based solid formulation ensured reproducible field efficacy, reducing disease by approximately 70-80%. Rhizosphere sequencing revealed increased fungal richness and distinct bacterial-fungal compositional shifts, indicating functional reassembly of the soil microbiome. Genome analysis and ultraviolet (UV) mutagenesis linked antifungal activity to a polyene biosynthetic gene cluster.

CONCLUSION: Streptomyces murinus JS029 integrates direct antagonism, immune priming and microbiome restructuring to support disease-suppressive soils. These findings provide mechanistic insights and a practical framework for deploying multifunctional Streptomyces bioinoculants as sustainable alternatives to chemical fungicides in integrated pest management systems. © 2026 Society of Chemical Industry.}, } @article {pmid41508656, year = {2026}, author = {Cheah, S and Burke, J and Bruinsma, FJ and Evans, M and Tsimiklis, H and Hodge, AM and Lynch, BM and Giles, GG and Sinha, R and Southey, MC and Milne, RL}, title = {Fecal Sample Collection for Gut Microbiome Research in a Prospective Cohort: A Pilot Study within the Australian Breakthrough Cancer Study.}, journal = {Cancer research communications}, volume = {6}, number = {1}, pages = {70-76}, doi = {10.1158/2767-9764.CRC-25-0445}, pmid = {41508656}, issn = {2767-9764}, support = {//Cancer Council Victoria/ ; //Gandel Foundation/ ; //Perpetual (Perpetual Ltd)/ ; //State Trustees Australia Foundation (STAF)/ ; //Winifred and John Webster Charitable Trust Fund/ ; //Pf - Alan (AGL)/ ; //Shaw Family Foundation (SFF)/ ; //Broomhead Family Foundation/ ; }, mesh = {Humans ; Pilot Projects ; *Gastrointestinal Microbiome/genetics ; *Feces/microbiology ; Prospective Studies ; Male ; Female ; *Specimen Handling/methods ; Middle Aged ; Australia ; Aged ; Occult Blood ; Adult ; *Neoplasms/microbiology ; Surveys and Questionnaires ; Metagenomics/methods ; }, abstract = {UNLABELLED: Large prospective analyses of human gut microbiome profiles are needed to elucidate the role of microbiome variation in the development of disease. We conducted a pilot study to assess the feasibility of home fecal sample collection within a cohort study. A subset of cohort study participants was randomly selected and randomized into four groups defined by fecal sample collection method and questionnaire components. Of 1,093 invited participants, 610 (56%) opted-in, and of those, 88% returned a sample. Of those asked to provide a fecal sample via fecal occult blood test (FOBT) card and complete a short "day-of-sample" questionnaire, 49% returned a sample. Sample return was comparable for participants additionally asked to provide a sample via ethanol tube (51%), complete a food frequency questionnaire (48%), or complete both additional activities (49%). Whole-genome sequencing and metagenomic analysis on paired FOBT and ethanol samples showed that both collection methods provided sufficient quality and quantity of DNA for downstream metagenomic analyses and displayed highly concordant microbiome profiles. Home fecal sample collection for microbiome analysis is feasible in a large prospective cohort. Including additional components did not reduce the likelihood of participants completing all requested items.

SIGNIFICANCE: The expansion of this successful pilot to the larger Australian Breakthrough Cancer Study will facilitate future metagenomic and other host- and microbiome-related analyses in this large prospective cohort and potentially as part of an extended international pooling project.}, } @article {pmid41508600, year = {2026}, author = {Black, TC and Demas, GE and Wellman, CL and Cusick, JA}, title = {Getting Over It: Maternal Stress and Gut Microbiome Manipulations Do Not Affect Rates of Offspring Habituation During Long Bouts of Stress.}, journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology}, volume = {}, number = {}, pages = {}, doi = {10.1002/jez.70057}, pmid = {41508600}, issn = {2471-5646}, support = {T32HD049336//National Institutes of Health (NIH)/ ; IOS-1656414//National Institutes of Health (NIH)/ ; //UVU Honor's Tuition Scholarship/ ; //UVU SAC and URSCA Dissemination Grants/ ; }, abstract = {Conspecific competitive interactions occur in a variety of contexts, including for resources and territory. These competitive interactions can vary in frequency and duration. The amount of aggression displayed and whether individuals alter their aggressive response during longer competitive bouts may be impacted by individual differences in stress response and behavior. The maternal environment, including maternal stress and the maternal microbiome, can have sex-specific, developmental effects on offspring's physiology and aggressive behavior. We tested whether the maternal environment affects changes to offspring aggressive behavior during long competitive bouts in Siberian hamsters (Phodopus sungorus). We exposed pregnant females to one of four treatments (social stressor, microbiome manipulation, combined social stress and microbiome manipulation, or no treatment) for ten days. Using a resident-intruder behavioral paradigm, adolescent offspring were exposed to a same-sex intruder for 15 min. We assessed differences in offspring behavioral responses during the first and last 5 min of the competitive interaction. All offspring displayed less aggression during the last 5 min compared to the first 5 min, regardless of maternal treatment. Regardless of maternal treatment, both female and male offspring reduced social behavior towards the intruder, while increasing non-social and decreasing anxiety like behavior across the 15-min trial. Our results are consistent with habituation towards an intruder and indicate that early development does not affect habituation during aggression with a conspecific, further confirming the complexity and highly conserved mechanisms involved in habituation.}, } @article {pmid41508594, year = {2026}, author = {Zhao, W and Zhang, Y and Ma, H and Sun, P and Zhang, Y}, title = {Characterization of the follicular fluid microbiome in endometriosis patients undergoing in vitro fertilization.}, journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology}, volume = {42}, number = {1}, pages = {2612148}, doi = {10.1080/09513590.2025.2612148}, pmid = {41508594}, issn = {1473-0766}, mesh = {Humans ; Female ; *Follicular Fluid/microbiology ; *Endometriosis/microbiology/complications ; *Fertilization in Vitro ; Adult ; *Microbiota/genetics ; Pregnancy ; *Infertility, Female/microbiology/therapy/etiology ; RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Pregnancy Rate ; }, abstract = {BACKGROUND: Endometriosis (EMs) is a common gynecological disorder associated with infertility. EMs patients often require assisted reproductive technology (ART) but exhibit lower success rates. This study aimed to characterize the follicular fluid microbiome in EMs patients undergoing in vitro fertilization (IVF) and provide insights into mechanisms underlying lower pregnancy rates.

METHODS: Follicular fluid samples were collected from EMs patients and control subjectsundergoing IVF. Microbial DNA was subjected to 16S rRNA gene sequencing. Bioinformatic analyses, including alpha and beta diversity analysis, microbial composition profiling and biomarker identification, were performed.

RESULTS: The follicular fluid microbiome in EMs patients exhibited altered alpha and beta diversity compared to controls. Distinct microbial compositions were observed at various taxonomic levels. Differentially abundant taxa were identified as potential biomarkers for EMs. Microbial profiles were associated with clinical parameters such as oocyte quality and fertilization rates. Models based on microbial profiles were constructed to elucidate the relationship between EMs and IVF outcomes. Functional predictions suggested alterations in metabolic pathways in the follicular fluid microbiome of EMs patients.

CONCLUSIONS: This study revealed significant alterations in the follicular fluid microbiome of EMs patients, providing a basis for further research into the role of the microbiome in EMs-related infertility.}, } @article {pmid41508551, year = {2026}, author = {Winn, M and Karra, P and Benson, R and Pauleck, S and Chaiyakunapruk, N and Khaing, W and Veettil, SK and McFarland, MM and Casucci, T and Xu, Y and Hu-Lieskovan, S and Litchman, M and Playdon, M and Hardikar, S}, title = {Metabolic Syndrome and Obesity-related cancer Risk and Survival: An Umbrella Review of Systematic Reviews With Meta-analysis of Observational Studies.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {}, number = {}, pages = {e70073}, doi = {10.1111/obr.70073}, pmid = {41508551}, issn = {1467-789X}, support = {NCIF30CA278348/CA/NCI NIH HHS/United States ; NCIK07CA222060/CA/NCI NIH HHS/United States ; NCIR00CA218694/CA/NCI NIH HHS/United States ; NCIK00CA2644000/CA/NCI NIH HHS/United States ; NCIF99CA264400/CA/NCI NIH HHS/United States ; T32DK091317/DK/NIDDK NIH HHS/United States ; }, abstract = {INTRODUCTION: Metabolic syndrome (MetS) may be associated with obesity-related cancer (ORC) owing to shared risk factors like physical inactivity, insulin resistance, gut microbiome dysfunction, and inflammation. We conducted an umbrella review of systematic reviews with meta-analysis to synthesize the evidence on the association between MetS and ORC risk and survival.

METHODS: Searches in five databases (Medline, Embase, CINAHL, Cochrane Library, and Scopus) retrieved 2524 systematic reviews with meta-analyses (SRMAs), which underwent title and abstract screening (2524), full-text review (41), and data extraction for included SRMAs (21). Summary effects and 95% confidence intervals were re-estimated using random-effects models. Methodological quality, certainty of evidence, and publication bias were assessed using the AMSTAR 2, modified Ioannidis criteria, and Egger's test, respectively.

RESULTS: A total of 25 associations between MetS and ORC risk and five between MetS and survival were evaluated. Overall, 10 associations evaluating MetS and ORC risk were highly suggestive (four) or suggestive (six), while the rest were classified as weak (seven) or nonsignificant (eight). One association was suggestive for MetS and ORC survival, while the rest were classified as weak (three) or nonsignificant (one). The Egger's and excess significance tests were significant for 8(32%) associations between MetS and ORC risk and 3(60%) associations between MetS and ORC survival.

CONCLUSION: This umbrella review suggests metabolic syndrome increases the risk of several obesity-related cancers and worsens colorectal cancer survival. Despite study variability, consistent associations across diverse populations highlight the urgency of prevention and management strategies targeting metabolic dysfunction to reduce cancer burden. Summary In this umbrella review, highly suggestive and suggestive evidence supports associations between MetS and the risk and survival of several obesity-related cancers. However, a better understanding of the relationship between metabolic syndrome and obesity-related cancers is still needed to provide appropriate clinical care, design optimal interventions, and prevent subsequent increases in the risks of cancer, morbidity, and mortality.}, } @article {pmid41508485, year = {2026}, author = {Wang, X and Qiu, M and Shao, Y and Tu, Z and Liu, J}, title = {Mechanism of high-fat diet exacerbating α-lactalbumin-induced allergic responses: Microbiome and metabolomic insights.}, journal = {Food research international (Ottawa, Ont.)}, volume = {225}, number = {}, pages = {118064}, doi = {10.1016/j.foodres.2025.118064}, pmid = {41508485}, issn = {1873-7145}, mesh = {Animals ; *Lactalbumin/immunology/adverse effects ; *Diet, High-Fat/adverse effects ; *Metabolomics ; Mice ; *Food Hypersensitivity/microbiology/metabolism/immunology/etiology ; *Gastrointestinal Microbiome ; Immunoglobulin E/blood ; Male ; Mice, Inbred C57BL ; Histidine/metabolism ; Staphylococcus ; Cytokines/metabolism ; Immunoglobulin G/blood ; *Microbiota ; }, abstract = {High-fat diet (HFD) is a key contributor in exacerbating food allergy, but there is little in-depth research on the mechanisms by which HFD affects allergic responses induced by α-lactalbumin (ALA). The mechanism of HFD exacerbating ALA-induced allergic responses (H-ALA) was studied via microbiome and metabolomics. HFD induced alterations in body weight and temperature in ALA-sensitized mice, while exacerbating allergic responses by increasing ALA-specific IgG/IgE levels and disrupting Th1/Th2 cytokine balance. In H-ALA, 16S rRNA gene sequencing revealed that Staphylococcus and Bilophila were the dominant genera, and untargeted metabolomics demonstrated an upregulation of histidine accompanied by reduced indole-3-acetic acid. Correlation analysis and subsequent mechanistic validation suggested that HFD might exacerbate ALA-induced allergic responses through promoting the expansion of Staphylococcus and elevating histidine levels. These findings will provide a theoretical foundation for the prevention and intervention of HFD-exacerbated food allergy.}, } @article {pmid41507958, year = {2026}, author = {Ramadan, YN and Alatawi, MN and Albalawi, AS and Hetta, HF}, title = {Bacterial contributions to cancer development: mechanisms, dysbiosis, and cross-cancer associations.}, journal = {Infectious agents and cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13027-025-00722-7}, pmid = {41507958}, issn = {1750-9378}, } @article {pmid41507781, year = {2026}, author = {Vlasblom, AA and Patel, S and Lawlor, PG and Claesson, MJ and Crespo-Piazuelo, D and Eckenberger, J and Huseyin, CE and Elend, C and Wagenaar, JA and Zomer, AL and Duim, B}, title = {Targeted isolation of bacteria with potential to competitively exclude Staphylococcus aureus in the upper respiratory tract of pigs.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04613-0}, pmid = {41507781}, issn = {1471-2180}, support = {50-52900-98-043//JPIAMR (JPIAMR-2017-1-B/ ; }, abstract = {BACKGROUND: Considering global antimicrobial resistance (AMR) prevalence, alternative or complementary strategies to antimicrobial use, are of interest. Livestock- associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is of particular interest as despite significant AMU reduction, LA-MRSA prevalence in pig husbandry has not decreased. To develop such strategy, we performed targeted isolation of bacterial species with potential antagonism against LA-MRSA in pig farms.

RESULTS: Duplicate piglet nasal swabs from three European countries (Germany, Ireland and The Netherlands) were taken longitudinally from birth up to 10 weeks, one for amplicon sequencing and qPCR, and the other was cryopreserved for culturing. We identified potential probiotic species by anticorrelation analysis of bacterial abundance from amplicon sequencing data with quantitative S. aureus estimates from qPCR data from the samples. A literature-screen was performed on the species identified, to determine their probiotic potential. Following this, 1302 isolates were grown from selected cryopreserved swabs and identified using MALDI-TOF and additional 16S rRNA gene sequencing to isolate the anticorrelating species. Ninety-five isolates of interest were screened for absence of tetracycline resistance and hemolytic activity and whole genome sequencing was conducted to verify their taxonomy and to assess their AMR and virulence gene profile. Additional phenotypic antimicrobial resistance testing selected three different Lactococcus lactis strains. During an in vitro challenge using spent medium, all three strains demonstrated inhibition against two S. aureus strains.

CONCLUSIONS: Our study, using an anticorrelation based targeted approach, identified three L. lactis strains with weak negative correlation with S. aureus, suitable for in vivo safety and efficacy testing in pigs. These L. lactis strains may have the ability to be used safely to reduce LA-MRSA carriage in the nasal passages of pigs but further in vivo testing is necessary to confirm this potential.}, } @article {pmid41507780, year = {2026}, author = {Gaonkar, PP and Santana-Pereira, ALR and Golden, R and Lambert, A and Higgins, C and Adhikari, Y and Bailey, M and Macklin, K and Huber, L}, title = {Microbiome and resistome dynamics in different stages of commercial broiler production with restricted antimicrobial use.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04664-3}, pmid = {41507780}, issn = {1471-2180}, support = {G00017930//United States Department of Agriculture (USDA)/ ; Intramural funding//Alabama Agricultural Experiment Station/ ; }, abstract = {BACKGROUND: Antimicrobial use (AMU) in poultry production is central to curb the Antimicrobial Resistance (AMR) crisis. Institutional and market pressure led many commercial poultry operations to practice distinct levels of AMU restriction. On-farm data remains one of the main bottlenecks in understanding the impacts of AMU restriction at the farm level and across production systems. However, AMR dynamics in company-wide production chains remain largely unexplored, precluding improvement of AMU policies and stewardship.

STUDY AIM: Here, we shotgun sequenced soil and litter samples from 26 poultry farms and carcass rinses from a processing plant to reconstruct the microbiome and resistome of two vertically integrated commercial poultry operations to explore their dynamics under AMU restriction.

RESULTS: Shotgun sequencing revealed that litter microbiome and resistome changed significantly by production stage and company, reflecting management practices and possible effects of historical AMU. Meanwhile, broiler farms had increased detection of potential pathogens and AMR diversity. We found no evidence of farm-to-fork transmission. Effective biosecurity protocols largely maintained the separation between the internal and external environments of the poultry houses, except on two farms where breaches might have led to external spread of pathogens and AMR.

CONCLUSION: Our study highlights that AMR in commercial poultry system reflects the combined effect of production-stage, company practices, and environmental boundaries. Future studies should integrate quantitative AMR data and culture-based techniques with metagenomic findings to strengthen tracking and surveillance of AMR in poultry farm environments.}, } @article {pmid41507771, year = {2026}, author = {Agorsor, IDK and Khadka, P and Danna, CH}, title = {The Arabidopsis UMAMIT30 transporter contributes to amino acid root exudation.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-025-07930-8}, pmid = {41507771}, issn = {1471-2229}, support = {SG00409//University of Virginia 4-VA grant/ ; IOS-1943120//National Science Foundation CAREER Award/ ; }, abstract = {BACKGROUND: Root exudation is an important trait that enables plants to shape their interactions with soil-borne organisms. Amino acids present in root exudates play important roles in bacterial chemotaxis, bacterial metabolism, and root colonization, contributing to plant nutrition and health. Notwithstanding the importance of amino acids in shaping the rhizosphere microbiome, the identities of the plant amino acid transporters that mediate their root exudation have remained elusive.

RESULTS: Here, we report that the Arabidopsis UMAMIT30 transporter, robustly expressed in root and shoot tissues, significantly contributes to amino acid root exudation. umamit30 loss-of-function mutants were compromised for amino acid root exudation as shown by the low concentration of amino acids, particularly glutamine, recovered from root exudates compared to wild-type plants. Amino acid quantification, as well as uptake and secretion assessments using radiolabelled glutamine, revealed that the shoots of umamit30 accumulate amino acids and have a reduced capacity to secrete glutamine, impacting root exudation.

CONCLUSIONS: Our results identify UMAMIT30 as a broadly specific amino acid exporter strongly expressed in Arabidopsis vasculature. Loss-of-function mutants displayed reduced amino acid levels in root exudates, with significant drops in glutamine and asparagine among others, yet exhibited no detectable growth defects under our growth conditions. UMAMIT30 disruption led to elevated shoot amino acid content and reduced glutamine efflux from shoots, suggesting a role in phloem uploading as an upstream step necessary for root exudation. Despite decreased levels of root-exuded amino acids, the plant growth-promotion conferred by the soil-borne beneficial bacterium Pseudomonas simiae WCS417r remained unmodified in umamit30 mutants.}, } @article {pmid41507594, year = {2026}, author = {Gandham, A and Prokopidis, K and Glavas, C and Scott, D and Lorentzon, M}, title = {Impact of probiotic, prebiotic, and synbiotic supplementation on the gut microbiome in older adults with sarcopenia, obesity, and sarcopenic obesity.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {}, number = {}, pages = {}, pmid = {41507594}, issn = {1433-2965}, abstract = {Gut microbiome plays an important role in several metabolic, immune, and inflammatory pathways; however, there is limited evidence for its role in body composition and musculoskeletal health. Sarcopenia, defined as a loss of skeletal muscle mass and function, and obesity, can co-exist in a condition known as sarcopenic obesity. This condition is highly prevalent among older adults, hence increasing the risk of negative health implications such as metabolic dysfunction, chronic inflammation, reduced physical performance, and poor quality of life. These age-related conditions are closely associated with alterations to the gut microbiome, including microbial profiles and a reduction in beneficial metabolites such as short-chain fatty acids (SCFAs). Probiotic, prebiotic, and synbiotic interventions are therefore emerging as promising strategies to improve the gut microbiome by enhancing microbial diversity and restoring microbial communities. This review utilizes current evidence on the impact of these interventions on gut microbiota composition, inflammatory and metabolic biomarkers, body composition, and functional outcomes in older adults with sarcopenia, obesity, and sarcopenic obesity. Probiotics, containing live beneficial microorganisms, have shown potential in enhancing SCFA production, reducing inflammation, and improving insulin sensitivity. Prebiotics are non-digestible fibers that selectively activate the growth of beneficial gut bacteria, further supporting gut health by proliferating the growth of SCFA-producing bacteria. Synbiotics, a combination of probiotics and prebiotics, provide a synergistic approach to gut health, accounting for the microbial composition and functional capability. Recent studies have demonstrated that probiotics, prebiotics, and synbiotics may reduce inflammation and improve muscle mass and strength among older adults with sarcopenia, obesity, and sarcopenic obesity. These interventions have the potential in mitigating obesity-related metabolic dysfunction and inflammation, particularly in individuals with sarcopenic obesity. Although, preclinical studies in mice exhibit beneficial effects, clinical studies in older adults remain limited, with heterogeneity of study design, intervention types, and outcome measures. This review highlights the need for robust, well-designed clinical trials to understand the mechanistic and molecular pathways through which probiotic, prebiotic, and synbiotic supplementation may modulate the gut microbiome and improve musculoskeletal health among older adults. These interventions may provide innovative, non-invasive therapeutic strategies for managing sarcopenia, obesity, and sarcopenic obesity, ultimately contributing to healthier aging and improved quality of life of older adults. This review also underscores the potential of microbiome-targeted interventions for aging populations, highlighting the need for further research.}, } @article {pmid41507585, year = {2026}, author = {Hsu, CL and Shukla, S and Freund, L and Chou, AC and Yang, Y and Bruellman, R and Raya Tonetti, F and Cabré, N and Mayo, S and Lim, HG and Magallan, V and Cordell, BJ and Lang, S and Demir, M and Stärkel, P and Llorente, C and Palsson, BO and Mandyam, C and Boland, BS and Hohmann, E and Schnabl, B}, title = {Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41507585}, issn = {2058-5276}, support = {BX004594//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; K99 AA031328/AA/NIAAA NIH HHS/United States ; R01 AA029106, R21 AA030654, P30 AR073761//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; }, abstract = {Auto-brewery syndrome (ABS) is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production. Despite case reports and a small cohort study, the microbiological profiles of patients remain poorly understood. Here we conducted an observational study of 22 patients with ABS and 21 unaffected household partners. Faecal samples from individuals with ABS during a flare produced more ethanol in vitro, which could be reduced by antibiotic treatment. Gut microbiome analysis using metagenomics revealed an enrichment of Proteobacteria, including Escherichia coli and Klebsiella pneumoniae. Genes in metabolic pathways associated with ethanol production were enriched, including the mixed-acid fermentation pathway, heterolactic fermentation pathway and ethanolamine utilization pathway. Faecal metabolomics revealed increased acetate levels associated with ABS, which correlated with blood alcohol concentrations. Finally, one patient was treated with faecal microbiota transplantation, with positive correlations between gut microbiota composition and function, and symptoms. These findings can inform future clinical interventions for ABS.}, } @article {pmid41507362, year = {2026}, author = {Elettrico, L and Piacenti, G and Levra Levron, C and Ansai, O and Croce, A and Duval, C and Proserpio, V and Donati, G}, title = {Omics-based decoding of molecular and metabolic crosstalk in the skin barrier ecosystem.}, journal = {Cell death and differentiation}, volume = {}, number = {}, pages = {}, pmid = {41507362}, issn = {1476-5403}, support = {IG2023 - Id.21640//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; postdoc fellowship//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; MFAG 2023 - Id.29203//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; postdoc fellowship//Fondazione Umberto Veronesi (Umberto Veronesi Foundation)/ ; }, abstract = {Skin homeostasis depends on interactions between epithelial cells and the microbiome mediated by molecular and biochemical factors. Perturbations of this interplay are linked to inflammatory disorders, including wound healing and cancer. While research has mainly illuminated shifts in microbial community composition, novel computational approaches are starting to reveal the host-microbe functional interactome in the cutaneous ecosystem. In this review, we specifically focus on known molecular and metabolic mechanisms linking skin epithelial cells and microorganisms in health and disease. Additionally, we summarise computational tools available to investigate these interactions integrating omics data. Furthermore, we present potential applications of this functional crosstalk to advance therapies targeting skin pathologies. Finally, we propose a comparative interactomics approach to envision the existence of ecological memories in the skin ecosystem, in parallel with the one described in the gut, hypothesising a link between epithelial and microbial memories in barrier tissues.}, } @article {pmid41507168, year = {2026}, author = {Lan, J and Wang, J and Huang, S and Li, C and Deng, Z and Hao, Z and Ma, Y}, title = {Neuropeptide SP protects against colitis and linked anxiety-like behavior through the putative roles of gut microbiota and metabolite inositol.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {295}, pmid = {41507168}, issn = {2041-1723}, support = {31772686//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Microglia/metabolism/drug effects ; *Colitis/chemically induced/metabolism/microbiology/prevention & control ; Mice ; *Inositol/metabolism ; Male ; *Anxiety/metabolism ; NF-kappa B/metabolism ; Mice, Inbred C57BL ; *Substance P/pharmacology/metabolism ; Dextran Sulfate ; Hippocampus/metabolism/drug effects/pathology ; Astrocytes/metabolism/drug effects ; Disease Models, Animal ; Signal Transduction ; }, abstract = {The gut-brain axis links gut inflammation to psychiatric symptoms in inflammatory bowel disease (IBD), but the underlying mechanisms remain unclear. We demonstrate that neuropeptide substance P (SP) alleviated intestinal injury and behavioral disorders induced by dextran sodium sulfate in mice. SP mitigated hippocampal neuroinflammation and inhibited microglial activation and astrocyte loss. Furthermore, SP improved gut microbiome dysregulation, and its protective effects depended on the putative roles of microbiota. Notably, through modulating microbiota, SP dampened the NF-κB pathway in microglia, and increased GABAergic/Ca[2+] signaling within astrocytes. SP elevated the microbiota-derived metabolite inositol. Supplementing inositol mimicked SP's benefits and activated GABAergic signaling, while the inositol inhibitor reversed SP's neuroprotective impacts, highlighting inositol's indispensable role. Collectively, SP exerts beneficial effects via microbiota's putative roles and inositol, involving the suppression of microglial NF-κB pathway while enhancing astrocytic GABAergic/Ca[2+] signaling. Our findings underscore SP's potential as a therapeutic intervention for these disorders in IBD.}, } @article {pmid41506609, year = {2026}, author = {Wang, W and Zhang, K and Liu, Z and Liu, X and Wang, X}, title = {Effects of Polyethylene Microplastics and Cadmium Co-contamination on the Soybean-Soil System:Integrated Metabolic and rhizosphere Microbial Mechanisms.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {127643}, doi = {10.1016/j.envpol.2026.127643}, pmid = {41506609}, issn = {1873-6424}, abstract = {The coexistence of microplastics (MPs) and heavy metals in agricultural soils presents complex and poorly understood ecological risks. While previous studies have examined the individual effects of these pollutants, the interactive mechanisms governing their combined impact on plant-soil systems, particularly through integrated metabolic and microbial pathways remain unclear. This study investigated the effects of polyethylene microplastics (PE-MPs) and cadmium (Cd) co-exposure on soybean-soil systems. Under moderate Cd exposure (20 mg/kg), specific PE-MPs concentrations (1% and 5%) enhanced Cd accumulation in soybean roots, whereas this trend reversed under high Cd levels (50 mg/kg). Co-exposure maintained stable shoot growth through activation of stress-response pathways (β-alanine, porphyrin, and pantothenate metabolism). Rhizosphere microbiome analysis revealed that 5% and 10% PE-MPs reduced the abundance of Sphingomonas and Bradyrhizobium in Cd-contaminated soil and suppressed nitrogen-cycling functionality. Integrated metabolite-microbe network analysis identified malonyldaidzin as a potential mediator linking soybean leaf metabolism with rhizobacterial interactions, associated with root Cd accumulation. These findings demonstrate that PE-MPs fundamentally alter Cd behavior through tripartite plant-metabolite-microbe interactions, thereby highlighting the need to incorporate MPs effects into ecological risk assessments of heavy metal contamination in agricultural ecosystems.}, } @article {pmid41506211, year = {2026}, author = {Zhao, N and Zhang, Z and Ding, H and Guillemot, T and Wang, D and Wang, H}, title = {Electron transfer versatility of a Geobacter sp. links PAH degradation with multi-electron acceptor respiration, including crystalline magnetite.}, journal = {Journal of hazardous materials}, volume = {502}, number = {}, pages = {141052}, doi = {10.1016/j.jhazmat.2026.141052}, pmid = {41506211}, issn = {1873-3336}, abstract = {Anaerobic degradation of polycyclic aromatic hydrocarbons (PAHs) is often constrained by the availability and accessibility of terminal electron acceptors in anoxic, metal-rich environments. Here we characterize a Geobacter sp. (strain GeoA) that couples phenanthrene oxidation to respiration with nitrate, Mn(IV), Fe(III)-citrate, sulfate, Cr(VI), and crystalline magnetite. Phenanthrene removal (initial 280 μM) proceeded fastest with Mn(IV) and nitrate (about 96 % within 5-7 d), followed by Fe(III)-citrate (about 95 % in 20 d), sulfate (about 95 % in 24 d), and Cr(VI) (about 61 % in 56 d, concomitant with complete reduction of 2.1 mM Cr(VI)). While previous studies mainly focused on amorphous or poorly crystalline Fe(III) minerals, the role of highly crystalline magnetite as an active electron sink has remained unclear. In this study, GeoA reduced ∼35 % of supplied magnetite (20 mM Fe(III) basis) and exhibited an acetate:Fe(III) stoichiometry (∼1:8) consistent with dissimilatory reduction. XPS and AQDS enhancement assays, together with upregulation of pilA and the flavin exporter yeeO, indicate that both direct and shuttle-facilitated extracellular electron transfer contribute to crystalline iron oxide reduction. Metabolite profiling with [13]C-bicarbonate labelling, together with genomic evidence, supports a carboxylation-initiated route for anaerobic phenanthrene activation. An analysis of Earth Microbiome Project datasets shows Geobacter predominance among dissimilatory iron-reducing genera in soils and sediments, consistent with ecological adaptation to solid-phase electron acceptors. These findings expand the known respiratory flexibility and bio-remediation potential of PAH-degrading bacteria and provide the first mechanistic evidence of PAH oxidation coupled to magnetite reduction by a single pure strain, highlighting crystalline magnetite as a relevant electron sink in PAH-metal co-contaminated anoxic environments.}, } @article {pmid41505994, year = {2026}, author = {Zhao, S and Xu, H and Liu, R and Wang, J and Zhi, B and Fu, X and Cao, X and Ma, X and Shao, Z}, title = {Biodegradation and disintegration of expanded polystyrene by sphaeromatid isopods Sphaeroma via their gut bacteria.}, journal = {Marine pollution bulletin}, volume = {225}, number = {}, pages = {119207}, doi = {10.1016/j.marpolbul.2025.119207}, pmid = {41505994}, issn = {1879-3363}, abstract = {Wood-boring isopods have been documented inhabiting the plastic floats of expanded polystyrene (EPS), which is extensively utilized in mariculture as buoyant material. However, little is known about their role in the plastic fragmentation and degradation. This report confirmed that globally distributed Sphaeroma gnawed and ingested EPS foam, and digested it via their gut microbiome. After 7 days of exposure, each Sphaeroma consumed 4.4 ± 0.2 mg EPS, ingested 50 microbeads and egested 2.5 ± 0.7 × 10[3] microplastics. Analyses using μFTIR, GPC, and GC-MS revealed polystyrene (PS) degradation in the gut of Sphaeroma. High throughput 16S rRNA sequencing revealed that Exiguobacterium spp. and Brevibacterium spp. were associated with PS diets in the gut microbiome of Sphaeroma, suggesting their potential key role in vivo. Further characterizations of PS weight loss, changes in chemical and thermal properties, and identification of metabolic intermediates confirmed that PS can be degraded by five gut bacteria from the above two genera. Antibiotic bioassay confirmed that gut microbes are essential for the EPS depolymerization in Sphaeroma by. All these results demonstrate that the gut microbiome contributes to EPS digestion in the host. Together, these results found marine isopods in coastal negatively influenced the environmental fats of the plastic fate, by fragmenting plastics and generating microplastics, via their PS-degrading gut microbiota.}, } @article {pmid41505190, year = {2026}, author = {McGarrity-Yoder, M and Cope, EK and Wayment, HA and Rodriguez-Pla, A and Crane, TE}, title = {Biopsychosocial Determinants, Diet Quality, Gastrointestinal Health, and Disease Activity in Adults With Rheumatoid Arthritis: Cross-Sectional Descriptive Study.}, journal = {JMIR research protocols}, volume = {15}, number = {}, pages = {e79889}, doi = {10.2196/79889}, pmid = {41505190}, issn = {1929-0748}, mesh = {Humans ; Cross-Sectional Studies ; *Arthritis, Rheumatoid/psychology/physiopathology ; Adult ; Female ; Male ; Arizona ; *Diet ; Middle Aged ; *Gastrointestinal Tract/physiopathology ; Aged ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) causes pain, fatigue, joint deformity, disability, and an increased risk for serious sequelae, often despite treatment, in 1.3 million Americans. RA is affected by numerous biopsychosocial determinants, which greatly complicate treatment, including altered efficacy.

OBJECTIVE: The purpose of this study is to examine associations between individual biopsychosocial determinants, diet quality, gastrointestinal (GI) health, and disease activity in adults with RA.

METHODS: This cross-sectional, descriptive study has been approved by the Northern Arizona University Internal Review Board (# 2111208-12). We will include 96 adults with RA recruited from across Arizona using social media and community events (through the Arthritis Foundation) and various primary care and rheumatology practices in Flagstaff and the greater Phoenix metro area. Individual biopsychosocial factors will be measured with a demographic survey and direct measures. The Arizona Food Frequency Questionnaire will measure dietary intake for the past 6 months, and Healthy Eating Index-2020 scores will be calculated from these data. The Automated Self-Administered 24-hour diet recall will measure recent dietary intake. Fecal analyses for gut microbiome diversity and composition and fecal calprotectin will measure current GI health. Disease activity will be measured by the Health Assessment Questionnaire-Disability Index and pain scale, Disease Activity Score of 28 Joints, and hematology results (C-reactive protein and erythrocyte sedimentation rate). In addition to descriptive statistics, hierarchical linear regression will examine hypothesized associations between diet quality, GI health, and disease activity. We hypothesize that individual biopsychosocial determinants will be associated with diet quality, which will be indirectly associated with disease activity through gut microbiome diversity and level of GI inflammation in adults with RA.

RESULTS: This study was funded in February 2024. As of December 19, 2025, a total of 80 individuals have been recruited. Data analysis has not yet commenced at the time of manuscript submission. Study results are expected to be published in fall 2026.

CONCLUSIONS: RA is a complicated disease that impacts millions. Few individuals reach sustained remission, even while following provider recommendations. A better understanding of the various factors that impact this complicated disease has the potential to support changes in research and care that will improve the lives of people with RA. The knowledge gained in this study will provide a foundation to inform future interventional research targeting diet quality to support GI health and decrease RA disease activity. Further, the details of this research plan provide methodological resources for other RA researchers, and research results have the potential to improve communication between rheumatology providers and patients.

PRR1-10.2196/79889.}, } @article {pmid41505077, year = {2026}, author = {Ghaemi, M and Ghaemi, A and Tavakkoli, H and Mashhadinejad, M and Kheradmand, D}, title = {The MOF-Microbiome Axis: a New Paradigm for Precision Nanomedicine.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41505077}, issn = {1867-1314}, abstract = {The gut microbiome is crucial for human health, and its imbalance, known as dysbiosis, is associated with diseases such as inflammatory bowel disease, metabolic disorders, and neurological disorders. Traditional treatments, such as probiotics and fecal microbiota transplants, often lack precision, making the emerging field of nanomedicine a promising alternative. This review introduces the "MOF-Microbiome Axis," which explores the interactions between metal-organic frameworks (MOFs), versatile, porous materials, and the gut microbiome. It focuses on designing gastrointestinal-targeted MOFs that are biocompatible and responsive to stimuli. We discuss how MOFs can serve as scaffolds, controlled-release vehicles, and metabolite scavengers, highlighting their therapeutic applications in targeted antimicrobial therapy, enhanced probiotic delivery, and immunomodulation. The review also addresses important challenges in biosafety, scalable production, and personalized treatment, suggesting future directions such as bio-hybrid systems and precision microbiome editing. Overall, the MOF-Microbiome Axis offers a new perspective on microbiome engineering and advanced therapeutic approaches.}, } @article {pmid41504923, year = {2026}, author = {Yousefi, F and Salehi, B and Ghorbani, N and Yaghmayee, S and Eslami, M}, title = {Integrative analysis of placental metabolic reprogramming and microbiome alterations in gestational diabetes mellitus (GDM).}, journal = {Acta diabetologica}, volume = {}, number = {}, pages = {}, pmid = {41504923}, issn = {1432-5233}, } @article {pmid41504672, year = {2026}, author = {Somboonna, N and Rujirawan, P and Wongsaroj, L and Promvaranon, T and Rerknimitr, P}, title = {Nail Fold Microbiome Alterations in Patients Treated With Epidermal Growth Factor Receptor Inhibitors.}, journal = {Experimental dermatology}, volume = {35}, number = {1}, pages = {e70201}, doi = {10.1111/exd.70201}, pmid = {41504672}, issn = {1600-0625}, support = {RA61/079//The Ratchadapiseksomphot Endowment Fund, Faculty of Medicine, Chulalongkorn University/ ; }, } @article {pmid41504597, year = {2026}, author = {Larner, W and Thölke da Silva Grego, N and Panfilio, KA}, title = {Intraspecific microbiome dynamics across the life cycle of the milkweed bug Oncopeltus fasciatus.}, journal = {Microbial genomics}, volume = {12}, number = {1}, pages = {}, doi = {10.1099/mgen.0.001583}, pmid = {41504597}, issn = {2057-5858}, mesh = {Animals ; *Heteroptera/microbiology/growth & development ; RNA, Ribosomal, 16S/genetics ; Female ; *Microbiota/genetics ; Life Cycle Stages ; *Bacteria/genetics/classification/isolation & purification ; Male ; *Hemiptera/microbiology ; Phylogeny ; }, abstract = {The microbiome is an important part of the complete nutritional and genomic profile of insects. The species-rich insect order Hemiptera (aphids, cicadas and true bugs) is highly diverse for mode of microbiome acquisition, with the conundrum that species in the seed-feeding subfamily Lygaeinae have lost obvious anatomy for housing bacteria, either in bacteriocytes or midgut crypts. Here, we characterize the microbiome of the milkweed bug Oncopeltus fasciatus as a tractable lygaeinid, using 16S rRNA gene sequencing. We assess how bacterial taxa vary between the sexes and across life history stages in a controlled environment, focusing on maternal-to-embryo transmission and distinguishing egg-stage constituents that are superficial or internal (transovarially transmitted). Among a core microbiome of 28 genera, the egg stage shows the greatest diversity, with a particular expansion of the family Comamonadaceae. We also analyse inter-individual variability in nymphs and adults and validate structured, stage-specific detection of seed material. Comparative analysis identifies Rhizobium as a notable microbiome constituent in seed-feeding Hemiptera, which we had previously shown to lack nitrogen metabolism components in the genome. Overall, we provide a nuanced assessment of bacterial abundance dynamics between individuals and across the life cycle and discuss the implications for acquisition and potential relevance as nutritional endosymbionts. This will underpin comparative investigations in seed-feeding bugs and future work in O. fasciatus on tissue-specific and diet-specific microbiome profiles, including in natural populations.}, } @article {pmid41504479, year = {2026}, author = {Vompe, AD and Hamidizade, M and López, MM and O'Connor, E and Kaur, L and Hockett, KL and Bull, CT}, title = {Translational microbiomes in agriculture: microbial communities as tools to effect host and system health for improved crop production.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0170425}, doi = {10.1128/aem.01704-25}, pmid = {41504479}, issn = {1098-5336}, abstract = {The boom of microbiome research in agriculture over the past several decades allows scientists, growers, policymakers, and businesses to collaborate on a unique opportunity-deploying microbiomes and microbiome attributes for the improvement of crop production. The idea of translational microbiomes is well established in the medical field; however, this framework is relatively new to agriculture. In this review, we discuss a series of methodologies grounded in microbiome science to enhance crop health. These include diagnostic approaches (pathogen and toxin detection and the monitoring of stress-related community ecology patterns) and intervention strategies (synthetic communities, microbiome-aware crop management practices, passaging microbiomes, and exploiting the vertical and lateral transmission of microbiomes to seeds). Developing and implementing these approaches remain challenging due, in part, to a shortage of long-term in situ studies demonstrating the robustness and effectiveness of translational microbiome efforts against the background of heterogeneity and ecological complexity of agricultural systems. Moreover, the cost and availability of 'omics methods central to microbiome analysis, disparate standards for microbiome product development, and limited longstanding relationships with stakeholders have slowed down the application of microbiome-based solutions. However, the increasing cost-effectiveness of microbiome approaches in crop management makes translational microbiomes likely assets in the movement toward precision agriculture. This "personalized treatment" for plants holds promise for improved food security and environmental sustainability, by reducing commonplace synthetic amendments and promoting native microbial biodiversity.}, } @article {pmid41504449, year = {2026}, author = {Xu, J and Ma, J and Lin, H and Yan, S and Niu, H}, title = {Metagenomic and metabolomic analyses of rumen fiber digestion in Mongolian cattle fed fresh grass versus hay.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0305125}, doi = {10.1128/spectrum.03051-25}, pmid = {41504449}, issn = {2165-0497}, abstract = {Mongolian cattle exhibit exceptional roughage tolerance due to their rumen microbiome's robust fiber-degrading capacity, enabling efficient utilization of low-quality forage under the Mongolian Plateau's seasonal fluctuations. This study compared rumen microbial composition, CAZyme profiles, fermentation parameters, and metabolic pathways in cattle fed fresh grass (FG) versus hay to elucidate microbe-metabolite interactions underlying fiber digestion. Thirty non-pregnant female Mongolian cattle (460 ± 35 kg, 3-4 years old) were randomly divided into two groups (n = 15/group): one grazed on FG, the other housed and fed autumn-harvested hay (HG). Six animals per group were subsampled for rumen fluid collection and multi-omics analyses (n = 6/group, total n = 12). Compared with the FG group, the HG group showed an increased molar proportion of acetate and a higher acetate-to-propionate ratio, along with reduced molar proportions of propionate and butyrate in rumen fermentation parameters. Metagenomic analysis revealed a higher abundance of Bacteroidalesbacteria and anaerobic fungi (including Neocallimastix sp.JGI-2020a and Piromyces sp.E2) in the HG group. Functional annotation further indicated enriched carbohydrate metabolism pathways in the HG group, along with a greater diversity of CAZymes, particularly those involved in hemicellulose and pectin degradation. Metabolomics identified 13 differentially abundant carbohydrate metabolites, with gluconolactone upregulated in the HG group. Additionally, carbohydrate metabolism pathways identified in the metabolome corroborated the reliability of the metagenomic functional annotations. Correlation network analysis revealed positive associations of Bacteroidaceaebacteria, Neocallimastix sp.JGI-2020a, and Piromyces sp.E2 with acetate, hemicellulose-degrading GHs, and carbohydrate metabolic pathways. In conclusion, hay feeding enhanced ruminal fiber degradation in Mongolian cattle through increased Bacteroidales and anaerobic fungi, diversified CAZymes (especially hemicellulases/pectinases), and upregulated carbohydrate metabolism, reflecting microbial adaptation to low-quality forage.IMPORTANCEMongolian cattle's superior roughage tolerance depends on a specialized rumen microbiome that degrades fibrous substrates via diverse CAZymes. However, microbe-metabolite interactions driving fiber digestion in this breed remain poorly understood. This study revealed an increased abundance of bacteria and fungi involved in rumen fiber degradation, which may be responsible for secreting enzymes associated with hemicellulose and pectin breakdown. Furthermore, the upregulation of key metabolites, including gluconolactone, indirectly promotes acetate production through pathways such as glycolysis and the pentose phosphate pathway. These findings reveal microbial adaptations enhancing low-quality forage utilization, offering new strategies for improving ruminant efficiency in seasonal or resource-limited grazing systems.}, } @article {pmid41504323, year = {2026}, author = {Lanzara, R and Conti, C and Zito, L and Anaclerio, F and Affaitati, GP and Giamberardino, MA and Stuppia, L and Porcelli, P}, title = {Gut Microbiota and Psychological Distress in Fibromyalgia: A Systematic Review.}, journal = {Biopsychosocial science and medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/PSY.0000000000001463}, pmid = {41504323}, issn = {2998-8756}, abstract = {OBJECTIVE: This systematic review aimed to summarize the recent evidence of the relationship between gut microbiota and psychological distress in patients with fibromyalgia (FM).

METHODS: According to PRISMA guidelines, we conducted a systematic search of the literature on PubMed, Scopus, EBSCO, WOS, and Cochrane. The records were selected using multiple combinations of relevant search terms involving microbiota, psychological distress, and FM. Articles in English with human participants were reviewed.

RESULTS: The initial search identified 135 records, excluding duplicates, of which 10 research reports met the predefined inclusion criteria and were analyzed. Most studies (n=7) were case-control, two were randomized controlled trials, and one was observational. Most studies found an imbalance in the gut microbial communities of FM patients and a significant difference between FM patients and HC in microbiome composition/diversity or gut permeability. Intestinal dysbiosis and gut permeability were also associated with high psychological distress (emotional, cognitive, and somatic symptoms).

CONCLUSION: Alterations in the gut microbiota of FM patients seem to support the hypothesis that gut-brain axis regulation is impaired in stress-related pain conditions. Although the results are promising, further studies are needed to clarify the role of the microbiota-gut-brain axis in the pathophysiological mechanisms underlying FM.}, } @article {pmid41504275, year = {2026}, author = {Xu, C and Antonacci, S and Marques, FZ}, title = {The maternal microbiome influence on pregnancy success: breeding comparison of germ-free and conventionalized mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609405}, doi = {10.1080/19490976.2025.2609405}, pmid = {41504275}, issn = {1949-0984}, mesh = {Female ; Animals ; Pregnancy ; Mice ; *Germ-Free Life ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Bacteria/classification/genetics/isolation & purification/metabolism ; Male ; Diet ; Fertility ; Breeding ; }, abstract = {Germ-free (GF) animals, which are entirely devoid of all microorganisms, are one of the most powerful tools for studying the role of the microbiome in a phenotype, moving the microbiome field from association to causation. They allow the introduction of specific microbes or microbial communities to interrogate the causality of microbiomes in protecting against or contributing to a phenotype. Here, we report critical and underappreciated challenges in using GF models to investigate the intergenerational effects of maternal diet and microbiota on offspring health. Using 57 GF and littermate conventionalized GF dams, we observed unexpectedly high maternal (odds ratio 11.5, p < 0.0001) and offspring (odds ratio 4.12, p < 0.0001) mortality in GF animals. Remarkably, GF dams had an extremely low pregnancy and parturition (pmicrobiome < 0.0001) and a high incidence of cecal torsion (18.2%) compared to the conventionalized group, underscoring the indispensable role of the maternal microbiome in reproductive success and early development. Notably, even conventionalized GF mothers on high-fiber diets exhibited poor fertility, suggesting that microbial colonization timing and maternal microbial capacity to metabolize fiber are crucial. These findings not only reveal significant limitations in GF breeding protocols but also indicate that the maternal microbiota might influence offspring health far earlier than previously recognized, with implications for the developmental origins of health and disease research.}, } @article {pmid41504254, year = {2026}, author = {Lin, P}, title = {The importance of the microbiome in uveitis.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001197}, pmid = {41504254}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: The purpose of this review was to summarize the literature on preclinical and clinical studies demonstrating the impact of the intestinal microbiome in noninfectious uveitis.

RECENT FINDINGS: Preclinical studies using the experimental autoimmune uveitis (EAU) model have shown commensals such as Desulfovibrio and Prevotella, as well as Ruminococcaceae, associated with uveitis, which overlap with some clinical studies in uveitis patients. Interventions that target the microbiome that can be developed for the treatment of uveitis include antibiotics, fecal metabolites or metabolite agonists that are protective in uveitis, probiotics, dietary interventions, or fecal microbial transplant.

SUMMARY: There is significant data supporting the importance of the intestinal microbiome in noninfectious uveitis through enrichment or depletion of certain gut bacteria as well as their metabolites. Targeting the intestinal microbiome or their metabolites might be a viable option for the treatment of noninfectious uveitis.}, } @article {pmid41504167, year = {2026}, author = {Zhou, Q and Gao, X and Wu, Q and Zeng, W and Cao, W and Zhou, T and Cui, X and Chen, J and Gao, D and Zhao, H}, title = {Cross-Kingdom Synthetic Microbiota Suppresses Wheat Fusarium Crown Rot by Remodeling the Rhizosphere Microbiome and Metabolome.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c11786}, pmid = {41504167}, issn = {1520-5118}, abstract = {Fusarium crown rot (FCR) of wheat lacks sustainable control. We assembled a cross-kingdom synthetic microbial community (SMC) of Trichoderma harzianum T19 and five Bacillus strains and tested it in nonsterile soil challenged with Fusarium pseudograminearum. The SMC treatment significantly suppressed FCR, reducing the disease severity index by approximately 70%. Wheat growth and yield were simultaneously enhanced. In the rhizosphere, SMC improved soil health by elevating soil organic matter and nitrogen levels by over 50%, while mitigating pathogen-induced nutrient imbalances and boosting nutrient-cycling enzyme activities. Amplicon sequencing revealed that SMC suppressed pathogenic Fusarium in the rhizosphere and enriched beneficial microbes, including antagonistic fungi (Trichoderma, Chaetomium) and plant growth-promoting bacteria (Pseudomonas, Paenibacillus). Co-occurrence network analysis showed that SMC treatment restructured the rhizosphere microbial network with higher connectivity, stability, and a prevalence of positive cooperative interactions under F. pseudograminearum stress. Defense-related metabolites, such as epi-jasmonic acid, allantoin, Nβ-acetyltryptamine, and dihydrodaidzein, accumulated to higher levels with SMC. These findings demonstrate that the cross-kingdom SMC modulates soil nutrients, microbial community structure, and rhizosphere metabolites to synergistically promote wheat growth and enhance resistance to FCR.}, } @article {pmid41504158, year = {2025}, author = {Chen, T and Guo, Y and Liang, D and Li, D and Xing, S and Li, D and Zhang, C and Wang, F}, title = {Discriminative Gut Microbial Signatures in Hyperuricemia and Overweight Populations Revealed by Metagenomic Sequencing.}, journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition}, volume = {95}, number = {6}, pages = {42590}, doi = {10.31083/IJVNR42590}, pmid = {41504158}, issn = {0300-9831}, support = {S2023KFKT-12//Ministry of Agriculture and Rural Affairs/ ; 2024YFF1107000//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Hyperuricemia/microbiology ; Male ; Female ; *Overweight/microbiology ; Middle Aged ; Cross-Sectional Studies ; Feces/microbiology ; Adult ; Metagenomics ; Metagenome ; }, abstract = {BACKGROUND: This cross-sectional study aimed to investigate the relationships between gut microbiota compositional alterations and chronic metabolic disorders by analyzing taxonomic diversity, community structure, and species-level differences in individuals with hyperuricemia (HUA) and a history of being overweight. Our findings offer novel insights into microbiota-targeted therapeutic strategies for managing metabolic diseases. A total of 144 participants were recruited and divided into three diagnostic categories: healthy controls (HL, n = 29), hyperuricemia group (HU, n = 24), and overweight (OW, n = 91).

METHODS: Comprehensive phenotypic profiles and metagenomes were analyzed for fecal samples from the three groups.

RESULTS: Significant differences were observed in psychological states and microbial ecology between the metabolic disorder groups (HU and OW) and the control group (HL) (p < 0.05). Both the overweight individuals and those with HUA presented significant changes in gut microbial composition, with reduced α-diversity indices (Shannon index: HU vs HL Mann-Whitney U = 306; p = 0.462; OW vs HL Mann-Whitney U = 1008; p = 0.040; richness index: HU vs HL Mann-Whitney U = 307; p = 0.469; OW vs HL Mann-Whitney U = 1072; p = 0.092) compared to healthy individuals. Moreover, analysis of the linear discriminant analysis effect size (LEfSe) identified four discriminatory species in the HU group (Alistipes putredinis, Mediterraneibacter faecis, Streptococcus oralis, and Gemella sanguinis), and five in the OW group (Pantoea endophytica, Pantoea vagans, Phocaeicola coprophilus, Ruminococcus SGB4421, and Klebsiella oxytoca), representing potential biomarkers for the progression of chronic metabolic diseases.

CONCLUSION: This study elucidates the characteristics of overweight individuals and those with HUA in terms of phenotypic features and gut microbiota, providing a theoretical reference for gut microbiota-targeted therapies and lifestyle interventions in chronic metabolic diseases.}, } @article {pmid41503894, year = {2026}, author = {Kim, HS}, title = {Do Akkermansia mutants underlie to the global metabolic disease epidemic?.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612582}, doi = {10.1080/19490976.2025.2612582}, pmid = {41503894}, issn = {1949-0984}, mesh = {Humans ; *Metabolic Diseases/epidemiology/microbiology ; *Mutation ; Anti-Bacterial Agents/pharmacology/adverse effects ; *Akkermansia/genetics/drug effects ; Gastrointestinal Microbiome/drug effects ; Epidemics ; }, abstract = {Antibiotic-induced mutations in Akkermansia muciniphila promote bacterial survival while compromising beneficial host interactions, revealing a potential new link between antibiotic-driven microbiome disruption and metabolic disease. The widespread presence of these mutants suggests that they may contribute to the increasing prevalence of metabolic disorders. If validated in diverse global human cohort studies, these mutants could serve as biomarkers of disease susceptibility and as targets for therapeutic intervention.}, } @article {pmid41503829, year = {2026}, author = {Zhang, H and Wang, Y and Ning, B and Wang, Y and Sun, T and Xu, J}, title = {The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2611203}, doi = {10.1080/07853890.2025.2611203}, pmid = {41503829}, issn = {1365-2060}, mesh = {Humans ; *Obesity/complications/microbiology/immunology ; *Breast Neoplasms/microbiology/immunology/pathology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Female ; *Dysbiosis/microbiology/complications/immunology ; Prognosis ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC.

METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening.

DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies.

CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.}, } @article {pmid41503825, year = {2026}, author = {Kang, K and Kim, JY and Yim, JJ and Kim, D}, title = {Gut-lung axis and microbiome alterations in mycobacterial infections: from pathogenesis to therapeutic potential.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612428}, doi = {10.1080/19490976.2025.2612428}, pmid = {41503825}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology/therapy ; *Lung/microbiology/immunology ; Animals ; Probiotics ; Fecal Microbiota Transplantation ; *Mycobacterium Infections/microbiology/therapy ; }, abstract = {Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), are increasingly recognized as disorders influenced not only by host immunity but also by microbiota. Emerging evidence identifies the gut-lung axis (GLA) as a key bidirectional communication network linking intestinal and pulmonary homeostasis. Mycobacterial infection itself induces airway and gut dysbiosis through immune and metabolic disturbances, which is further exacerbated by prolonged antibiotic therapy. Dysbiosis within either site reciprocally affects the other via GLA, leading to reduced microbial diversity, impaired epithelial integrity, and systemic inflammation. These alterations disrupt metabolite-mediated immunoregulation and attenuate IL-22-driven epithelial defense, thereby weakening bacterial clearance and promoting chronic inflammation. Distinct microbial features, such as the depletion of beneficial SCFA-producing taxa and enrichment of pro-inflammatory anaerobes, are observed in both TB and NTM-PD. Moreover, therapy-induced microbiome remodeling influences treatment response and disease relapse. Restoring microbial balance through probiotics, prebiotics, postbiotics, dietary modulation, or fecal microbiota transplantation offers a promising adjunctive strategy. This review integrates current evidence linking microbiome dysbiosis to mycobacterial pathogenesis and highlights microbiome-targeted interventions as an emerging therapeutic frontier in pulmonary mycobacterial diseases.}, } @article {pmid41503704, year = {2026}, author = {De Palma, G and Costanzini, A and Mohan, V and Sidani, S and Saqib, Z and Pigrau, M and Lu, J and Causada Calo, N and Pinto-Sanchez, I and Verdu, EF and Marcon, M and Barbara, G and Stanghellini, V and De Giorgio, R and Collins, SM and Bercik, P}, title = {The role of gut microbiota in chronic intestinal pseudo-obstruction: exploring fecal microbiota transplantation as a treatment option.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2610597}, doi = {10.1080/19490976.2025.2610597}, pmid = {41503704}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; *Intestinal Pseudo-Obstruction/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; Male ; Female ; Middle Aged ; Adult ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation & purification ; Chronic Disease/therapy ; Aged ; Feces/microbiology ; Disease Models, Animal ; Italy ; }, abstract = {Chronic intestinal pseudo-obstruction (CIPO) is characterized by bowel dilation and obstructive symptoms without any structural blockage. Although the microbiota is known to affect gastrointestinal function, its role in CIPO is poorly understood. We aimed to characterize the CIPO microbiota, investigate its role in disease expression and explore the therapeutic role of fecal microbiota transplantation (FMT). CIPO patients (n = 14) and healthy controls (HC, n = 12) were recruited from Italy and Canada. Microbiota profiles and functions were assessed by 16S rRNA sequencing and PICRUSt. Germ-free NIH Swiss mice were colonized with HC and CIPO microbiota, their intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT), and the expression of host genes by NanoString®. The CIPO microbiota exhibited reduced microbial diversity with dominance of Proteobacteria and altered metabolic function. Mice with CIPO microbiota developed marked bowel distension and slow intestinal transit associated with altered expression of multiple genes related to immunity, the intestinal barrier and neuromuscular function. FMT from a HC improved the microbiota profile, intestinal transit and bowel distension in both CIPO mice and a selected CIPO patient, in whom a marked clinical improvement was sustained for 8 y. Thus, our findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.}, } @article {pmid41503689, year = {2026}, author = {Broedlow, CA and McGaugh, A and Glynn, TR and Cherenack, EM and Miller, C and Alcaide, ML and Bauermeister, JA and Grov, C and Parisi, R and Martinez, D and Carrico, AW and Klatt, NR and Manuzak, JA}, title = {Douching Is Associated With Dysregulated Rectal Mucosal Immunity in Sexual Minority Men.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf577}, pmid = {41503689}, issn = {1537-6613}, support = {//AIDS Healthcare Foundation/ ; //IDSA GERM/ ; P30AI073961//University of Miami Center for AIDS Research/ ; T32AI007433//University of Miami Center for AIDS Research/ ; K23DA060719//University of Miami Center for AIDS Research/ ; L60DA059128//University of Miami Center for AIDS Research/ ; 1F32AI162229//University of Miami Center for AIDS Research/ ; }, abstract = {BACKGROUND: Receptive condomless anal sex (CAS) associates with elevated rectal inflammation and mucosal injury, increasing HIV acquisition risk. Although douching may amplify rectal inflammation and alter microbial communities, this has not been well characterized in sexual minority men (SMM).

METHODS: Ninety-two SMM (median age, 34.6 years) who were HIV negative and reported receptive CAS provided rectal swabs during sexually transmitted infection (STI) clinic visits. Associations among rectal douching, rectal cytokine/chemokine levels, and microbial communities, evaluated via immunoassay and 16S rRNA gene sequencing, respectively, were assessed.

RESULTS: When compared with nondouching SMM (n = 27), SMM who douched (n = 64) reported more receptive CAS partners and displayed elevations in rectal cytokine/chemokines linked to immune activation and inflammation. Lower microbial richness, evenness, and Shannon diversity in SMM who reported douching were observed. Significant associations were identified between microbial alpha diversity metrics and rectal chemokine/cytokine levels. Finally, significant correlations were observed between rectal cytokine/chemokine levels and individual microbial genera.

CONCLUSIONS: Among SMM engaging in receptive CAS, douching may identify those with amplified biobehavioral HIV and STI risk. Elucidating the mechanisms whereby douching dysregulates rectal immune function and alters rectal microbial communities could yield targets for biomedical approaches to optimize HIV/STI prevention in SMM during receptive CAS.}, } @article {pmid41503622, year = {2026}, author = {Briard, M and Guillon, B and Venot, E and Grauso, M and Bruneau, A and Rossignol, MN and Fenaille, F and Castelli, F and Thomas, M and Lezmi, G and Leite-de-Moraes, M and Adel-Patient, K and Saint-Criq, V}, title = {Datasets of 16S rRNA gene amplicon sequences, metabolites, and soluble immune components in bronchoalveolar lavage samples from severe asthmatic and age-matched control children.}, journal = {Data in brief}, volume = {64}, number = {}, pages = {112359}, pmid = {41503622}, issn = {2352-3409}, abstract = {Severe asthma (SA) is a heterogeneous condition characterized by multiple phenotypes, each characterized by different endotypes. Understanding the mechanisms occurring in the lungs of children with SA can help in understanding pathogenesis and in providing the most effective therapeutic strategies. This article describes microbiota, metabolites, and soluble immune components assessed in bronchoalveolar lavage (BAL) fluids from children with severe asthma (n = 20) and age-matched disease controls (n = 10). The article includes: (i) the protocol used to process BAL samples for 16S rRNA gene amplicon sequencing, metabolomic profiling and immune components assays; (ii) the bioinformatics steps applied to 16S rRNA and metabolomics dataset; (iii) an overview of the raw 16S rRNA gene amplicon sequencing data, presented as ASV and affiliation tables, raw data from untargeted metabolomics and the abundances of each of the eighty eight metabolites annotated with the highest confidence level, and concentrations of seventy three cytokines and of total IgG, IgA and IgE. Each dataset is available in the INRAE data repository (https://entrepot.recherche.data.gouv.fr/dataverse/inrae) with respective DOI: MICROBIOTA: 10.57745/LL3TFW, METABOLITES: 10.57745/1L8VRI, IMMUNE COMPONENTS: 10.57745/JOOGRQ These datasets provide valuable resources for further investigating the molecular mechanisms underlying severe asthma in children and its trajectories. They also offer the potential to identify a local signature of severe asthma through complementary multi-omics analyses and to discover local biomarkers associated with asthma endotypes. Datasets can also be reused to compare with other cohorts (children or adults) or to serve as reference datasets for other pulmonary diseases.}, } @article {pmid41503571, year = {2026}, author = {Bajaj, JS and Fagan, A and Sterling, RK and Sikaroodi, M and Gallagher, ML and Lee, H and Matherly, SC and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Thacker, LR and McGinley, JP and Khoruts, A and Gillevet, PM}, title = {The multi-omic basis for hepatic encephalopathy recurrence: Analysis of the THEMATIC trial.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {1}, pages = {101634}, pmid = {41503571}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: The THEMATIC trial demonstrated that fecal microbiota transplantation (FMT) reduces recurrence of hepatic encephalopathy (HE) in patients already receiving lactulose and rifaximin. The aim of this analysis was to identify multi-omic predictors of HE recurrence among THEMATIC trial participants.

METHODS: The THEMATIC trial enrolled patients with cirrhosis and HE who received oral or enema FMT vs. placebo (1-3 administrations) and were followed for 6 months. Outcomes included safety and HE recurrence. Serum, urine, and stool samples were collected at baseline and post-FMT for all participants. Stool metagenomics, serum and urine metabolomics, inflammatory cytokines, and clinical data were analyzed. Differences between patients with and without HE recurrence were assessed using pathway, random forest, and latent factor analyses.

RESULTS: HE recurred in 10 of 60 patients (17%), with significantly higher recurrence in the placebo vs. the FMT groups (40% vs. 8%; p = 0.005). Due to the low recurrence rate in the FMT arms, all patients with recurrence were combined and compared with those without recurrence. Stool metagenomics showed that the abundance of short-chain fatty acid (SCFA) producers (Faecalibacterium, Eubacterium, Bacteroides, Blautia spp.) was lower, while that of GABA-producing taxa (Lactobacillus, Bifidobacterium spp.) was higher, in patients with recurrence. Urine and serum metabolomes separated HE recurrence groups on PLS-DA, with serum butyrate and isobutyrate being most significantly associated (p = 0.008). Pathway analyses revealed upregulation of GABA and neurotransmitter pathways in patients with HE recurrence. Random forest and latent factor analysis indicated that SCFA producers and secondary bile acids were protective, whereas IL-6, GABA producers, nicotine metabolites, and primary bile acids were associated with HE recurrence.

CONCLUSIONS: Secondary analysis of the THEMATIC randomized controlled trial indicates that HE recurrence in patients on lactulose and rifaximin is associated with distinct microbiome and metabolomic profiles, particularly involving SCFAs, GABA metabolism, bile acids, and IL-6.

IMPACT AND IMPLICATIONS: Fecal microbiota transplantation (FMT) reduced hepatic encephalopathy (HE) recurrence in patients receiving lactulose and rifaximin in the THEMATIC trial, but the multi-omic mechanisms underlying this effect were unclear. In this secondary analysis, we found that HE recurrence - regardless of FMT or placebo assignment - was associated with distinct multi-omic signatures, including reduced short-chain fatty acid-producing and increased pathobiont taxa, lower urinary and serum short-chain fatty acids, secondary bile acids, and acetaminophen derivatives, and higher GABA-related and nicotine metabolites, along with elevated IL-6 levels. Notably, patients with greater donor microbiota engraftment had lower rates of HE recurrence. These findings suggest that HE recurrence after FMT reflects a multifactorial process involving alterations in gut metagenomics, systemic metabolomics, inflammation, and donor engraftment.

TRIAL REGISTRATION: www.clinicaltrials.gov: NCT03796598.}, } @article {pmid41503489, year = {2026}, author = {Goddard, TR and Carlson-Jones, JA and Morton, J and Ooi, CY and Tai, A and Warner, MS and Wong, J and Evans, IE and Hopkins, E and Iredell, JR and Jersmann, HP and Whiteson, KL and Bouras, G and Doane, MP and Falk, NW and Green, R and Grigson, SR and Mallawaarachchi, V and Martin, B and Roach, MJ and Ryan, FJ and Tarasenko, A and Papudeshi, B and Drigo, B and Giles, SK and Harker, CM and Hesse, RD and Hodgson, RJ and Hussnain, A and Hutton, A and Inglis, LK and Keneally, C and Kerr, EN and Liddicoat, C and Peddle, SD and Watson, CD and Yang, Q and Decewicz, P and Speck, PG and Mitchell, JG and Dinsdale, EA and Edwards, RA}, title = {Microbial Ecological Signatures Predict Pathogen Emergence and Multidrug Resistance in Cystic Fibrosis Airways up to a Year in Advance.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.28.25342520}, pmid = {41503489}, abstract = {Chronic infections in cystic fibrosis (CF) emerge from gradual ecological transitions in the airway microbiome, yet early predictive markers remain poorly defined. We developed a new autoencoder-based framework that outperforms read-based or metagenome-assembled genome-based analyses at capturing the continuum from health-associated commensals to pathogen-dominated, antibiotic-tolerant communities. This improvement is achieved by integrating taxonomic and functional data from 127 sputum and bronchoalveolar lavage metagenomes from 64 people with CF into latent "Clusters of Phylogeny and Functions" (COPFs). Coupled with gradient-boosted random forests, COPFs predicted Pseudomonas aeruginosa colonisation, multidrug resistance, and impending infection up to a year before clinical detection. The multidrug-resistant P. aeruginosa signature showed the same resistance-mechanism evolution as found in laboratory experiments. The inclusion of eukaryotic markers revealed persistent Aspergillus fumigatus signatures even during culture-negative intervals. Applying our South Australian-trained model to over 1,000 global metagenomes from 22 independent CF datasets, we achieved 94% accuracy in predicting P. aeruginosa status across platforms and geographies, validating the model's universal utility. Our results demonstrate that combining datasets with deep learning reveals conserved ecological and metabolic mechanisms in disease progression, transforming metagenomics into a predictive framework for managing chronic infections.}, } @article {pmid41503459, year = {2026}, author = {Steuart, R and Atkinson, SN and Hoffman, LR and Hung, L and Ding, X and Salzman, N and Russell, CJ}, title = {Longitudinal dynamics of respiratory microbiome composition in infants after tracheostomy placement.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.29.25342834}, pmid = {41503459}, abstract = {Abnormal respiratory microbiomes are reported in children with artificial airways, yet the timing and persistence of these disruptions have not been defined in infants following new tracheostomy placement. We conducted a prospective longitudinal study to characterize airway microbiome dynamics following new tracheostomy placement during early life, a critical period for microbiome development. Fifteen hospitalized infants <=12 months contributed 84 tracheal aspirate samples collected from day 1 through 3 to 4 months post-procedure. 16S rRNA sequencing revealed immediate and sustained community shifts. Staphylococcus abundance increased after tracheostomy, peaking at 40 days (mean 27%) before declining, with a more pronounced bloom in infants without home mechanical ventilation (HMV). Alpha diversity decreased significantly in the first 30 days (p<0.05) and returned to baseline by 61 to 90 days. Beta diversity analysis demonstrated marked compositional changes immediately post-tracheostomy and ongoing divergence through 3 to 4 months. Time since tracheostomy and clinical factors (gestational age, HMV, neurologic impairment) were significantly associated with microbiome structure (p=0.001). These findings provide novel evidence that tracheostomy induces rapid and prolonged airway microbiome disruption in infants, highlighting a previously uncharacterized window of vulnerability with implications for respiratory health and individualized care.}, } @article {pmid41503395, year = {2026}, author = {Oosthuysen, H and Coetzer, K and Madisha, MT and Coetzer, WG}, title = {An Analysis of Vegetation and Microbiome Recovery in Abandoned Agricultural Fields.}, journal = {Ecology and evolution}, volume = {16}, number = {1}, pages = {e72865}, pmid = {41503395}, issn = {2045-7758}, abstract = {Biodiversity is a key indicator of an ecosystem's resilience to disturbances, but farming practices like monocultures can be disruptive. Assessing the biodiversity levels in abandoned fields can help to reveal recovery patterns and inform strategies to conserve biodiversity in agricultural landscapes. The main aim of this study was to assess the pace of natural recovery for a chronosequence of formerly planted fields in a grassland habitat in the Eastern Cape, South Africa. The plant communities were evaluated using species counts, while the bacterial communities were assessed through high-throughput sequencing (HTS) of the 16S rRNA gene. The alpha diversity indices indicated that the diversity levels within the old fields have started to resemble natural conditions for both the plant and microbial communities. Furthermore, the NMDS analyses identified clear variations in bacterial and plant community compositions among differently aged successional groups and the natural habitats. This study provides evidence that biodiversity levels within crop fields can recover from agricultural disturbances. However, considering the significant changes in climate and rainfall patterns in the study area, it remains unclear whether the community structures of the crop fields will reach native conditions in the coming decades, if at all.}, } @article {pmid41503377, year = {2026}, author = {Bonato, A and Parisi, C and Cascetta, P and Reni, A and Meyer, ML and Riudavets, M and Planchard, D and Besse, B and Remon, J and Facchinetti, F and Belluomini, L and Derosa, L and Barlesi, F}, title = {Gut Dysbiosis as a Potential Guide for Immunotherapy (Dis)Continuation After 2 Years in NSCLC: A Brief Report.}, journal = {JTO clinical and research reports}, volume = {7}, number = {1}, pages = {100928}, pmid = {41503377}, issn = {2666-3643}, abstract = {BACKGROUND: Although most phase III pivotal trials have set the duration of immune checkpoint blockers (ICB) for advanced NSCLC at 2 years, the criteria for safely discontinuing ICB remain undefined. Growing evidence links ICB efficacy to gut microbiota, positioning gut microbial taxonomic profiling as a promising biomarker to guide treatment decisions. We performed a retrospective analysis exploring clinical outcomes and the utility of multiomic decision-making tools in patients with NSCLC at Gustave Roussy who completed 24 months of ICB-based therapy without disease progression (PD).

METHODS: Patients receiving ICB between July 2016 and January 2023 were identified from the ONCOBIOTICS (NCT04567446) and STING (NCT04932525) study datasets. We selected those who reached 24 months of treatment without disease progression. Clinical characteristics and multiomic assessments, including gut microbiota profiling (TOPOSCORE by whole-genome sequencing), positron emission tomography-18-fluorodeoxyglucose imaging, and circulating tumor DNA, collected at 24 months, were analyzed. Key outcomes included overall survival (OS), progression-free survival (PFS), and PFS rates at 24 months after the completion of 2 years of ICB, stratified by molecular, metabolic, and microbial signatures.

RESULTS: Out of 123 patients treated for at least 18 months, 35 completed 24 months, with 31 eligible for the analysis. Of these, 68% continued ICB, whereas 32% discontinued therapy at the physician's decision. Clinical characteristics were similar across groups. After a median follow-up of 59.1 months, OS and PFS did not differ significantly between those who discontinued and those who continued treatment (OS p = 0.9012). Among all multiomic tools, gut microbiota composition exhibited a trend (though not statistically significant) association with PFS rates at 24 months after the completion of 2 years of ICB. Patients with a favorable microbiota profile had a higher rate of sustained response at 24 months compared with those with dysbiotic signatures (81% versus 44%, respectively, p = 0.0870).

CONCLUSIONS: Discontinuing ICB after 24 months did not negatively impact OS in our real-world cohort. Although limited by the small sample size, these findings support the potential of gut microbiota profiling as a promising tool to guide ICB duration. Integrating a translational multiomic algorithm, in particular microbial signals, may help personalize treatment strategies and safely shorten immunotherapy courses.}, } @article {pmid41503356, year = {2025}, author = {Alobaidi, S}, title = {The gut-kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1675458}, pmid = {41503356}, issn = {2296-858X}, abstract = {Chronic kidney disease (CKD) remains a major global health issue, affecting millions and presenting persistent diagnostic and therapeutic challenges. Conventional biomarkers such as serum creatinine and estimated glomerular filtration rate have well-recognized limitations, underscoring the need for novel diagnostic tools and interventions. Emerging evidence highlights the gut-kidney axis as a central contributor to CKD pathogenesis, shaped by microbial dysbiosis and altered metabolite production. Harmful metabolites such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide promote inflammation, endothelial dysfunction, and fibrosis, while loss of protective short-chain fatty acids impairs barrier integrity and immune regulation. This review integrates mechanistic, translational, clinical, and therapeutic perspectives, offering a comprehensive and distinctive synthesis of current knowledge. We emphasize both harmful and protective microbial metabolites, incorporate the often-overlooked oral-gut-kidney axis, and highlight advances in multi-omics and computational approaches for biomarker discovery. Microbiome-targeted interventions-including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation-are critically evaluated with respect to efficacy, safety, and translational readiness. By bridging basic science, clinical evidence, and therapeutic implications, this review provides a forward-looking framework for integrating microbiome insights into CKD diagnosis and management. Our synthesis complements existing literature while highlighting unmet needs, thereby informing future research priorities and guiding the development of clinically relevant microbiome-based strategies.}, } @article {pmid41502987, year = {2026}, author = {Mohan, R and Johnson, SD and Dean, PN and Acharya, A and Byrareddy, SN}, title = {Methods to characterize the vaginal microbiome in a rhesus macaque model of simian human immunodeficiency virus (SHIV) transmission uncover epithelium-associated enrichment of Prevotella.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100526}, pmid = {41502987}, issn = {2666-5174}, abstract = {The vaginal microbiome plays a crucial role in maintaining mucosal integrity and mitigating pathogen transmission, yet its comprehensive characterization remains challenging due to limited sampling and analysis methods. In this study, we aimed to characterize bacterial and fungal taxa diversities in the vaginal microbiomes of Simian Human Immunodeficiency (SHIV)-infected rhesus macaques, as well as their metabolic activities, using three sampling methods. The cervicovaginal lavage (CVL), vaginal swab, and vaginal mucosal tissue methods offer novel insights into microbial diversity and their potential impacts on HIV transmission. Using 16S rRNA and Internal Transcribed Spacer (ITS) sequencing, we assessed bacterial and fungal community composition and abundances, respectively, across all sampling methods. PICRUSt2 was used for functional predictions, and a modified glycosidase assay to further characterize glycan-degrading enzymatic activity in CVL samples. Our findings reveal that tissue samples were uniquely enriched for microbial taxa such as Prevotella spp. and Helicobacter spp., showing notable abundance differences compared to CVL and swab samples. Tissue samples exhibited higher alpha diversity and distinct metabolic prediction profiles, particularly elevated sialidase activity. While fewer differences were found in fungal microbiome composition and diversity, marked correlations were observed between bacterial and fungal taxa, emphasizing complex interkingdom interactions. These results highlight the significance of sampling methods in microbial ecology studies, which should be carefully considered due to their potential influence on pathogen transmission risk.}, } @article {pmid41502951, year = {2025}, author = {Oliveira, RA and McSpadden, E and Pandey, B and Lee, K and Yousef, M and Chen, RY and Triebold, C and Haro, F and Aksianiuk, V and Patel, R and Shriram, K and Ramanujam, R and Kuehn, S and Raman, AS}, title = {Statistical design of a synthetic microbiome that suppresses diverse gut pathogens.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.28.582635}, pmid = {41502951}, issn = {2692-8205}, abstract = {Engineering functional microbiomes is challenging due to complex interactions between bacteria and their environments [1-6] . Using a set of 848 gut commensal strains and clearance of multi-drug resistant Klebsiella pneumoniae (Kp -MH258) as a target function, we engineered a functional 15-member synthetic microbiome-SynCom15-through a statistical approach agnostic to strain phenotype, mechanism of action, bacterial interactions, or composition of natural microbiomes. Our approach involved designing, building, and testing 96 metagenomically diverse consortia, learning a generative model using community strain presence/absence as input, and distilling model constraints through statistical inference. SynCom15 cleared Kp -MH258 across in vitro , ex vivo , and in vivo environments, matching the efficacy of a fecal microbiome transplant in a clinically relevant murine model of infection. The mechanism of suppression by SynCom15 was related to fatty acid production coupled with environmental acidification. SynCom15 also suppressed other pathogens- Clostridioides difficile , Escherichia coli , and other K. pneumoniae strains-but through different mechanisms. Sensitivity analysis revealed models trained on strain presence/absence captured the statistical structure of pathogen suppression, illustrating that community representation was key to our approach succeeding. Our framework, 'Constraint Distillation', could be a general and efficient strategy for building emergent complex systems, offering a path towards synthetic ecology more broadly.}, } @article {pmid41502883, year = {2025}, author = {Zhang, C and Lin, G and Lu, X and Yu, X}, title = {Exploring the role of the gut microbiome in pediatric gastrointestinal and neurological health.}, journal = {Translational pediatrics}, volume = {14}, number = {12}, pages = {3449-3472}, pmid = {41502883}, issn = {2224-4344}, abstract = {The gut microbiome, a complex ecosystem of microorganisms that inhabit the gastrointestinal (GI) tract, is now understood to be a central regulator of pediatric health and development. This review discusses its centrality in GI and neurological outcomes, with a particular focus on the devastating effects of malnutrition. It also discusses how microbial homeostasis (dysbiosis), especially that induced by protein-energy and micronutrient deficiencies, interferes with nutrient absorption, enhances intestinal inflammation, and alters gut-brain communication. Dysbiosis is mechanistically connected to the pathogenesis and severity of other pediatric disorders, such as inflammatory bowel disease (IBD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). The most important pathways of gut dysbiosis-related disease mechanisms. include the altered production of microbial metabolites such as short-chain fatty acids (SCFAs), impaired gut barrier integrity ("leaky gut"), and disrupted immune and neuroendocrine signaling. To address these issues, this article outlines potential therapeutic solutions that seek to restore microbial balance. Targeted probiotic and prebiotic supplementation, dietary interventions, and the emerging field of precision nutrition, which enables interventions to be tailored based on a child's individual microbiome and genetic makeup, are also mentioned as possible ways to improve the GI and neurological health of malnourished children. Learning how these interactions between the gut microbiome, nutrition, and the gut-brain axis (GBA). Work could revolutionize the development of new treatments for preventing and treating pediatric diseases caused by microbial imbalances.}, } @article {pmid41502856, year = {2025}, author = {Sherwani, SK and Kahsen, JJ and Wu, LYA and Green, SJ}, title = {Novel short primers for next-generation 16S rRNA gene amplicon sequencing.}, journal = {Journal of biomolecular techniques : JBT}, volume = {36}, number = {4}, pages = {5-18}, pmid = {41502856}, issn = {1943-4731}, mesh = {*RNA, Ribosomal, 16S/genetics ; *High-Throughput Nucleotide Sequencing/methods ; *DNA Primers/genetics ; Sequence Analysis, DNA/methods ; Feces/microbiology ; }, abstract = {Primers for 16S rRNA gene amplification are generally degenerate to account for mismatches between primers and templates, but primer lengths are typically not adjusted. However, prior research has shown that primers are most sensitive to mismatches at the 3' end, and 3' mismatches can limit the ability of primers to amplify target genes from complex microbial communities. We present here a novel approach to primer design by creating staggered and truncated (both the 5' and 3' ends) versions of commonly used microbial 16S ribosomal RNA (rRNA) primers while maintaining consistent melting temperatures. Genomic DNA extracted from complex microbial communities (skin, feces, wastewater, soil) was profiled using deep sequencing of 16S rRNA gene amplicons generated with standard and truncated primers. Sequence data were compared using standard bioinformatics pipelines evaluating alpha and beta diversity. Despite using primers as short as 10 bases, observed microbial communities generated with truncated primer pools were highly similar to those generated with standard primer pools. In analyses of skin, truncated amplicons had significantly increased relative abundance of Cutibacterium which contain 3' mismatches with standard primers. Further analysis revealed a single nucleotide position in a common 16S rRNA gene primer that enriched microorganisms from the domain Archaea with truncated primers. These results demonstrate the viability of using short primers for amplicon NGS, indicating the availability of greater primer design flexibility for future studies.}, } @article {pmid41502473, year = {2026}, author = {Joyce, J and K, PV and K, J and K, RE}, title = {Application of AI for the functional elucidation of rice associated microbial community for the improved productivity.}, journal = {3 Biotech}, volume = {16}, number = {1}, pages = {63}, pmid = {41502473}, issn = {2190-572X}, abstract = {UNLABELLED: Rice microbiome plays a critical role in the growth, health, stress tolerance, nutrient uptake, root development, and productivity of its host. In this study, advanced machine learning algorithms were applied to analyze the genomic data from 1365 rice-associated bacteria sourced from Bacterial and Viral Bioinformatics Resource Center (BV-BRC) database. After filtering, the genomic data of 280 organisms were selected and annotated to identify their respective genes. These were further categorized into ortholog groups, and based on the presence and absence of the ortholog groups, the organisms were clustered into eight groups. Genes encoding amino acid transport, inorganic ion transport and metabolism were the most common Clusters of Orthologous Genes (COG) categories observed across the various clusters while cellular process, biological regulation, and response to stimuli were the most common gene ontology terms. However, the presence of a large proportion of genes having unknown functions suggests the distribution of novel genes which could facilitate the functions including the plant colonization. Further to this, machine learning models were used to classify the organisms as either beneficial or pathogenic. Here, Support Vector Machine based analysis showed the highest accuracy (92.98%) when compared to the Logistic Regression (90.16%) and Random Forest (57.80%). From the analysis, ABC-type transporters such as ABC-type oligopeptide transport system were more abundantly distributed in beneficial bacteria. On the other hand, transposase such as Transposase InsA were observed to be common among pathogenic strains. From the results obtained, the presence of genes responsible for the nutrient transport and metabolic versatility was found to be significant for the beneficial bacteria, while the genetic variability was remarkable for the pathogens. The information generated in this study hence highlights the power of AI for predicting the beneficial interactions between the rice and its microbiome, and thereby offer its applications in enhancing the crop resilience and productivity for the sustainable agricultural practices.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04665-z.}, } @article {pmid41502470, year = {2026}, author = {Shukla, A and Yadav, M and Malik, MZ and Aditya, AK and Kumar, A and Tandon, R and Shalimar, and Ray, AK}, title = {Soil influences on rural versus urban human gut microbiota and implications on cardio-metabolic health: a comparative pilot study.}, journal = {3 Biotech}, volume = {16}, number = {1}, pages = {62}, pmid = {41502470}, issn = {2190-572X}, abstract = {UNLABELLED: Humans are exposed to surrounding soil environment and this exposure has reduced with growing urbanisation. Limited evidence exists on how rural and urban soils shape human gut microbiome and related functions. Here, we performed metagenomic analysis, functional prediction, gene ontology using QIIME2, PICRUSt, and DAVID by taking human stool and soil samples (n = 20) from rural and urban settings to characterise gut microbiota and their resemblance to their respective soil microbiota and its functional implications. Our findings demonstrated that soil environment affects gut microbial diversity and abundance of its immediate human inhabitants in both groups and observed shared microbial and functional properties in rural- and urban-guts characteristic of their respective soil microbiota. In rural-group, phylum Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, class Actinobacteria were major overlapping features, while in the urban-counterpart phylum Proteobacteria, Firmicutes, class Gammaproteobacteria were observed. We also demonstrated implication of this differential composition on human health in both settings, and observed enrichment of cytokines like IL-12, IFN-ϒ, and oxidative phosphorylation pathway in rural group vital to metabolic homeostasis. While enrichment of response to toxic substances, methane metabolism, and potentially low levels of alanine in the urban counterpart, linked to impaired immune response and metabolism, suggests urban group may be prone to the cardio-metabolic disease risk. These observations were consistent with other findings emphasising rural groups have healthy sets of microbiome compared to their urban counterpart. In conclusion, our findings unveil the significance of soil microbiota in evolution and shaping of human gut microbiota, thereby potentially beneficial to human health.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04675-x.}, } @article {pmid41502453, year = {2026}, author = {Xie, H and Hu, X and Wang, S and Liu, H and He, Z and Ji, H and Lv, K and Zhu, T and Wang, J}, title = {Unraveling the differences in meat flavor of duck and its regulatory mechanisms based on microbiomics, metabolomics, and flavoromics sequencing.}, journal = {Current research in food science}, volume = {12}, number = {}, pages = {101281}, pmid = {41502453}, issn = {2665-9271}, abstract = {Consumers increasingly demand high-quality duck meat flavor, with reports showing notable flavor variations among different duck breeds. This study aims to clarify the flavor differences between Jinling white duck (JL), Cherry Valley duck (CV), and Liancheng white duck (LC), as well as to elucidate the regulatory mechanisms. Electronic-nose results revealed distinct flavor differences among LC, CV, and JL. The analysis showed that the JL vs. CV group contains 330 differential VOCs and 119 differential water-soluble compounds, while the JL vs. LC group has 112 differential VOCs and 74 differential water-soluble compounds. Metabolomic analysis of the pectoral muscle revealed 74 differential precursors compounds in the JL vs. CV comparison, and 147 in JL vs. LC comparison. Multi-omics analysis suggested that Anaerotruncus and Lautropia may negatively regulate the deposition of flavor precursor LPE O-14:1 in pectoral muscle, influencing 3-methyl-pentadecane and cholic acid levels, thereby affecting the duck meat flavor. These findings demonstrate that JL exhibits distinct flavor characteristics compared to LC and CV, providing valuable insights for meat quality improvement in the poultry industry.}, } @article {pmid41502447, year = {2025}, author = {van Bentum, S and O'Banion, BS and Gates, AD and Van Pelt, HA and Bakker, PAHM and Pieterse, CMJ and Lebeis, SL and Berendsen, RL}, title = {Microbiome responses to natural Fusarium infection in field-grown soybean plants.}, journal = {Plant and soil}, volume = {516}, number = {2}, pages = {1347-1363}, pmid = {41502447}, issn = {0032-079X}, abstract = {AIMS: The rhizosphere microbiome influences plant health, for example, by mediating plant-pathogen interactions. Plants can recruit protective microbes in response to disease, but the consistency of this process in field conditions is unclear. We aimed to identify candidate beneficial microbes enriched during pathogen infection across multiple fields, offering potential to support crop resilience against disease.

METHODS: DNA amplicon sequencing was employed to examine the rhizosphere microbiome of field-grown soybean (Glycine max L.) naturally infected with root pathogens across three commercial fields in Kentucky, USA. Symptomatic and asymptomatic plants were sampled to assess disease-associated shifts in the bacterial and fungal rhizosphere microbiome.

RESULTS: We identified a diverse Fusarium community, with one Fusarium solani amplicon sequence variant (ASV) consistently enriched in diseased plants, identifying it as the likely pathogen. While microbial communities differed between diseased and healthy plants, these shifts were largely field-specific. Several fungal ASVs with known biocontrol potential (Clonostachys rosea, Penicillium, and Trichoderma) were enriched in healthy plants, implying a role in disease suppression. A Sphingomonas ASV, representing a genus previously linked to plant protection, was more abundant in diseased plant rhizospheres in two fields, suggesting pathogen-triggered recruitment. Conversely, Macrophomina phaseolina, a generalist root pathogen, was enriched in the rhizosphere of diseased plants in all fields, indicating possible co-infection with F. solani.

CONCLUSIONS: These findings reveal complex pathogen-associated patterns in the rhizosphere microbiome of field-grown plants and emphasize the need for field-specific microbiome research to inform sustainable disease management strategies.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11104-025-07798-5.}, } @article {pmid41502197, year = {2025}, author = {Hasan, I}, title = {Short-Chain Fatty Acids in the Gut-Brain-Liver Axis: Implications for Hepatic Encephalopathy.}, journal = {Acta medica Indonesiana}, volume = {57}, number = {4}, pages = {433-435}, pmid = {41502197}, issn = {2338-2732}, mesh = {Humans ; *Hepatic Encephalopathy/metabolism/etiology/epidemiology/microbiology ; *Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism ; *Liver Cirrhosis/complications ; Indonesia/epidemiology ; *Liver/metabolism ; *Brain/metabolism ; Cross-Sectional Studies ; Feces/chemistry ; }, abstract = {Hepatic encephalopathy (HE) is one of the serious complications of liver cirrhosis, characterized by a broad spectrum of neuropsychiatric symptoms, ranging from subtle cognitive impairment to coma, due to brain dysfunction associated with acute or chronic liver failure and/or portosystemic shunting. Globally, the prevalence of hepatic encephalopathy (HE) is reported to range from 20% to 80% in patients with liver cirrhosis, depending on whether the assessment includes minimal (MHE) or overt (OHE) forms. In Indonesia, determining the true prevalence of HE is challenging due to diagnostic difficulties, with estimates ranging from 30% to 84%. At Cipto Mangunkusumo General Hospital, the prevalence of HE in 2009 was 63.2%. In recent years, evidence has highlighted the role of the gut microbiota in the pathogenesis of hepatic encephalopathy (HE), a concept now widely referred to as the "gut-liver-brain axis." Short-chain fatty acids (SCFAs) are gut microbial-derived metabolites that provide numerous health benefits. SCFA has been demonstrated to impact gut barrier function, immunomodulation, and glucose homeostasis. In this issue, Ferdianto et al. conducted a cross-sectional observational study comparing the amount and composition of fecal SCFA in cirrhotic patients with and without HE. The study revealed no significant difference in SFA levels between HE and non-HE groups; however, the HE groups demonstrated higher levels of total SCFA, acetate, and butyrate compared to the non-HE groups. While this study contributes valuable early evidence from an Indonesian cohort, several important limitations should be acknowledged. First, the diagnostic approach for covert or minimal HE requires clarification. The authors did not explicitly state the neuropsychological tools and specific criteria used. Clear definitions are essential, as minimal and covert HE is susceptible to the choice of diagnostic method and can substantially influence group classification. Second, although SCFAs represent key microbial metabolites, the study did not explore the underlying microbiome composition. Without bacterial taxonomy or species-level data, it remains difficult to determine whether differences in SCFA levels truly reflect gut dysbiosis or altered microbial diversity. SCFA concentrations may be influenced by multiple factors, and therefore, inclusion of metagenomic or sequencing data would strengthen the mechanistic interpretation and allow linking specific bacterial taxa with cognitive impairment. Future studies that include larger and more heterogeneous cohorts, alongside integrated analyses of microbiome composition and validated neurocognitive testing, will be crucial to validate the role of SCFAs in HE development.}, } @article {pmid41502172, year = {2026}, author = {Ushijima, B and Beurmann-Grant, S and Ruiz-Toquica, J and Gongaware, CK and Jefferson, T and Weber, WC and Videau, P and Häse, CC}, title = {The Coral Host Microbiome Modulates the Virulence of the Bacterial Pathogen Vibrio coralliilyticus.}, journal = {Environmental microbiology}, volume = {28}, number = {1}, pages = {e70224}, pmid = {41502172}, issn = {1462-2920}, support = {//University of North Carolina Wilmington/ ; //Oregon State University/ ; }, mesh = {*Anthozoa/microbiology ; Animals ; *Vibrio/pathogenicity/genetics ; Virulence ; *Microbiota ; Quorum Sensing/genetics ; Coral Reefs ; Pseudoalteromonas/pathogenicity ; Host-Pathogen Interactions ; }, abstract = {Coral disease outbreaks pose a major threat to reef ecosystems, often leading to widespread mortality and declines in coral cover. A key factor predicted in disease susceptibility is the coral microbiome, which is thought to protect corals from pathogens like Vibrio coralliilyticus. However, this protective function has not been empirically demonstrated with live coral, nor is it well understood how these microbiome-pathogen interactions contribute to the observed variation in virulence among different V. coralliilyticus strains. This study investigated the role of the Hawaiian rice coral (Montipora capitata) microbiome in susceptibility to infection by endemic and non-endemic strains of V. coralliilyticus. Laboratory infection experiments revealed that antibiotic-induced dysbiosis generally increased host susceptibility, though infection rates varied between strains. Notably, the type of M. capitata colour morph did not influence infection outcomes, and induced dysbiosis did not affect susceptibility to another pathogen, Pseudoalteromonas piratica. Additionally, the quorum sensing genes vcpR and aphA were examined for their roles in V. coralliilyticus pathogenicity in relation to the host microbiome. These findings underscore the protective function of the coral microbiome and highlight the complexity of host-pathogen interactions, contributing to a deeper understanding of coral disease dynamics and informing future mitigation strategies.}, } @article {pmid41501907, year = {2026}, author = {Ben Fredj, S and Kechiche, H and Chouchen, A and Akkari, I and Ghammam, R and Zammit, N and Douss, N and Skhiri, A and Maoua, M and Maatoug, J and Harrabi, I and Maalel, OE}, title = {Probiotic intake and mental health in healthy working adults: a systematic review and meta-analysis of randomized controlled trials.}, journal = {BMC psychology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40359-025-03885-5}, pmid = {41501907}, issn = {2050-7283}, abstract = {BACKGROUND: Workers face significant mental health challenges from stress, anxiety, and depression, impacting individuals, organizations, and society. Emerging research indicates a link between the gut microbiome and mental well-being, suggesting probiotics as a potential support. This study objectively evaluated probiotic supplementation's effects on depression, anxiety, stress, sleep, and related biological markers in this population.

METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. EMBASE, Cochrane Library, and PubMed were searched for randomized controlled trials assessing probiotic supplementation on a range of psychological outcomes. The primary outcomes were perceived symptoms of depression, anxiety, stress, and sleep quality. The secondary outcomes were physiological markers of mental health, such as cortisol and C-reactive protein levels, in working populations. Eligible studies included healthy employed adults (≥ 18 years), without psychiatric, neurodegenerative, genetic, infectious, or endocrine disorders, including pregnancy.

RESULTS: Twelve studies involving 3,350 participants were incorporated. Probiotic consumption had a modest yet statistically significant positive effect on subclinical psychological outcomes, including symptoms of depression, anxiety, and stress, in healthy working adults (standardised mean difference (SMD) = -0.21, 95% CI [-0.34, -0.09], p = 0.001). These findings were maintained despite moderate statistical heterogeneity that was likely due to variations in probiotic strains, dosages, and duration of supplementation used. Moreover, the probiotic interventions were associated with a statistically significant reduction in cortisol levels, a key biomarker of physiological stress (SMD = -0.26, 95% confidence interval [CI] [-0.45, -0.08], p = 0.005). Conversely, no statistically significant effects were observed for probiotic supplementation on the C-reactive protein levels, a marker of systemic inflammation. However, due to the lack of available evidence, it was impossible to draw firm conclusions about the effects of probiotics on sleep quality and biomarkers of oxidative stress.

CONCLUSION: This systematic review and meta-analysis provide preliminary evidence suggesting that probiotic supplementation may hold promise as an approach to improve mental well-being within working populations. However, further high-quality randomised controlled trials targeting this population are needed to determine the optimal probiotic strains, dosages, and treatment durations for addressing specific mental health outcomes.

TRIAL REGISTRATION: PROSPERO number CRD42024510170.}, } @article {pmid41501865, year = {2026}, author = {Sun, J and Meng, Y and Chen, Z and Zhao, T and Yang, C and Chen, S and Wang, J and Tian, L and Song, F and Duan, Y and Cai, W and Zhang, X and Li, H}, title = {Gut microbiome convergence and functional adaptation underlie the evolution of predation in stink bugs (Heteroptera: Pentatomidae).}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02300-w}, pmid = {41501865}, issn = {2049-2618}, support = {31730086//National Natural Science Foundation of China/ ; 110202101046[LS-06]//Pests and Diseases Green Prevention and Control Major Special Project/ ; xinkywdzc-2025001-91//Project of Fund for Stable Support to Agricultural Sci-Tech Renovation/ ; }, abstract = {BACKGROUND: True bugs (Heteroptera) have undergone repeated evolutionary shifts between phytophagous and carnivorous feeding strategies. Although gut microbiomes are recognized for aiding dietary adaptation, their function in mediating these transitions is still unclear, specifically, how microbial communities change during dietary evolution and influence the diversification of feeding traits.

RESULTS: Here, we selected a stink bug lineage of the subfamily Asopinae (Pentatomidae), representative of an independent feeding trait transition from phytophagy to carnivory. Their gut microbiomes were analyzed and compared to those of closely related phytophagous species within the Pentatomidae family, as well as predatory assassin bugs from the Reduviidae family, which represent the ancestral heteropteran feeding trait of predation. It was found that Asopinae lack the gammaproteobacterial symbionts and midgut crypts that are conserved in their phytophagous counterparts. Instead, their gut microbiomes converged on a community dominated by Enterococcus (Firmicutes) and select Proteobacteria (Serratia, Yokenella, Proteus), mirroring the microbiome of assassin bugs. This core community persisted despite prey variation, likely maintained through pentatomid ancestral eggshell-piercing behavior, enabling vertical transmission. Metagenomic analysis linked the Asopinae microbiome to functions potentially associated with predation adaptation, including the digestion of chitinous substrates likely sourced from prey's internal body. Through bacterial isolation, genomics, and functional assays, we demonstrated that Serratia mediates chitin degradation, which along with a potential coordination in diet digestion, may also have been involved in an antifungal effect. Meanwhile, an Enterococcus strain exhibits inhibition to multiple pathogens such that may provide protections to the host, potentially via a class III lanthipeptide.

CONCLUSIONS: Our findings reveal a coordinated restructuring of the gut microbiome during dietary shifts. The convergence of Asopinae and Reduviidae microbiomes underscores how microbial communities may have facilitated the ecological adaptation, likely by enabling hosts to exploit new dietary niches and providing defense against bacterial and fungal pathogens. Video Abstract.}, } @article {pmid41501528, year = {2026}, author = {Huang, Z and Liu, Y and Wu, Y and Zhang, F and Yu, L and Gao, S and Wen, W and Wang, G and Su, R and Xia, P and Zhou, Q and Bie, Y and Hu, P and Burgermeister, E and Lan, P and Wu, X and Zhang, H and Zhang, F and El-Omar, EM and Zuo, T}, title = {Gut mucosal mycobiome profiling in Crohn's disease uncovers an AMP-mediated anti-inflammatory effect of Cladosporium sphaerospermum.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {41501528}, issn = {2522-5812}, support = {82172323//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100134//National Natural Science Foundation of China (National Science Foundation of China)/ ; 823B2010//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32372334//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82304144//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Crohn's disease (CD) is a subtype of inflammatory bowel disease that most commonly affects the terminal ileum and is associated with abnormal gut microbiome composition. However, the fungi of the small bowel mucosa and their metabolic functions, particularly protective ones, remain largely unexplored. We enrolled patients with CD and healthy individuals from three independent cohorts and conducted multi-omics profiling of the ileal mucosal mycobiome and bacteriome, along with the faecal mycobiome, bacteriome and metabolome. We show that compared to a healthy mucosa, the fungus Cladosporium sphaerospermum is remarkably depleted in the mucosa of patients with CD, yet remains unchanged in faeces. Subsequent causality studies reveal that C. sphaerospermum occupies the intestinal crypt niche and counteracts intestinal inflammation partly by adenosine 5'-monophosphate (AMP) production, as demonstrated in mice, in vitro and in fungal cultures. Mechanistically, C. sphaerospermum upregulates epithelial cell junctions and the Wnt signalling pathway. Our study unveils a mucosa-associated beneficial fungus, suggesting potential novel microbial intervention strategies for CD.}, } @article {pmid41500802, year = {2026}, author = {Lee, CH and Bui, TPN and Petitfils, C and Jian, C and Wong, GC and Puel, A and Le Roy, T and Bellais, S and Ben Abdallah, B and Nehlich, M and Leicht, T and Jia, M and Hoyles, L and Federici, M and Fernández-Real, JM and Burcelin, R and Dumas, ME and Delzenne, NM and Clavel, T and Boeren, S and Troise, AD and Scaloni, A and Muccioli, GG and De Vos, WM and Van Hul, M and Cani, PD}, title = {Novel myo-inositol to butyrate fermentation pathway in the prevalent human gut species Dysosmobacter welbionis, a bacterium associated with improved metabolic and liver health.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336617}, pmid = {41500802}, issn = {1468-3288}, abstract = {BACKGROUND: Dysosmobacter welbionis is a recently discovered butyrate producer whose presence in stool correlates with improved metabolic health. Whether its abundance is reduced in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. Mechanistic insight into its butyrate production from myo-inositol, a dietary compound from fruits, beans, grains and nuts with metabolic benefits, is also limited.

OBJECTIVE: To assess population-level distribution, relative abundance and strain diversity of D. welbionis in humans, and to elucidate its metabolic capacity to ferment myo-inositol into butyrate.

DESIGN: We analysed several human cohorts for associations with liver health and evaluated D. welbionis J115[T] supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined [13]C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics.

RESULTS: We found that D. welbionis and two related species (D. hominis and D. segnis) are prevalent gut bacteria in the human gut. D. welbionis abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with D. welbionis J115[T] improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical myo-inositol-to-butyrate fermentation pathway. 19 human strains were isolated, comparative genomics of 23 strains revealed an open pangenome (about 2100 core genes) including the full myo-inositol fermentation pathway.

CONCLUSION: D. welbionis possesses a unique, conserved route to convert dietary myo-inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.}, } @article {pmid41500696, year = {2025}, author = {Huang, Y and Yang, X and Zhang, S}, title = {[Multi-target mechanism and clinical transformation of hyperbaric oxygen therapy in the treatment of hypoxic-ischemic brain injury after cardiopulmonary resuscitation].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {37}, number = {12}, pages = {1170-1175}, doi = {10.3760/cma.j.cn121430-20250605-00317}, pmid = {41500696}, issn = {2095-4352}, mesh = {Humans ; *Hyperbaric Oxygenation ; *Cardiopulmonary Resuscitation/adverse effects ; *Hypoxia-Ischemia, Brain/therapy/etiology ; Heart Arrest/therapy ; Oxidative Stress ; Apoptosis ; Blood-Brain Barrier ; }, abstract = {Cardiopulmonary resuscitation (CPR) is a critical life-saving intervention for patients who have suffered cardiac arrest (CA), which helps the organism of CA patients to rapidly restore respiratory and circulatory functions. However, the survival rate of patients after CPR is extremely low. Globally, sudden cardiac arrest causes over 3 million deaths annually, and the survival rate after CPR is less than 8%. Hypoxic ischemic brain injury (HIBI) is the primary cause of death in 68% of these cases. Hyperbaric oxygen therapy (HBOT) enhances the dissolution of oxygen in plasma, increases the arterial blood oxygen partial pressure in the body, and improves tissue hypoxia. It is widely used in conditions of cerebral ischemia and hypoxia (such as stroke, CA, etc), but its role in HIBI following CPR has not been fully studied. Therefore, this article systematically reviews the multi-target mechanisms of HBOT in the treatment of HIBI, including the inhibition of cell apoptosis and necrosis, improvement of oxidative stress, reduction of neuroinflammation, and enhancement of blood-brain barrier permeability and collateral circulation. It also discusses emerging treatment strategies such as HBOT combined with gut microbiome modulation and active abdominal compression-decompression CPR (AACD-CPR), exploring their potential as new therapeutic targets for HIBI post-CPR, with the aim of identifying more promising clinical translation paths to improve neurological functional prognosis and quality of life after CPR.}, } @article {pmid41500417, year = {2026}, author = {Derrick, A and Zheng, Y and Fred, B and Boateng, AG and Wang, H and Mrope, P and Azupio, S and Zhang, S}, title = {Effects of short-term exposure to ferrous sulfate on bioaccumulation, oxidative stress biomarkers, immunity, and intestinal microbiota in Litopenaeus vannamei.}, journal = {Comparative biochemistry and physiology. Toxicology & pharmacology : CBP}, volume = {302}, number = {}, pages = {110450}, doi = {10.1016/j.cbpc.2026.110450}, pmid = {41500417}, issn = {1532-0456}, abstract = {The accumulation of heavy metals in aquatic environments poses critical threats to aquaculture, with iron (Fe) being one of the most prevalent contaminants from industrial and agricultural effluents. This study evaluated the acute toxicity and mechanistic impacts of ferrous sulfate (FeSO4) on the Pacific white shrimp (Litopenaeus vannamei). Acute toxicity tests established the 96-h median lethal concentration (LC50) of Fe at 2.52 mg/L, determined across exposure intervals of 0, 24, 48, 72, and 96-h at nominal concentrations ranging from 0.2, 1.0, 5.0, 25.0, 125.0, and 625.0 mg/L. No mortality occurred in control shrimp, whereas mortality increased progressively with both concentration and duration of FeSO4 exposure. FeSO4 exposure caused significant Fe accumulation in hepatopancreas and muscle, accompanied by elevated reactive oxygen species and malondialdehyde, and suppression of key antioxidant and immune enzymes; superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM). Transcriptional analysis revealed strong upregulation of stress proteins (HSP70, HSP90, GSH-Px), apoptotic regulators (caspase-3, p53), and immune effectors (metallothionein), whereas ferritin expression decreased, indicating disruption of Fe homeostasis. Microbiota sequencing demonstrated pronounced dysbiosis: control shrimp maintained balanced commensal taxa, while Fe-exposed groups were enriched in stress-tolerant and opportunistic genera such as Shewanella and Vibrio. Functional prediction (Tax4Fun) indicated that Fe exposure enhanced xenobiotic biodegradation, immune diseases, and cell-death-related pathways, while functions associated with energy, amino-acid and carbohydrate metabolism, and nervous system were comparatively downregulated. Collectively, FeSO4 exposure impaired antioxidant defences, triggered apoptosis, and induced intestinal dysbiosis, with implications for aquaculture health management and environmental risk assessment.}, } @article {pmid41500324, year = {2026}, author = {Stiernborg, M and Yang, LL and Skott, E and Giacobini, M and Melas, PA and Debelius, JW and Lavebratt, C}, title = {Altered gut microbiome function in ADHD: More Prevotella, less vitamin B12 biosynthesis, and beneficial modulation by synbiotic treatment.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106259}, doi = {10.1016/j.bbi.2026.106259}, pmid = {41500324}, issn = {1090-2139}, abstract = {The effect of psychostimulant medication in ADHD on the gut microbiome remains unknown. Oral Synbiotic 2000, comprising multiple lactic acid bacteria and dietary fibers, reduces psychiatric symptoms and plasma immune markers in ADHD, but its impact on the gut microbiome is unexplored. This study aimed to (i) study the fecal bacterial microbiome, focusing on species and bacterial gene modules, in ADHD patients and neurotypical controls, and (ii) examine microbiome changes attributable to Synbiotic 2000. Fecal samples were collected from 147 participants at baseline, and 106 completers at follow-up from a randomized placebo-controlled trial of Synbiotic 2000 conducted in children and adults with ADHD. At baseline, adult samples were compared to those of 52 adult controls, and patients on psychostimulants were compared to those not on psychostimulants in adults and children separately. The fecal microbiome was sequenced using shallow shotgun sequencing and analyzed for diversity and differential abundance using machine learning. Plasma short-chain fatty acids (SCFAs) and serum vitamin B12 levels were measured. At baseline, adult ADHD patients had significantly different abundances of four species compared to controls. In children, those on psychostimulants exhibited a higher abundance of species from the genus Prevotella, alongside a lower abundance of the vitamin B12-synthesis module, M00122, than those not on such medication. The lower M00122 abundance was associated with a looser stool consistency, implicating a shorter colonic transit time. Synbiotic 2000 did not affect taxonomic or functional α-diversity in adults or children. However, looser baseline stool consistency was linked to greater increases in evenness in the Synbiotic group over time. There was a significant Synbiotic-specific effect on taxonomic and functional β-diversity, not only the increased abundance of the Synbiotic 2000 species. Plasma levels of formic acid and propionic acid increased towards control levels in the Synbiotic group. In conclusion, distinct species were differently abundant in adults with ADHD compared to controls. The implications of the lower abundance of the vitamin B12-synthesis module, in children on psychostimulant medication, for the gut ecosystem and host intestine remain to be elucidated. Synbiotic 2000 influenced the taxonomy and functionality of the fecal microbiome and increased plasma SCFA levels towards normal. Further research is warranted to explore the clinical implications of microbiome modulation in the treatment of ADHD.}, } @article {pmid41353192, year = {2025}, author = {Hamann, LK and Washburn, RL and Makii, M and Brown, E and Hampton, M and Schlabritz-Lutsevich, N and Ventolini, G and Rumbaugh, KP and Tipton, C and Redman, WK}, title = {Microbial load and composition of intrauterine device string correlates with symptomatic removals in parous women.}, journal = {Contraception and reproductive medicine}, volume = {11}, number = {1}, pages = {5}, pmid = {41353192}, issn = {2055-7426}, abstract = {BACKGROUND: A contraceptive intrauterine device (IUD) is a US Food and Drug Administration (FDA) approved method of contraception that is effective and generally well tolerated by patients. However, reports show that IUDs might be associated with inflammation, leading to symptoms like abnormal bleeding and pelvic pain. Pelvic inflammation potentially could be linked to IUD pathogenic biofilm colonization. However, the role of non-pathological microbial communities in this context is not well understood. The aim of the present observational study was to describe the microbiome of the IUD string located in the vagina and cervix in patients with and without IUD related complications.

METHODS: Patients being seen for the removal of their IUD were identified for this study and were grouped according to removal for ‘asymptomatic’ or ‘symptomatic’ reasons. Asymptomatic removals included IUD expiration and desire to conceive while symptomatic removals stemmed from patient complaints, including abnormal bleeding, pelvic pain, and vaginitis. The IUD strings were sent for microbiome profiling by 16S ribosomal ribonucleic acid (rRNA) gene sequencing to characterize bacterial composition and universal 16S quantitative polymerase chain reaction (qPCR) to estimate bacterial bioburden. Microbial composition was compared to determine if symptomatic IUD removal was associated with altered bacterial load, diversity, or composition, with an emphasis on Lactobacillus and non-Lactobacillus abundance.

RESULTS: Asymptomatic removals (group A, n = 8) had higher parity (p = 0.012) while relative abundance of Lactobacilli did not differ between groups (p = 0.57). Group A demonstrated a higher abundance of Lactobacillus reuteri compared to symptomatic removals (group S, n = 5), which showed increased overall bacterial load (p = 0.011) and a greater relative abundance of non-Lactobacillus species (p = 0.054), including potentially pathogenic genera such as Fusobacterium and Haemophilus.

CONCLUSIONS: This study revealed differences in bacterial populations associated with symptomatic IUD removal with a higher overall bacterial burden and abundance of non-Lactobacillus genera. Though the current study is not powered to make conclusions on whether different types of IUDs have differential microbiota or how IUD type relates to complications, these results suggest that the microbiome may contribute. Future research should investigate bacterial composition through the duration of IUD use as well as the variation of the bacterial composition on the different components of the IUD device and explore the potential of targeted intervention with probiotics or antibiotics to prevent or reduce complications associated with IUD contraception.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40834-025-00413-z.}, } @article {pmid41202214, year = {2026}, author = {Feng, Z and Ronholm, J}, title = {Examining the competitive exclusion and pathogenic potential of Pseudomonadota isolated from healthy chickens.}, journal = {Canadian journal of microbiology}, volume = {72}, number = {}, pages = {1-11}, doi = {10.1139/cjm-2025-0179}, pmid = {41202214}, issn = {1480-3275}, mesh = {Animals ; *Chickens/microbiology ; Probiotics ; Genome, Bacterial ; Phylogeny ; Poultry Diseases/microbiology ; Gastrointestinal Microbiome ; Intestines/microbiology ; }, abstract = {The chicken intestine presents a complex environment for microbial survival due to high interbacterial competition, high bile salt concentrations, a low pH, and microaerophilic conditions. While most probiotics contain members of the Bacillota phylum, members of the Pseudomonadota phylum are known to be more important in competitive exclusion-which may be an important consideration in the formulation of future probiotics. Little is known about commensal Pseudomonadota in healthy chickens, or what benefits members of this phylum may offer the host; most studies on Pseudomonadota focus on aspects of opportunistic pathogenesis and dysbiosis. In this study, we use an in silico approach to evaluate the pathogenic potential, competition strategies, and potential host benefits of Pseudomonadota isolates from healthy chickens. We analyzed the draft genomes of 29 representative isolates of Pseudomonadota using Bagle4, AntiSMash, SeCreT6, KEGG mapper, and Virsorter2 to identify key interbacterial competition strategies including secondary metabolite biosynthesis, secretion systems, quorum sensing, and prophages. Our results revealed that each isolate exhibits distinct interbacterial competitive strategies, often independent of their taxonomic affiliation. Including Pseudomonadota in future poultry probiotics may be critical to improving colonization resistance in industrially raised poultry.}, } @article {pmid41500299, year = {2026}, author = {Zhang, W and Gu, L and Yan, W and Zhao, D and Liu, J}, title = {Acetochlor and sulfamethoxazole co-selection alter soil microbial nitrogen metabolism and resistome in agroecosystem.}, journal = {Environmental research}, volume = {292}, number = {}, pages = {123688}, doi = {10.1016/j.envres.2026.123688}, pmid = {41500299}, issn = {1096-0953}, abstract = {Agricultural soils increasingly face co-contamination by herbicides and antibiotics, yet the ecological impacts of such multipollutant exposure remain poorly understood. This study employed a soil-plant microcosm combined with metagenomic sequencing to investigate the co-selective effects of acetochlor (ACE) and sulfamethoxazole (SMX) on soil microbiomes and antibiotic resistance genes (ARGs). The results showed that SMX functioned as the dominant ecological filter, significantly reducing microbial diversity and restructuring community composition via suppressing Pseudomonadota while enriching Acidobacteriota. Co-exposure further decreased diversity and shifted nitrogen metabolic pathways: SMX inhibited denitrification and nitrogen fixation, whereas co-combination synergistically enhanced the potential of nitrous oxide emission. Critically, herbicide-antibiotic co-exposure drove the emergence of clinically relevant ARGs (e.g., CMY-80, MCR-2.5) and enhanced their dissemination by increasing network complexity among host microorganisms. Moreover, ACE acted as an 'antibiotic adjuvant', accelerating resistance evolution through stress-induced physiological responses and mobility activation. ACE dose-dependent responses revealed the dual ecological role of agrochemicals: signaling molecules at low concentrations (2.5 mg/kg) and stressors at elevated levels (5.0 mg/kg). Genomic analysis further showed a higher chromosomal than plasmid-borne ARG abundance, reflecting a dynamic equilibrium between persistent and mobile resistance under fluctuating environmental pressures. These findings underscore the necessity of incorporating multipollutant scenarios into risk assessment, as single-contaminant evaluations underestimate the ecological and public health risks in agricultural ecosystems.}, } @article {pmid41500160, year = {2026}, author = {Shahid, MAH and Jha, R and Mishra, B}, title = {Changes in the gut microbiome, metabolic pathways, and intestinal gene expression during the peak, mid, and decline egg production phases in laying hens.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106372}, doi = {10.1016/j.psj.2026.106372}, pmid = {41500160}, issn = {1525-3171}, abstract = {The decline in egg production due to aging poses a significant challenge for the egg industry. This study investigated the cecal microbiota, predicted metabolic pathways, and ileal gene expression to clarify how gut health, nutrient availability, and physiological status influence egg production in laying hens across different ages. Cecal digesta and ileal tissues were collected from Hy-Line-W36 laying hens at peak-production (37-weeks of age), mid-decline (67-weeks of age), and decline-phase (87-weeks of age) (n = 15/ group). DNA from cecal digesta (8/group) was used for 16S rRNA gene sequencing with the Illumina and QIIME2 platforms to refine the raw reads. Ileal tissues were used for RNA extraction, and gene expression was quantified through qPCR. R, PICRUSt2, and STAMP were used for statistical analysis. Despite similar richness, hens in the mid-decline and decline-phases of egg production exhibited reduced microbial diversity. At peak production, the microbiome was dominated by carbohydrate-fermenting genera such as Prevotella, Megasphaera, and Anaerotignum; mid-decline hens acquired more Limosilactobacillus and butyrate-producing Acutalibacteraceae, while the decline-phase hens were enriched with maintenance-oriented taxa, including Peptostreptococcaceae. Functional predictions mirrored these shifts, where peak-production hens' profiles favored glycolysis, nucleotide synthesis, and rapid acetyl-CoA turnover; mid-decline hens showed enhanced amino acid biosynthesis, iron scavenging, and SCFA production; and decline-phase hens emphasized nucleotide/cofactor repair and stress-response pathways while central-carbon routes declined. Additionally, age-related changes in enzymatic functions suggested reduced metabolic efficiency. In decline-phase, the expression of ileal antioxidant (SOD1, SOD2, GPX1) and tight-junction genes (CLDN1, OCLN) significantly decreased. The higher expression of Gadd45b at the decline-phase suggests cellular damage and leakage at the ileum. Moreover, decline-phase hens exhibited decreased levels of TLR4 and NF-κB, along with higher levels of IL-4 and IL-12, indicating a compromised immune response. Additionally, reduced expression of solute carrier transporter SLC1A1, SLC5A1 (amino acid and peptide), SLC7A6 (L-lysine, L-arginine), SLC19A2 (Thiamin), and FATP4 (Fatty acid) during the decline-phase, indicating insufficient energy availability for the hens, ultimately leading to a decrease in egg production. These findings reveal age-related changes in gut microbiota, nutrient transport, and immunity, contributing to decreased egg production in hens. This information could be pivotal for developing dietary and management strategies to enhance flock health and productivity.}, } @article {pmid41500036, year = {2026}, author = {Wanli, J and Xingyue, S and Xinning, L and Yashuo, Z and Xiaojing, Q and Cheng, H and Yan, H}, title = {Banxia Xiexin Decoction modulates short-chain fatty acid metabolism and mitigates ulcerative colitis by reshaping the intestinal microbiota.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {271}, number = {}, pages = {117332}, doi = {10.1016/j.jpba.2025.117332}, pmid = {41500036}, issn = {1873-264X}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disorder that significantly impacts the quality of life for patients. Dysbiosis of gut microbiota and changes in short-chain fatty acid (SCFA) metabolism play a role in both the initiation and progression of UC. Banxia Xiexin Decoction (BXD), a formula in traditional Chinese medicine, has shown therapeutic effects; however, its underlying mechanism remains unclear. A rat model of colitis induced by dextran sulfate sodium (DSS) was created, and various doses of BXD were administered. The principal components of BXD were analyzed through high-pressure liquid chromatography (HPLC). In order to clarify the mechanisms, 16S rRNA sequencing, serum metabolomics, targeted profiling of SCFAs via gas chromatography-mass spectrometry (GC-MS), and assessments of enzyme activity were conducted. BXD exerted protective effects against DSS-induced UC, as indicated by attenuated histological damage and reduced expression of pro-inflammatory cytokines. Untargeted metabolomics revealed that BXD modulated multiple metabolic pathways, enhancing SCFA-related processes, such as propanoate and butanoate metabolism. GC-MS revealed that BXD could increase the level of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate and hexanoate. Microbiome sequencing indicated that BXD increased the abundance of beneficial taxa (e.g. Firmicutes, Bacteroidetes), while reducing pro-inflammatory genera. Altogether, BXD restored the microbial balance and promoted anti-inflammatory metabolite production. Our results demonstrated that BXD ameliorated UC by reprogramming gut microbial composition and enhancing SCFA biosynthesis, thereby suppressing intestinal inflammation. The potential of BXD as a therapy aimed at the microbiota for UC is emphasized in these studies, which also offer mechanistic insights using multi-omics approaches.}, } @article {pmid41499990, year = {2026}, author = {Chen, C and Wang, C and Li, H and Wang, T and Jiao, X}, title = {Sweet poison for the eyes: High-Fructose diets as drivers of metabolic disruption and ocular diseases - Insights and therapeutic horizons.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110852}, doi = {10.1016/j.exer.2026.110852}, pmid = {41499990}, issn = {1096-0007}, abstract = {Excess consumption of added sugars, commonly delivered through sucrose and high-fructose corn syrup, has increased in parallel with obesity, metabolic syndrome, and type 2 diabetes. These systemic metabolic disturbances are consistently associated with a range of ocular conditions. However, whether high-fructose intake exerts independent and fructose-specific effects on ocular tissues remains uncertain, because most human evidence is indirect, often mediated through metabolic syndrome phenotypes, and frequently confounded by mixed dietary exposures and total energy intake. This review synthesizes mechanistic pathways that are plausibly enriched by fructose biology, including hepatic fructose metabolism with ATP depletion and uric acid generation, oxidative and inflammatory signaling, altered lipid handling, and gut barrier and microbiome perturbations. We evaluate how these systemic changes may intersect with ocular surface homeostasis, retinal neurovascular integrity, intraocular pressure regulation, and choroidal and macular vulnerability. Across dry eye disease, diabetic retinopathy, glaucoma-related outcomes, age-related macular degeneration and choroidal neovascular responses, and cataract, we distinguish fructose-specific exposure studies from metabolic syndrome only and mixed diet reports, and we emphasize limitations related to exposure definition, replication, and translation to humans. Overall, current evidence supports the view that excess fructose may amplify ocular susceptibility in metabolically stressed states, but direct causal links in humans remain preliminary. We conclude by outlining methodological priorities and testable study designs needed to clarify fructose-specific contributions to ocular disease risk. Some experimental findings, particularly those related to ocular-surface responses, originate from single research groups and require independent replication, underscoring that current evidence remains preliminary and hypothesis-generating.}, } @article {pmid41499871, year = {2026}, author = {Rasta, M and Lashkaryan, NS and Shi, X and Taleshi, MS and Vayghan, AH and Ahmadi, A and Kakakhel, MA and Zahid, A and Jarf, MP and Manke, J and Liu, L and Wu, Y}, title = {Flow-dependent modulation of microplastic toxicity in grass carp: Insights from multi-level biological endpoints and machine learning.}, journal = {Journal of hazardous materials}, volume = {502}, number = {}, pages = {141020}, doi = {10.1016/j.jhazmat.2025.141020}, pmid = {41499871}, issn = {1873-3336}, abstract = {Microplastics (MPs) are emerging contaminants in freshwater systems, yet how hydrodynamic conditions modulate their biological effects remains unclear. This study investigated the accumulation, histopathology, immune response, and gut microbiota disruption in Ctenopharyngodon idella exposed to 5 µm polystyrene MPs (1000 µg/L; ∼ 1.46 × 10[7] particles/L) under static conditions and water velocities of 1, 3, and 5 Body Lengths per second (BL/s), representing low, medium, and high flow. Water velocity alone caused notable tissue damage, including gill lesions and intestinal alterations, and significantly upregulated immune response genes, with the strongest responses observed at high flow. MPs accumulated in both gill and intestinal tissues, with highest concentration observed under high velocity flow. Combined exposure (MPs + flow) induced more severe effects, including gill necrosis, lamellar fusion, intestinal mucosal degeneration, inflammatory infiltration, and further immune gene upregulation, with IL-6 and TNF-α demonstrating the most substantial effect sizes (Cohen's d > 5). Gut microbiome evaluations indicated trends towards reduced alpha diversity and an elevation in pathogenic taxa in different groups, specifically with increased abundance of Aeromonas and Vibrio under the influence of combined stressors. Mediation analysis suggested a possible role for tissue damage in dysbiosis development, although wide confidence intervals precluded definitive conclusions. These initial findings indicate that hydrodynamic conditions alone can impact fish physiology and microbiota, and that flow can exacerbate MPs accumulation and toxicity through multiple biological pathways, emphasizing the imperative for extensive research efforts to confirm these relationships within aquatic ecological systems.}, } @article {pmid41499519, year = {2026}, author = {Ocampo Morales, BN and Hernández Montes, A and Estrada, K and Valadez Moctezuma, E}, title = {Physicochemical and microbiome changes in queso Crema de Chiapas during ripening.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0323038}, doi = {10.1371/journal.pone.0323038}, pmid = {41499519}, issn = {1932-6203}, mesh = {*Microbiota ; *Cheese/microbiology/analysis ; Bacteria/genetics/classification/isolation & purification ; Food Microbiology ; }, abstract = {The dynamic changes in the physicochemical, microbiological, and metagenomic profiles of Crema de Chiapas cheese were evaluated across three ripening stages (2, 29, and 58 days). Although the main physicochemical properties -including fat content- remained remarkably stable, salt and protein levels showed noticeable variation throughout ripening. Protein content had the strongest influence on sample differentiation across ripening stages in unsupervised multivariate models, enabling the clustering of microbial diversity according to maturation time. A clear shift in microbial diversity was detected, marked by a reduction in bacterial genera and a concurrent decline in fungal and yeast populations as ripening advanced. The predominant bacterial genera throughout ripening were Streptococcus, Lactobacillus, and Lactococcus. While Streptococcus and Lactobacillus increased over time, Lactococcus exhibited the opposite trend. Metagenomic analysis revealed a decrease in Candida etchellsii and a concomitant increase in Candida tropicalis as ripening progressed. Quantitative PCR (qPCR) confirmed the presence of C. etchellsii at T1 (Ct = 7.22) and C. tropicalis at T3 (Ct = 9.84). The presence of three additional bacterial genera-Chryseobacterium, Aeromonas, and Enterobacter-identified by next-generation sequencing (NGS), was also assessed by qPCR. Chryseobacterium was detected at T2 (Ct = 3.26), whereas Aeromonas and Enterobacter were absent across all stages. Collectively, these findings suggest that potentially pathogenic microorganisms were not present at biologically relevant levels.}, } @article {pmid41499160, year = {2026}, author = {Hai, Q and Li, D and Huang, T and Dang, X and Xu, J and Ma, Z and Zhou, Z}, title = {The Honeybee Gut Microbiome: A Novel Multidimensional Model of Antimicrobial Resistance Transmission and Immune Homeostasis from Environmental Interactions to Health Regulation.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuag001}, pmid = {41499160}, issn = {1574-6976}, abstract = {The honeybee gut microbiome has emerged as a model system in microbial ecology, valued for its structural stability and host specificity, and has garnered significant attention for elucidating universal principles of host-microbe interactions. This review advocates for the honeybee as a multidisciplinary model organism, highlighting the unique role of its gut microbiota in maintaining colony immune homeostasis, driving host co-evolution, unraveling the transmission mechanisms of antibiotic resistance genes (ARGs), and enhancing host adaptability to environmental stressors. By integrating multidimensional factors, including environmental gradients and apicultural practices, we construct an "Environment-Microbiota-Host Health" interaction framework to transcend the limitations of single-factor analyses. This framework provides a novel paradigm for the ecological containment of antimicrobial resistance, the conservation of pollinator resources, and microbiome-based engineering interventions. The review underscores the unique value of the honeybee model in unraveling social insect-microbe coevolution and resistance transmission dynamics, while also prospecting its application potential in developing novel antimicrobial peptides, designing probiotic formulations, and monitoring environmental resistance.}, } @article {pmid41499051, year = {2026}, author = {Maulvi, FA and Desai, DT and Vyas, BA and Shah, DO and Willcox, MD}, title = {Fasting as a Multisystem Health Modulator: A Narrative Review of Metabolic, Cardiovascular, Immune, Neurocognitive, and Psychospiritual Effects.}, journal = {Current nutrition reports}, volume = {15}, number = {1}, pages = {4}, pmid = {41499051}, issn = {2161-3311}, mesh = {Humans ; *Fasting/physiology/psychology ; Gastrointestinal Microbiome/physiology ; *Cognition/physiology ; Immune System/physiology ; Energy Metabolism ; Cardiovascular System/metabolism ; Circadian Rhythm ; Cardiovascular Diseases/prevention & control ; }, abstract = {BACKGROUND: Fasting, practiced in clinical, cultural, and faith-based contexts, has emerged as a non-pharmacological strategy capable of modulating multiple physiological systems. Contemporary evidence suggests that diverse fasting patterns (intermittent and time-restricted fasting, Ramadan fasting, alternate-day and periodic fasting, dry fasting, and fasting-mimicking diets) converge on shared metabolic-circadian-immune pathways and can be conceptualized within an integrated resilience framework.

AIM: This narrative review synthesizes current experimental and human data on fasting as a multisystem health modulator, linking metabolic, cardiovascular, immune, gut-liver-microbiome, neurocognitive, endocrine, and psychospiritual effects to common regulatory axes, particularly the Metabolic-Circadian-Immune (MCI) and Energy-Information-Resilience (EIR) models.

RESULTS: Across fasting modalities, activation of energy-sensing pathways (AMPK-SIRT1-mTOR), metabolic switching to lipolysis and ketogenesis, enhanced autophagy/mitophagy, and improved insulin sensitivity have been shown to support the management of obesity, type 2 diabetes, dyslipidemia, hypertension, and non-alcoholic fatty liver disease. Fasting also modulates immune and inflammatory tone, reshapes the gut microbiome, and may benefit autoimmune conditions such as rheumatoid arthritis and multiple sclerosis. Cardiovascular, endocrine, and neurocognitive domains show improvements in blood pressure, lipid profiles, neurotrophic signaling, mood, and cognitive resilience, while structured religious fasting (e.g., Ramadan) can additionally reinforce psychological discipline and spiritual well-being. At the same time, responses are heterogeneous, and prolonged or intensive regimens may pose risks in vulnerable populations.

CONCLUSION: Fasting can be viewed as a low-cost, multidimensional "biopsychospiritual" health intervention acting through interconnected metabolic, circadian, immune, and neurobehavioral pathways. By integrating traditional and religious fasting practices with contemporary mechanistic and clinical data, this review highlights shared energy- and immune-regulatory axes and underscores the potential of fasting within integrative, preventive, and personalized care. Standardized protocols, long-term outcomes, and multimodal trials combining immunophenotyping, microbiome/metabolomic profiling, and neuroimaging remain priorities for future research.}, } @article {pmid41498979, year = {2026}, author = {Tischer, J and Dietze, N and Marx, K and Trawinski, H and Lübbert, C}, title = {[New antimicrobial substances to combat increasing resistance].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {41498979}, issn = {2731-7099}, abstract = {Increasing antimicrobial resistance (AMR) is one of the greatest threats to global health. In 2021, 4.71 million deaths worldwide were closely associated with AMR, and 1.14 million deaths could be directly attributed to infections caused by multidrug-resistant organisms (MDROs), particularly multidrug-resistant Gram-negative bacteria (MDRGN). Enterobacterales (e.g., Escherichia coli and Klebsiella spp.) resistant to third-generation cephalosporins and carbapenems, multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (CRAB) have been identified by the World Health Organization as the most problematic pathogens. In addition to new diagnostic methods for the rapid identification of AMR, several new antibiotics have been approved in the last 10 years, expanding the treatment options, particularly for MDRGN infections. Pharmaceutical strategies have so far focused primarily on modifying already known classes of antibiotics with the aim of circumventing class-specific resistance mechanisms and reducing resistance rates. In addition to cefiderocol, the first siderophore cephalosporin, new combinations of β‑lactam antibiotics and β‑lactamase inhibitors (BLIs) such as ceftolozan/tazobactam, ceftazidime/avibactam, cefepime/enmetazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam, as well as the monobactam/BLI combination aztreonam/avibactam, have been approved and successfully implemented in clinical care. In addition, there is the synthetic tetracycline antibiotic eravacycline, which has a broad spectrum of activity against Gram-positive, Gram-negative (particularly clinically relevant Enterobacterales), anaerobic, and multidrug-resistant bacteria, and the new glycopeptide antibiotic dalbavancin, which is effective against Gram-positive bacteria. Since a change in legislation in 2021, the Joint Federal Committee (Gemeinsamer Bundesausschuss, G‑BA) in Germany has been authorized to classify newly approved antibiotics as reserve antibiotics. This classification allows for an exception to the regular additional benefit assessment as part of the early benefit assessment. The pipeline of antibiotics in development with novel targets and chemical structures-which had almost completely dried up-has been re-filled with new candidates for clinical trials. Some of these agents have already been tested with promising results in smaller phase 1/2 studies. In addition, monoclonal antibodies, antimicrobial peptides, small molecules, microbiome-modifying biotherapeutics, and bacteriophages, all enabling targeted and personalized treatment, are currently being investigated in studies.}, } @article {pmid41498910, year = {2026}, author = {Li, Y and Shen, X and Wang, D and Sun, K}, title = {The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-025-04367-1}, pmid = {41498910}, issn = {2730-6011}, } @article {pmid41498848, year = {2026}, author = {Protachevicz, AP and Boldt, ABW and Pileggi, M}, title = {The microbiota-epigenome axis in healthy longevity: roles of microbial and gerobiotic metabolites - a narrative exploratory review.}, journal = {Biogerontology}, volume = {27}, number = {1}, pages = {34}, pmid = {41498848}, issn = {1573-6768}, support = {process 8888.7.884402/2023-00.//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; process 307602/2025-7.//CNPq Productivity Fellowship/ ; }, mesh = {Humans ; *Longevity/genetics/physiology ; *Gastrointestinal Microbiome/physiology ; *Epigenesis, Genetic ; *Healthy Aging/genetics ; Animals ; *Aging ; }, abstract = {Aging is a dysbiotic and pro-inflammatory process that increases susceptibility to multiple chronic comorbidities. Centenarians and supercentenarians offer a unique biological model for elucidating the molecular determinants of healthy aging and exceptional longevity, as they display distinctive epigenetic signatures and a gut microbiome configuration that diverges from both younger and typically aging individuals, although substantial interindividual variability exists. The gut microbiota constitutes a strategic hub of microorganisms and bioactive metabolites with probiotic and postbiotic potential that modulate host epigenetic circuits through precursors and substrates for epigenetic "writer" and "eraser" enzymes, thereby shaping the aging trajectory. In this review, we examine the interactions between the microbiota and its metabolites, including short-chain fatty acids, lipopolysaccharides, trimethylamine N-oxide (TMAO), p-cresol, and secondary bile acids, and their roles in epigenetic modulation associated with healthy aging. We highlight (i) the attenuation of classical pro-inflammatory pathways through downregulation of NF-κB/COX-2, modulation of the Th17/Treg balance, and also the lower systemic LPS levels of centenarians, which are associated with enhanced SIRT1 activity (↑LPS/↓SIRT1); (ii) the reprogramming of energy metabolism via activation of SIRT1/AMPK and SIRT1/p-53, modulation of mTOR, and attenuation of the IGF-1/insulin axis; (iii) the strengthening of the intestinal barrier through upregulation of tight junction proteins such as ZO-1, occludin, and claudins, resulting in reduced permeability and zonulin levels; and (iv) the optimization of antioxidant defenses. Collectively, these findings suggest translational potential for microbiota-derived metabolites in gerobiotic strategies, although clinical evidence remains limited.}, } @article {pmid41498557, year = {2026}, author = {Zhao, Y and Gao, K and Shang, Y and Cheng, S and Ren, Q and Guo, F and Wang, Y}, title = {Clostridium butyricum RH2 ameliorates diarrhea in juvenile mice under continuous antibiotic exposure by modulating gut microbiota and metabolome.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0197625}, doi = {10.1128/spectrum.01976-25}, pmid = {41498557}, issn = {2165-0497}, abstract = {Antibiotic-associated diarrhea (AAD) is a self-limiting disorder triggered by antibiotic therapy in pediatric populations. Although multiple probiotics are clinically employed for AAD management, the therapeutic efficacy of Clostridium butyricum (C. butyricum) in pediatric AAD and its underlying mechanisms remain poorly characterized. This study aimed to establish a juvenile mice model of AAD and investigate the therapeutic potential of oral C. butyricum administration in juvenile mice subjected to continuous antibiotics exposure. We systematically assessed pathological changes in colonic tissue, colitis severity, intestinal epithelial barrier integrity, fecal metabolomic profiles, and gut microbiota diversity. Our analysis demonstrates that C. butyricum ameliorates intestinal inflammation, enhances barrier function by modulating the gut microbiota and its metabolites, and significantly alleviates diarrhea symptoms in juvenile AAD mice. Collectively, these findings indicate that the therapeutic benefits of C. butyricum are closely linked to its ability to tolerate continuous antibiotic exposure, providing a scientific rationale for its co-administration with antibiotics.IMPORTANCEClostridium butyricum demonstrates significant therapeutic potential for pediatric antibiotic-associated diarrhea (AAD) by dual modulation of gut microbiota and host physiology. This study reveals its capacity to alleviate intestinal inflammation, restore barrier integrity via upregulation of tight junction proteins and mucins, and rebalance gut microbiota linked to key anti-inflammatory metabolites-even under ongoing antibiotic exposure. These findings position C. butyricum as a targeted probiotic therapy for AAD, offering mechanistic insights to advance microbiome-driven interventions for antibiotic-induced diarrhea in children.}, } @article {pmid41498552, year = {2026}, author = {Schussman, MK and Feng, S and Schmoldt, A and Bootsma, MJ and Dennis, K and Janssen, KH and McLellan, SL}, title = {Environmental reservoirs account for high levels of carbapenem resistance genes in wastewater.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0173725}, doi = {10.1128/spectrum.01737-25}, pmid = {41498552}, issn = {2165-0497}, abstract = {UNLABELLED: Wastewater surveillance has moved to the forefront as a practical and informative public health tool for assessing viral and bacterial pathogens in the human population; however, the usefulness for tracking antimicrobial-resistance genes (ARGs) of clinical concern is not straightforward given the large reservoir of free-living bacteria within sewer systems. In this study, we examined six high-priority carbapenem resistance gene targets and common host organisms in wastewater collected from two treatment plants. Polymerase chain reaction (PCR)-based assays demonstrated an extremely high abundance of blaKPC, blaOXA-24/40, and blaOXA-48 with mean concentrations as high as 3.55E+06 copy number (cn)/L for blaKPC. In addition, blaVIM and blaIMP were detectable in ~99% of samples at lower levels of ~1.5E+05 cn/L and 1.0E+04 cn/L, respectively. The target blaNDM was readily detected but quantifiable in only 49% of samples with levels of ~1.0E+03 cn/L. Each PCR target showed one to two dominant sequence types that matched exactly to reported clinical strains, indicating that high levels could not be attributed to non-specific amplification. Select ARG targets showed moderate-to-weak correlations to human fecal markers and Klebsiella pneumoniae or Escherichia coli, whereas blaOXA-24/40 most closely correlated to Acinetobacter baumannii. The two treatment plants showed different dynamics, suggesting that the inherent characteristics of the individual conveyance systems influence concentrations. Culture on selective media revealed an abundance of Aeromonas in addition to sporadic Enterobacteriaceae carrying blaKPC. Understanding the ecological dynamics of bacteria harboring ARGs will be important for understanding reservoirs and interpreting wastewater surveillance data.

IMPORTANCE: Wastewater surveillance for carbapenem-resistant bacteria has been proposed as a potentially valuable tool for assessing the human burden, but their distribution in environmental reservoirs is not well understood. Untreated sewage contains a high density of resident organisms mixed with human inputs, which are transported through the complex environment of sewer conveyance systems. In addition to resident microbial community members, organisms seeded into the system from the human microbiome have the potential to grow. This work shows that environmental bacteria may be a significant source of carbapenem resistance genes collected from sewer systems, making wastewater surveillance data difficult to interpret or use for public health actions. More knowledge is needed to unravel the ecology of these systems and identify targets for surveillance that are meaningful to clinicians. This work sheds light on the complex dynamics and confounding factors for antimicrobial-resistance gene wastewater surveillance, which will improve the interpretation of wastewater surveillance data.}, } @article {pmid41498506, year = {2025}, author = {He, L and He, Z and Zhang, Y and Wu, F and Liu, H and Liu, XG and Zheng, DX and Shao, RQ and Hu, L and Jiang, QS}, title = {Divergent Oral Microbiome after Rinsing with of H2O2, Chlorhexidine and Essential Oil Mouthrinses: a Proof of Principle Study.}, journal = {The Chinese journal of dental research}, volume = {28}, number = {4}, pages = {297-305}, doi = {10.3290/j.cjdr.b6745473}, pmid = {41498506}, issn = {1867-5646}, mesh = {Humans ; *Mouthwashes/pharmacology ; *Chlorhexidine/pharmacology ; *Oils, Volatile/pharmacology ; *Hydrogen Peroxide/pharmacology ; *Microbiota/drug effects ; Male ; Adult ; Female ; Saliva/microbiology ; *Mouth/microbiology ; Young Adult ; RNA, Ribosomal, 16S/genetics ; Anti-Infective Agents, Local/pharmacology ; }, abstract = {OBJECTIVE: To compare the effects on the oral microbiome after rinsing with hydrogen peroxide (H2O2), chlorhexidine and essential oil mouthrinses and identify formulations that suppress pathogenic bacteria while preserving beneficial species and maintaining oral microbial bal-ance.

METHODS: Twelve healthy volunteers were randomly assigned to three groups: H2O2, chlorhexi-dine and essential oil mouthrinse. Saliva samples were collected at three time points: before and 5 minutes and 1 hour after rinsing with mouthrinse. Microbiome composition was analysed using 16S rRNA gene sequencing.

RESULTS: Alpha and beta diversity showed no statistically significant differences among time points. The genus-level microbiome composition remained relatively stable in the H2O2 and essential oil groups but changed significantly in the chlorhexidine group. In the H2O2 group, Neisseria decreased significantly, while Actinomyces increased. In the chlorhexidine group, Porphyromonas, Veillonella, Streptococcus, Neisseria and Gemella decreased significantly. In the essential oil group, Leptotrichia decreased, and Haemophilus increased significantly.

CONCLUSION: Essential oil mouthrinse and chlorhexidine exhibit stronger bacteriostatic effects against oral pathogens than H2O2. However, chlorhexidine may disrupt microbial equilibrium, whereas essential oil mouthrinse more effectively preserves a stable oral microbiome. Thus, es-sential oil mouthrinse could serve as a viable alternative to chlorhexidine for oral microbiome management, though its long-term efficacy requires further investigation.}, } @article {pmid41498123, year = {2026}, author = {Ladewig, L and Kinfu, BM and Fokt, H and Bethge, H and Tufail, MA and Baines, JF and Schmitz, RA}, title = {Exploring Bacteroidota strains from human stool and animal feces: phenotyping and functional diversity.}, journal = {microLife}, volume = {7}, number = {}, pages = {uqaf039}, pmid = {41498123}, issn = {2633-6693}, abstract = {Bacteroidota, a diverse phylum of bacteria, includes classes whose members are increasingly recognized for their significant contributions to host health, particularly through their antimicrobial properties. This study investigates the functional diversity of 42 new Bacteroidia and Sphingobacteriia strains enriched and identified from diverse hosts, including mouse ceca and human stool samples. Using 16S rRNA gene sequencing, we phylogenetically characterized the strains of the genera Bacteroides, Phocaeicola, and Sphingobacterium and assessed their functional properties related to potential beneficial functions. The strains were evaluated concerning their ability to inhibit biofilm formation of the World Health Organization-declared clinically significant pathogens, including Gram-positive Staphylococcus aureus and Staphylococcus epidermidis, Gram-negative Klebsiella oxytoca and Pseudomonas aeruginosa, and the eukaryotic yeast Candida albicans. Additionally, we investigated bile salt hydrolase and quorum-quenching (QQ) activities of the strains, as these functions contribute to microbial community interactions and host-microbe dynamics. Our findings demonstrate that all examined Bacteroidota strains consistently exhibit a capacity to inhibit biofilm formation but to different extents. Furthermore, 14 strains showed QQ activity, and 39 bile salt hydrolase activity, indicating functional diversity among the isolates. High biofilm inhibition as well as QQ activity against both autoinducers, AHL and AI-2, were predominantly observed in Bacteroides caecimuris and Bacteroides muris. These traits suggest that such strains may play important roles in shaping microbial communities and interfering with pathogens and their communication. Overall, this study provides valuable insights into strain-specific functions that could support future microbiome-based strategies for pathogen control and host health modulation.}, } @article {pmid41497693, year = {2025}, author = {Rusman, RD and Akil, F and Parewangi, ML and Daud, NA and Bachtiar, R and Kusuma, SH and Rifai, A}, title = {Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention.}, journal = {World journal of experimental medicine}, volume = {15}, number = {4}, pages = {107316}, pmid = {41497693}, issn = {2220-315X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease, closely linked with metabolic syndrome. Recent evidence spotlights the gut-liver axis as a major player in MASLD pathogenesis. Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia, hepatic inflammation, insulin resistance and fibrosis. Microbial metabolites including short-chain fatty acids, bile acids and ethanol impact host metabolism and immunity, and their dysregulation contributes to disease progression. This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition, leaky gut, toll-like receptor signalling and immune dysregulation. It also reviews microbially targeted therapeutic strategies, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation, diet changes, and postbiotic metabolites. Although these interventions may have clinical potential, the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions. Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach. Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic. In conclusion, modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.}, } @article {pmid41497648, year = {2025}, author = {Trepka, KR and Van Blarigan, EL and Kyaw, TS and Olson, CA and Partipilo, G and Ortega, EF and Noecker, C and Upadhyay, V and Zhang, C and Gempis, D and Steiding, P and Stanfield, D and Venook, AP and Atreya, CE and Kidder, WA and Turnbaugh, PJ}, title = {Shifts in the human gut microbiome during cancer chemotherapy are diet-dependent.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41497648}, issn = {2692-8205}, abstract = {Numerous studies have implicated both dietary intake and the human gut microbiome in colorectal cancer (CRC) treatment outcomes. However, little is known about how patients adjust their dietary intake during cancer chemotherapy or if these dietary changes contribute to treatment-associated alterations in the gut microbiome. We performed paired longitudinal diet and microbiome analysis during CRC treatment with oral fluoropyrimidines (NCT04054908) and validated key associations using cell culture assays. Diet quality significantly decreased during chemotherapy. Carbohydrate and refined grain intake increased, accompanied by decreased consumption of fats, nuts and seeds, and fat-soluble micronutrients. Multiple individual dietary components were strongly linked to the gut microbiome. Decreases in theobromine intake correlated with decreases in overall microbial diversity and more gastrointestinal toxicities. Diet shifts partly explained changes in bacterial abundance during chemotherapy, including more severe depletion of Faecalibacterium prausnitzii in patients with decreased vitamin K1 intake. Changes in diet were correlated with multiple bacterial gene families involved in micronutrient metabolism and drug sensitivity. Increased copper intake was linked to decreased Fusobacterium nucleatum in patients and inhibited F. nucleatum in cell assays. Together, these data suggest that chemotherapy-related decreases in diet quality and micronutrient intake contribute to changes in gut bacterial diversity, taxonomic composition, and gene abundance. Our approach may generalize to other cancer therapies and emphasizes the need for collecting more robust dietary data in clinical microbiome studies.}, } @article {pmid41497646, year = {2025}, author = {Anyaso-Samuel, SC and Li, S and Herrera-Ossa, G and Vogtmann, E and Wang, X and Hua, X and Qin, F and Zhao, W and Rahman, M and Yang, X and Brown, K and Zhu, B and Moore, S and Abnet, C and Zhang, T and Landi, MT and Yu, K and Albert, P and Shi, J}, title = {Identifying High-Dimensional Genomic Factors Modulating Biological Networks Across Multi-Omics Data.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.18.695273}, pmid = {41497646}, issn = {2692-8205}, abstract = {Biological traits such as genes, metabolites, and microbial taxa interact within complex networks, yet how genomic factors shape these interactions remains poorly understood. Here, we introduce GFBioNet, a computationally efficient method for identifying factors that modulate direct associations between biological traits within network models. Our two-stage strategy first estimates a baseline network using Gaussian graphical models and then tests whether genomic factors modulate specific network edges (trait-trait relationships), enabling scalable analysis of high-dimensional multi-omics data while explicitly controlling the false discovery rate (FDR). Simulations demonstrate reliable FDR control and high statistical power across a broad range of settings. Applied to multiple datasets, GFBioNet reveals host genetic variants influencing oral microbiome relationships, gut microbial taxa modulating metabolite networks in colorectal cancer, and somatic mutations and copy-number alterations reshaping gene expression networks in lung adenocarcinoma. By expanding network analysis to evaluate modifiers of trait-trait relationships, GFBioNet offers a versatile tool for uncovering the genomic architecture of biological networks across multi-omics studies.}, } @article {pmid41497638, year = {2025}, author = {Liou, CS and Louwies, T and Iakiviak, M and Rajniak, J and Murugkar, PP and Higginbottom, SK and Weakley, A and Meng, X and Htet, P and Cabrera, AV and Jasper, M and Dimas, A and Schulman, EA and Fischbach, MA and Kashyap, PC and Sattely, ES}, title = {Gut microbiota gate host exposure to cholinesterase inhibitors from dietary Solanums.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.20.584512}, pmid = {41497638}, issn = {2692-8205}, abstract = {Dietary plants are molecularly rich but the fates of these compounds post-ingestion and their implications for human health are largely unknown. Here, we systematically characterized the major chemical contributions of widely consumed Solanum species (nightshades) to the human metabolome. Using untargeted metabolomics, we found that a series of steroidal alkaloids resulting from glycoalkaloids tomatine, solanine, and chaconine are dominant diet-derived compounds in systemic circulation following ingestion of tomato and potato. By comparing serum and tissue metabolomes of colonized and microbiome-depleted mice, we determined that the gut microbiota modifies these compounds extensively, altering their absorption and gating host exposure. By screening the metabolic products in human urine and stool samples, we established that steroidal glycoalkaloid metabolism varies inter-individually in a population. Furthermore, using a collection of representative human commensal type strains, we found that a limited set of strains is responsible for steroidal glycoalkaloid metabolism, with the chemical output of a community determined by its strain-level composition. These findings enabled the rational design of complex synthetic microbial communities that controlled host exposure to steroidal alkaloid metabolites in vivo . Importantly, microbial metabolism of Solanum metabolites alters their acetylcholinesterase inhibition in vitro and gut motility in vivo . Our study provides insights into the molecular mechanisms of a diet-microbiome interactions and the effects of dietary metabolites on host physiology.}, } @article {pmid41497462, year = {2025}, author = {Dunisławska, A and Bełdowska, A and Yatsenko, O and Biesek, J and Siwek, M}, title = {Molecular response in the pectoral muscles and livers of broiler chickens to mitochondrial stimulation by in ovo administration of prebiotics.}, journal = {Journal of veterinary research}, volume = {69}, number = {4}, pages = {639-646}, pmid = {41497462}, issn = {2450-7393}, abstract = {INTRODUCTION: Mitochondria are the primary sites for adenosine triphosphate production through oxidative phosphorylation, thus supporting the high metabolic demands of avian physiology. By administering prebiotics in ovo, the aim was to analyse how an early host-supporting strategy can modulate mitochondrial activity and affect the physicochemical composition of the pectoral muscles of chickens.

MATERIAL AND METHODS: Three hundred incubated Ross 308 broiler eggs were injected: 60 with 0.2 mL of 0.2 mmol/L physiological saline (control group), and 60 each with 0.5 mg of xylotriose (XOS3 group), xylotetraose (XOS4 group), mannotriose (MOS3 group) or mannotetraose (MOS4 group) carried in 0.2 mL of physiological saline. On day 42 after hatching, the liver and pectoral muscle were collected from eight individuals from each group after sacrifice, and the muscle was evaluated physicochemically. Relative mitochondrial DNA (mtDNA) copy numbers were analysed in a real-time quantitative PCR (qPCR). Gene expression was determined by a reverse-transcription qPCR (RT-qPCR) for a mitochondrial gene panel.

RESULTS: The experimental factor was not shown to affect pectoral muscle weight. Water loss was significantly greater in the XOS4 group's muscles. The overall mtDNA copy number was stable in both tissues. The XOS3 and MOS4 groups' gene expression was significantly changed in pectoral muscle. Contrastingly, the XOS4 and MOS3 groups' gene expression was more altered in the liver. Statistically significantly different expression was detected of the CS, EPX, CYCS, TFAM and NRF1 genes in pectoral muscles and of all tested genes in livers.

CONCLUSION: The potential of in ovo prebiotic administration is indicated as a strategic approach to optimise mitochondrial function, ultimately contributing to better growth rates and enhanced health in broiler chickens.}, } @article {pmid41497397, year = {2025}, author = {Miyauchi, E and Yamaoka, M and Kamimura, I and Mizuta, M and Takenaka, M and Akiyama, U and Kawasumi, M and Sasaki, N and Ohno, H and Ando, S and Yamasaki, S and Nishida, A and Mogi, K and Nagasawa, M and Kikusui, T}, title = {Dog ownership during adolescence alters the microbiota and improves mental health.}, journal = {iScience}, volume = {28}, number = {12}, pages = {113948}, pmid = {41497397}, issn = {2589-0042}, abstract = {Adolescents who own dogs have higher well-being than those who do not; however, it is unclear what the underlying mechanism explains how dog ownership affects adolescents' well-being. As dog ownership influences the composition of the microbiota in the home environment, we examined the microbiome of dog-owning adolescents and analyzed associations with mental health and behavior in the teenage cohort participants (n = 345). Our findings reveal that dog-owning adolescents showed fewer problems with psychological scores, and some commensals were correlated with adolescents' psychological scores. Mice treated with the microbiota of dog-owning adolescents showed a higher social approach to a trapped cagemate. An association analysis was conducted between the adolescents' psychological scores and the mouse behavior with the abundance of each amplicon sequence variant (ASV) of the microbiome, and we found that ASVs belonging to Streptococcus were correlated with the social approach in ex-germ-free mice and mental scores in adolescents. These results suggest that microbiota may be partly involved in improving the well-being of adolescents living with dogs.}, } @article {pmid41497367, year = {2025}, author = {Aftab, G and Arab, P and Faranoush, P}, title = {A Comparative Study on the Impact of FIV and FeLV Infection on the Ocular Microbiota in Persian Cats: Insights From Co-Infection and Single Infections.}, journal = {Veterinary medicine international}, volume = {2025}, number = {}, pages = {8146795}, pmid = {41497367}, issn = {2090-8113}, abstract = {BACKGROUND: The ocular microbiome of cats infected with feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV) might differ from that of healthy cats. This study aimed to examine and compare the conjunctival bacterial and fungal flora in these groups.

METHODS: Bacterial and fungal cultures were conducted from the conjunctiva of 80 Persian cats, categorized into four groups: normal, FIV-infected, FeLV-infected, and co-infected with both FIV and FeLV. PCR assays confirmed the presence of FIV, FeLV, Chlamydia, and Mycoplasma. The microbiological analysis was compared across the different.

RESULTS: The conjunctival bacterial flora of normal cats was predominantly Gram-positive, with Staphylococcus species as the most common isolates. Escherichia coli was absent in the normal group but present in all infected groups, with the highest prevalence in the co-infected group (17.5%). Co-infection with FIV and FeLV led to a distinct microbiota with Streptococcus agalactiae, Corynebacterium renale, Fusarium, and Aspergillus brasiliensis exclusively found in this group.

CONCLUSIONS: The co-infection of FIV and FeLV significantly alters the conjunctival microbiome, promoting the colonization of specific opportunistic pathogens. These findings may influence the clinical management of cats with these viral infections, especially in combination, and may create a more favorable environment for the growth of certain bacteria and fungi in the conjunctiva.}, } @article {pmid41497166, year = {2026}, author = {Mehmood, MS and Danaf, N}, title = {Bacteroides fragilis toxin in colorectal tumors activates STAT3 and drives microsatellite instability.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {957-958}, pmid = {41497166}, issn = {2049-0801}, abstract = {Colorectal cancer (CRC) remains a global malignancy with over 1.9 million new cases annually. Emerging evidence implicates enterotoxigenic Bacteroides fragilis (ETBF) and its toxin (BFT) in activating STAT3 and promoting microsatellite instability (MSI), a novel microbial oncogenic axis. In analyses of more than 1200 CRC tumors, B. fragilis abundance correlated with a 2.14-fold higher MSI-high frequency and increased CpG island methylator phenotype. Mechanistically, BFT triggers E-cadherin cleavage, β-catenin activation, and IL-6/IL-17 up-regulation, fostering inflammation, oxidative stress, and mismatch-repair suppression. Animal models demonstrate a more than 60% rise in tumor burden following ETBF colonization, while human studies show B. fragilis present in about 80% of CRC tissues versus 50% of controls. These findings establish BFT-induced STAT3 signaling as a driver of genomic instability and tumor evolution. Targeting this pathway offers new prospects for biomarker development and precision therapy in colorectal cancer.}, } @article {pmid41497144, year = {2026}, author = {Mehmood, MS and Qasim, Z and Rauf, S and Danaf, N}, title = {Intratumoral Fusobacterium nucleatum metabolizes chemotherapy before it reaches cancer cells.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {939-940}, pmid = {41497144}, issn = {2049-0801}, abstract = {Fusobacterium nucleatum (Fn) has emerged as a crucial microbial determinant of chemotherapeutic failure in colorectal cancer. Detected in nearly 50% of all colorectal tumors, its presence is consistently associated with poorer prognosis and higher recurrence rates. Recent translational studies demonstrate that Fn metabolically interferes with cytotoxic drugs such as 5-fluorouracil and oxaliplatin, reducing active drug availability by up to 45%. This bacterium expresses nitroreductases and oxidoreductases capable of enzymatic inactivation, while its dense biofilms further hinder drug diffusion within the tumor microenvironment. Experimental depletion of Fn restores intratumoral drug levels and enhances tumor regression by approximately 60%, underscoring its direct role in metabolic resistance. Clinically, Fn-positive patients show diminished chemotherapy response and heightened inflammatory profiles. These findings collectively highlight that intratumoral microbiota, particularly Fn, can metabolize or neutralize chemotherapeutics before they reach cancer cells, an overlooked mechanism that challenges current cancer treatment paradigms.}, } @article {pmid41497134, year = {2026}, author = {Mehmood, MS and Abid, M and Hajj, F}, title = {Engineered Lactobacillus expressing tumor-killing cytokines: a novel biotherapeutic.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {1040-1041}, pmid = {41497134}, issn = {2049-0801}, abstract = {Cancer accounts for over 10 million deaths annually, with solid tumors responsible for nearly 90% of cases worldwide. Systemic cytokine administration remains limited by severe toxicity, high-dose interleukin-2 (IL-2) therapy induces grade 3-4 adverse effects in >60% of patients, and treatment-related mortality is around 4%. In this context, engineered Lactobacillus strains designed to express tumor-killing cytokines such as IL-12, IL-15, and TRAIL represent a novel biotherapeutic strategy that combines microbial safety with precision immune activation. Experimental evidence shows that Lactobacillus plantarum secreting IL-12 reduces colorectal tumor volume by 65%, L. casei expressing TRAIL decreases pancreatic tumor mass by 40%, and L. reuteri producing IL-15 enhances CD8+ T-cell infiltration by 45% and improves survival by 30% in murine models. These data illustrate that cytokine-expressing probiotics can replicate the efficacy of systemic cytokine therapy while avoiding dose-limiting toxicity. Integrating synthetic biology tools such as inducible promoters and biosafety kill switches further refines control and containment, making this a viable candidate for translational development. The convergence of immunotherapy and microbiome engineering thus establishes engineered Lactobacillus as a novel, locally acting, and low-toxicity antitumor biotherapeutic with the potential to reshape next-generation cancer treatment.}, } @article {pmid41497123, year = {2026}, author = {Mehmood, MS and Hajj, F}, title = {Noninvasive early detection of colorectal cancer through gut microbiome-derived biomarkers.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {997-998}, pmid = {41497123}, issn = {2049-0801}, abstract = {Colorectal cancer (CRC) remains a major global burden, with 1.9 million new cases and 935000 deaths reported in 2024. Despite available screening tools, nearly 45% of cases are still diagnosed at advanced stages, where the 5-year survival rate falls below 14%, compared to >90% in early detection. The limitations of colonoscopy its invasiveness, cost, and poor compliance (<40% globally) demand innovative, noninvasive diagnostic solutions. Gut microbiome profiling has recently emerged as a transformative approach, with specific bacterial signatures such as Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius showing AUC values between 0.85 and 0.93 for early CRC identification. Integrating metagenomic and metabolomic data enhances diagnostic accuracy to 89% sensitivity and 91% specificity. Moreover, altered microbial metabolites including decreased short-chain fatty acids and elevated secondary bile acids correlate with a 2.3- to 3.1-fold higher risk of carcinogenesis. Novel CRISPR-Cas13a-based assays further allow sub-attomolar detection of microbial RNA transcripts, underscoring a new frontier in microbiome-driven cancer diagnostics. Collectively, gut microbiome-derived biomarkers represent a noninvasive, mechanistically grounded, and highly sensitive platform for early CRC detection with significant translational potential.}, } @article {pmid41497081, year = {2026}, author = {Mazandarani, M and Lashkarbolouk, N and Ejtahed, HS and Qorbani, M}, title = {Effect of probiotics and synbiotics on antimicrobial resistance in frequent infections: a systematic review of clinical trials.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {698-717}, pmid = {41497081}, issn = {2049-0801}, abstract = {BACKGROUND: Antibiotic resistance and recurrent infections, driven by increased antibiotic use, represent a global health problem. This study aims to evaluate the effect of probiotics and synbiotics consumption on antibiotic resistance in common infections.

METHODS: A systematic search was performed on international electronic databases (PubMed/Medline, Scopus, and Web of Science) using predefined keywords to identify relevant clinical trials published prior to 1 March 2025. Study quality was assessed, and the PRISMA 2020 guideline was followed.

RESULTS: In our systematic review, 47 studies were included. Twenty studies reported positive effects on antibiotic resistance, eradication rates, and recurrence, particularly in gastrointestinal infections. In contrast, 10 studies reported no effect, and 2 indicated a negative effect of these interventions on infection recurrence and antibiotic resistance. In three studies focusing on children, probiotics significantly lowered the risk of urinary tract infection (UTI) recurrence and antibiotic resistance. However, an adult study found that probiotics had minimal effect on UTI recurrence. Four studies examined the effect of probiotics on respiratory infections in both children and adults, showing improvements in antibiotic resistance outcomes. Three studies involving preterm infants found that probiotics could modify their gut microbiome composition, with two studies confirming this effect.

CONCLUSION: Our study indicates that incorporating probiotics and synbiotics into common infection therapy could improve antibiotic resistance, eradicate rates, minimize side effects, and boost treatment compliance. However, concerns remain regarding the potential transfer of antibiotic resistance genes via probiotics.}, } @article {pmid41497069, year = {2026}, author = {Mehmood, MS and Danaf, N}, title = {Microbial metabolites regulating PD-L1 and checkpoint pathways: translational implications.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {953-954}, doi = {10.1097/MS9.0000000000004267}, pmid = {41497069}, issn = {2049-0801}, abstract = {Recent advances in microbiome research reveal that microbial metabolites directly regulate programmed death ligand-1 (PD-L1) expression and influence checkpoint immunotherapy outcomes. Multi-cohort analyses of over 1300 patients show that elevated short-chain fatty acids, indole derivatives, and secondary bile acids modulate PD-L1 and T-cell activity through histone deacetylase inhibition, STAT3 phosphorylation, and aryl hydrocarbon receptor signaling. High fecal butyrate correlates with a 2.4-fold higher response rate and 6.3-month improvement in progression-free survival during PD-1 blockade. Conversely, dysbiosis-associated metabolites, including lipopolysaccharide and succinate, induce PD-L1 hyperexpression and immune resistance. Metabolomic profiling now achieves AUCs of 0.82-0.89 in predicting immunotherapy response, outperforming tumor mutational burden and PD-L1 IHC. These findings establish microbial metabolites as active immunoregulatory mediators, offering new translational strategies for microbiome-informed immunotherapy personalization and biomarker integration in oncology.}, } @article {pmid41497008, year = {2026}, author = {Mehmood, MS and Masood, M and Danaf, N}, title = {Engineered food-borne probiotics delivering checkpoint-inhibitor modulators.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {27-28}, pmid = {41497008}, issn = {2049-0801}, abstract = {Engineered food-borne probiotics represent an emerging food-oncomicrobiology strategy that unites synthetic biology, nutrition, and cancer immunotherapy. Preclinical models demonstrate potent antitumor effects: Lactococcus lactis secreting soluble CD80-reduced tumor growth by 64%; Escherichia coli Nissle 1917 producing PD-L1 nanobodies achieved complete regression in 50% of treated mice with a two-fold rise in CD8[+]IFNγ[+]TNFα[+] T-cell infiltration; and Lactobacillus plantarum delivering IL-2 enhanced NK-cell activity 2.5-fold and extended survival by 30%. Clinical meta-analyses reveal that gut-microbiome diversity increases checkpoint-inhibitor response by 40% and median progression-free survival by 12 months. A phase I trial in Non-Small Cell Lung Cancer (NSCLC) showed reduced immune-related colitis (from 14% to 6%) and higher response rates (36% vs 21%) with probiotic co-therapy. Remaining challenges in colonization and biosafety, together with advances in controllable genetic circuits, make edible biologics a promising, low-toxicity immunotherapeutic platform.}, } @article {pmid41496990, year = {2026}, author = {Saif, P and Tausif, M and Fatima, M and Imtiaz, A and Hassan, M}, title = {CRISPR-targeted microbiome modulation in rare Henoch-Schonlein purpura IgA nephropathy-gastritis: insights into the gut-kidney axis.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {1090-1091}, pmid = {41496990}, issn = {2049-0801}, } @article {pmid41496973, year = {2026}, author = {Mehmood, MS and Abid, M and Danaf, N}, title = {Microbiome-selective DNA Pol IIIC inhibitors in oncology infection management.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {1070-1071}, pmid = {41496973}, issn = {2049-0801}, abstract = {Oncology patients experience high rates of bacterial infection due to chemotherapy-associated mucosal injury and immunosuppression, with up to 60% developing infectious complications and 20-30% of hematopoietic transplant recipients requiring hospitalization. Broad-spectrum antibiotics, although essential, frequently induce gut microbiome dysbiosis, which is associated with recurrent infection and reduced immune checkpoint inhibitor (ICI) effectiveness. Meta-analyses indicate that antibiotic exposure near ICI initiation leads to a 30-50% decrease in overall survival and a 25-40% reduction in progression-free survival. DNA polymerase IIIC inhibitor antibiotics, including ibezapolstat, have demonstrated 88-96% clinical cure rates in Clostridioides difficile infection while preserving gut microbial diversity and limiting expansion of antimicrobial-resistant organisms. Recent conference data suggest these microbiome-sparing effects may be class-wide. This targeted antimicrobial mechanism offers a potential strategy to maintain immune function, reduce recurrent infection, and support anticancer treatment response in immunocompromised patients.}, } @article {pmid41496941, year = {2026}, author = {Mehmood, MS and Iqbal, I and Hajj, F}, title = {CRISPR-Cas13a diagnostics for circulating microbial transcripts in pancreatic cancer.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {1}, pages = {1038-1039}, pmid = {41496941}, issn = {2049-0801}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of global cancer deaths, with a 5-year survival rate below 11% and over 80% of cases diagnosed at advanced, unresectable stages. Current biomarkers such as CA19-9 show suboptimal diagnostic accuracy (sensitivity 65-75%; specificity 70-80%), necessitating more precise and minimally invasive diagnostic tools. Recent advances in CRISPR-Cas13a technology, an RNA-guided, RNA-targeting system with attomolar sensitivity and >95% diagnostic accuracy, enable rapid detection of circulating RNA molecules. Concurrently, microbial transcriptomic studies have revealed distinct bacterial RNA fragments in plasma of PDAC patients, including Fusobacterium and Enterobacter small RNAs, detected in up to 68% of advanced and 41% of early-stage cases. Integrating Cas13a platforms with microbial RNA biomarkers could revolutionize liquid biopsy diagnostics by providing a fast (<30 min), low-cost (90% similarity) were found to have a different microbiome when compared to individuals where the protease was not detected. Phylogenetic analysis of pathogen IgA proteases along with IgA proteases from members of the microbiota suggested that there may be a unique subset of microbiota-derived IgA proteases. Our results highlight the importance of taxonomic resolution in microbiome studies and identify a subgroup of S. wadsworthensis that may be of potential clinical relevance.}, } @article {pmid41496455, year = {2026}, author = {Ramesh, A and Subbarayan, R and Shrestha, R and Adtani, PN}, title = {Exploring Fecal Microbiota Transplantation: Potential Benefits, Associated Risks, and Challenges in Cancer Treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {9}, number = {1}, pages = {e70455}, pmid = {41496455}, issn = {2573-8348}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Tumor Microenvironment/immunology ; Immunotherapy/methods ; Animals ; Risk Assessment ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a groundbreaking strategy for modulating the gut microbiome and improving cancer treatment outcomes. This review synthesizes the current evidence on the role of FMT in oncology, focusing on its potential to enhance the efficacy of immunotherapy, restore microbiome homeostasis, and mitigate cancer-associated complications.

RECENT FINDINGS: Preclinical and clinical studies have demonstrated that FMT can reprogram the tumor microenvironment, augment immune checkpoint inhibitor responses, and reduce chemotherapy-induced toxicity. However, risks such as pathogen transmission, immune dysregulation, and unintended microbial shifts necessitate rigorous donor screening and a personalized approach. Challenges in standardization, regulatory frameworks, and mechanistic understanding further complicate their clinical translation. Emerging innovations, including precision microbial consortia, synthetic biology, and biomarker-driven strategies, have the potential to address these limitations.

CONCLUSION: While FMT holds transformative potential in cancer care, its integration into oncological practice requires robust clinical validation, long-term safety assessments, and interdisciplinary collaboration to harness its full therapeutic potential.}, } @article {pmid41496451, year = {2026}, author = {Wang, P and Jiang, F and Xue, Z and Bu, F and Zhu, W and Zhang, Y and Wen, T and Li, Y and Zhang, P and Cai, Y and Niu, C and Li, S and Zhou, Y and Cheng, X}, title = {The Medicago SPX1/3-PHR2 Network Relays Phosphate Signaling to Orchestrate Root Nodulation-dependent Nitrogen Acquisition by Controlling Flavonoid Biosynthesis.}, journal = {Plant communications}, volume = {}, number = {}, pages = {101695}, doi = {10.1016/j.xplc.2026.101695}, pmid = {41496451}, issn = {2590-3462}, abstract = {The formation of symbiotic associations with rhizospheric microbes is an important strategy for sessile plants to acquire nitrogen and phosphorus from the soil. Root exudate plays a key role in shaping the rhizosphere microbiome. Depending on their needs for nitrogen or phosphorus, plants can adjust the composition of root exudate to attract the appropriate microbes. Flavonoids, a group of secondary metabolites, have been well studied for their role in shaping the root microbiome, particularly in mediating root nodule symbiosis in legumes. However, the mechanism by which plants regulate the absorption of microbe-mediated nitrogen and phosphorus remains unclear. Here, we show that the Medicago truncatula phosphate starvation response regulatory network SPX1/3-PHR2 controls flavonoid biosynthesis to recruit nitrogen-fixing microbes for nitrogen acquisition. Nitrogen-fixing microbes, including rhizobia, were fewer recruited in the rhizosphere of the spx1spx3 double mutant. This was caused by lower flavonoid levels in the root exudate compared to wild-type plants R108. Further results indicate that the control of flavonoid biosynthesis is exerted via PHR2, the interacting transcription factor of SPX1/3. Under phosphate-limiting conditions, PHR2 suppresses the expression of flavonoid biosynthetic genes to reduce root nodule symbiosis levels. Under phosphate-sufficient conditions, the interaction between SPX1/3 and PHR2 releases this suppression, thereby promoting root nodule symbiosis. We further showed that PHR2 can bind to the promoter regions of flavonoid biosynthetic genes in yeast. We propose that the SPX1/3-PHR2 network can modulate root nodule-dependent nitrogen acquisition in response to phosphate levels. Thus, the SPX1/3-PHR2 module contributes to maintaining a balance in microbe-mediated nitrogen and phosphorus acquisition for optimal plant growth.}, } @article {pmid41496347, year = {2026}, author = {Saghafi, S and Yaghoubi, MA and Safarpour, H and Raeisi, H and Mousavi, Z}, title = {Protecting the endocrine axis in immuno-oncology: GLP-1 receptor agonists as host-directed modulators in colorectal cancer.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {194}, number = {}, pages = {118948}, doi = {10.1016/j.biopha.2025.118948}, pmid = {41496347}, issn = {1950-6007}, abstract = {Immune checkpoint inhibitors (ICIs) have transformed colorectal cancer (CRC), particularly in microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) tumors, delivering durable responses and long-term survival. Yet this success is shadowed by immune-related adverse events (irAEs). Among them, endocrine toxicities including thyroiditis, hypophysitis, adrenalitis, and insulin-deficient diabetes are relatively frequent, irreversible, and frequently life-long. Survivors who might otherwise be considered cured remain tethered to chronic hormone replacement, underscoring a striking gap in immuno-oncology: management is reactive, supportive, and devoid of preventive strategies. Concurrently, glucagon-like peptide-1 receptor agonists (GLP-1RAs), introduced for type 2 diabetes (T2D) and obesity, are emerging as systemic modulators of inflammation, immunometabolism, and the gut microbiome. These three axes converge on mechanisms central to endocrine irAEs. Preclinical and epidemiologic data suggest that GLP-1RAs may also be associated with reduced cancer incidence and alterations in tumor-associated immune responses, raising the possibility of dual utility: mitigating endocrine autoimmunity while preserving or even augmenting anti-tumor efficacy. At the same time, their appetite-suppressing and weight-reducing effects highlight the countervailing risk of exacerbating cancer cachexia, demanding careful integration with nutritional and exercise strategies. Here, we synthesize current understanding of ICI-induced endocrine injury, delineate the immunobiology of GLP-1RAs, and develop a unified mechanistic framework linking these domains in CRC. We propose a translational roadmap spanning retrospective pharmacoepidemiology, biomarker-driven stratification, and prospective clinical trials. More broadly, GLP-1RAs exemplify host-directed therapies that may help shift the therapeutic focus of immuno-oncology toward preserving survivorship and endocrine health as integral endpoints of cancer care.}, } @article {pmid41496313, year = {2026}, author = {Sun, L and Sun, X and Qiao, C and Lu, Y and Li, Q and Wang, Q and Gao, H}, title = {Precision medicine in Crohn's disease: Navigating the path from biomarker discovery to clinical implementation.}, journal = {Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association}, volume = {}, number = {}, pages = {}, pmid = {41496313}, issn = {1998-4049}, abstract = {Crohn's disease (CD) is a highly heterogeneous inflammatory bowel disorder. Despite an expanding therapeutic arsenal, treatment selection remains largely empirical, often leading to delayed effective control and suboptimal outcomes. Precision medicine, which tailors therapy to individual patient characteristics, offers a promising alternative. Advances in biomarker discovery are enabling more personalized approaches. Research has moved beyond conventional markers to high-dimensional data from genomics, proteomics, and microbiome studies. Over 200 genetic susceptibility loci have been identified, and dysbiosis is recognized as a key modulator of disease and treatment response. Integrating these multi-omics data is crucial for building predictive models, a task increasingly aided by artificial intelligence and machine learning. However, translating these discoveries into clinical practice faces significant hurdles. These include insufficient validation across diverse populations, methodological heterogeneity, and a lack of real-world evidence. Biomarker performance may vary significantly across genetically diverse patient cohorts, raising concerns that precision medicine tools validated only in homogeneous populations could inadvertently propagate health disparities. It is also important to consider regional contexts, such as the Middle East and Saudi Arabia, where rising IBD incidence due to urbanization and unique genetic architectures may affect biomarker performance and therapy response. This review synthesizes recent progress, outlines the major barriers to implementation, and discusses future directions, such as leveraging digital health technologies and international collaborations, to accelerate the adoption of precision medicine and improve outcomes for CD patients.}, } @article {pmid41496250, year = {2026}, author = {Anyango, OV and Aool, OW and Lukindu, M and Nakayiki, T and Lutwama, J and Kayondo, JK and Phillips, CD and Lutomiah, J and Mutisya, J and Brelsfoard, CL and Onyango, MG}, title = {Molecular detection of medically important rickettsiae, including Rickettsia prowazekii in Rhipicephalus appendiculatus and Hyalomma rufipes: A microbiome perspective.}, journal = {Ticks and tick-borne diseases}, volume = {17}, number = {1}, pages = {102596}, doi = {10.1016/j.ttbdis.2025.102596}, pmid = {41496250}, issn = {1877-9603}, abstract = {The East African region hosts more than 50 % of Africa livestock and 9 % of global cattle, creating an ideal environment for ticks to thrive and transmit pathogens. Little is known of the full spectrum of tick-associated bacterial pathogens that circulate in the vast pastoralist-intense regions of East Africa, the range of the pathogens and their genetic relationships. To define this, we need to first delineate the microbial composition of the medically and veterinary important East African tick species. This study focused on the likely vectors of Orthonairovirus haemorrhagiae in Kenya and Uganda, specifically H. rufipes and R. appendiculatus. To characterize the bacterial microbiome associated with these two tick species, the V3-V4 hypervariable region of the 16S rRNA gene was sequenced from a total of 25 R. appendiculatus and 24 H rufipes specimens using the Illumina MiSeq platform. Microbial abundance and diversity were subsequently analysed to assess the composition and structure of their bacterial communities. We observed a richer and balanced bacterial microbiome profile among the H. rufipes compared to that of the R. appendiculatus, which was mainly dominated by Coxiella-like endosymbionts. Furthermore, a few bacterial taxa were unique to each sampling site, while several were common across all sampling sites. This study identified several medically important Rickettsia species, including R. aeschlimannii, R. conorii, and, for the first time, R. prowazekii, the causative agent of epidemic typhus, in H. rufipes sampled from Northeast Kenya. Furthermore, our findings demonstrate that R. africae exhibits a broad tick host tropism. Our present findings provide insights into the microbial community of medically important tick species of East Africa. The observation of a significant level of Coxiella-like endosymbionts in R. appendiculatus warrants an investigation into their transmissibility and impacts on the transmission of other pathogens. The identification of R. prowazekii in H. rufipes suggest that R. prowazekii is broadening its host tropism in Kenya.}, } @article {pmid41496086, year = {2026}, author = {Gao, Y and Yu, X}, title = {Acupuncture treatment for insomnia based on the microbiome-gut-brain axis theory: A review.}, journal = {Medicine}, volume = {105}, number = {1}, pages = {e46967}, pmid = {41496086}, issn = {1536-5964}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy/microbiology ; *Acupuncture Therapy/methods ; *Gastrointestinal Microbiome/physiology ; Brain ; *Brain-Gut Axis/physiology ; }, abstract = {Insomnia, a prevalent sleep disorder, significantly impacts patient social function and quality of life, creating a substantial burden on individuals. This underscores the need for effective treatments. Acupuncture, an essential part of complementary and alternative medicine, has received increasing attention for its therapeutic effect on insomnia, although its mechanism is still not fully understood. In recent years, some studies have focused on the microbiome-gut-brain axis, a promising area of study that may shed light on how acupuncture alleviates insomnia. This review explores the possible mechanisms by which acupuncture therapy improves insomnia through the microbiome-gut-brain axis. These mechanisms include adjusting the types and diversity of intestinal microbiome and altering short-chain fatty acid levels, inhibiting inflammatory responses, improving the tight connection of the intestinal mucosal barrier, controlling the release and production of brain-gut peptides, and regulating the pathways associated with the hypothalamic-pituitary-adrenal axis and the vagus nerve. The findings aim to provide a more objective basis for the use of acupuncture and moxibustion in treating insomnia.}, } @article {pmid41496083, year = {2026}, author = {Wang, X and Qin, W}, title = {Effect of gut microbiome and blood metabolites on colorectal cancer: A bidirectional Mendelian randomization and mediation analysis based on STROBE-MR guidelines.}, journal = {Medicine}, volume = {105}, number = {1}, pages = {e46936}, pmid = {41496083}, issn = {1536-5964}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics/physiology ; *Colorectal Neoplasms/blood/genetics/microbiology ; Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; Mediation Analysis ; }, abstract = {Previous studies have shown that gut microbiome as well as blood metabolites are involved in the development of colorectal cancer (CRC). Therefore, this study attempted to discover the causal effects of gut microbiome and blood metabolites on CRC. Using genetic data from published genome-wide association studies, the 2-sample Mendelian randomization (MR) and 2-step MR analyses were applied to evaluate the causal connections between gut microbiome (exposure) and CRC (outcome) with blood metabolites as the mediators, as well as between blood metabolites (exposure) and CRC (outcome) with gut microbiome as the mediators. Moreover, a reverse MR analysis was done to measure the impact of CRC on gut microbiome and blood metabolites. The inverse variance weighted method was primarily utilized to analyze causal effects, with the robustness of the findings further assessed by sensitivity analyses. The 2-sample MR analyses illustrated that 14 gut microbes, 23 gut bacterial pathways, and 96 blood metabolites exerted an evidence of causal effect on CRC. However, there were no causal relationships between CRC and gut microbes and blood metabolites. Additionally, mediation analyses revealed that 5 gut microbiome (three gut microbes and 2 gut bacterial pathway abundance) influenced CRC through 4 blood metabolites, and 9 blood metabolites influenced CRC through 7 gut microbiome (four gut microbes and 3 gut bacterial pathways). Sensitivity analyses indicated that all results were reliable. Our study further highlights the complex relationship among gut microbiome, blood metabolites, and CRC and provides insights into clinical interventions for CRC.}, } @article {pmid41496069, year = {2026}, author = {Zhao, Y and Wang, H and Lu, Y and Lou, D}, title = {Evolving landscapes in childhood asthma-gut microbiota research: A bibliometric analysis from 2000 to 2024.}, journal = {Medicine}, volume = {105}, number = {1}, pages = {e46594}, pmid = {41496069}, issn = {1536-5964}, support = {ZHGF2024-1//The Key Construction Discipline of Immunology and Pathogen biology in Zhuhai Campus of Zunyi Medical University/ ; NO. QKHRC-CXTDã€"2025〕046//The Program for High level Innovative Talents in the Guizhou Province/ ; }, mesh = {Humans ; *Asthma/microbiology/immunology ; *Bibliometrics ; *Gastrointestinal Microbiome ; Child ; Dysbiosis ; *Biomedical Research/trends ; }, abstract = {BACKGROUND: Pediatric asthma, a chronic inflammatory airway disorder, is increasingly recognized for its association with gut microbiota dysbiosis, mediated through immune dysregulation and systemic inflammation. Recent advancements in multi-omics technologies and the "gut-lung axis" hypothesis have propelled this field into a research frontier. This bibliometric study delineates global research trends, collaborative networks, and emerging directions in pediatric asthma-gut microbiota research.

METHODS: Publications from the Web of Science Core Collection (2000-2024) were systematically retrieved using keywords related to asthma, children, and gut microbiota. Data from 635 articles (392 original studies, 243 reviews) were analyzed via CiteSpace and VOSviewer to map country/institutional contributions, author networks, citation metrics, and keyword clusters. Non-English publications, patents, and conference abstracts were excluded.

RESULTS: Global output demonstrated exponential growth, with 62% of articles published between 2018 to 2022. The United States led in productivity (180 articles, 28.35%) and citations (10,851), while Canada achieved the highest citation impact (121.12 citations/article). Key contributors included Prof Stuart E. Turvey (19 articles, 2463 citations) and Prof B. Brett Finlay (140.07 citations/article). The University of British Columbia dominated institutional contributions (28 articles, 149.11 citations/article). The Journal of Allergy and Clinical Immunology emerged as the top journal (33 articles, 126.48 citations/article). Seminal works highlighted early-life gut dysbiosis (e.g., reduced Lachnospira and Faecalibacterium) and cesarean delivery's role in asthma risk. Keyword clustering revealed 6 themes: disease phenotypes (asthma-allergy comorbidity), microbiota dynamics (dysbiosis, short-chain fatty acids [SCFAs]), immune mechanisms (T helper 17 cells/Treg imbalance, gut-lung axis), developmental exposures (antibiotics, breastfeeding), methodologies (metagenomics), and therapeutic strategies.

CONCLUSION: This study underscores a paradigm shift from descriptive microbial profiling to mechanistic exploration of microbiota-derived metabolites (e.g., SCFAs) and early-life interventions. Future priorities include elucidating causal pathways via longitudinal cohorts, developing microbiota-targeted therapies, and leveraging multi-omics integration. Despite limitations in database scope, this analysis highlights accelerating translation from basic research to clinical applications through global collaboration. Researchers should prioritize interdisciplinary studies to unravel the "microbiome-immune-development" triad and optimize personalized asthma management.}, } @article {pmid41496014, year = {2026}, author = {Yan, Y and Hu, M and Liu, C and Liu, Q and Xiong, T and Su, K}, title = {Unveiling the causal relationships between gut microbiota, circulating metabolic biomarkers, and benign prostate hyperplasia: A Mendelian randomization study.}, journal = {Medicine}, volume = {105}, number = {1}, pages = {e46466}, pmid = {41496014}, issn = {1536-5964}, mesh = {Male ; Humans ; *Prostatic Hyperplasia/microbiology/blood/genetics ; *Gastrointestinal Microbiome/physiology/genetics ; Mendelian Randomization Analysis ; Biomarkers/blood ; *Dysbiosis/microbiology/complications ; Genome-Wide Association Study ; Risk Factors ; }, abstract = {The complex roles of gut microbiome (GM) dysbiosis and circulating metabolites in benign prostatic hyperplasia (BPH) pathogenesis have been widely hypothesized but lacked causal evidence. Critically, no Mendelian randomization (MR) study has established whether GM and metabolites exert direct causal effects or act through mediating pathways in BPH development. Using genome-wide association studies data, we conducted comprehensive 2-sample and mediation MR analyses. Causal effects were estimated via inverse-variance weighted methods with sensitivity analyses. Six bacterial phyla/genera showed significant causal links to BPH, including Actinobacteria (genus Bifidobacterium), Bacteroidetes (genus Bacteroides), Firmicutes (genera Blautia, Holdemania), and Proteobacteria (genus Comamonas). Additionally, 2 circulating metabolites - the mean diameter of low-density lipoprotein (LDL) particles and the free cholesterol to total lipids ratio in small very LDL - were significantly associated with BPH. However, no mediation effect was found for any circulating metabolites on BPH. In summary, our 2-sample and mediation MR analysis revealed 18 GM and 2 circulating metabolites significantly linked to BPH, highlighting their potential as risk factors. While no mediation effects for circulating metabolites were detected, these findings enhance our understanding of preventive strategies for BPH, emphasizing the intricate relationship between GM dysbiosis, circulating lipid metabolites, and disease onset.}, } @article {pmid41495909, year = {2026}, author = {Derollez, E and Roson-Calero, N and Rouzé, P and Dedieu-Berne, A and Ballesté-Delpierre, C and Fraikin, N and Iorga, BI and Huang, TD and Bigot, S and Vila, J and Bogaerts, P and Lesterlin, C}, title = {Specific killing and resensitization of pathogenic Escherichia coli strains carrying blaCTX-M-15 β-lactamase using targeted-antibacterial-plasmids (TAPs).}, journal = {Nucleic acids research}, volume = {54}, number = {1}, pages = {}, pmid = {41495909}, issn = {1362-4962}, support = {//Joint Programming Initiative on Antimicrobial Resistance/ ; JPIAMR2021-194//JPIAMR/ ; FRM-EQU202103012587//Foundation for Medical Research/ ; ANR-20-PAMR-0010//French Priority Research Program/ ; //Agence Nationale de la Recherches/ ; }, mesh = {*beta-Lactamases/genetics/metabolism ; *Escherichia coli/genetics/drug effects/enzymology ; *Plasmids/genetics ; CRISPR-Cas Systems ; Humans ; Anti-Bacterial Agents/pharmacology ; Conjugation, Genetic ; Drug Resistance, Multiple, Bacterial/genetics ; Escherichia coli Infections/microbiology ; }, abstract = {Targeted-Antibacterial-Plasmids (TAPs) offer a precise approach to combat multidrug-resistant bacteria by selectively removing resistant strains while preserving commensals. Here, we assess TAPs that deliver CRISPR/Cas systems via conjugation to kill or resensitize extended-spectrum β-lactamase (ESBL)-producing Escherichia coli carrying the blaCTX-M-15 gene. We systematically tested multiple variables in the TAP approach, including two commensal E. coli donors, three distinct helper plasmids encoding the transfer machineries, and six recipient strains harbouring the resistance gene either chromosomally or on a plasmid. Cas9-based TAPs induced double-stranded breaks in chromosomal blaCTX-M-15 genes, resulting in immediate bacterial death. When the target gene was plasmid-borne, Cas9 cleavage triggered plasmid loss and partial toxin-antitoxin-mediated killing. In contrast, dCas9-based TAPs inhibited blaCTX-M-15 expression without affecting cell viability, thereby restoring third-generation cephalosporin susceptibility. In mixed-culture experiments, TAPs specifically eliminated only blaCTX-M-15-carrying E. coli while sparing other non-targeted bacterial species. Conjugation assays in human faeces demonstrated substantial suppression of cefotaxime-resistant (CtxR) E. coli by both Cas9- and dCas9-based TAPs, underscoring their efficacy in complex microbial environments. These findings highlight TAPs' decolonization promise, paving the way for future microbiome-editing interventions against multidrug-resistant carriage or infection.}, } @article {pmid41495831, year = {2026}, author = {Éliás, AJ and Földvári-Nagy, KC and Al-Gharati, YZ and Veres, DS and Schnabel, T and Teutsch, B and Erőss, B and Hegyi, P and Lenti, K and Földvári-Nagy, L}, title = {Effect of probiotic supplementation on the gut microbiota diversity in healthy populations: a systematic review and meta-analysis of randomised controlled trials.}, journal = {BMC medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12916-025-04602-0}, pmid = {41495831}, issn = {1741-7015}, abstract = {BACKGROUND: Probiotics are widely used dietary supplements promoted to positively influence gut health and microbiota diversity, making them popular among healthy individuals. One of the purported benefits of probiotics is their ability to enhance gut microbiota diversity, a feature associated with improved resilience and overall health. However, evidence supporting this claim remains inconclusive. We aimed to investigate whether probiotics significantly modify gut microbiota diversity in healthy populations through a systematic review and meta-analysis.

METHODS: A systematic search of MEDLINE, Embase, and Cochrane databases was conducted on 12/04/2024, following the search strategy registered in PROSPERO (CRD42022286137). Out of 9217 identified articles, 47 met the inclusion criteria of the current review, and 22 studies with data from 1068 individual subjects were eligible for meta-analysis of changes in gut microbiota diversity assessed by diversity indices. A random-effects model was employed to estimate the means of median differences (MedD) with 95% confidence intervals (CI) due to the expected heterogeneity.

RESULTS: The quantitative synthesis revealed no statistically significant effects of probiotics on Shannon diversity (MedD = - 0.08, 95% CI [- 0.16 to 0.01]), observed operational taxonomic units (MedD = 2.19, 95% CI [- 2.20 to 6.57]), Chao1 (MedD = - 3.19, 95% CI [- 27.28 to 20.89]), or Simpson's index of diversity (MedD = - 0.01, 95% CI [- 0.02 to 0.00]) indices compared to unsupplemented controls. Subgroup and sensitivity analyses suggest that the probiotic taxonomic family, the risk of bias, or the duration of intervention did not change our findings. Insufficient data prevented us from meta-analysing other diversity indices; however, most of the included studies reported no difference in other reported α- and ß-diversity indices between the probiotic and control groups.

CONCLUSIONS: Our results indicate that probiotic supplementation does not produce statistically significant changes in gut microbiota diversity in healthy individuals. This study highlights the need for further research to determine whether specific probiotic strains or formulations may influence diversity in targeted subgroups or under specific conditions.}, } @article {pmid41495822, year = {2026}, author = {Xie, S and Zhi, Y and Badehnoosh, B}, title = {Microbial modulators of the epigenome: probiotic regulation of MiRNAs and LncRNAs in health and disease and preventive medicine.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {4}, pmid = {41495822}, issn = {1757-4749}, abstract = {Current improvements in microbiome research have illuminated the serious function of probiotics in modulating host gene expression through epigenetic mechanisms, particularly via the regulation of non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These regulatory RNAs are essential mediators of gene silencing, chromatin remodeling, and cellular signaling pathways implicated in immunity, inflammation, cancer, and neurodegenerative diseases. This review comprehensively examines current evidence on how specific probiotic strains influence miRNA and lncRNA expression, leading to beneficial outcomes in various pathological and physiological conditions. We explore the underlying molecular mechanisms by which probiotic-derived metabolites, like extracellular vesicles and short-chain fatty acids, interrelate with host transcriptional machinery and ncRNA biogenesis. Special emphasis is placed on disease models including inflammatory bowel disease, colorectal cancer, metabolic syndrome and Alzheimer's disease, highlighting the beneficial possible of targeting the gut microbiota-ncRNA axis. Moreover, we discuss the prospects for personalized microbiome-based interventions, challenges in clinical translation, and future directions for leveraging probiotic-ncRNA interactions in precision medicine. The integration of probiotics into epigenetic therapy represents a promising, non-invasive strategy for modulating gene expression and restoring homeostasis in complex diseases.}, } @article {pmid41495581, year = {2026}, author = {Cheng, Y and Yang, Y and Guo, Y and Shi, Y and Feng, J and Jiang, X and Yang, Z and Zhu, H and Liu, X}, title = {Exploring the pathogenesis of NAFLD: a study of the correlation of gut microbes and metabolites in humanized mouse gut microbiota.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {104}, number = {1}, pages = {24}, pmid = {41495581}, issn = {1432-1440}, support = {2022YFF0710600//Key Technologies Research and Development Program/ ; }, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/microbiology/metabolism/pathology/etiology ; *Gastrointestinal Microbiome ; Humans ; Mice ; Disease Models, Animal ; Male ; Liver/pathology ; Female ; Feces/microbiology ; *Metabolome ; }, abstract = {There is mounting scientific evidence indicating a robust association between gut microbiota and nonalcoholic fatty liver disease (NAFLD). Exposure to commensal microbiota in germ-free mice has a significant impact on the regulatory mechanisms of gut genes, in contrast to those conventionally raised. In this study, we have successfully inoculated the gut microbiota from healthy individuals and NAFLD patients into germ-free mice, with the objective of developing a humanized mouse model that accurately replicates the gut microenvironment of NAFLD patients. Changes in blood composition and liver pathology in these mice were systematically measured. Furthermore, we have conducted a detailed analysis of the variations in fecal microbiota and differential metabolites in the blood composition. Our findings indicate a high degree of similarity in disease characteristics between mice colonized with microbiota and humans suffering from NAFLD. Notably, we have observed a strong correlation between alterations in serum differential metabolites and gut microbiota in these mice. KEY MESSAGES: A humanized NFALD mouse model was established based on sterile mice. In microbiota-colonized mice and humans with NAFLD, disease characteristics showed a high degree of similarity. There was a strong association between changes in serum differential metabolites and gut microbiota in mice colonized by intestinal microbiota.}, } @article {pmid41495500, year = {2026}, author = {Huang, JS and Zhang, ZY and Zhong, QH and Guo, FL and Wu, JY and Chen, S and Lin, WW and Lin, JB}, title = {ASO Visual Abstract: Tumor-Intrinsic Microbiome-Based Subtyping of Esophageal Cancer as Predictive Biomarkers for Postoperative Survival.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1245/s10434-025-19013-x}, pmid = {41495500}, issn = {1534-4681}, } @article {pmid41436819, year = {2025}, author = {Lim, JK and Kim, JA and Lee, N and Oh, C and Woo, S}, title = {Comparison of microbial assemblages associated with the stalked barnacle Neolepas marisindica from two adjacent hydrothermal vent fields on the Central Indian Ridge.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {597}, pmid = {41436819}, issn = {2045-2322}, support = {PEA0314//Korea Institute of Ocean Science and Technology/ ; 20170411//Ministry of Ocean and Fisheries, Korea/ ; }, abstract = {Neolepas marisindica, a stalked barnacle endemic to the Central Indian Ridge (CIR), hosts microbial communities that remain poorly characterized. In this study, we performed 16S rRNA amplicon sequencing to characterize the microbiome associated with N. marisindica collected from two geographically adjacent hydrothermal vent fields along the Central Indian Ridge (CIR): Solitaire (Site A) and Onnuri (Site D). We further used PICRUSt2 to infer the functional potential of these microbial communities and to assess whether differences in in situ geochemical conditions between the two vents shape microbiome composition and metabolic capacity. Both sites harbored microbiota dominated by Proteobacteria, yet displayed distinct taxonomic and functional differences. Site D was enriched in methanotrophic genera (Methylobacter, Methylomicrobium), while Site A was dominated by sulfur-oxidizing taxa such as Thiotrichaceae. Although alpha diversity was higher at Site D, the difference was not statistically significant. Beta diversity analysis showed clear clustering by site. Functional prediction using PICRUSt2 revealed elevated pathways for oxidative phosphorylation, lipid metabolism, and secondary metabolite biosynthesis in Site D samples, suggesting adaptation to methane-rich conditions. LEfSe analysis supported these site-specific functional patterns. Overall, this study reveals both a shared microbial core and localized differences in microbiome structure and function in N. marisindica, underscoring the influence of geochemical variation on host-associated microbiota in deep-sea hydrothermal ecosystems.}, } @article {pmid41327018, year = {2025}, author = {Gajjar, K and Patel, S and Chaudhary, M and Agrawal, D and Maniyar, R and Chaudhary, D and Patel, CK and Joshi, C and Joshi, M and Dharajiya, D}, title = {Metagenomic insights reveal the impact of natural farming on soil nutrients, enzyme activities, microbial communities, and yield in turmeric cultivation.}, journal = {BMC plant biology}, volume = {26}, number = {1}, pages = {28}, pmid = {41327018}, issn = {1471-2229}, support = {GSBTM/JD(R&D)/661/2022-23/00172688//Gujarat State Biotechnology Mission/ ; }, abstract = {BACKGROUND: Turmeric (Curcuma longa L.) is a key spice, medicinal and industrially important crop that is increasingly being cultivated under sustainable practices such as natural farming system (NFS). This study compares NFS and conventional/chemical farming system (CFS) in terms of soil physicochemical properties, enzyme activities, microbial diversity, and yield parameters, providing a comprehensive understanding of their ecological and agronomic impacts.

RESULTS: Field experiments evaluated nine NFS treatments alongside CFS for high throughput amplicon (16S rRNA and ITS) metagenomics, soil physicochemical properties, enzyme activities, and yield parameters. NFS treatments with ≥ 5 t/ha mulching and 4 t/ha Ghanjeevamrit (i.e. NFS-T6 and NFS-T9) significantly enhanced soil organic carbon (~ 0.25%), nitrogen (~ 239.9 kg/ha), and phosphorus (~ 38.16 kg/ha), alongside elevated enzyme activities like alkaline phosphatase (ALP; ~112.11 µg PNP/g/hr) and protease (PR; ~16.22 µg Tyrosine/g/hr). These treatments also exhibited significantly higher microbial richness and evenness (Shannon index: ~5.09; Simpson index: ~0.981). NFS enriched beneficial bacterial (e.g., Priestia, unclassified Acidobacteria, etc.) and saprophytic fungal genera (e.g., Humicola, Mortierella, etc.), enhancing soil nutrient cycling and soil health. Conversely, CFS enriched chemical-resilient and pathogenic taxa (e.g., Alternaria, Curvularia, etc.). NFS-T5 (40.66 t/ha) and NFS-T9 (40.47 t/ha) yielded over twice the fresh rhizome compared to CFS. NFS treatments recorded higher net returns and Benefit-Cost Ratios (BCRs) of 7.51 to 10.57. Microbial profiling of natural farming (NF) inputs (Beejamrit, Jeevamrit, and Ghanjeevamrit) showed distinct bacterial and fungal communities influencing soil microbiome structure. Co-occurrence network analysis of NF soils revealed that microbial taxa introduced via NF inputs had limited integration into native soil communities, indicating selective incorporation governed by competitive ecological interactions.

CONCLUSIONS: Natural farming practices significantly enhanced soil fertility, microbial community structure, enzymatic activity (ALP and PR), and turmeric productivity with superior BCRs. These findings provide scientific evidence supporting natural farming as a viable and sustainable agricultural approach, contributing to improved soil health and crop performance in turmeric cultivation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-025-07781-3.}, } @article {pmid41495419, year = {2026}, author = {Bang, YH and Choi, JH and Park, K and Lee, B and Han, KY and Pyo, DH and Cho, YB and Kim, TY and Park, KJ and Ryoo, SB and Kang, SB and Yu, CS and Lee, J and Lee, KY and Kim, KT and Lee, JY and Chu, HBK and Shah, N and Gupta, S and Sonpatki, P and Kim, YJ and Park, WY}, title = {Colorectal microenvironment determines the prognosis of colorectal cancer.}, journal = {Experimental & molecular medicine}, volume = {}, number = {}, pages = {}, pmid = {41495419}, issn = {2092-6413}, support = {NRF2017M3A9A7050803//National Research Foundation of Korea (NRF)/ ; 2022R1C1C1012415//National Research Foundation of Korea (NRF)/ ; 2021R1A4A3031875//Ajou University/ ; }, abstract = {Here we aimed to evaluate the feasibility of distinguishing colorectal microenvironments that support cancer cell growth from those that do not. We hypothesized that patients whose non-tumor-bearing tissue (NBT) obtained from the furthest margins of resected cancer specimens resembled the tumor had a poorer prognosis. Patients with colorectal cancer were divided into groups with tumor-supportive (TSM) or healthy microenvironments using bulk RNA sequencing data from 273 paired NBT and tumor samples. Patients in the TSM group exhibited significantly poorer 5-year recurrence-free survival and overall survival compared with those in the healthy microenvironment group. Pathway and 16S rRNA sequencing analyses revealed that NBT and tumors from the TSM group shared a microbiome composition, along with decreased pathway activity related to microvilli maintenance and flavonoid or vitamin metabolic processes. Single-cell RNA sequencing uncovered upregulated interactions between IL1B[high] neutrophils and OLFM4[+] epithelial cells in NBTs from the TSM group, as well as organized microniches in TSM tumors, featuring interactions between EMP1[high] epithelial cells, IL1B[high] neutrophils and GZMK[high] CD8[+] T cells. Collectively, the colorectal microenvironment can serve as a prognostic biomarker to effectively predict cancer invasiveness and tumor-promoting inflammation. Maintaining a healthy colorectal mucosal microenvironment, potentially through dietary intervention, is crucial.}, } @article {pmid41495254, year = {2026}, author = {Kukreja, B and Jeon, S and Cao, W and Rusu, B and Harrison, CF and Ghazisaeidi, S and Tahmasian, N and Feng, MY and Chan, R and Loan, A and Johnston, WB and Padhy, S and Rakoff-Nahoum, S and Wang, J and Yim, YS and Kalish, BT}, title = {Spatial transcriptomics of the developing mouse brain immune landscape reveals effects of maternal immune activation and microbiome depletion.}, journal = {Nature neuroscience}, volume = {}, number = {}, pages = {}, pmid = {41495254}, issn = {1546-1726}, abstract = {Immune molecules and their cognate receptors are developmentally regulated in brain and dynamically expressed in the context of neurodevelopmental disorders. Despite the importance of immune molecules to brain wiring, a comprehensive map of the neuroimmune landscape is lacking in developing brain. Here we employed multiplexed in situ spatial transcriptomics to measure the expression of major immune ligands and receptors in developing mouse brain during mid and late gestation. Given the importance of maternal environment in shaping fetal neurodevelopment, we determined how embryonic neuroimmune landscape was altered after maternal immune activation (MIA) and maternal microbiome depletion. Our study revealed notable sex-specific patterns in gene expression and spatial architecture within developing brain. We observed changes in the CXCL12/CXCR7 chemokine network after MIA and microbiome depletion, suggesting a potential common mechanism underlying neural progenitor abnormalities. This resource underscores how the maternal environment programs precise regulation of immune molecules in developing brain, highlighting sex-specific vulnerability.}, } @article {pmid41495071, year = {2026}, author = {Suryavanshi, M and Mukherjee, SD and Miller, AW}, title = {Predicting probiotic success: lessons from Oxalobacter and oxalate metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00896-3}, pmid = {41495071}, issn = {2055-5008}, support = {R01KD121689//NIH NIDDK/ ; }, abstract = {The gut microbiota influences host metabolism, immunity, and organ physiology, making it an attractive therapeutic target. However, clinical probiotic trials often produce inconsistent results, reflecting context-dependent effects shaped by metabolic, ecological, dietary, and host-specific factors. We critically synthesized the literature on hyperoxaluria, a condition of elevated urinary oxalate associated with kidney stones and chronic kidney disease, as a mechanistically tractable model for probiotic development. We examined evidence from clinical studies, microbiome analyses, and mechanistic experiments to identify factors influencing efficacy, with a focus on Oxalobacter formigenes, a specialist oxalate-degrading anaerobe. Across trials, probiotic success depended less on dose, strain identity, or persistence, and more on the ecological context - particularly the baseline abundance of oxalate-degrading genes (oxc, frc) in the native microbiota. Efficacy was highest when these metabolic niches were vacant. Diet, delivery format, and broader microbial community structure also shaped outcomes. A taxon-centric approach is insufficient for predicting probiotic efficacy. We propose a three-phase framework for rational design: (1) case-control microbiome studies to identify metabolically relevant deficits; (2) mechanistic in vivo and in vitro validation to establish causality; and (3) complex systems modeling to predict context-specific responses. This metabolism-first, ecology-grounded strategy is generalizable to other microbiota-linked conditions and supports precision microbial therapeutics.}, } @article {pmid41495007, year = {2026}, author = {Khan, A and Mushtaq, M and Shah, M and Khan, RU and Alonaizan, R and Naz, S and Abudabos, A and Israr, M}, title = {Synergistic Effects of Garlic Extract and Mannan-Oligosaccharide Prebiotic Supplementation on Growth Performance, Carcass Quality, Immunity, Gut Morphology and Microbiome in Broiler Chickens.}, journal = {Veterinary medicine and science}, volume = {12}, number = {1}, pages = {e70751}, doi = {10.1002/vms3.70751}, pmid = {41495007}, issn = {2053-1095}, mesh = {Animals ; *Chickens/growth & development/microbiology/immunology/anatomy & histology/physiology ; *Prebiotics/administration & dosage/analysis ; *Garlic/chemistry ; *Mannans/administration & dosage/pharmacology/metabolism ; *Plant Extracts/administration & dosage/pharmacology/metabolism ; Dietary Supplements/analysis ; Animal Feed/analysis ; *Gastrointestinal Microbiome/drug effects ; *Oligosaccharides/administration & dosage/pharmacology ; Diet/veterinary ; Drug Synergism ; Male ; }, abstract = {This study evaluated the effects of dietary supplementation with garlic extract, mannan oligosaccharide (MOS) and their combinations on growth performance, immunity, gut morphology and microbiota in broilers. A total of 250 Hubbard chicks were allocated into five groups: control (basal diet), garlic extract, MOS, Combo-I (half doses of both) and Combo-II (full doses of both). The trial lasted 42 days under standard management conditions. Results demonstrated that Combo-I consistently improved body weight gain and feed conversion ratio (FCR) during the starter, grower and finisher phases (p < 0.05), highlighting a synergistic effect of the combined supplements. Carcass weight was significantly enhanced in Combo-II (p = 0.03), although dressing percentage and organ weights were not affected (p > 0.05). Immunological parameters were strongly influenced by supplementation. Combo-I induced the highest antibody titres against Newcastle disease and infectious bursal disease (p < 0.05), with Combo-II ranking second, whereas single additives showed moderate improvements compared to the control. Similarly, serum immunoglobulin concentrations (IgM, IgA and IgG) were greatest in Combo-I, confirming enhanced humoral immunity. Gut morphology was significantly improved in the combination groups, particularly Combo-I, which showed increased villus height, wider villi, reduced crypt depth, and the highest villus:crypt ratio (p < 0.05), reflecting superior absorptive potential. Although differences in ileal microbiota were not statistically significant, both combination treatments reduced Escherichia coli and Salmonella counts while promoting Lactobacillus spp. populations. In conclusion, the combined use of garlic extract and MOS, especially at half doses (Combo-I), optimally improved growth, immune response, gut architecture and microbial balance, offering a synergistic strategy for enhancing broiler performance.}, } @article {pmid41494844, year = {2026}, author = {Nguyen, P and Rehan, S}, title = {Integrating behaviour and microbiomes into considerations of bee health.}, journal = {Genome}, volume = {69}, number = {}, pages = {1-11}, doi = {10.1139/gen-2025-0047}, pmid = {41494844}, issn = {1480-3321}, mesh = {Bees/microbiology/physiology ; Animals ; *Microbiota ; Pollination ; *Behavior, Animal ; Symbiosis ; }, abstract = {Relationships between individuals play an important role in their behaviour and health, ranging from interactions between individuals to symbioses with microorganisms. Defining bee health may benefit from examining these relationships at different levels of biological organization, suggesting that bee genetics could be influencing microbial communities or that the social microbiome may be a unique way of characterizing pollinator health. Here, we review research in bee behaviour and microbiomes to examine different perspectives influencing health and how factors such as an individual's physiology, genetics, behaviour, social role, and environment can interact with its microbiota. As the role of the microbiome is explored across wild bee species and sociality, examining these factors together rather than in isolation provides a more comprehensive understanding of microbial communities and their impact on their bee hosts. Considering increasing environmental threats to bees, holistic perspectives can inform conservation efforts and actionable methods to support pollinators in altered environments.}, } @article {pmid41494802, year = {2026}, author = {Mayorga, L and Noguera Segura, A and Campderros, L and Pons-Tarin, M and Soler, Z and Vega-Abellaneda, S and Serrano-Gomez, G and Herrera-deGuise, C and Robles-Alonso, V and Borruel, N and Manichanh, C}, title = {Distinct microbial mediators link diet to inflammation in Crohn's disease and ulcerative colitis.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-337480}, pmid = {41494802}, issn = {1468-3288}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) arises from complex interactions among diet, host and gut microbiome. Although diet influences intestinal inflammation, the microbial and metabolic pathways involved, and their differences between Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of IBD remain unclear.

OBJECTIVE: To investigate how the gut microbiome mediates the effects of habitual diet on inflammatory activity in IBD.

DESIGN: This longitudinal study included 198 adults (100 healthy controls, 49 CD, 49 UC), participants completed a validated food frequency questionnaire. Dietary quality was evaluated using established indices (Alternative Mediterranean Diet, Healthy Eating Index-2015, Índice de Alimentación Saludable, Mean Adequacy Ratio, Plant-Based Dietary Indexes, Healthy Food Diversity). Participants also provided two stool samples (baseline and 6 months). Shotgun metagenomics (n=366) enabled taxonomic and functional profiling. Causal mediation analyses were used to identify microbial features mediating the effect of diet on inflammation.

RESULTS: IBD patients exhibited lower dietary diversity, fibre intake and nutritional adequacy compared with controls. Microbiome diversity was lowest in CD, intermediate in UC and correlated positively with higher intake of fibre, fruit, vegetables and nuts, and negative with processed foods and sugary beverages. Causal mediation analyses revealed that in CD, coffee, whole wheat bread and healthier diets lowered the Harvey-Bradshaw index through specific bacterial species and metabolites. In UC, Mediterranean-like diets, fruits and coffee reduced C reactive protein via greater microbial richness, reduced dysbiosis and short-chain fatty acid-related functions.

CONCLUSION: Diet quality influences inflammation in IBD through distinct microbiome pathways: specific taxa and metabolites mediate effects in CD, whereas microbial richness and global composition drive protection in UC.}, } @article {pmid41494643, year = {2026}, author = {Takahashi, H and Harada, N and Hayamizu, Y and Dungubat, E and Nakazawa, M and Kitakaze, T and Sugimoto, K and Inui, H and Yoshihara, E and Takahashi, Y and Yamaji, R}, title = {Testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis through gut microbiota and pyruvate in mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpendo.00518.2025}, pmid = {41494643}, issn = {1522-1555}, support = {22H02289 and 25K01971//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; #2022-006//Thomas J. Beatson Jr. foundation Grant/ ; R01DK136888//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; 5-CDA-2022-1178-A-N//JDRF/United States ; }, abstract = {Hepatic steatosis is the initial stage of metabolic dysfunction-associated steatotic liver disease (MASLD) and is highly prevalent among middle-aged men. Low testosterone levels and dietary fructose intake are independent risk factors for MASLD, although these can occur simultaneously. This study investigated the combined effects of testosterone deficiency and fructose intake on hepatic steatosis and gut microbiota involvement. Male mice were castrated or sham-operated at 8 weeks of age and administered fructose water with or without antibiotics for 8 weeks after being divided into six groups: Sham/Control, Sham/Fructose, Sham/Fructose+Antibiotics, Castration/Control, Castration/Fructose, and Castration/Fructose+Antibiotics. The castrated groups had lower body weights than the sham-operated groups, whereas castration did not affect portal and circulating fructose concentration. Although castration alone did not affect hepatic lipid accumulation, it synergistically promoted fructose-induced triglyceride accumulation, which was alleviated by antibiotic treatment. The expression of lipogenesis-related genes (Srebp-1c), fatty acid transporters (Cd36), and fructose metabolism-related genes (Aldob, Khk-A, and Khk-C) was upregulated by the combination of castration and fructose intake, but antibiotic administration did not suppress this effect. Castration, fructose intake, and their combination influenced β-diversity, but not α-diversity of gut microbiota composition. Cecal pyruvate concentrations were increased by the combination of castration and fructose intake and were suppressed by antibiotics. PICRUSt2 and MaAslin2 analyses supported pyruvate accumulation mediated by alterations in the gut microbiota. Furthermore, pyruvate promoted triglyceride accumulation in primary hepatocytes in the presence of fructose. Our results indicated that testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis, which is partly mediated by gut-derived pyruvate.}, } @article {pmid41494563, year = {2026}, author = {Zhao, C and Zhang, W and Zhang, S and Zhang, L and Han, F and Lei, J and Li, Y and Zhou, W}, title = {Co-regulation of substrate flux and biomass density for enhanced ammonia assimilation under saline conditions.}, journal = {Bioresource technology}, volume = {}, number = {}, pages = {133947}, doi = {10.1016/j.biortech.2026.133947}, pmid = {41494563}, issn = {1873-2976}, abstract = {Drawing inspiration from the self-regulating carbon-nitrogen cycling of saline ecosystems, this study investigates how substrate flux and biomass density co-regulate the structure and function of marine sediment-derived halophilic heterotrophic ammonia assimilation (HAA) microbiome cultivated in saline ammonia-containing wastewater with a COD/N radio of 20 under volumetric exchange ratios (VER) of 75 %, 50 %, and 25 % and mixed liquor suspended solids (MLSS) increasing from 5 to 15 g/L. The combined variation in VER and MLSS generated a gradient in food-to-microorganism radio (F/M). With increasing in biomass, COD removal efficiencies peaked at 94.4-99.3 % at 15 g MLSS/L, whereas ammonia removal efficiencies reached at 90.3-96.8 % at 12.5 g MLSS/L before declining. A VER of 25 % reduced sludge activity, while a VER of 75 % impaired floc settleability. The directed HAA community shifted in substrate flux and biomass density, centering on dominant genera such as Halomonas and Marinobacter, ultimately forming a stable microbiome.}, } @article {pmid41494226, year = {2025}, author = {Xiao, Y and Long, J and Liu, L and Wang, Z and Wang, W and Huang, P}, title = {Water extract of Ampelopsis grossedentata improves reproductive performance in laying hens by regulating gut microbiota and PI3K/AKT signaling pathway.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106368}, doi = {10.1016/j.psj.2025.106368}, pmid = {41494226}, issn = {1525-3171}, abstract = {Reproductive function plays a central role in health but declines with aging. Recent studies have focused on natural flavonoids to mitigate reproductive aging, with the water extract of Ampelopsis grossedentata (WEA) showing promise due to its antioxidant, antitumor, antibacterial, and anti-inflammatory properties. However, the specific bioactive constituents and mechanisms of WEA in alleviating reproductive aging remain unclear. This experiment analyzed the active flavonoid components in WEA and predicted the molecular mechanism by which WEA alleviates reproductive system aging through network pharmacology. Furthermore, based on the predicted molecular mechanisms, the effects of WEA on laying hens' production performance, reproductive function, and intestinal health were explored. A total of 288 laying hens (55 weeks old) were assigned to four groups: control and three WEA doses (50, 150, 250 mg/kg). During the experiment, production performance indicators such as egg weight were recorded daily. After the 8-week period, biological samples were collected for analysis. Network pharmacology identified dihydromyricetin, myricetin, and (-)-epicatechin as key active components, primarily affecting the PI3K/AKT signaling pathway. WEA significantly improved egg quality, immune parameters, reproductive organ morphology, intestinal morphology, and serum sex hormone levels, and reduced inflammatory factor levels. WEA improved ovarian apoptosis by regulating the PI3K/AKT/mTOR pathway and alleviated oviduct inflammation by inhibiting the NF-κB pathway. WEA enhanced intestinal anti-inflammatory and antioxidant functions by regulating NF-κB and Nrf2 pathways and increased short-chain fatty acids in the hindgut. WEA altered the intestinal microbiome, particularly reducing the relative abundance of Methylobacterium-Methylorubrum in the foregut and Bacteroides in the hindgut. Correlation analysis revealed that WEA may alleviate oxidative and inflammatory responses by regulating intestinal microbiota, further impacting the PI3K/AKT cascade. In conclusion, WEA improves antioxidant, anti-inflammatory, and reproductive functions in laying hens by regulating the PI3K/AKT pathway and may alleviate oxidative and inflammatory responses by modulating microbiota. This study provides insights into the mechanism of WEA in improving reproductive performance and intestinal regulation.}, } @article {pmid41493848, year = {2026}, author = {Kawaguchi, Y and Terui, K and Fumita, T and Shibata, R and Yoshizawa, H and Ogasawara, S and Kondo, T and Ozawa, Y and Inaba, Y and Hishiki, T}, title = {Cholestasis-reducing effects of bezafibrate on survivors of biliary atresia with native livers: A prospective phase II trial.}, journal = {Hepatology communications}, volume = {10}, number = {1}, pages = {}, pmid = {41493848}, issn = {2471-254X}, mesh = {Humans ; Male ; Female ; *Bezafibrate/therapeutic use/administration & dosage ; *Biliary Atresia/complications/surgery ; *Cholestasis/drug therapy/etiology ; Prospective Studies ; Adult ; *Hypolipidemic Agents/therapeutic use/administration & dosage ; Young Adult ; Adolescent ; Alkaline Phosphatase/blood ; Liver ; Treatment Outcome ; Survivors ; gamma-Glutamyltransferase/blood ; }, abstract = {BACKGROUND: Long-term survivors of biliary atresia (BA) require liver transplantation owing to cholestasis-associated complications. Bezafibrate (BZF), an antihyperlipidemic agent, can improve cholestasis-induced liver damage. Herein, we evaluated the cholestasis-reducing effect of BZF on survivors of BA with native livers, a condition that has not been previously assessed in any study.

METHODS: In this single-center, single-arm, open-label, uncontrolled, prospective phase II trial, patients were enrolled from a central registry system at the Chiba University Data Center. Postoperative patients (n=10) aged older than 18 years (median age, 29 y) with BA and increased serum ALP levels were enrolled between July 2021 and March 2022. Patients with high total bilirubin or alanine aminotransferase levels, recent changes in BA medication, cholangitis within 3 months, renal dysfunction, or liver transplantation were excluded. Participants were administered 400 mg BZF orally in 2 daily doses for 12 weeks and subsequently underwent a 12-week observation. Other drugs were continued. The primary endpoint was the change in ALP levels after 12 weeks of oral BZF administration. The secondary and exploratory endpoints were changes in gamma-glutamyl transpeptidase and triglyceride levels, fecal microbiota, and bile acids.

RESULTS: The mean change in the ALP level was -67 U/L (±20 U/L; p=0.0042). Changes in ALP and gamma-glutamyl transpeptidase levels differed between week 0 and week 6. Adverse events occurred in 5 patients. BZF administration increased the number of Fusicatenibacter without affecting microbiome diversity or bacterial phylum abundance while decreasing lithocholic acid levels and increasing chenodeoxycholic acid levels.

CONCLUSIONS: BZF decreased cholestasis markers in survivors of BA with native livers, indicating its potential as an alternative to delayed liver transplantation for this population.}, } @article {pmid41493605, year = {2026}, author = {Ben-Dahan, O and Gutvirtz, G and Wainstock, T and Sheiner, E}, title = {Exposure to maternal vaginal flora during labor and long-term infectious morbidity of the offspring.}, journal = {Archives of gynecology and obstetrics}, volume = {313}, number = {1}, pages = {15}, pmid = {41493605}, issn = {1432-0711}, mesh = {Humans ; Female ; Pregnancy ; *Vagina/microbiology ; Adult ; *Labor, Obstetric ; *Cesarean Section/adverse effects/statistics & numerical data ; *Microbiota ; Cohort Studies ; Hospitalization/statistics & numerical data ; Delivery, Obstetric ; Proportional Hazards Models ; Young Adult ; Kaplan-Meier Estimate ; Incidence ; Infant, Newborn ; }, abstract = {PURPOSE: Cesarean delivery (CD) has been linked to increased long-term infectious morbidity in offspring, potentially due to limited exposure to the maternal vaginal microbiome, which may influence immune development. We hypothesized that the degree of exposure to vaginal microbiota during labor would be associated with differences in long-term infectious morbidity.

METHODS: We conducted a population-based cohort study including 348,332 singleton deliveries. Offspring were classified into four groups: vaginal delivery (VD, reference), CD for non-progressive labor in the first stage (NPL1), CD for non-progressive labor in the second stage (NPL2), and elective (pre-labor) CD. Infectious-related hospitalizations up to age 18 were assessed. Kaplan-Meier curves compared cumulative incidence between the groups and a Cox proportional hazards model adjusted for various potential confounders.

RESULTS: Of the cohort, 89.2% were VD, 1.4% NPL1, 0.6% NPL2, and 8.8% elective CD. Infectious-related hospitalization rates were higher for NPL1 and elective CD (26.2% each) compared to NPL2 (24.3%) and VD (23.8%) (p < 0.001). Kaplan-Meier analysis demonstrated a dose-response pattern, with the lowest cumulative incidence in VD, followed by NPL2, NPL1, and highest in elective CD (log-rank p < 0.001). In adjusted analysis, NPL1 (aHR 1.10) and elective CD (aHR 1.13) were associated with increased long-term infectious morbidity, whereas NPL2 was not significantly different from VD.

CONCLUSION: Reduced exposure to vaginal microbiota, as in elective CD and NPL1, is associated with increased long-term infectious morbidity in offspring, while exposure during the second stage of labor (NPL2) may confer immunological benefits.}, } @article {pmid41493557, year = {2026}, author = {Talha, M and Faisal, M and Mujtaba, A and Amjad, A and Abbas, N and Shamim, L and Mahin, FE and Hassan, M and Hassan, MD and Awaisi, MAR}, title = {Virophages: mechanisms, ecological Roles, and therapeutic potential in combating giant virus infections.}, journal = {Archives of microbiology}, volume = {208}, number = {2}, pages = {96}, pmid = {41493557}, issn = {1432-072X}, mesh = {Humans ; *Virophages/physiology/genetics ; *Giant Viruses/physiology/genetics ; Virus Replication ; *DNA Virus Infections/therapy/virology ; Animals ; }, abstract = {Virophages, identified when scientists discovered Sputnik, a double-stranded DNA (dsDNA) viruses that form a unique group of viral entities that can parasitize giant viruses. They rely on these giant viruses for replication and inhibiting them from spreading inside eukaryotic hosts. This review seeks to bring together current knowledge on dsDNA virophages. It details how they work, explains their roles in the host, giant virus, and virophage system, and evaluates their potential as new antiviral treatments. Mechanistically, virophages disrupt the giant by replication through competitive resource depletion inside the viral factory. It modifies viral gene expression, and disrupts progeny formation, thus supporting the survivability of the host cell. In addition to these intracellular effects, virophages participate in ecological processes, such as controlling microbial communities and facilitating nutrient recycling. The therapeutic potential of virophages is hypothesized in the context of diseases where the giant viruses have been detected (e.g., hospital-acquired pneumonia), though causal roles remain debated. Furthermore, their possible use as genetic vectors is being fully investigated. However, there are several challenges to overcome before clinical translation is possible: restricted host range, risks of immune activation, and difficulties in scalable production. Future research should focus on the discovery of new virophage species, their mechanism of actions, and bioengineering strategies to improve their antiviral characteristics.}, } @article {pmid41493496, year = {2026}, author = {Barton, XW and S Tobe, S and Fontaine, JB and Oskam, CL}, title = {A framework for optimising arthropod DNA quality and quantity for modern sequencing tools using hard ticks (Ixodidae).}, journal = {Parasitology research}, volume = {125}, number = {1}, pages = {5}, pmid = {41493496}, issn = {1432-1955}, mesh = {Animals ; *DNA/isolation & purification/genetics ; *Specimen Handling/methods ; *Sequence Analysis, DNA/methods ; *Amblyomma/genetics ; *Ixodidae/genetics ; }, abstract = {Advanced sequencing technologies require strict standards for DNA input and integrity. This study addresses the challenge of extracting high-quality, endogenous DNA from smaller arthropods with mixed DNA sources (arthropod, host, and microbiome), using Amblyomma triguttatum as a model organism. We evaluated three tissue types (Whole, Bisected, and Legs), three disruption methods (Undisrupted, Sliced, and liquid nitrogen bead Homogenisation), and two extraction kits (Qiagen DNeasy Blood & Tissue and MagAttract HMW) to optimise DNA yield, quality, and composition. The Qiagen MagAttract High Molecular Weight Kit significantly increased the proportion of large DNA fragments (20-48.5 kbp) by 11-fold compared to the Qiagen DNeasy Blood & Tissue Kit. Aggressive homogenisation methods produced the highest proportion of short fragments (97%, 1-10 kbp). Whole-Homogenised specimens yielded the highest DNA concentration (198 ng µL[-1]), whereas Bisected-Undisrupted specimens achieved 146 ng µL[-1] with a greater proportion of large fragments (3.15%). Bacterial DNA content remained consistent across treatments. Our findings highlight the importance of selecting appropriate extraction methods to ensure optimal DNA quality for advanced sequencing applications. These results provide useful guidelines for optimising DNA extractions from smaller-bodied arthropods (~ 10-20 mg) and establish a framework for future studies to consider DNA quantity, quality, and composition.}, } @article {pmid41493385, year = {2026}, author = {Xu, Y and Wang, X and Chen, M and Xiong, J and Cheng, G}, title = {Gut microbiome as a predictor for positive youth development transition from childhood to early adolescence: a cohort study.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpp.70109}, pmid = {41493385}, issn = {1469-7610}, support = {82304135//National Natural Science Foundation of China/ ; U25A20154//National Natural Science Foundation of China/ ; 2024NSFSC1806//the Department of Science and Technology of Sichuan Province/ ; 2025ZNSFSC0641//the Department of Science and Technology of Sichuan Province/ ; 2023M742451//the China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: The gut microbiome is increasingly implicated in childhood mental health and may influence positive youth development (PYD). This study aims to characterize PYD transition patterns from childhood to adolescence and explore the predictive value of the gut microbiome.

METHODS: This cohort study used two waves of data from the Chinese Adolescent Cohort study, including children aged 8-11 years at Wave 1, from Sichuan, Guizhou, and Chongqing provinces. PYD was assessed at both time points, and latent transition analysis identified changes over the 3-year follow-up period. Baseline stool samples were analyzed using 16 s rRNA sequencing. A light gradient boosting machine model was developed to link gut microbiota with PYD transition type in a training set (70%, n = 461), and validated with multinominal logistic analysis within a test set (30%, n = 200). Linear regression models were performed to assess dietary modifications on the gut microbiome.

RESULTS: Three PYD transition profiles were identified: downgraded (declining to a lower pattern), promoted (advancing to a higher pattern), and stable development type (remaining in the same pattern). Fifteen microbial genera were identified as predictors of PYD transitions, and children with higher abundance of these taxa were more likely to transition to a stable or promoted profile rather than a downgraded profile (odds ratio ranging from 2.03 to 5.45). This predictive model demonstrated excellent performance, with an area under the curve of 0.91 (95% CI: 0.89, 0.93). The microbiome-PYD transition association was more pronounced in children in earlier stages of puberty. Furthermore, a diet high in fruits, vegetables, and soybeans was positively linked with PYD stable or promoted transition type.

CONCLUSIONS: The gut microbiome presents predictive value in PYD transition from childhood to adolescence. Targeting these microbial taxa may inform future health promotion programs to optimize child development, particularly during the critical pubertal transition.}, } @article {pmid41493379, year = {2026}, author = {Forry, SP and Servetas, SL and Kralj, JG and Hunter, ME and Dootz, JN and Jackson, SA}, title = {A mathematical framework to correct for compositionality in microbiome data sets.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0112625}, doi = {10.1128/aem.01126-25}, pmid = {41493379}, issn = {1098-5336}, abstract = {The increasing use of metagenomic sequencing (MGS) for microbiome analysis has significantly advanced our understanding of microbial communities and their roles in various biological processes, including human health, environmental cycling, and disease. However, the inherent compositionality of MGS data, where the relative abundance of each taxon depends on the abundance of all other taxa, complicates the measurement of individual taxa and the interpretation of microbiome data. Here, we describe an experimental design that incorporates exogenous internal standards in routine MGS analyses to correct for compositional distortions. A mathematical framework was developed for using the observed internal standard relative abundance to calculate "Scaled Abundances" for native taxa that were (i) independent of sample composition and (ii) directly proportional to actual biological abundances. Through analysis of mock community and human gut microbiome samples, we demonstrate that Scaled Abundances outperformed traditional relative abundance measurements in both precision and accuracy and enabled reliable, quantitative comparisons of individual microbiome taxa across varied sample compositions and across a wide range of taxon abundances. By providing a pathway to accurate taxon quantification, this approach holds significant potential for advancing microbiome research, particularly in clinical and environmental health applications where precise microbial profiling is critical.IMPORTANCEMetagenomic sequencing (MGS) analysis has become central to modern characterizations of microbiome samples. However, the inherent compositionality of these analyses, where the relative abundance of each taxon depends on the abundance of all other taxa, often complicates interpretations of results. We present here an experimental design and corresponding mathematical framework that uses internal standards with routine MGS methods to correct for compositional distortions. We validate this approach for both amplicon and shotgun MGS analysis of mock communities and human gut microbiome (fecal) samples. By using internal standards to remove compositionality, we demonstrate significantly improved measurement accuracy and precision for quantification of taxon abundances. This approach is broadly applicable across a wide range of microbiome research applications.}, } @article {pmid41493185, year = {2026}, author = {Zhang, X and Zhan, T and Liu, Q and Xing, M and Yu, W and Chen, B and Peng, Y}, title = {BbCFEM7 plays an important role in the pathogenicity and gut microbial community formation in the co-infection of Beauveria bassiana with Metarhizium rileyi.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0245725}, doi = {10.1128/spectrum.02457-25}, pmid = {41493185}, issn = {2165-0497}, abstract = {UNLABELLED: This study investigated the effects of the BbCFEM7 gene in Beauveria bassiana on host pathogenicity and the gut microbial community during co-infection with Metarhizium rileyi in Spodoptera litura. Our results showed that BbCFEM7 significantly enhanced the virulence of B. bassiana and significantly reduced the host LT50 in the 1:0, 9:1, and 1:1 (Bb:Mr) groups. Sequencing of the gut microbial diversity showed that the presence of BbCFEM7 significantly altered the structure of the host gut microbial community, particularly in the 9:1 group. The presence of BbCFEM7 increased the relative abundance of Enterococcus and decreased that of Thomasclavelia. Furthermore, BbCFEM7 was found to play a pivotal role in enhancing B. bassiana's tolerance to chemical stress and promoting its rapid colonization of the host's hemolymph, thereby giving it an advantage over M. rileyi. These results suggest that BbCFEM7 plays an important role not only in fungal pathogenicity but also in indirectly influencing host health by regulating gut microbial communities. This study provides a new perspective on the interactions between entomopathogenic fungi, hosts, and gut microorganisms and establishes a theoretical basis for optimizing the application of entomopathogenic fungi in pest control.

IMPORTANCE: This study investigates the role of BbCFEM7 in B. bassiana during co-infection with M. rileyi in S. litura. It reveals that BbCFEM7 significantly enhances fungal pathogenicity, shortens the time taken for the host to die, and alters gut microbial communities. These findings provide novel insights into the interactions between entomopathogenic fungi, hosts, and gut microbes, offering a theoretical basis for optimizing the application of entomopathogenic fungi in pest control, while also contributing to our understanding of the insect microbiome and immunology.}, } @article {pmid41493072, year = {2026}, author = {Martinsen, T and Brennan, L}, title = {Key evidence for personalised nutrition: a review of randomised controlled trials.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo02969d}, pmid = {41493072}, issn = {2042-650X}, abstract = {The field of personalised nutrition is growing and is based on the concept that delivering personalised dietary advice will be more effective than generic healthy eating guidelines for individuals to improve their diet and metabolic health. While there is substantial interest in the field, there is also a need to examine the evidence base. The objective of this review was to examine existing literature on the efficacy of personalised nutrition approaches and to identify research gaps and future needs. A literature search was conducted in PubMed for randomised controlled trials published between 2000 and 2025. Studies investigating the effects of personalised nutrition were included, and relevant papers were identified through the reference lists of existing papers. In total, 24 papers were included, with 12 studies investigating personalised nutrition based on current diet, phenotype, and metabolic biomarkers, five studies examining the effects of genotype-based personalised nutrition, and seven studies exploring approaches based on gut microbiome and machine learning algorithms. Overall, evidence from the included studies indicates that personalised nutrition approaches consistently improved dietary quality and led to significant improvements in metabolic markers, including HbA1c, triglycerides, and insulin sensitivity. However, few studies showed significant between-group differences in weight loss, and most studies did not find significant differences in blood pressure. While the results are promising, there are key challenges and research gaps that remain. Some approaches demonstrated potential for targeted improvements, but further high-quality research is needed to confirm their effectiveness and long-term impact. Future research should prioritise longer-term studies, better stratification of responders and non-responders, and cost-effectiveness evaluations to determine where and for whom personalised nutrition adds the most value.}, } @article {pmid41493000, year = {2026}, author = {Shah, S and Ilyas, M and Refaie, A and Yang, FL}, title = {Microbial Chemical Sensing of Microplastic-Derived Compounds in Insect Gut Ecosystems.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c12962}, pmid = {41493000}, issn = {1520-5851}, abstract = {Microplastic (MP) pollution threatens terrestrial and aquatic ecosystems worldwide. Insects, essential for pollination, decomposition, and nutrient cycling, ingest MPs through feeding and contact. Despite growing evidence of MP-caused gut microbe imbalance, how insect gut microbiomes detect and react to MP leachates, mainly organic additives like phthalates and bisphenol A, is still unclear, limiting our understanding of adaptive resilience against toxicity. This perspective reviews microbial sensing pathways, including two-component systems, ligand-responsive transcriptional regulators, and quorum sensing, which differentiate responses to soluble leachates from inert polymers and orchestrate either enzymatic biodegradation in plastivorous species like Tenebrio molitor or detrimental shifts toward oxidative stress, immune activation via Toll and Imd pathways, and epithelial disruption. These host-microbiota feedbacks influence metabolic homeostasis, vector competence, and ecological processes including trophic transfer and biodiversity. By linking these molecular interactions to ecological processes, we propose the utilization of insect-associated symbionts in bioremediation, guided by omics-based approaches, to develop targeted interventions that mitigate plastic pollution while maintaining ecosystem functionality.}, } @article {pmid41492861, year = {2026}, author = {Koshida, T and Nittono, H and Takei, H and Murakoshi, M and Yamashiro, Y and Suzuki, Y and Gohda, T}, title = {A Comprehensive Analysis of Serum and Urine Bile Acid Profiles in Chronic Kidney Disease: An Exploratory Study of Clinical Associations.}, journal = {Nephrology (Carlton, Vic.)}, volume = {31}, number = {1}, pages = {e70156}, doi = {10.1111/nep.70156}, pmid = {41492861}, issn = {1440-1797}, support = {JP24K19136]//JSPS KAKENHI/ ; }, mesh = {Humans ; Male ; Female ; *Bile Acids and Salts/urine/blood ; Cross-Sectional Studies ; Middle Aged ; *Renal Insufficiency, Chronic/blood/urine/physiopathology/diagnosis ; Aged ; Glomerular Filtration Rate ; Biomarkers/urine/blood ; Adult ; Gastrointestinal Microbiome ; Case-Control Studies ; }, abstract = {AIM: Dysbiosis contributes to systemic inflammation and the accumulation of uremic toxins, leading to end-stage kidney disease. However, the role of bile acids (BAs), key metabolic products of the gut microbiota, in the pathophysiology of chronic kidney disease (CKD) remains incompletely understood. Profiling BA metabolism may provide valuable insights into CKD pathophysiology and help in identifying novel therapeutic targets.

METHODS: This cross-sectional study recruited 29 patients with advanced CKD and 30 sex- and age-matched individuals with normal renal function (NRF). Serum and urine BA profiles were compared between the two groups.

RESULTS: Total BA levels in serum did not differ significantly between the CKD and NRF groups. However, patients with CKD exhibited lower serum levels of unconjugated BAs and significantly higher levels of sulfate-conjugated BAs than those with NRF. In contrast, urinary total BA levels and most BA subgroups were significantly lower in patients with CKD. Additionally, the serum levels of ursodeoxycholic, chenodeoxycholic acid and sulfated-conjugated BAs were associated with a decline in the estimated glomerular filtration rate, even after adjusting for demographic factors and diabetes status.

CONCLUSION: This study provides a comprehensive analysis of serum and urinary BAs in patients with advanced CKD. Our findings highlight the association between specific BAs and CKD, suggesting a distinct pathophysiological role of BA metabolism in CKD progression.}, } @article {pmid41492732, year = {2026}, author = {Luo, J and Wu, Y and Ahsan, H and Olopade, CO and Pinto, JM and Aschebrook-Kilfoy, B}, title = {The Role of the Oral Microbiome in Circulating Metabolic Biomarkers and the Influence of Air Pollution.}, journal = {Oral diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/odi.70197}, pmid = {41492732}, issn = {1601-0825}, support = {//NIEHS/ ; /NH/NIH HHS/United States ; }, abstract = {AIMS: The oral microbiome is at the frontline for environmental exposure and plays an important role in human metabolism. This study explores the relationship between PM2.5 exposure, the oral microbiome, and metabolic biomarkers including ghrelin, resistin, and insulin.

METHODS: Data from 473 adult participants (97.7% Black; median age: 53.6) were analyzed. PM2.5 exposure was retrospectively assigned based on residential addresses, metabolic biomarkers were measured from blood samples, and oral microbiome profiles were obtained from saliva samples. Multivariate linear regression, weighted quantile sum regression, and high-dimensional mediation analysis were employed to estimate microbiome-biomarker associations, the association of the oral microbiome mixture, and mediation effects for PM2.5 exposure.

RESULTS: A total of 20 oral microbiome taxa were significantly associated with at least one biomarker, with genus Atopobium linked to all three. Insulin demonstrated the strongest sensitivity to the oral microbiome influence. Genera in phyla Actinomycetota and Bacillota played key roles in the relationship between the oral microbiome and metabolic biomarkers. Mediation analysis revealed that the oral microbiome mediated 16.5% and 11.1% of PM2.5's associations with resistin and insulin, respectively.

CONCLUSION: This study suggests potential mechanisms regarding how the oral microbiome influences metabolic biomarkers and mediates the metabolic effects of PM2.5 exposure.}, } @article {pmid41492650, year = {2026}, author = {Wu, Y and Chen, W and Ye, X and Hao, X and Wen, Y and Wu, J and Li, D and Xu, L}, title = {Targeted C3G delivery by engineered milk exosomes for effective therapy in microplastics-induced colitis.}, journal = {Materials today. Bio}, volume = {36}, number = {}, pages = {102639}, pmid = {41492650}, issn = {2590-0064}, abstract = {Microplastic polystyrene (PS) ingestion through the food chain induces chronic colitis, with no effective intervention strategy, posing a public health concern globally. Cyanidin-3-O-glucoside (C3G), an anthocyanin abundant in red bayberry, can alleviate colitis while has limited therapeutic efficacy due to its low colonic bioavailability after oral administration. Targeted delivery strategies may enhance colonic C3G concentration and improve its therapeutic efficacy. Exosomes are engineerable nanoparticles with excellent biocompatibility and unique biological activities. In this study, the mucosal addressin cell adhesion molecule 1 (MAdCAM-1, F6) antibody, which specifically binds to colonic inflammatory MAdCAM-1 marker, was conjugated to the raw milk derived-exosome surface to form C3G@Exo-F6, aiming to enhance colonic C3G targeting. In vitro, C3G@Exo-F6 exhibited significantly enhanced stability in simulated digests and was more efficiently taken up by colon cells. In a PS-induced in vivo chronic colitis mice model, C3G@Exo-F6 demonstrated superior efficiency compared to C3G only by inhibiting inflammatory responses, restoring gut barriers integrity and modulating the gut microbiota. Mechanically, 16S rRNA sequencing and untargeted metabolomics demonstrated that C3G@Exo-F6 significantly increased the Lactobacillus abundance and subsequently upregulated the metabolic L-Proline level. Molecular docking identified that L-Proline binds effectively to nuclear receptor subfamily 1 group D member 1 (NR1D1) protein, inhibiting the expression of inflammatory TLR-4/COX-2 pathway. Additionally, Exo-F6 carries exhibited similar therapeutic effects, indicating that exosomes derived from raw milk possess collaborative anti-inflammatory activities. Collectively, these findings emphasize the potential of C3G@Exo-F6 for targeted treatment of chronic colitis, providing a food-derived therapeutic approach for microplastics-induced colonic inflammation.}, } @article {pmid41492481, year = {2026}, author = {Joshi, A and Cornu, A and Luxner, J and Zarfel, G and Braun, C and Nicolas, JF and Gallo, RL and Vocanson, M and Wolf, P and Patra, V}, title = {Atopic Dermatitis-like mouse model using early inoculation of patient-derived S. aureus together with MC903.}, journal = {JID innovations : skin science from molecules to population health}, volume = {6}, number = {2}, pages = {100436}, pmid = {41492481}, issn = {2667-0267}, abstract = {Staphylococcus aureus (S. aureus) worsens atopic dermatitis (AD), but how individual strains differ in pathogenicity remains unclear. Mouse models that mimic AD and allow direct manipulation of S. aureus in early stages of disease are limited. Moreover, these models rarely incorporate clinical S. aureus strains isolated from patients with AD. In this study, we investigated the inflammatory potential of clinical S. aureus and S. epidermidis isolates from patients with AD in a mouse model. Clinical S. aureus strains showed significant variability in their ability to elicit inflammation. The inflammation was associated with differences in virulence factor expression and, to a lesser extent, with genomic variation. In contrast, S. epidermidis strains (taken from the same lesional skin sites of patients) induced only mild but consistent inflammation, with less variability at the strain level. Next, we examined the impact of a pathogenic clinical S. aureus strains in the presence of an MC903-induced type 2 immune environment. Under these conditions, S. aureus enhanced colonization; increased inflammation; and promoted type 1, type 2, and type 17/22 immune responses. These responses were less evident with either treatment alone. Our findings suggest that clinical S. aureus strains from patients with AD differ in their capacity to modulate skin inflammation, particularly within a type 2-skewed environment. These results highlight the potential value of incorporating clinically relevant S. aureus isolates into early-stage in vivo models to better understand AD immunopathology and to inform microbiome-targeted therapeutic strategies.}, } @article {pmid41492371, year = {2026}, author = {Li, N and Dong, Z and Zhang, S and Ma, J and Liu, S}, title = {Pathogenesis of various pulmonary diseases by tuning immune response: insight from host-microbial crosstalk.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100531}, pmid = {41492371}, issn = {2666-5174}, abstract = {Growing research has highlighted the participation of lung microbiota in various pathological processes. Despite its low bacterial biomass compared with other organs, the resident flora of the healthy lung is essential for immune system development, immune tolerance fostering, and defense against foreign substance incursion. The host-microbial crosstalk, typically mediated by microbial metabolites, pattern recognition receptors, and immune cells, exerts bidirectional regulatory effects on the pulmonary immune microenvironment. Specifically, the lung microbiota modulates the activation status or tolerance of mucosal immune cell populations to maintain immune balance; conversely, perturbations to the lung's homeostatic microbiome, arising from dysbiosis, immune dysfunction, or pathogenic invasion, drive lung disease by inciting chronic inflammation and tissue remodeling via direct and immune mediated damage. Although the importance of host-microbial interactions in lung health is well recognized, the mechanisms of the relationship between changes in microbiota composition and immune dysregulation in different diseases have not been fully elucidated. Therefore, we summarize the latest research progress on the involvement of the lung microbiota in pulmonary disease development, focusing on the interaction mechanisms among microorganisms, immune homeostasis, and lung diseases. The aim of this review is to expand our mechanistic understanding of the lung microbiota-mediated regulation of immune cell function. Insights from various disciplines into lung microbiota could pave the way for innovative ideas and technologies aimed at preventing and treating respiratory illnesses.}, } @article {pmid41492366, year = {2026}, author = {Su, K and Yan, Y and Huang, J and Chen, Y and Shang, X and Wang, X and Liu, Y and Lai, Z and Song, F and Zhang, Z and Wu, P and Wu, K and Liang, XJ}, title = {Mitochondrial-targeted injectable hydrogel for periodontitis therapy via oral immunity and flora regulation.}, journal = {Bioactive materials}, volume = {58}, number = {}, pages = {348-369}, pmid = {41492366}, issn = {2452-199X}, abstract = {The therapy of chronic periodontitis poses a perennial challenge due to its intricate etiology, specific bacterial involvement, and the presence of an inflammatory immune microenvironment. The misuse of antibiotics not only triggers bacterial resistance but also disrupts the balance of oral microbiota, exacerbating the host's inflammatory response. Herein, a novel integrated synergistic hydrogel delivery platform (named GM/OHA-GZN&M) was designed to facilitate rapid, non-invasive, and antibiotic-free periodontitis treatment. This injectable hydrogel delivery platform fulfils three distinct roles: as a subgingival plaque disruptor, immune microenvironment remodeler, and microbiome modulator. As a subgingival plaque disruptor, GM/OHA-GZN&M hydrogel effectively disrupted bacterial membrane homeostasis, depolarized it, and induced the leakage of materials in the membrane. As an immune microenvironment remodeler, it effectively mediates the targeted clearance of mitochondrial reactive oxygen species (mtROS) through polyphenols, restores mitochondrial function, and disrupts the free radical cycle of inflammation. As a microbiome modulator, it effectively suppressed pathogenic bacterial overgrowth, restored oral gingival microbiota balance in rats, and created a favorable subgingival microenvironment for periodontitis treatment. In in vivo experiments, the GM/OHA-GZN&M hydrogel was used to treat a periodontitis model established by silk thread ligation in rats. Histological, microbiological, and biochemical analyses demonstrated that the hydrogel could significantly suppress inflammation and effectively promote alveolar bone regeneration through immunomodulation. To sum up, this study presents a supports therapeutic potential approach for managing periodontitis.}, } @article {pmid41492364, year = {2025}, author = {Solly, EF and Jaeger, ACH and Barthel, M and Six, J and Mueller, RC and Hartmann, M}, title = {Soil water limitation intensity alters nitrogen cycling at the plant-soil interface in Scots pine mesocosms.}, journal = {Plant and soil}, volume = {516}, number = {1}, pages = {705-723}, pmid = {41492364}, issn = {0032-079X}, abstract = {BACKGROUND AND AIM: More intense episodes of drought are expected to affect terrestrial nitrogen (N) cycling by altering N transformation rates, the functioning of soil microorganisms, and plant N uptake. However, there is limited empirical evidence of how progressive water loss affects N cycling at the plant-soil interface.

METHODS: We adopted [15]N tracing techniques and metagenomic analyzes of microbial genes involved in N cycling to assess how different levels of soil water availability influenced the fate of N derived from decomposing litter in mesocosms with Scots pine saplings.

RESULTS: With increasing water limitation, the release of N from decomposing litter into the soil declined rapidly. However, moderate levels of water limitation barely affected the microbial metagenome associated with N cycling and the uptake of N by the saplings. Comparatively, severe levels of water limitation impaired plant N uptake, and increased the prevalence of microbial N-cycling genes potentially involved in mechanisms that protect against water stress. Genes associated with the uptake and release of N during mineralization and nitrification declined under low soil water contents.

CONCLUSIONS: When soil water becomes largely unavailable, the cycling of N at the plant-soil interface is slowed down, and microbial and plant tolerance mechanisms may prevail over N uptake and microbial decomposition.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11104-025-07758-z.}, } @article {pmid41492235, year = {2026}, author = {Zou, Q and Tan, M and Li, D and Fu, Z and Wang, Y}, title = {Effects of Neutral Electrolytic Water on Growth, Carcass, and Gut Microbiota of Arbor Acres Plus (AA+) Broilers.}, journal = {Animal science journal = Nihon chikusan Gakkaiho}, volume = {97}, number = {1}, pages = {e70141}, doi = {10.1111/asj.70141}, pmid = {41492235}, issn = {1740-0929}, support = {S202210160027//National College Students' Innovation and Entrepreneurship Training Program/ ; 2023py06//Research on the Effects of Compound Water Treatment Agents on Waterline Microecological Flora and Growth Performance of Broilers/ ; 2023py01//Effect and Correlation Analysis of Electrolyzed Water on Growth Performance and Cecal Microflora of Broiler Chickens/ ; }, mesh = {Animals ; *Chickens/growth & development/microbiology ; *Gastrointestinal Microbiome/drug effects ; Cecum/microbiology ; *Water/pharmacology/administration & dosage ; *Bone Development/drug effects ; Lactobacillus/isolation & purification ; Weight Gain/drug effects ; Male ; Housing, Animal ; *Animal Nutritional Physiological Phenomena ; Eating ; *Diet/veterinary ; Electrolysis ; }, abstract = {The purpose of this study was to examine the influence of neutral electrolytic water (NEW) on the growth performance, slaughter performance, bone development, and cecum microbiome of Arbor Acres Plus (AA+) broilers. A total of 120 broilers were raised in an environmentally controlled room with four rows of battery cages, each equipped with a water line housing 30 broilers. Two lines supplied normal water (CK), and the other two supplied NEW (TRT), with 10 broilers per cage (six replicates per group) over a 42-day trial. Results showed that broilers in the TRT group had significantly higher average daily gain (ADG) (p < 0.05) and lower feed consumption-to-gain ratio (F/G) (p < 0.05) at 22-42 and 1-42 days compared with the CK group. NEW consumption had no significant impact on slaughter performance or bone development (p > 0.05). The TRT group increased cecal flora diversity and abundance, with Lactobacillus as the dominant genus at the genus level. Correlation analysis revealed Oscillospira abundance was significantly positively correlated with F/G (R > 0.6, p < 0.05). Lactobacillus abundance was significantly positively correlated with ADG and average daily feed intake (ADFI) (R > 0.6, p < 0.05) and significantly negatively correlated with F/G (R < -0.6, p < 0.05). In summary, NEW improved growth performance, enhanced cecal flora diversity, and increased Lactobacillus abundance in AA+ broilers.}, } @article {pmid41492068, year = {2026}, author = {Grant, ET and Monzel, E and Desai, MS}, title = {Navigating the duality of Akkermansia muciniphila.}, journal = {Nature microbiology}, volume = {11}, number = {1}, pages = {20-30}, pmid = {41492068}, issn = {2058-5276}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics ; *Akkermansia/physiology ; Mucins/metabolism ; Intestinal Mucosa/microbiology/metabolism ; Animals ; *Verrucomicrobia/physiology ; Polysaccharides/metabolism ; }, abstract = {Akkermansia muciniphila is a prominent member of the intestinal microbiota that has the unique ability to subsist on the mucin O-glycans that form a protective barrier between the host and the gut microbiome. Numerous studies highlight its positive role in metabolic regulation and mucosal barrier maintenance, leading to propositions that A. muciniphila could be used as a next-generation probiotic. However, other work indicates that the effects of A. muciniphila vary depending on nutrition, host genetics and the interaction with surrounding microbes. Furthermore, strain-specific differences in the ability to modulate intestinal barrier function and antimicrobial resistance profiles remain underexplored. Here, by focusing on potential sources of this variation, we provide a nuanced discussion on the complex role of A. muciniphila in human health. With A. muciniphila as an example, we argue that a microbe's specific environment must be considered to enable critical evaluation of next-generation probiotics.}, } @article {pmid41492042, year = {2026}, author = {Mikkonen, RS and McClung, H and Giersch, G and Van Cutsem, J and Wright, H and O'Leary, TJ and Greeves, JP}, title = {Menstrual Health in Servicewomen: The Menstrual Cycle, Menstrual Disturbances, and Occupational Consequences.}, journal = {Sports medicine - open}, volume = {12}, number = {1}, pages = {2}, pmid = {41492042}, issn = {2199-1170}, abstract = {BACKGROUND: Most women serving in the military do so during their reproductive life and enter service at a young gynecological age. This review provides an overview of the menstrual cycle and summarizes the evidence for menstrual cycle disturbances in the military and how these disturbances to the menstrual cycle impact health and performance in the military.

MAIN TEXT: Servicewomen often manage the practical challenges of menstruation and symptoms of the menstrual cycle or menstrual disturbances/dysfunction in an austere environment with no formalized support and/or education, and with unknown stigma and risks. Menstrual health in the military context implies that those who experience a menstrual cycle can access timely information, diagnosis, and support/treatment to achieve "a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity, in relation to the menstrual cycle." Herein we describe how menstrual health is impacted in a multistressor environment, including nutrition (energy balance and energy availability, micronutrients, and microbiome), physical activity, and recovery (occupational tasks, sleep, psychological stress, environment), and how menstrual disturbances can affect occupational performance and the lived experience of the female workforce.

CONCLUSIONS: We call for action of militaries worldwide to protect the health of Servicewomen to maximize their potential. Low representation, relatively recent full integration of women into the military workforce, and the exclusion of women from military research have led to policies developed from evidence on men, with the potential to impact the health and performance of Servicewomen.}, } @article {pmid41492005, year = {2026}, author = {Miyamoto, K and Sujino, T}, title = {Microbiota-derived D-amino acids in intestinal homeostasis and inflammatory bowel disease.}, journal = {Inflammation and regeneration}, volume = {}, number = {}, pages = {}, doi = {10.1186/s41232-025-00403-3}, pmid = {41492005}, issn = {1880-9693}, abstract = {Inflammatory bowel disease (IBD) encompasses chronic, relapsing inflammatory disorders of the gastrointestinal tract, which are driven by intricate interactions between the host immune system and intestinal microbiota. Recent studies have revealed that microbiota-derived D-amino acids (D-AAs), once considered biologically inert, play critical roles in maintaining mucosal homeostasis and modulating immune responses. These metabolites, which are increasingly classified as postbiotics, directly influence epithelial barrier integrity, immune cell activity, and microbial ecology. In this review, we summarize the current insights into the biosynthesis, bacterial functions, and immunological implications of D-AAs in the gut, with a particular focus on their involvement in IBD pathogenesis. Specific D-AAs, such as D-alanine, contribute to bacterial cell wall integrity and quorum sensing and interact with host immune cells, alter microbial communities, and regulate mucosal barrier function. Evidence from both human studies and murine models highlights how disrupted D-AAs' metabolism through dysbiosis or impaired host sensing via enzymes such as D-amino acid oxidase (DAO) exacerbates inflammation. Finally, we discuss the translational potential of D-AAs as non-invasive biomarkers and therapeutic targets in IBD, emphasizing the need for integrative multi-omics approaches that connect microbial metabolism with host immune regulation and disease outcomes.}, } @article {pmid41491874, year = {2026}, author = {Thassakorn, P and Fungbun, N and Sukon, P and Phuektes, P}, title = {Characterization and comparative analysis of urinary bacterial microbiome profiling in healthy cats and cats with feline idiopathic cystitis.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-34196-9}, pmid = {41491874}, issn = {2045-2322}, support = {KKU Vet. Res. VM025/2565//Faculty of Veterinary Medicine, Khon Kaen University/ ; KKU Vet. Res. VM025/2565//Faculty of Veterinary Medicine, Khon Kaen University/ ; KKU Vet. Res. VM025/2565//Faculty of Veterinary Medicine, Khon Kaen University/ ; KKU Vet. Res. VM025/2565//Faculty of Veterinary Medicine, Khon Kaen University/ ; }, abstract = {Over the past decade, the make up of urinary microbiota and its association with disease has garnered substantial attention. However, the urinary microbiota patterns in healthy cats remain unclear, as do the potential dysbiosis conditions in cats with feline idiopathic cystitis (FIC). We hypothesized that urinary microbiota differ by age and sex in healthy cats, and vary between healthy cats and those with FIC. Using 16S rRNA gene sequencing, we analyzed the urinary microbiota of 25 healthy cats and 15 cats with FIC. Our results indicate that the feline urinary microbiota is primarily composed of Proteobacteria. While no significant differences in bacterial abundance were found between sexes in healthy cats, some taxa showed variations by age. Cats with FIC demonstrated microbiota disruption, characterized by an increase in Firmicutes and Bacilli, along with a decrease in Proteobacteria, particularly a reduction in the Pseudomonas genus, compared to healthy cats. These results demonstrate the presence of a bacterial microbiome in the urine of cats and suggest a potential association between altered microbiota and FIC. Multi-omics approaches could provide further insights into the core urobiome and its role in feline urinary tract disease.}, } @article {pmid41491791, year = {2026}, author = {Seo, J and Araneta, RP and Lee, JH and Montecillo, JA and Yoo, HJ and Lee, YY and Park, CM and Cho, A and Lee, H and Yoon, HY and Kim, MJ and Kim, JM and Lee, YH and Lee, NY and Park, NJ and Han, HS and Seo, I and Chong, GO}, title = {Standardizing vaginal microbial profiling: evaluating swab materials, storage conditions, and host DNA depletion strategies.}, journal = {BMC microbiology}, volume = {26}, number = {1}, pages = {2}, pmid = {41491791}, issn = {1471-2180}, support = {RS-2023-KH135444//Ministry of Health and Welfare/ ; }, abstract = {BACKGROUND: Studies on understanding female health from a microbial perspective have proliferated in recent years; however, validated protocols for swab materials, storage conditions, and host DNA depletion remain limited for vaginal microbiome studies. This study investigates these critical aspects to enhance microbial profiling accuracy.

RESULTS: Three swab materials were evaluated, with minimal variations in bacterial composition observed across different swab materials. The DNA yield and host DNA contamination remained comparable. Mock samples, used to assess the effects of storage conditions (without freezing, -20 °C, and -80 °C), revealed no significant impact on microbial composition. Additionally, the NEBNext® Microbiome DNA Enrichment Kit demonstrated effective performance in host DNA removal and bacterial community recovery, even with reduced reagent volumes.

CONCLUSIONS: These findings underscore the importance of optimizing swab selection and host DNA depletion strategies to enhance microbiome profiling in clinical samples.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04523-1.}, } @article {pmid41491699, year = {2026}, author = {Wang, R and Zhang, W and He, Z and Zhou, Y and Chen, C and Song, K and Shang, Q and Wu, Y and Gu, P and Shu, D and Zhao, L}, title = {Core microbiota recruited by healthy grapevines enhance resistance against root rot disease.}, journal = {Genome biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13059-025-03905-y}, pmid = {41491699}, issn = {1474-760X}, support = {2023BCF01026//Key Research and Development Program of Ningxia/ ; 2025NC-YBXM-068//Key Research and Development Projects of Shaanxi Province/ ; 32372501//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Root rot disease caused by fungal pathogens of wine grapevines poses a serious threat to their growth and results in a substantial economic impact on grape industry. The rhizosphere microbiome recruited to plants is critical for mitigating soil-borne pathogens. However, how beneficial microbes influence disease resistance remains unclear.

RESULTS: We investigate the composition and gene functions of microorganisms in wine grapevines with root rot disease and healthy controls by amplicon and metagenomic sequencing. We use culturomics and in vivo experiments to verify the pathogen and beneficial strains to improve plant health. We find that root rot disease in grapevines significantly affects rhizosphere microbiome diversity and composition. The microbial interkingdom network indicates that the disease destabilizes the bacteria-fungi co-occurrence network. We find that plants recruit the potentially beneficial bacteria Pseudomonas, Bacillus and Streptomyces in healthy rhizosphere soil. By culturomics, we confirm that Fusarium solani is the main pathogen causing root rot disease. We further observe that these three key beneficial bacteria from the co-occurrence networks enhance the resistance of grapevines to pathogens. Furthermore, metagenomic analysis reveals that beneficial bacterial strains suppress pathogens by enriching potential functional genes in pathways involved in disease resistance.

CONCLUSIONS: Our findings highlight the critical role of disease resistance pathways of potentially beneficial microorganisms in fighting disease and supporting plant health, offering new insight for the exploration of beneficial microbial resources and providing a basis for the development of biological control of grape root rot disease.}, } @article {pmid41491653, year = {2026}, author = {Mihori, S and Nichols, FC and Jellison, ER and Blesso, CN and Graziano, V and Rathinam, V and Clark, RB}, title = {Harnessing the microbiome to regulate myeloid TREM2 expression and innate immune responses.}, journal = {ImmunoHorizons}, volume = {10}, number = {1}, pages = {}, pmid = {41491653}, issn = {2573-7732}, support = {300714//UConn Health AEF/ ; }, mesh = {Animals ; *Membrane Glycoproteins/metabolism/genetics ; *Immunity, Innate ; *Receptors, Immunologic/genetics/metabolism ; Mice ; *Gastrointestinal Microbiome/immunology ; Mice, Inbred C57BL ; *Macrophages, Peritoneal/immunology/metabolism ; NF-kappa B/metabolism ; Inflammation/immunology ; Monocytes/immunology ; *Microbiota/immunology ; Signal Transduction ; }, abstract = {The composition of the gastrointestinal microbiome is correlated with numerous immune-mediated systemic diseases, but underlying mechanisms remain unclear. In murine studies, we recently identified microbiome Bacteroidota-derived bacterial molecules, serine-glycine lipodipeptides (S/G lipids), as mediators of microbiome-systemic innate immune system crosstalk. By altering microbiome production of S/G lipids, we documented that proinflammatory responses of splenic monocytes could be regulated. Transcriptomic analysis revealed that this regulation occurred by modulating the mRNA levels of inhibitors of the TLR/NF-κB pathways such as Trem2. The present murine study had 2 goals: (1) to determine if our approach allows for modulation of activated innate immune cells, that is, macrophages rather than splenic monocytes, in a site of inflammation and (2) to document that our approach regulates cellular expression of the disease-relevant TLR/NF-κB pathway inhibitor, TREM2, at the protein level. We now report that decreasing microbiome-derived S/G lipid levels enhances proinflammatory responses and decreases expression of TREM2 in activated peritoneal macrophages (PMs). Furthermore, after lowering microbiome S/G lipid production, administering S/G lipids normalizes both PM proinflammatory responses and TREM2 expression. The harnessing of the microbiome and S/G lipids to modulate proinflammatory responses and TREM2 expression in activated innate immune cells suggests the therapeutic potential of this approach in inflammatory diseases such as Alzheimer's disease, atherosclerosis, autoimmunity and liver disease.}, } @article {pmid41491581, year = {2026}, author = {Chen, T and Yu, S and Li, K and Huang, K and Shi, W and Chen, H and Hong, Q and Zhang, Y and Wang, J and Yu, Z and Wang, J}, title = {Rumen microbiota inoculation indicates collaborative mechanisms enhancing propionate supply to alleviate weaning stress in lambs.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02283-8}, pmid = {41491581}, issn = {2049-2618}, support = {2023YFD1300901//the Ministry of Science and Technology of the People's Republic of China/ ; D21C170001//the Natural Science Foundation of Zhejiang Province/ ; 31622056//the National Natural Science Foundation of China/ ; 226-2025-00026//Fundamental Research Funds for the Central Universities/ ; }, abstract = {BACKGROUND: The transition from milk to solid feed during weaning often imposes metabolic stress on young ruminants due to energy deficits. Previous studies suggest that ruminal microbiota transplantation from adults to juveniles can alleviate weaning stress, but the underlying mechanisms remain poorly defined.

RESULTS: In this study, 48 Hu lambs were randomly assigned to two groups (n = 24 each): an inoculated group (Inoc) that received lyophilized ruminal microbiota and a control group (Ctrl) that received no inoculation. We evaluated rumen fermentation characteristics, blood metabolites, hepatic glycogen levels, expression of hepatic gluconeogenic genes, and shifts in the rumen microbiome at three key time points-the end of weaning, 1 and 2 weeks post-weaning. Oral inoculation significantly elevated rumen propionate concentration, upregulated the gene expression of hepatic pyruvate carboxylase (EC 6.4.1.1) and glucose-6-phosphatase (EC 3.1.3.9), and increased hepatic glucose production. Microbiome analysis revealed increased colonization by lactic acid-producing bacteria (e.g., Olsenella and Sharpea) and propionate producers, such as Megasphaera elsdenii, alongside enriched families associated with propionate production, including Prevotellaceae, Succinivibrionaceae, and Erysipelotrichaceae. Genome-resolved metagenomics further demonstrated an increased abundance of metagenome-assembled genomes (MAGs) carrying polysaccharide utilization loci (PULs) and genes involved in lactate-to-propionate conversion. Notably, the inoculation promoted co-occurrence of functionally complementary MAGs-such as s_Megasphaera elsdenii (MAG98), s_Bilifractor sp902797025 (MAG125), s_Prevotella sp002391185 (MAG342), and s_Prevotella sp900540375 (MAG298)-that carry a wide repertoire of genes involved in polysaccharide degradation and lactate-to-propionate fermentation. In vitro co-culture experiments with Megasphaera elsdenii and Bilifractor porci confirmed their synergistic role in promoting propionate production.

CONCLUSIONS: This study demonstrates that oral inoculation of pre-weaned lambs with starter feed-adapted adult rumen microbiota facilitates the establishment of a microbial consortium capable of enhanced lactate and propionate production, thereby enhancing hepatic gluconeogenesis and energy homeostasis, which ultimately mitigates weaning stress. This approach may offer a promising strategy to facilitate dietary transition and enhance metabolic resilience in young ruminants during weaning by modulating rumen microbial composition toward a propionate-producing community. Video Abstract.}, } @article {pmid41491300, year = {2026}, author = {Helm, ET and Burrough, ER and Gabler, NK and Leite, FL}, title = {Lawsonia intracellularis infection induces changes in microbial community function and composition associated with reduced pig growth and feed efficiency.}, journal = {Animal microbiome}, volume = {8}, number = {1}, pages = {1}, pmid = {41491300}, issn = {2524-4671}, abstract = {BACKGROUND: Lawsonia intracellularis and its resulting disease remains a troubling pathogen for pork producers worldwide. In the current experiment, we aimed to characterize the microbiome of pigs challenged with L. intracellularis through peak disease impact to better understand microbial community function and how microbial changes may contribute to disease and resulting decreased growth. Twenty-four L. intracellularis negative barrows were assigned to either L. intracellularis negative (NC) or L. intracellularis challenged (PC) treatment groups (n = 12 pigs/treatment). On days post-inoculation (dpi) 0, PC pigs were inoculated with L. intracellularis. Feed disappearance was monitored daily, body weights and fecal samples were collected weekly. At dpi 21, pigs were euthanized for sample collection and macroscopic lesion scoring.

RESULTS: Pigs challenged with L. intracellularis had sustained reductions in growth performance and feed intake throughout the 21-day period (P < 0.001). This was accompanied by changes to fecal microbial communities, particularly increased abundance of Chlamydia suis in challenged pigs at dpi 7, 14, and 21. Changes to microbial communities were also accompanied by differences in microbial metabolism, marked most notably by signatures of lesser amino acid biosynthesis and greater nucleotide synthesis in challenged pigs.

CONCLUSIONS: In summary, L. intracellularis challenge produced reductions in growth and feed intake. This was accompanied by sustained changes to fecal microbial communities, particularly sustained increased abundance of C. suis in challenged pigs. Changes to microbial communities were also accompanied by differences in microbial metabolism which likely play a role disease.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00501-0.}, } @article {pmid41491103, year = {2026}, author = {Bryant, JA and Vulić, M and Walsh, EA and Allen, EG and Beauchemin, NJ and Chafee, ME and Diao, L and Fenn, K and Ford, KA and Hasson, BR and Litcofsky, KD and Lombardo, MJ and Martinez, A and O'Brien, EJ and Straub, TJ and Sykes, SM and Marshall, LF and Winkler, JA and McGovern, BH and Ford, CB and Wortman, JR and Henn, MR}, title = {The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41491103}, issn = {1546-170X}, abstract = {VOWST (VOWST oral spores, VOS; fecal microbiota spores, live-brpk, formerly SER-109) is an FDA-approved, orally administered consortium of purified Firmicutes spores developed to prevent recurrent Clostridioides difficile infection (CDI). Although 86.7% (26/30) of patients with recurrent CDI did not experience a subsequent recurrence over 8 weeks in an open-label phase 1b study, a subsequent double-blind phase 2 study (NCT02437487) did not demonstrate a significant benefit over placebo (rate of recurrence at 8 weeks in SER-109 versus placebo: 44.1% versus 53.3%). These discordant outcomes were hypothesized to be due to suboptimal dosing. This hypothesis was addressed in a pivotal phase 3 trial (NCT03183128) using an approximately tenfold higher dose. In phase 3, only 12% of VOS-treated patients versus 40% of placebo patients recurred by week 8 (relative risk 0.32, P < 0.001). Here in this follow-up post hoc analysis, across-trial comparisons confirmed that the higher, efficacious phase 3 dose is associated with improved pharmacokinetics, assessed by VOS engraftment (patients with available samples: phase 1b: 28, phase 2: 79, phase 3: 170). In-depth phase 3 analyses revealed that VOS significantly altered microbial composition, significantly enriching the diversity and abundance of Firmicutes species and reducing the prevalence and abundance of C. difficile and opportunistic pathogens (for example, Enterobacteriaceae species). Consistent with these taxonomic changes, significant changes in key bioactive metabolites were observed, including depletion of conjugated and deconjugated primary bile acids, enrichment of secondary bile acids and increases in short-chain and medium-chain fatty acids. In vitro, VOS batches produced these C. difficile-inhibiting metabolites. These findings on the pharmacology of VOS underscore the importance of rapidly restoring key protective functions of the microbiome in patients with recurrent CDI to achieve durable prevention of recurrence, as observed in the phase 3 study; they also highlight the need to include the microbiome in the clinical management of CDI. ClinicalTrials.gov registrations: NCT02437487 and NCT03183128 .}, } @article {pmid41491008, year = {2026}, author = {Ajene, IJ and Tanga, CM and Akutse, KS and Karanu, SW and Khamis, FM}, title = {Multi-omics comparison of two emerging storage pests (Necrobia rufipes and Tribolium castaneum) of dried black soldier fly larvae product.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-34902-7}, pmid = {41491008}, issn = {2045-2322}, support = {ProteinAfrica: LS/2020/154//Australian Centre for International Agricultural Research/ ; WAVE-IN: 2021 FOD 030//Rockefeller Foundation/ ; G-2204-02144//IKEA Foundation/ ; NESTLER Project: 101060762 and INNOECOFOOD project: 101136739//European Commission/ ; }, abstract = {The black soldier fly (BSF) larvae is a rich and promising source of alternative protein that continues to increasingly gain global traction as a functional ingredient for sustainable livestock and fish production. The key setback to postharvest processing of stored BSF larvae (BSFL) products is the significant damage caused by two notable storage pests (Tribolium castaneum and Necrobia rufipes). Here, we present a comparative analysis of the complete mitochondrial genomes and gut microbiome profiles of T. castaneum and N. rufipes. The study mitogenomes were similar in size and structure to other coleopteran mitogenomes. The gut microbiome profiles of the two pests showed a high abundance of bacteria in the Proteobacteria and Firmicutes phyla. However, T. castaneum had 78% more phyla represented within its microbiome than N. rufipes. The most abundant genera in T. castaneum were Staphylococcus and Streptococcus, while in N. rufipes, the dominant genera were Klebsiella and Synechococcus. We also identified the presence of potentially clinically harmful microbial genera (Stenotrophomonas maltophilia) in the gut of T. castaneum and N. rufipes in relatively high abundance. These results provide insight into potential harmful associations in the gut of the storage pest, picked from contaminated, poorly processed BSFL products.}, } @article {pmid41490763, year = {2026}, author = {Mazur, M and Pooranachandran, N and Zawisza, M and Baran, Z and Michalik, A and Adamek, M and Marcinkowska, M and Surachetpong, W and Prajsnar, TK and Rakus, K and Pijanowski, L and Chadzinska, M}, title = {The role of the circadian clock gene cry1 in the regulation of the antiviral response in zebrafish (Danio rerio) larvae.}, journal = {Fish & shellfish immunology}, volume = {}, number = {}, pages = {111098}, doi = {10.1016/j.fsi.2026.111098}, pmid = {41490763}, issn = {1095-9947}, abstract = {All living organisms are influenced by the circadian clock. This mechanism generates rhythms that affect organismal processes involved in cellular activity, behavior and immunity. In the present study we investigated the function of the circadian clock genes: cry1a and cry1b in zebrafish larvae, focusing on their roles in early development, behavior, microbiota composition, and antiviral immune response. Using Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9) gene editing, we generated zebrafish lines with targeted mutations in cry1a and cry1b genes and found that cry1 genes are not essential for larval survival or development. However, both mutations led to significant behavioral changes, with mutant larvae exhibiting increased locomotor activity compared to their wild type (WT) counterparts. Microbiome analysis revealed that cry1a mutation, in particular, resulted in a higher abundance of Proteobacteria in the larval microbiota. When challenged with Tilapia lake virus (TiLV), both cry1a and cry1b mutants displayed increased viral loads and reduced survival rates, indicating a compromised antiviral response. Specifically, cry1a mutants had lower initial expression of tlr22, while cry1b mutants showed reduced gene expression of antiviral Mxa at later stages post-infection, both contributing to decreased resistance against TiLV. Overall, the findings demonstrate that while cry1a and cry1b mutations do not significantly affect an early development, both genes play important roles in regulating behavior, shaping the microbiome, and modulating innate antiviral immunity in zebrafish larvae. The study highlights the multifaceted functions of circadian clock genes in vertebrate physiology and immunity.}, } @article {pmid41490313, year = {2025}, author = {Mahnoor, and Ullah, R and Sonyia, and Khan, R and Bahadar, A and Elbatel, I and Khan, I and Alnahari, AA and Haider, A and Jamal, SB and Khan, R}, title = {A modified targeted culturing approach provided a snapshot into interdependencies and resistome among core anaerobic bacteria of the healthy human gut.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0318225}, doi = {10.1128/spectrum.03182-25}, pmid = {41490313}, issn = {2165-0497}, abstract = {The core anaerobic component of the human microbiome plays a critical role in preserving the overall structure and function of the microbiome. However, how these core strains interact with each other and with other gut microbes is largely unknown. We employed a modified culturomics approach to selectively culture these core genera from the human gut and provided a snapshot into their ecological interactions, clinically relevant resistome, and whole genome sequence (WGS)-based insights into their observed phenotypes. This strategy successfully isolated representatives of the targeted 21 core genera, with some isolates reported for the first time. Cross-interactions and resistome-based profiling revealed important insights. Out of the 440 interaction assessments, a significant proportion exhibited either cooperative or competitive effects on other core genera. Interestingly, Bacteroides thetaiotaomicron displayed dual roles, inhibiting potential pathogens while enhancing the growth of beneficial probiotic strains. Moreover, resistome profiling revealed variable resistance and susceptibility toward various antibiotics. WGS analysis revealed the ability of the selected organism to produce metabolites consistent with the observed phenotype. Our unique culturomics approach successfully isolated key anaerobic genera and revealed their complex interdependencies and clinically relevant resistance. Furthermore, our approach lays the foundation for exploring larger-scale microbial community dynamics in terms of interdependencies and for assessing how clinically significant antibiotics impact the key microbiome, something that may be important when making therapy decisions. In summary, our research improves our knowledge of the interactions present among core gut microorganisms and hints at possible mechanisms responsible for sustaining gut microbial homeostasis and rehabilitation. IMPORTANCE This study presents a unique strategy for the targeted isolation and characterization of key interaction dynamics as well as the resistome of core anaerobic bacteria in the healthy human gut. By utilizing this targeted single, optimized core anaerobe-specific growth medium approach, we were able to culture a major proportion of the core anaerobic gut species, where some of those were cultured for the first time. Through the combinatorial approach of cross-interaction, antimicrobial resistance profiling, and whole genome sequencing (WGS) resolved functional insights, we uncovered interesting insights into interdependencies and competition among these core strains as well as their ecological flexibilities. Moreover, we observed that some strains, such as Bacteroides thetaiotaomicron and Bifidobacterium angulatum, are capable of either inhibiting or promoting the growth of certain strains, depending on the pairing. Such findings go against the traditional binary view of microbes as being purely commensal or pathogenic and suggest that microbial behavior is highly context-dependent. Furthermore, WGS analysis provided useful insights into the potential genomic basis of the observed phenotype. Taken together, our findings provide valuable data and enhance our current understanding of how core anaerobes interact with each other, survive, and adapt within the gut environment. Moreover, our work also lays the critical basis for a more rational design of synthetic microbial communities as well as precision-based microbiome aimed at targeted gut health rehabilitation, both with accuracy and sensitivity.}, } @article {pmid41490089, year = {2026}, author = {Hobbs, A and Ochoa-Rojas, D and Humphrey, CE and Kyndt, JA and Moore, TC}, title = {Soil microbiome perturbation impedes growth of Bouteloua curtipendula and increases relative abundance of soil microbial pathogens.}, journal = {PloS one}, volume = {21}, number = {1}, pages = {e0312218}, pmid = {41490089}, issn = {1932-6203}, mesh = {*Soil Microbiology ; *Microbiota ; *Poaceae/growth & development/microbiology ; Soil/chemistry ; Bacteria/genetics ; }, abstract = {Bouteloua curtipendula (sideoats grama) is a valuable prairie grass for livestock forage, supporting food webs of herbivorous insects, reducing soil erosion, and limiting weed infiltration in urban grasslands. Efficient establishment of B. curtipendula in prairie restorations and urban plantings could drastically improve long-term functionality of the space. Soil microbial communities have been linked to plant germination, growth, and drought tolerance in many plant species, however little is known about the factors contributing to B. curtipendula germination and early growth. In this study, we used sterilized soil to examine the impact of soil microbes on B. curtipendula growth under greenhouse conditions. We found Bouteloua curtipendula emergence and growth to be impaired in sterilized soil compared to not-sterilized soil. Using high throughput sequencing of the soil, we found that B. curtipendula grown in sterilized soil induced a greater proportion of plant pathogens and fewer nitrifying bacteria as compared to when grown in not-sterilized soil. For example, there was a significantly higher proportion of Acidovorax, Cellvibrio, and Xanthomonas which are known to contain plant pathogens, while plant-growth promoting bacteria, like Rhodopseudomonas, were significantly higher in the not-sterile soil conditions. We found that soil sterilization and growth of B. curtipendula changed the relative abundance of metabolic subsystem genes in the soil, however, by seven weeks after seeding, B. curtipendula transformed the bacterial community of sterile soil such that it was indiscernible from not-sterile soil. In contrast, fungal communities in sterilized soil were still different from not-sterilized soil seven weeks post-seeding. It appears that the bacteria are involved in the initial establishment of beneficial conditions that set the stage for a robust fungal and plant seedling development.}, } @article {pmid41489381, year = {2026}, author = {Zhou, Y and Ying, G and Shen, W and Cui, Y and Xiang, B and Jiang, M and Bao, J and Jin, Q}, title = {Variation in microbiome and metabolites is associated with advantageous effects of cholestyramine on primary biliary cholangitis with pruritus.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0074725}, doi = {10.1128/spectrum.00747-25}, pmid = {41489381}, issn = {2165-0497}, abstract = {Emerging evidence implicates bile acid-intestinal microbiota interactions in the pathogenesis of pruritus associated with primary biliary cholangitis (PBC). Cholestyramine, a bile acid sequestrant, is clinically recommended for pruritus alleviation. This study investigates its regulatory effects on gut microbiome composition and metabolite profiles. A prospective cohort of 54 pruritic PBC patients and 25 asymptomatic controls underwent longitudinal multi-omics profiling. Fecal 16S rRNA sequencing and untargeted metabolomics were performed pre-/post-4-week cholestyramine intervention (4 g twice daily). Serum autotaxin, as a biomarker for pruritus assessment, and liver function tests were completed simultaneously. Four important findings were listed as follows. (i) Pruritus phenotype characteristics: Pruritic patients exhibited elevated cholestasis indices (total bilirubin, alkaline phosphatase [ALP], and gamma-glutamyl transferase), higher ATX levels, and increased Gp210 antibody positivity compared to controls (all P < 0.01). Cholestyramine significantly reduced 5-D pruritus scores, ATX levels, and cholestasis markers (P < 0.01). (ii) Microbial dysbiosis: Gut microbiota diversity (Shannon/Simpson indices) was markedly decreased in pruritic patients, with taxonomic enrichment of Romboutsia, Stenotrophomonas, and Achromobacter, whereas Lachnospiraceae and Bacteroidaceae predominated in controls. (iii) Metabolomic perturbations: Metabolomic analysis identified diminished medium-chain fatty acids and indole derivatives (e.g., norharman) in pruritic patients. (iv) Therapeutic efficacy: Microbial-metabolite-clinical correlations revealed the pivotal role of the Romboutsia-norharman-ATX/ALP axis in the pathogenesis of pruritic PBC. Post-treatment, cholestyramine restored microbial diversity, normalized metabolite levels, and attenuated pruritus. Enterobacteriaceae/long-chain fatty acids have been identified as a significant marker for predicting the efficiency of the response to cholestyramine.IMPORTANCEPruritus in primary biliary cholangitis arises from synergistic cholestasis and gut microbiome-metabolite dysregulation. Cholestyramine mitigates symptoms by modulating the microbiome-metabolite-host axis, highlighting its therapeutic potential through microbiota remodeling and metabolic homeostasis restoration.}, } @article {pmid41489355, year = {2026}, author = {Cheong, KL and Chen, W and Li, J and Zhong, HJ and Wang, D and Zhong, S}, title = {Nature-inspired oligosaccharides: plant and algal routes to human milk functionality.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/10408398.2025.2609753}, pmid = {41489355}, issn = {1549-7852}, abstract = {Human milk oligosaccharides (HMO) shape early-life health by guiding microbiome assembly, fortifying the mucosal barrier, calibrating immune responses by enhancing secretory IgA at mucosal surfaces, blocking pathogen adhesion, and influencing the microbiota-gut-brain axis. Direct deployment of structurally diverse HMO at population scale remains constrained by manufacturing complexity and cost. This review examines "nature-inspired" oligosaccharides derived from plant and marine algal as affordable, scalable HMO mimetics, mapping chemistry to biology across five functional domains: microbiota architecture & metabolism, inhibition of pathogen adhesion via glycan decoy mechanisms, immune education, mucosal barrier enhancement and gut-brain regulation. We synthesize and critically appraise evidence on plant-derived fructo-, xylo-, and mannan-oligosaccharides, as well as on red-algal agaro-oligosaccharides and brown-algal fuco-oligosaccharides. Although these glycans do not fully replicate individual HMO structures, they can exhibit convergent mechanisms: selective fueling of saccharolytic consortia to produce functional metabolites (SCFAs), multivalent fucose-rich decoying of viral/bacterial adhesins, dendritic-cell/T- and B-cell tuning, epithelial junction and mucus programs, and neuroactive/metabolite signaling along the gut-brain axis. Framed as functional mimicry rather than strict structural emulation, plant and marine oligosaccharides emerge as promising "glycobiotics" to deliver HMO-like benefits across the lifespan, with opportunities for precision, personalized, and sustainable formulations guided by multi-omics and glycoinformatics.}, } @article {pmid41489339, year = {2026}, author = {Romero-Alfano, I and Julia López, A and Piña, B and Gómez-Canela, C and Barata, C}, title = {From Gut to Brain: Glyphosate and Triclosan Impair Microbiome Composition, Neuroactive Metabolites, and Cognitive and Ecological Fitness in Daphnia magna.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c15302}, pmid = {41489339}, issn = {1520-5851}, abstract = {Gut microbiome dysbiosis is a major off-target effect of many pharmaceuticals, personal care products (PPCP), and plant protection products (PPP). This study aims to characterize these effects for two compounds, glyphosate (a PPP) and triclosan (a PPCP), in Daphnia magna juveniles and to trace the downstream consequences for gut- and brain-associated metabolite levels, reproductive performance, and behavior. Both compounds altered levels of neurotransmitters and related metabolites in both head and gut at the ppb-ppt dose range, promoting anxiogenic behavior and inhibiting reproductive traits in a concentration-related manner. These effects occurred concomitantly with alterations in the gut microbiome, analyzed by 16S rDNA sequencing. Correlation analyses between the observed metabolic, reproductive, and behavioral effects and the changes in the metabolic pathway prediction for the treated gut microbiomes revealed an enrichment in pathways related to the biosynthesis of vitamins, of essential fatty acids, and production of short chain fatty acids, which are known to affect systemic serotonin levels. The results suggest a direct link between gut microbiome dysbiosis and cognitive and reproduction effects in D. magna, with implications for the environmental and human health hazard assessment of these and other substances with broad antimicrobial spectra.}, } @article {pmid41489138, year = {2026}, author = {Reed, FE and DeFilipp, Z}, title = {Innovative approaches in acute graft-versus-host disease: emerging therapeutics and novel clinical trial design.}, journal = {Leukemia & lymphoma}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/10428194.2025.2610407}, pmid = {41489138}, issn = {1029-2403}, abstract = {Acute graft-versus host disease (aGVHD) is a major early complication of allogeneic hematopoietic cell transplantation and is associated with substantial morbidity and mortality, particularly in severe cases. The use of corticosteroids as first-line therapy remains standard of care, despite limited efficacy in high-risk cases and associated toxicities. Ruxolitinib has emerged as the treatment of choice for patients who fail corticosteroids, but there remains a need for novel treatment strategies. In this review, we examine the evolving therapeutic landscape of aGVHD and summarize emerging approaches including small molecule inhibitors, biologics, and cellular- and microbiome-modulating therapies. We explore how improved understanding of aGVHD pathophysiology continues to inform new interventions while also addressing the operational and conceptual challenges that constrain clinical trial design and regulatory progress. Finally, we discuss new innovations in biomarker-driven strategies and adaptive clinical trial designs that may facilitate future therapeutic development and advance outcomes for patients with aGVHD.}, } @article {pmid41489025, year = {2026}, author = {Pace, R and Monti, MM and Cuomo, S and Affinito, A and Ruocco, M}, title = {Machine Learning Approaches to Assess Soil Microbiome Dynamics and Bio-Sustainability.}, journal = {Physiologia plantarum}, volume = {178}, number = {1}, pages = {e70719}, pmid = {41489025}, issn = {1399-3054}, mesh = {*Soil Microbiology ; *Machine Learning ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Fungi/genetics ; Soil/chemistry ; Agriculture ; Principal Component Analysis ; }, abstract = {Understanding soil microbiota dynamics is essential for enhancing bio-sustainability in agriculture, yet the complexity of microbial communities hampers the prediction of their functional roles. Artificial intelligence (AI) and machine learning (ML) offer powerful tools to analyse high-dimensional microbiome data generated by high-throughput sequencing. Here, we apply unsupervised AI-based algorithms to uncover microbial patterns that are not immediately recognisable but are crucial for characterising the biological status of agricultural soils. Soil samples were collected from a site in Northern Italy managed under four strategies: conventional farming without organic matter (C), with organic matter (C + O), with beneficial microorganisms but without organic matter (M), and with both beneficial microorganisms and organic matter (M + O). Metagenomic amplicon sequencing of the 16S ribosomal RNA (rRNA) gene and the internal transcribed spacer (ITS) region was used to profile bacterial and fungal communities. Principal component analysis (PCA), k-means clustering, and t-distributed stochastic neighbour embedding (t-SNE) revealed coherent temporal trajectories in both datasets, with sampling time and crop presence emerging as dominant drivers of community assembly and only subtle compositional shifts attributable to treatments. Fungal communities exhibited higher plasticity and a stronger response to management than bacterial communities, which converged towards a stable oligotrophic core. Our findings highlight the complementary roles of fungal and bacterial guilds and show that unsupervised ML-based workflows provide an effective framework to disentangle temporal and treatment effects in complex microbiome datasets. This exploratory study lays the groundwork for future predictive models aimed at identifying microbial indicators of soil biological status and supporting bio-sustainable agronomic decisions.}, } @article {pmid41488894, year = {2025}, author = {Lin, B and Zhu, Z and Yang, X and Li, Z and Zhou, H and Luo, M and Guan, J and Zou, Y and Chen, H and Zhuang, Z and Meng, S and Li, W and Yang, Q and Dai, D}, title = {Protocol for the efficacy and safety of fecal microbiota transplantation in children with autism spectrum disorder: a prospective single-center, single-arm interventional study.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1660773}, pmid = {41488894}, issn = {2296-2360}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 0.7% of children globally, with 90% experiencing comorbid gastrointestinal (GI) symptoms. Fecal microbiota transplantation (FMT) may modulate ASD symptoms via the microbiota-gut-brain axis (MGBA).

METHODS: This open-label single-arm trial enrolls 30 children (2-12 years) with moderate-to-severe ASD, defined as a Childhood Autism Rating Scale (CARS) score of ≥36. Participants receive 3 nasojejunal FMTs (5 mL/kg) over 5 days. The primary outcomes are GI symptom improvement, assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and ASD severity, assessed using the CARS. Secondary outcomes include social responsiveness (Social Responsiveness Scale, SRS), aberrant behaviors (Aberrant Behavior Checklist, ABC), and gut microbiota changes assessed by metagenomic next-generation sequencing (mNGS).

ETHICS AND DISSEMINATION: Ethical approval obtained from Shenzhen Children's Hospital Ethics Committee. Results will be disseminated via peer-reviewed publications and conference presentations.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=229136, identifier ChiCTR2400083998. Registered on 2024-05-08. Registered title: "Efficacy and safety of fecal microbiota transplantation in treatment of autism spectrum disorder: a prospective single-center intervention study".}, } @article {pmid41488762, year = {2025}, author = {Zhao, Y and Hu, X and Li, C and Huang, J and Guo, K and Pan, Q and Yu, Z}, title = {Comprehensive Analysis of Vaginal and Gut Microbiome Alterations in Endometriosis Patients.}, journal = {International journal of women's health}, volume = {17}, number = {}, pages = {5775-5786}, pmid = {41488762}, issn = {1179-1411}, abstract = {PURPOSE: Endometriosis (EMS) is a chronic gynecological disorder with unclear pathogenesis. While the vaginal and gut microbiomes are known to influence EMS, few studies have analyzed both microbiomes integrally. This study aims to characterize the vaginal and gut microbiome profiles in EMS patients and evaluate their diagnostic potential.

PATIENTS AND METHODS: We conducted metagenomic sequencing on 22 paired vaginal and fecal samples from EMS patients and controls. Microbial composition, diversity, and metabolic pathways were analyzed. Machine learning models were employed to assess the predictive performance of microbiome features in EMS diagnosis.

RESULTS: EMS patients exhibited pronounced shifts in the vaginal microbiome, characterized by reduced Lactobacillus and increased Bifidobacterium and Gardnerella, which correlated with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. The gut microbiome displayed decreased diversity, with a depletion of beneficial taxa such as Ruminococcus and Prevotella, alongside an enrichment of Dialister. Metabolic pathways in both microbial communities were significantly altered. Machine learning analyses demonstrated that gut microbiome features outperformed both vaginal microbiome and hormonal indices in predicting EMS, highlighting their strong diagnostic potential.

CONCLUSION: This study underscores the pivotal role of the gut microbiota in EMS and elucidates the complex interplay between microbial dysbiosis and disease pathogenesis. Our findings indicate that gut microbiome signatures may serve as superior diagnostic biomarkers for EMS, thereby paving the way for microbiome-based diagnostic and therapeutic strategies.}, } @article {pmid41488660, year = {2025}, author = {Wilburn, AN and Korkmaz, RÜ and McAlees, JW and Hargis, JM and Shirdel, S and Lingel, I and Watanabe-Chailland, M and Romick-Rosendale, L and Schmudde, I and Bridges, JP and Chougnet, CA and Deshmukh, H and Zacharias, WJ and Köhl, J and Konig, P and Laumonnier, Y and Rothenberg, M and Haslam, DB and Lewkowich, IP}, title = {Maternal antibiotic exposure-mediated alterations in basal, and allergen-induced lung function are associated with altered recruitment of eosinophils to the developing lung.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1715675}, pmid = {41488660}, issn = {1664-3224}, mesh = {Animals ; *Eosinophils/immunology/drug effects ; Female ; Mice ; *Lung/immunology/drug effects/embryology/growth & development ; *Anti-Bacterial Agents/adverse effects ; Allergens/immunology ; *Prenatal Exposure Delayed Effects/immunology ; *Maternal Exposure/adverse effects ; Pregnancy ; Asthma/immunology ; Dysbiosis/chemically induced/immunology ; Mice, Knockout ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: Early-life dysbiosis is associated with increased risk of asthma development but the underlying mechanisms remain unclear. Although eosinophils have been reported in the developing lung, their contributions to alveolar morphogenesis and lung mechanics have not been functionally interrogated.

METHODS: Maternal exposure to antibiotics (ABX) was used to induce early-life offspring dysbiosis, and the effects on lung function and development was assessed. Similar measurements were made in mice lacking eosinophils due to genetic modification, or administration of IL-5 blocking agents.

RESULTS: ABX exposure between Embryonic Day 15 (E15) and post-natal day 28 (PN28), increased allergen-induced, and baseline airway hyperreactivity (AHR). Similar observations were made when maternal ABX exposure was limited to PN10 to PN20. Complete characterization of baseline lung mechanics demonstrated downward-shifted pulmonary PV loops, increased small airway resistance, decreased compliance, and reduced inspiratory capacity at weaning and 14 months of age. Consistent with observation of small airway dysfunction, offspring of ABX-exposed dams demonstrated significantly smaller alveoli at multiple stages of lung development. Examination of recruitment to developing lungs demonstrated an exaggerated recruitment of eosinophils at key developmental periods (PN14) in offspring of ABX-exposed dams. Mice with fewer eosinophils (through genetic knockout, or treatment with anti-IL-5) display altered patterns of lung mechanics opposite to that seen in offspring of ABX-exposed dams.

DISCUSSION: These data underscore an underappreciated role of eosinophils in homeostatic lung development and suggest that early life modulation of pulmonary eosinophil activity has long-term effects on susceptibility to the development of chronic lung diseases such as asthma.}, } @article {pmid41488481, year = {2025}, author = {Xie, Z and Chen, Z and Ma, G}, title = {Dynamic changes in the pregnancy microbiome and their role in preterm birth.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1683610}, pmid = {41488481}, issn = {2235-2988}, mesh = {Humans ; Female ; Pregnancy ; *Premature Birth/microbiology/etiology ; *Microbiota ; Vagina/microbiology ; Dysbiosis/microbiology/complications ; Gastrointestinal Microbiome ; Probiotics ; Mouth/microbiology ; Pregnancy Outcome ; }, abstract = {Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality worldwide, posing significant challenges to maternal and child health. Recent advances have highlighted the critical role of the maternal microbiome-encompassing vaginal, gut, and oral microbial communities-n influencing pregnancy outcomes. This review comprehensively summarizes the dynamic changes of the pregnancy microbiome and elucidates its association with PTB. During healthy pregnancy, the vaginal microbiome is dominated by Lactobacillus with low diversity, while dysbiosis with fewer Lactobacilli and more anaerobes increases PTB risk. The gut microbiome also shifts, with reduced beneficial bacteria and more pro-inflammatory species linked to adverse outcomes. Changes in the oral microbiome and periodontal disease can promote systemic inflammation contributing to PTB. Microbial imbalance may trigger PTB through inflammation, immune changes, and microbial spread to the uterus. Targeting the microbiome via probiotics shows promise, but more clinical studies are needed. This review highlights the pregnancy microbiome as a key biomarker and intervention target to reduce PTB.}, } @article {pmid41488368, year = {2025}, author = {Wang, Q and Chen, J and Chen, H and Liang, D and Zhou, H and Chen, J and Gui, Y and Yao, F and Chen, Y and Zeng, X and Ma, Y and Zhou, D and Fu, H}, title = {Indole-3-propionic acid exacerbates cisplatin-induced chronic kidney disease through the AHR/NF-κB signaling pathway.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114149}, pmid = {41488368}, issn = {2589-0042}, abstract = {Cisplatin is a commonly used chemotherapy agent for treating various solid tumors, but its clinical application is limited by nephrotoxicity. While the potential for cisplatin to cause chronic kidney disease (CKD) following repeated administration has been underexplored, effective therapeutic strategies for cisplatin-induced CKD are lacking. We found that cisplatin-induced CKD is characterized by renal dysfunction and inflammation, along with intestinal barrier impairment. 16S rRNA and metabolomics revealed that cisplatin disrupts the gut microbiome and raises levels of tryptophan metabolites-indole-3-propionic acid (IPA). Notably, oral administration of IPA reproduced similar harmful effects in cisplatin-induced CKD. Integrated analyses of the microbiome, metabolomics, Raman spectroscopy, and DESI-MSI indicated that IPA supplementation exacerbates the production of uremic toxins linked to tryptophan metabolism and promotes the growth of pathogenic bacteria. Our findings demonstrates that IPA exacerbates renal inflammation and fibrosis by regulating AHR/NF-κB signaling pathways, altering intestinal microbiome composition, and disrupting tryptophan metabolism.}, } @article {pmid41488316, year = {2025}, author = {Seo, K and Min, JY and Min, KB and Oh, KH and Ryoo, SW and Son, SY and Lee, JH}, title = {Change of oral microbiome diversity by smoking across different age groups.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1714229}, pmid = {41488316}, issn = {1664-302X}, abstract = {INTRODUCTION: The oral microbiome, a complex ecosystem linked to both oral and systemic diseases, undergoes compositional and functional changes with aging. Tobacco exposure is a known disruptor of microbial homeostasis, yet its effect on microbial diversity remains inconsistent. Whether agingmodifies the relationship between smoking and the oral microbiome remains unclear. This study aimed to evaluate (1) the association between serum cotinine and oral microbial diversity, (2) whether this association varies by age, and (3) taxonomic shifts that may explain smoking-related dysbiosis.

METHOD: We analyzed data from 4,387 adults aged 30-69 years in the U.S. National Health and Nutrition Examination Survey 2009-2012. Serumcotinine, an objective biomarker of nicotine exposure, was used as the primary exposure. Oral microbiome diversity was assessed via 16S rRNA gene sequencing of oral rinse samples. Microbial profiles were analyzed using observed amplicon sequence variants and Bray-Curtis. Alpha diversity declined progressively with age, with the most pronounced reduction among current smokers.

RESULTS: Serum cotinine was inversely associated with alpha diversity, particularly in current smokers aged 60-69 years (adjusted β = -0.1081, p = 0.0002). Beta diversity differed significantly by smoking status (PERMANOVA p < 0.0001). Analysis identified 29 genera were associated with serum cotinine: Haemophilus, Neisseria, and Gemella decreased with higher exposure, while Atopobium and Lactobacillus increased. Tobacco exposure is associated with reduced oral microbial diversity, particularly in older adults.

DISCUSSION: This highlights the synergistic impact of aging and smoking on the oral microbiome and underscores the need for age-specific prevention strategies. Prospective studies are warranted to confirm causality and assess the reversibility of smoking-induced dysbiosis.}, } @article {pmid41488298, year = {2025}, author = {Adams, S and Lakamp, A and Aluthge, N and Laible, E and Loy, JD and Spangler, ML and Fernando, SC}, title = {Investigating the establishment of the rumen and oral bacterial communities in beef cattle and assessing the applicability of using the oral bacterial community composition as a proxy for rumen bacterial community structure in cattle.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1667498}, pmid = {41488298}, issn = {1664-302X}, abstract = {INTRODUCTION: Studies have investigated the rumen microbiome composition and functions to improve ruminant agriculture and its environmental impacts. Yet, sample collection for rumen microbiome analysis can be difficult and invasive, hindering the ability to sample large animal populations. Studies have proposed using oral swabs as an alternative to rumen sample collection. Here, we investigated the potential of using the oral bacterial community as a proxy for the rumen bacterial community during the cattle production cycle.

METHODS: We investigated the development of the bovine rumen and oral bacterial communities using longitudinal sampling and the applicability of using the oral to predict host phenotypes. To this end, we utilized 16S rRNA gene sequencing to characterize and compare the rumen and oral bacterial community composition over multiple time points using amplicon sequence variants (ASVs) in a beef cattle population of 166 animals. Additionally, host phenotype of weaning weight was predicted using the Bayesian ridge regression model to evaluate the applicability of using the oral bacterial community for phenotype prediction.

RESULTS: Our results identified the rumen and oral bacterial communities to have different trajectories of assembly. The proportion of Proteobacteria and Actinobacteriota was higher (p < 0.0001) in the oral samples. Whereas rumen samples had greater abundance of members of the phyla Bacteroidota, Firmicutes, Verrucomicrobiota, Fibrobacterota, and Spirochaetota. The investigation of the oral and rumen bacterial community establishment demonstrated considerable dynamism, where diet and age-related factors to contribute toward bacterial colonization through introduction of new species and the proliferation of early colonizers. Finally, a Bayesian ridge regression model was developed to estimate weaning weight using the centered and scaled log-transformed relative abundance of ASVs. The proportion of variation explained in weaning weight by the oral and rumen bacterial communities were 30 and 37%, respectively.

DISCUSSION: Results from this study suggest that oral and rumen bacterial communities are distinctive, and the oral bacterial community may not serve as a good proxy for the rumen bacterial community even in adult animals with a well-established microbiome. However, the oral bacterial community may serve as a proxy for phenotypic traits of interest in beef cattle.}, } @article {pmid41488297, year = {2025}, author = {Tye, KD and Ran, X and Liu, X}, title = {Moderate physical activity during late pregnancy enhances gut microbial network stability in pregnant women.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1731350}, pmid = {41488297}, issn = {1664-302X}, abstract = {AIM: This study aimed to investigate the impact of moderate physical activity during late pregnancy on the overall structure and stability of the maternal gut microbiota, with particular emphasis on microbial network interactions and their potential implications for mucosal immune resilience.

METHODS: A prospective cohort study was initiated at 32 weeks of gestation, during which physical activity was assessed, and fecal samples were subsequently collected at full-term admission for delivery. Fecal samples were collected and analyzed using 16S rDNA sequencing, and daily physical activity levels were recorded. Participants were categorized into two groups based on the duration of moderate-intensity physical activity: T1 (≥30 min/day, 18 women) and T2 (<30 min/day, 5 women). Bioinformatics analyses were used to compare gut microbiota composition, diversity, and network interactions between the groups, and to assess correlations between microbial abundance and physical activity levels.

RESULTS: Firmicutes, Bacteroidetes, Actinomycetes, and Proteobacteria were the dominant phyla in both groups. Alpha diversity and principal coordinate analysis (PCoA) showed no significant differences in overall diversity. However, LEfSe analysis revealed an enrichment of Christensenellaceae and Prevotella stercorea in the T2 group. The gut microbial network in the T1 group was more complex and stable, with predominantly positive microbial correlations. Spearman analysis indicated significant associations between physical activity levels and specific gut microbes: sedentary behavior correlated negatively with Romboutsia (p = 0.033, R = -0.445) and was positively correlated with Senegalimassilia (p = 0.043, R = 0.443), light-intensity activity correlated negatively with Phascolarctobacterium (p = 0.015, R = -0.500), and moderate-intensity activity correlated positively with Parasutterella (p = 0.040, R = 0.432).

CONCLUSION: Moderate physical activity during late pregnancy promotes a more stable and functionally interactive gut microbiota network. Such microbial resilience may strengthen mucosal immune regulation and reduce infection susceptibility during gestation. These findings highlight the potential of physical activity as a non-pharmacological strategy to modulate the maternal gut microbiome for improved host defense and health outcomes.}, } @article {pmid41488292, year = {2025}, author = {Zaki, R and Bourne, E and Storino, A and Nadeau, J}, title = {Microbial communities of selected regions of the Deep Springs Lake aquifer system.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1689006}, pmid = {41488292}, issn = {1664-302X}, abstract = {Deep Springs Lake is a small, isolated, highly alkaline soda lake in Inyo County of Eastern California, USA. It is a seasonally filled salt lake or playa, and is part of a closed aquifer system. Such closed systems are globally rare, occurring only in arid zones where annual evaporation is greater than annual rainfall. Deep Springs Lake's hydrology and geology have been well studied, and it is home to a unique toad species, but its microbiome remains unexplored. Here we perform 16S, 18S, and ITS amplicon sequencing of the lake water, dried salt crust at the edges the lake, and nearby feeder springs to investigate the community composition of prokaryotes, eukaryotes, and fungi. Bacterial communities in the lake water consist predominantly of Pseudomonadota and Bacteroidota. Nearby springs and salt crust contain different genera of Pseudomonadota than the lake water but similar Bacteroidota, along with an abundant population of Chlorobiota. Noticeably rare in the lake itself but abundant in the biofilms and crust are populations of photosynthetic Cyanobacteria. Archaea are found only in the lake water, largely Halobacterota. Fungi are mostly Ascomycota, with some Chytridiomycota and Rozellomycota; chytrid fungi show no evidence of pathogens related to amphibian die-offs. Eukaryotes in the lake water consist mostly of flagellates, notably the photosynthetic Dunaliella, and brine shrimp (Artemia). In order to compare these sites with source waters elsewhere in the watershed, we also perform 16S amplicon sequencing of three feeder springs found at higher elevations remote from the lake. The Pseudomonadota found in the remote sites differ from those in the lake at the genus level or higher. Some of the genera of Bacteroidota found in the lake are also seen in the remote springs, while most are unique to the springs. Taxonomy and Bayesian source/sink analysis show that the microbiome of Deep Springs Lake derives very little input from the remote feeder springs, but contains extremophiles similar to those of soda lakes worldwide. Further investigation of the lake and its surrounding springs may lead to the identification of new species of bacteria, fungi, and eukaryotes and allow comparisons with other closed aquifer systems.}, } @article {pmid41488241, year = {2025}, author = {Uğur, K}, title = {The influence of endocrine disruptors on the gut microbiota.}, journal = {Turkish journal of medical sciences}, volume = {55}, number = {7}, pages = {1635-1640}, pmid = {41488241}, issn = {1303-6165}, mesh = {Humans ; *Endocrine Disruptors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; }, abstract = {Endocrine disruptors (EDs) are closely associated with the second brain, the microbiota-derived enteric nervous system, commonly referred to as the gut microbiota. The microbiota plays a crucial role in human health and the development of diseases. In today's industrialized world, the presence of EDs in air, water, and soil leads to primary human exposure through dermal contact and ingestion. The impact of these EDs on the microbiota remains unclear. EDs that disrupt the balance of the gut microbiota may contribute to a range of disorders, including metabolic (obesity, diabetes mellitus), cardiovascular (vascular stenosis, cerebrovascular disease), reproductive (infertility, ovarian and testicular tumors), neurological (dysfunction of the amygdala, cortex, and cerebellum), and behavioral disorders (dementia, depression, anxiety, and schizophrenia). This review examines the effects of commonly encountered environmental EDs on the gut microbiota and summarizes the most recent findings on this topic. The concept of the microbiota-derived enteric nervous system and the modulation of the hormonal system through interactions between microorganisms and environmental chemicals have prompted specialists in endocrinology and metabolism to reconsider patient management and treatment strategies. This necessitates a comprehensive evaluation of treatment options that incorporate microbiome data. The information presented in this review will help illuminate future research directions and serve as a valuable resource for subsequent studies.}, } @article {pmid41488081, year = {2025}, author = {Li, Y and Chen, D and Feng, Y and Li, Q and Mao, W and Yu, P and Zhang, Y}, title = {A pilot study of cervicovaginal microbiome patterns associated with embryo implantation outcomes in endometriosis-associated infertility.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1642770}, pmid = {41488081}, issn = {2296-858X}, abstract = {BACKGROUND: The cervicovaginal microbiome-spanning from the vagina to endometrium-remains undercharacterized in endometriosis-associated infertility. Objective: To determine whether combined vaginal and cervical microbial profiles predict frozen embryo transfer (FET) outcomes.

METHODS: In 22 endometriosis patients undergoing FET, paired vaginal and cervical samples were collected on transfer day. 16S rDNA sequencing quantified microbial composition; alpha/beta diversity, PCoA, LEfSe, and PICRUSt analyses identified taxonomic and functional signatures linked to implantation success. Conduct a differential analysis of microorganisms in different body parts through DMI.

RESULTS: Microbial profiles associated with successful pregnancies featured a higher relative abundance of Lactobacillus and Bifidobacterium, whereas Gardnerella, Streptococcus, and Atopobium were more enriched in failures. Cervical alpha diversity was significantly lower in successful transfers. LEfSe highlighted differential taxa including Peptostreptococcales in successes and Pseudomonadaceae in failures. Functional inference predicted dysregulated metabolic pathways in failure-associated communities. Furthermore, the cervical microbiota exhibited higher DMI, indicating greater individual specificity.

CONCLUSIONS: Our pilot findings suggest that a continuous cervicovaginal microbial ecosystem presents distinct taxonomic and functional patterns associated with FET success in endometriosis. Specifically, cervical microbiota profiling emerges as a promising, minimally invasive approach worthy of further investigation to potentially personalize ART strategies.}, } @article {pmid41488054, year = {2025}, author = {Diao, X and Zhang, H and Wang, S and Zhang, Q and Wang, Z}, title = {Bridging ancient wisdom and modern technology: an AI and multi-omics framework for three causes tailored treatment in personalized medicine.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1732340}, pmid = {41488054}, issn = {2296-889X}, abstract = {The 'one-size-fits-all' therapeutic model is inadequate to address individual patient variability, creating an urgent need for an integrative framework for precision medicine. The 'Three Causes Tailored Treatment' (TCTT) principle from traditional Chinese medicine offers a time-tested, holistic blueprint that simultaneously considers the individual, temporal, and environmental dimensions of health. Here, we argue that the synergy of artificial intelligence (AI) and multi-omics technologies is the key to transforming this ancient wisdom into a modern, quantitative clinical paradigm. We demonstrate how multi-omics data provides the foundational layers to quantify the TCTT principle-for instance, using integrated omics (e.g., genomics, proteomics, microbiome) to establish the individual's molecular baseline ("Who"); chronomics to capture temporal fluxes ("When"); and the exposome to decipher the internalized environmental imprint ("Where")-while AI-powered multimodal integration models their complex interactions. By synthesizing evidence across the disease continuum, this review provides a translational roadmap for building dynamic clinical decision-support systems, thereby charting a course toward truly personalized, time-sensitive, and context-aware healthcare.}, } @article {pmid41487796, year = {2025}, author = {Waqas, M and Sarwar, I}, title = {Efficacy of Probiotic Supplementation in the Management of Psoriasis: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e98265}, pmid = {41487796}, issn = {2168-8184}, abstract = {Psoriasis is a chronic immune-mediated skin disease that is increasingly associated with alterations in gut microbiota through the gut-skin axis. This systematic review assessed the efficacy of probiotic supplementation in managing psoriasis. A comprehensive search was performed across PubMed, Scopus, and the Cochrane Library for studies published between 2010 and 2025. After screening 688 unique records and removing duplicates and incomplete entries, 10 studies were found relevant, and eight with accessible full texts were included for qualitative synthesis. Across included randomized controlled and observational studies, probiotic or synbiotic supplementation either alone or as an adjunct to topical or systemic therapy was associated with reductions in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores. Several included studies also reported improvements in inflammatory biomarkers and gut microbiota composition, which were narratively presented in this review. Due to heterogeneity in study designs and interventions, findings were synthesized narratively. Multistrain formulations containing Lactobacillus, Bifidobacterium, or Lactiplantibacillus plantarum consistently demonstrated clinical benefits, whereas single-strain products yielded variable outcomes. All interventions were well tolerated, with only mild gastrointestinal discomfort noted in a small minority of participants. The available evidence suggests that probiotic supplementation may reduce disease severity, improve quality of life, and support immune and barrier function in individuals with psoriasis. The therapeutic effect appears strain-dependent and more pronounced in mild-to-moderate disease. Larger, well-controlled trials with standardized probiotic strains, defined dosages, and longer follow-up are needed to clarify the long-term clinical value of probiotics as adjunctive therapy in psoriasis management.}, } @article {pmid41487676, year = {2025}, author = {Yang, R and He, S and Wang, J and Yang, J and Su, R and Zhao, W}, title = {Inhibitory effects and amino acid metabolism regulations of active polyphenol from foxtail millet bran on chronic colitis in mice.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1714755}, pmid = {41487676}, issn = {2296-861X}, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD) is frequently associated with metabolic imbalances. Polyphenols have demonstrated efficacy in alleviating colitis by restoring the metabolic disorders. Our previous studies revealed that bound polyphenols extracted from millet bran could alleviate acute colitis and colitis-associated colorectal cancer (CRC) via restoring the gut microbiome and that the low molecular weight (MW) (<200 Da) portion of bound polyphenol (BPLP) constituted the primary active component, comprising six phenolic acids.

METHODS: To further evaluate the effects of BPLP on inflammation, a dextran sodium sulfateb(DSS)-induced experimental colitis model was constructed, and BPLP was gavaged on mice. The effects of BPLP on colitis were assessed by detecting the weight, mouse status, gut barrier integrity, and inflammatory cytokine secretion. Additionally, non-targeted metabolomics was used to identify altered metabolites.

RESULTS AND DISCUSSION: BPLP administration restored body weight and colon length, protected epithelial structure from DSS-induced damage, and relieved chronic colitis. In colons, BPLP reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), enhanced the secretion of the anti-inflammatory cytokine IL-10, and upregulated the expression of tight junction proteins. Nontarget metabolomic results showed that BPLP alleviated colitis by modulating amino acid metabolism pathways, including valine/leucine/isoleucine biosynthesis,phenylalanine/tyrosine/tryptophan biosynthesis, and phenylalanine metabolism. Furthermore, alterations in specific amino acids, such as valine and beta-alanine, were consistent with profiles observed in clinical IBD patients. Collectively, these results indicate that BPLP effectively alleviates chronic colitis in mice and regulates inflammation-related amino acid metabolism in vivo.}, } @article {pmid41487523, year = {2025}, author = {Gómez-Cebrián, N and Trull, MC and Gras-Colomer, E and Edo Solsona, MD and Poveda Andrés, JL and Puchades-Carrasco, L}, title = {Systemic metabolic reprogramming and microbial dysbiosis in Fabry disease: Multi-omics mechanisms and implications for drug development.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1702682}, pmid = {41487523}, issn = {1663-9812}, abstract = {Current treatments, including enzyme replacement and pharmacological chaperones, have improved disease outcomes but often fail to fully prevent progression or alleviate persistent symptoms, underscoring the need for novel therapeutic strategies. Recent systems biology and multi-omics approaches have revealed consistent and previously underappreciated alterations in systemic metabolism and the gut microbiota in FD. Here, we synthesize evidence from metabolomic, lipidomic, transcriptomic, and metagenomic studies in patients and experimental models, highlighting disturbances in redox balance, mitochondrial function, energy metabolism, and microbiota-derived metabolites such as short-chain fatty acids and tryptophan catabolites. These findings point to new mechanisms underlying gastrointestinal, inflammatory, and metabolic complications in FD, with direct implications for biomarker discovery and drug development. We further discuss the challenges of integrating multi-omics data into clinical research, the value of mechanistic studies in disease models, and the potential for translating omics-derived insights into precision diagnostics and targeted therapies. By framing FD as a systemic disorder of metabolic and microbial dysregulation, this review outlines a roadmap for mechanism-based interventions that extend beyond canonical glycosphingolipid targets.}, } @article {pmid41487351, year = {2025}, author = {Xie, Y and Dai, D and Zeng, H and Tian, Y and Zou, C and Meng, Y and Wu, Z and Li, J}, title = {Endophyte community shifts in Rubus chingii during fruit ripening are associated with key metabolites.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1727436}, pmid = {41487351}, issn = {1664-462X}, abstract = {INTRODUCTION: The fruit of Rubus chingii Hu is a prized traditional medicine and functional food, with its quality predominantly determined by its secondary metabolites. While the metabolic dynamics during fruit ripening are documented, the role of the endophytic microbiome, a key regulator of plant physiology, remains entirely unexplored.

METHODS: An integrated approach, combining 16S/ITS amplicon sequencing with spectroscopic and chromatographic analyses, were employed to investigate the correlation between the endophytic microbiome and the metabolome across four distinct ripening stages of R. chingii fruit.

RESULTS: Significant stage-dependent shifts in the community structure of both bacterial and fungal endophytes were revealed in this study. Notably, Spearman correlation analysis identified specific microbial taxa, including the bacterial genera Geodermatophilus and Brevundimonas, and the fungal yeasts Metschnikowia and Starmerella, that were significantly positively correlated with the accumulation of key secondary metabolites (ellagic acid, flavonoids, and phenolic acids). Concurrently, the content of these beneficial metabolites and the fruit's antioxidant capacity decreased markedly as ripening progressed.

DISCUSSION: This study provides the first evidence of a structured succession in the endophytic microbiome of R. chingii fruit and its close association with the dynamics of medically relevant metabolites. The findings propose that the ripening process is a tripartite interplay between host development, microbial succession, and metabolic reprogramming. The identified keystone taxa represent promising targets for future microbiome-based strategies to manipulate fruit quality, offering novel insights into the role of the microbiome in medicinal plant biology and its potential application in sustainable agriculture.}, } @article {pmid41487047, year = {2026}, author = {Xie, W and Wang, X and Liu, Y and Cai, L and Song, B and Zhang, S and Shao, Y and Wang, W and Xue, X and Li, J and Cui, W and Jiang, Y and Wang, X and Tang, L}, title = {Gut Microbiota-Derived Ursodeoxycholic Acid Mediates the Resistance to Colonic Inflammation in Pigs.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c08687}, pmid = {41487047}, issn = {1520-5118}, abstract = {Microbes in the gut are crucial for host health, yet their role in disease resistance remains unclear. Using fecal microbiota transplantation from disease-resistant Min pigs to Duroc × Landrace × Yorkshire (DLY) pigs, combined with 16S rRNA sequencing and metabolomics, we investigated this relationship. The transferred microbiota alleviated lipopolysaccharide-induced intestinal inflammation and barrier damage in the DLY piglets. Key bacterial genera and bile acid metabolites have been identified, with in vitro evidence showing that the gut microbiome can convert bile acids to secondary forms, primarily ursodeoxycholic acid (UDCA). Subsequent mechanistic validation in a mouse model demonstrated that UDCA acts via the gut-liver axis on the farnesoid X receptor, inhibiting PI3K/AKT/NF-κB pathways and reducing inflammatory responses, thereby preserving tissue structure in the liver and colon. These findings establish a causal link between gut microbiota and disease resistance, indicating that targeting microbial bile acid metabolism may restore intestinal and hepatic health.}, } @article {pmid41486934, year = {2025}, author = {Yun, M and Son, D and Kim, N and Lee, SH and Cho, E and Lim, S}, title = {Synergistic anti-obesity effects of Bifidobacterium breve BR3 and Lactiplantibacillus plantarum LP3 via coordinated regulation of lipid metabolism and gut microbiota.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {63}, number = {12}, pages = {e2511001}, doi = {10.71150/jm.2511001}, pmid = {41486934}, issn = {1976-3794}, support = {KE2503-1//Ministry of Science and ICT/ ; RS-2023-00218423//Ministry of SMEs and Startups/ ; }, mesh = {Animals ; *Probiotics/administration & dosage/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism/therapy/microbiology ; *Lipid Metabolism/drug effects ; Mice, Inbred C57BL ; Mice ; Male ; Diet, High-Fat/adverse effects ; *Bifidobacterium breve/physiology ; *Anti-Obesity Agents/pharmacology/administration & dosage ; Adipose Tissue/metabolism ; Liver/metabolism ; }, abstract = {The global rise in obesity and its associated metabolic complications underscores the urgent need for safe and effective interventions. This study investigated the anti-obesity efficacy of a probiotic mixture containing Bifidobacterium breve BR3 and Lactiplantibacillus plantarum LP3 in C57BL/6 mice with high-fat diet (HFD)-induced obesity. After obesity was established by feeding a 60% kcal HFD, the probiotic mixture was administered orally for 4 weeks. Compared with the control group, mice receiving the L. plantarum LP3 and B. breve BR3 mixture exhibited significant reductions in body weight and total fat mass, as assessed by Dual-energy X-ray Absorptiometry (DXA) and Echo Magnetic Resonance Imaging (EchoMRI). The probiotic treatment also lowered serum Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and glucose levels, and attenuated lipid accumulation in both hepatic and epididymal adipose tissues. Transcriptomic profiling revealed upregulation of lipolytic genes (Sirt1, Pparα) and downregulation of lipogenic genes (Srebp1c, Fas), suggesting that the probiotic mixture promotes lipid catabolism while suppressing lipid synthesis. Additionally, serum adipokine levels were favorably modulated, indicating improved metabolic homeostasis. Gut microbiota analysis demonstrated an increased relative abundance of beneficial genera, including Akkermansia and Bacteroides, highlighting a microbiome-mediated contribution to the observed metabolic benefits. Overall, our findings indicate that the combined administration of Lactiplantibacillus plantarum LP3 and Bifidobacterium breve BR3 exerts multi-faceted anti-obesity effects by enhancing lipolysis, regulating lipid metabolism, and restoring a healthy gut microbial balance. This probiotic mixture represents a promising therapeutic approach for managing obesity and related metabolic disorders.}, } @article {pmid41486930, year = {2025}, author = {Gan, X and Wen, Y and Chen, S and Ke, F and Liu, S and Wang, Z and Zhang, C and Wang, X and Wang, Q and Gao, X}, title = {Multi-omic profiling reveals the impact of keratinase kerZJ on mouse gut homeostasis.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {63}, number = {12}, pages = {e2509011}, doi = {10.71150/jm.2509011}, pmid = {41486930}, issn = {1976-3794}, support = {2024NSFSC2097//Science and Technology Program of Sichuan province/ ; SKLSIM-F-202458//Open Fund of State Key Laboratory of Neurology and Oncology Drug Development/ ; 2024NSFSC2097//Science and Technology Program of Sichuan province/ ; SKLSIM-F-202458//Open Fund of State Key Laboratory of Neurology and Oncology Drug Development/ ; 2024LZXNYDJ054//Science and Technology Strategic Cooperation Program of Luzhou Municipal Peoples Government and Southwest Medical University/ ; 2023XYXNYD06//Strategic Cooperation program of Xuyong County Peoples Hospital and Southwest Medical University/ ; DZFHXM202318//Phoenix Project of Dazhou/ ; }, mesh = {Animals ; Mice ; *Homeostasis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Peptide Hydrolases/metabolism/pharmacology/administration & dosage ; Proteomics ; Intestinal Mucosa/drug effects/microbiology/metabolism ; Male ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Immunity, Mucosal/drug effects ; Multiomics ; }, abstract = {Keratinase kerZJ is a multifunctional protease with potential as a feed additive and functional ingredient. Here we performed an integrated multi‑omics evaluation of its biosafety and impact on gut homeostasis in mice. Our findings confirm that kerZJ is well-tolerated, with no evidence of systemic toxicity or intestinal epithelial damage. Integrated transcriptomic and proteomic analyses revealed that kerZJ reinforces intestinal barrier integrity by upregulating extracellular matrix components, including collagen IV, and modulates mucosal immunity by enhancing B-cell activation and antimicrobial peptide defenses without inducing inflammation. Furthermore, kerZJ administration led to a significant upregulation of digestive enzymes and a dose-dependent increase in short-chain fatty acids production. Microbiome analysis showed that while high-dose kerZJ altered community composition, it enriched for beneficial taxa like Lactobacillaceae and did not induce dysbiosis. These results demonstrate that kerZJ safely enhances gut barrier function, promotes a favorable immune and metabolic environment, and fosters a resilient gut ecosystem, supporting its development as a safe feed additive and nutraceutical component.}, } @article {pmid41486857, year = {2026}, author = {Xin, L and Chen, Y and Guan, D and Huang, L and Lv, Y and Rong, W and Li, X}, title = {Integrated Analysis of Midgut Transcriptome and Microbiome Reveals That Manganese-Induced Dysbiosis Drives Metabolic Disruption and Developmental Toxicity in Bombyx mori.}, journal = {Environmental microbiology}, volume = {28}, number = {1}, pages = {e70223}, doi = {10.1111/1462-2920.70223}, pmid = {41486857}, issn = {1462-2920}, support = {Heke ZY230301//Local Science and Technology Development Fund project guided by the Central Government/ ; 23-026-08//2023 Annual Operation Subsidy Project of the Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology/ ; 2020XJZC002//Research Project of Hechi University/ ; 2023GXCSSC04//Special Project of Guangxi Collaborative Innovation Center of Modern Sericulture and Silk/ ; }, mesh = {Animals ; *Bombyx/microbiology/growth & development/drug effects/metabolism ; *Manganese/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Transcriptome/drug effects ; Larva/drug effects/growth & development/microbiology ; *Dysbiosis/chemically induced ; Bacteria/genetics/classification/drug effects/isolation & purification ; }, abstract = {Manganese (Mn) contamination poses a significant environmental threat, yet the mechanisms underlying its toxicity remain poorly characterised. Here, we used an integrative multi-omics approach to elucidate how dietary Mn disrupts the gut-microbiome axis in the silkworm, Bombyx mori. High-dose Mn exposure triggered severe, dose-dependent growth retardation, reducing larval weight by 55.1%. This was concurrent with profound gut microbiome dysbiosis, evidenced by reduced bacterial diversity, community homogenisation and a sharp decline in beneficial genera such as Delftia, alongside the complete elimination of key commensals like Bifidobacterium. Host midgut transcriptomics revealed 1255 differentially expressed genes, with significant upregulation of detoxification and stress pathways and marked suppression of genes involved in nutrient metabolism. Critically, integrative analysis demonstrated a strong correlation between microbiome disruption and host metabolic gene expression, suggesting that Mn toxicity operates by disrupting the gut microbiome-host metabolic axis. Our findings provide crucial mechanistic insights into heavy metal ecotoxicology and highlight the vulnerability of beneficial insect-microbe symbioses to environmental contamination, with important implications for sustainable agriculture in metal-polluted regions.}, } @article {pmid41486530, year = {2025}, author = {Zabolotnyi, D and Serezhko, Y and Zabolotna, D and Maliarenko, Y and Voroshylova, N and Verevka, S}, title = {ON THE POSSIBLE MECHANISMS OF MICROBIOME INVOLVEMENT IN INDUCTION OF MALIGNANCY.}, journal = {Experimental oncology}, volume = {47}, number = {3}, pages = {389-392}, doi = {10.15407/exp-oncology.2025.03.389}, pmid = {41486530}, issn = {2312-8852}, mesh = {Humans ; *Neoplasms/microbiology/etiology/pathology ; *Microbiota ; *Biofilms/growth & development ; Animals ; }, abstract = {The сlose coexistence of organisms of different biological species is one of the leading principles of the organization of living matter. The interaction of microbial biofilms with adjacent tissues of the host deserves special attention. The article raises controversial issues related to the possible malignant effect of microbial biofilms.}, } @article {pmid41486484, year = {2025}, author = {Boogari, M and Mohebbi, M and Hadidi, N}, title = {Genetically Engineered Probiotics: Design, Therapeutics, and Clinical Translation.}, journal = {Iranian biomedical journal}, volume = {29}, number = {6}, pages = {374-383}, doi = {10.61882/ibj.5197}, pmid = {41486484}, issn = {2008-823X}, abstract = {Genetically engineered probiotics aim to address transient colonization and the intra- and inter-subject variability that limit conventional probiotics. These strains utilizes CRISPR/Cas editing, programmable gene circuits, and biosensors in chassis such as E. coli Nissle 1917 and L. lactis. This narrative review summarizes the current engineering toolkits and standards (e.g., SEVA), chassis selection criteria, biocontainment strategies, and translational requirements under CMC/GMP frameworks and discusses regulatory considerations for clinical translation. Representative examples include IL-10-secreting L. lactis and phenylalanine-metabolizing strains for PKU (SYNB1618/SYNB1934), which illustrate pharmacodynamic target engagement and short-term preclinical safety. We outline clinical advancements in predefined pharmacodynamics, durability of function, monitoring shedding and HGT, and genomic-microbiome-informed patient stratification. Systems modeling approaches (GEM/ABM) are discussed as tools to guide rational design. GEPs offer programmable "sense-and-respond" therapeutics, with successful clinical adoption depending on durable efficacy, long-term safety, and clearly defined regulatory pathways.}, } @article {pmid41486395, year = {2026}, author = {Hajjar, R and Mars, RAT and Kashyap, PC}, title = {Harnessing the microbiome for cancer therapy.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {41486395}, issn = {1740-1534}, abstract = {The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.}, } @article {pmid41486317, year = {2026}, author = {Arya, AS and Mythili, A}, title = {Gut microbiota centered approaches for breast cancer intervention leveraging probiotics and postbiotics.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-025-04344-8}, pmid = {41486317}, issn = {2730-6011}, } @article {pmid41486169, year = {2026}, author = {Pei, X and Zhang, N and Deng, X and Li, R and Wang, Y and Wang, Y and Huang, W and Yue, Y and Geisen, S and Gao, Z and Guo, S and Tian, D and Shen, Q and Kowalchuk, GA and Li, R}, title = {Biofertilizer induces soil disease suppression by activating pathogen suppressive protist taxa.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00897-2}, pmid = {41486169}, issn = {2055-5008}, support = {42307171//the National Natural Science Foundation of China/ ; 42277294//the National Natural Science Foundation of China/ ; 2023M731724//the Postdoctoral Science Foundation of China/ ; KTTQ2025018//the Fundamental Research Funds for the Central Universities/ ; CX(22)2043//the Agricultural Science and Technology independent innovation fund project of Jiangsu Province/ ; 2060302//the key project at central government level: the ability establishment of sustainable use for valuable Chinese medicine resources/ ; }, abstract = {Given the increasing demand for sustainable agricultural solutions utilizing the microbiome, particularly the use of biofertilizer (BF), it is essential to understand the mode of action and the role of predatory protists, along with their interactions with biocontrol strains and resident community members. We therefore examined these interactions through a long-term field experiment and a series of greenhouse and pot experiments. In field and greenhouse studies, we observed that Bacillus significantly stimulated the growth of Cercomonas, a genus of predatory protists, in the soil. In turn, these protists promoted the growth of Bacillus, leading to increased detection of polyketide synthase (PKS) genes and the inhibition of bacterial wilt pathogen Ralstonia solanacearum. We here reveal a positive feedback loop between the biocontrol agent Bacillus and predatory protists, which explains the biofertilizer-induced reduction of plant pathogens. These findings highlight the significance of synergistic interactions between functional microbes and predatory protists in suppressing soil-borne diseases. Moreover, it underscores the potential of incorporating predator-prey interactions into agricultural practices to foster more sustainable ecosystem development.}, } @article {pmid41486167, year = {2026}, author = {Chen, Y and Fang, Y and Lyu, Z and Tian, Y and Niu, S and Li, YR and Yang, L}, title = {Microbiome modulation of tumorigenesis and immune responses.}, journal = {Journal of biomedical science}, volume = {33}, number = {1}, pages = {4}, pmid = {41486167}, issn = {1423-0127}, support = {UCLA MIMG M. John Pickett Post-Doctoral Fellow Award//University of California, Los Angeles/ ; UCLA BSCRC Innovation Award//University of California, Los Angeles/ ; }, mesh = {Humans ; *Carcinogenesis/immunology ; *Neoplasms/immunology/microbiology/therapy ; *Microbiota/immunology ; Gastrointestinal Microbiome ; Immunotherapy ; }, abstract = {The microbiome has emerged as a critical, context-dependent regulator of tumorigenesis and anticancer immunity, capable of either promoting cancer progression or protecting against malignancy. This dual role is mediated by multiple interconnected mechanisms-including chronic inflammation, modulation of immune responses, and alterations in host metabolic signaling. These microbiome-cancer interactions vary across organs, influencing malignancies in the colon, breast, lung, and beyond. Clinically, the microbiome significantly affects patient responses to cancer therapies, particularly immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR)-T cell therapy. Although emerging therapeutic strategies aimed at modulating the microbiome have shown promising early results, challenges remain, including individual microbiome variability and the dynamic interplay between the immune system and microbial communities. Nevertheless, harnessing the microbiome holds significant potential to transform precision oncology, offering personalized cancer prevention and treatment strategies tailored to each patient's unique microbial ecosystem.}, } @article {pmid41486026, year = {2025}, author = {Nguyen, VH and Pereira, LR and Shannon, OM and Stephan, BC and Siervo, M}, title = {Dietary patterns and endothelium dysfunction: a literature review.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {}, number = {}, pages = {104484}, doi = {10.1016/j.numecd.2025.104484}, pmid = {41486026}, issn = {1590-3729}, abstract = {The integrity of the vascular endothelium is fundamental to regulating cardio-metabolic and neurological functions. Endothelial dysfunction (ED) is a key driver of atherosclerosis and is strongly linked to the pathogenesis of heart disease, peripheral arterial disease, and stroke. This review describes the relationship between dietary patterns and endothelial health, focusing on observational and experimental studies that investigate the protective effects of healthy dietary patterns in the maintenance of endothelial integrity and prevention of ED. Plant-based diets, including Mediterranean and Dietary Approaches to Stop Hypertension (DASH) dietary patterns, have been linked to improvement of endothelial function through multiple mechanisms such as increased nitric oxide bioavailability, reduced oxidative stress and inflammation, and fostering a healthy gut microbiome. Traditional Japanese, Nordic, and Palaeolithic dietary patterns also show potential cardiovascular benefits through improved vascular biomarkers and significant anti-inflammatory effects, though evidence on effects on endothelial function remains less established. The consequences of poor endothelial health extend to all systems, and the brain is one of the organs crucially affected by ED. ED has been increasingly recognised as a critical contributor to cognitive decline, dementia, and stroke, largely accounted and explained by mechanisms impairing cerebral blood flow, neuronal metabolism, neuro-vascular coupling and compromised integrity of the blood-brain barrier. This review highlights the importance of maintaining endothelial health as a protective strategy for cognitive function and reduction of dementia risk. Adherence to dietary patterns with protective effects on endothelial integrity may represent an effective strategy to promote lifelong health for both the heart and brain.}, } @article {pmid41486021, year = {2025}, author = {Yao, CC and Tai, WC and Liang, CM and Tsai, MC and Tsai, YC and Wu, CK and Huang, PY and Chen, CH and Kuo, YH and Chuah, SK and Lian, WS and Chiu, YC and Kuo, CM and Wu, KL}, title = {Alternation of the oral, gastric and stool microbiome in patients with reflux esophagitis and Barrett's esophagus.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2025.12.007}, pmid = {41486021}, issn = {1995-9133}, abstract = {BACKGROUND: The imbalance of human microbiota has been associated with various inflammatory disease. Compared to intestinal flora, the esophageal microbiome has been understudied,and it remains unclear whether dysbiosis is related to reflux esophagitis (RE) and Barrett's esophagus (BE).This study aimed to synthesize findings on microbial composition changes across different regions of the gastrointestinal tract and their relationship with chronic esophageal reflux diseases.

METHODS: We recruited 29 RE patients (10 Grade A; 10 Grade B; 9 Grade C), 9 BE patients, and 10 healthy volunteers to study microbial composition in saliva, gastric juice, and stool using 16S rRNA gene pyrosequencing and analyzed serum inflammatory cytokines using ELISA.

RESULTS: Microbiota alpha diversity exhibited no significant changes between groups. In terms of taxonomy, RE and BE patients had more gram-negative anaerobic bacteria in salivary microbiota. Notably, increased Tannerellaceae abundance correlated with elevated serum IL-6 levels, which have been linked to chronic inflammation. Helicobacter was more abundant in gastric fluid of controls. Stool analysis revealed BE patients had higher abundance of phylum Bacteroidetes, and the genus Prevotella, while Fusobacterium was more prevalent in controls.

CONCLUSIONS: The increased abundance of Tannerellaceae in saliva was correlated with elevated serum IL-6 levels and may be a contributing factor in chronic esophageal reflux disease. BE patients had a higher abundance of Prevotella, a gram-negative bacterium, which may be linked to early stage esophageal inflammation in chronic reflux disease. Conversely, the increased abundance of Helicobacter in gastric juice may serve as a protective factor.}, } @article {pmid41485840, year = {2026}, author = {Jurgiel, J and Gromowski, T and Król, J and Bomba-Opoń, D and Kościółek, T and Wielgoś, M}, title = {The impact of maternal microbial transfer on the infant gut microbiome after cesarean delivery: a systematic review.}, journal = {American journal of obstetrics and gynecology}, volume = {233}, number = {6S}, pages = {S541.e1-S541.e16}, doi = {10.1016/j.ajog.2025.09.001}, pmid = {41485840}, issn = {1097-6868}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cesarean Section ; Female ; Infant, Newborn ; Pregnancy ; *Fecal Microbiota Transplantation ; Vagina/microbiology ; Bacteroides ; Lactobacillus ; Bifidobacterium ; }, abstract = {OBJECTIVE: To systematically review the results of maternal microbial transfer in shaping microbial diversity, improving neonatal development, and evaluating the microbial transfer procedure's adverse events.

DATA SOURCES: A comprehensive search was conducted on April 25, 2024, using PubMed/MEDLINE, Academic Search Ultimate, and ClinicalTrials.gov for studies published in English from 2000 to 2023. The following keywords were used: "vaginal seeding," "microbiota," "maternal fecal microbiota transplantation," "maternal microbial transfer," and "bacterial baptism."

STUDY ELIGIBILITY CRITERIA: The review included English-language, peer-reviewed randomized controlled trials and nonrandomized interventional studies investigating maternal microbial transfer in neonates born via elective cesarean delivery.

Data were extracted and analyzed for key outcomes, including severe adverse effects, alpha diversity, beta diversity, and the abundance of key taxa such as Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp.

RESULTS: A total of 10 studies, including 4 randomized controlled trials and 6 nonrandomized interventional studies with 1450 participants, were included in this qualitative review. The findings regarding changes in alpha diversity (a measure of microbial richness within individual samples) were inconclusive, while several studies indicated a potential increase in beta diversity (reflecting differences in microbial composition between samples) associated with the procedure. Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp. were the most frequently assessed taxa, with some studies suggesting beneficial changes in their abundance. Developmental outcomes, such as anthropometric measures and allergy risks, showed limited evidence of benefit, with one study reporting preliminary findings of improved neurodevelopmental scores. No significant increase in severe adverse effects was observed in any of the included studies.

CONCLUSION: The efficacy of maternal microbial transfer in restoring neonatal microbiota and promoting health outcomes remains uncertain, with neonatal outcomes addressed in only 3 of the included studies-one on allergy and one on neurodevelopment. However, while no serious adverse effects have been consistently reported, data on safety remain limited.}, } @article {pmid41485837, year = {2026}, author = {Sanchez-Ramos, L and Preis, R and Romero, R}, title = {Prophylactic antibiotics to prevent postcesarean infection: which antimicrobial, when, how, and why?.}, journal = {American journal of obstetrics and gynecology}, volume = {233}, number = {6S}, pages = {S483-S503}, doi = {10.1016/j.ajog.2025.09.044}, pmid = {41485837}, issn = {1097-6868}, mesh = {Humans ; Female ; *Antibiotic Prophylaxis/methods ; *Surgical Wound Infection/prevention & control ; *Anti-Bacterial Agents/therapeutic use/administration & dosage ; *Cesarean Section/adverse effects ; Cefazolin/therapeutic use ; Pregnancy ; Clindamycin/therapeutic use ; Endometritis/prevention & control ; Azithromycin/therapeutic use ; Gentamicins/therapeutic use ; }, abstract = {Before the introduction of routine antibiotic administration, the rate of postcesarean infection exceeded 30% to 50%. Since the 1970s, postpartum infection occurs in approximately 1% to 2% of patients after vaginal birth and in 5% to 20% following cesarean delivery. Evidence from randomized clinical trials and systematic reviews has demonstrated that the administration of a single dose of antibiotics within 60 minutes before skin incision significantly reduces maternal infection-related morbidity without adverse neonatal outcomes. These results have informed clinical guidelines of professional organizations. Antibiotic selection is empiric and primarily guided by knowledge of the microbiology of intra-amniotic and puerperal infection. Cefazolin is the standard prophylactic agent due to its broad-spectrum activity, favorable pharmacokinetics, and established safety. However, its lack of activity against organisms such as Ureaplasma species has motivated investigation of adjunctive azithromycin, particularly in high-risk or unscheduled cesarean deliveries, where randomized trials and meta-analyses show additional benefit in reducing wound infections and endometritis. For patients with severe beta-lactam allergies, clindamycin and gentamicin are commonly used, although use of these agents is associated with higher rates of surgical site infection, increased antimicrobial resistance, and risks such as nephrotoxicity and necrotizing enterocolitis due to Clostridioides difficile infection. Special considerations include obesity, which doubles the risk of surgical site infection and alters antibiotic pharmacokinetics, prompting recommendations for a 3-gram cefazolin dose in patients ≥120 kg. Prolonged operative time and excessive blood loss also warrant intraoperative redosing to maintain therapeutic levels. In addition, emerging evidence suggests that adjunctive postcesarean antibiotic administration (eg, cephalexin with metronidazole) may reduce wound complications in obese women, although professional guidelines remain in evolution. In summary, judicious use of antibiotic prophylaxis is essential to reduce cesarean-related infections and optimize maternal outcomes, while continued research seeks to refine strategies that mitigate unintended neonatal consequences.}, } @article {pmid41485817, year = {2026}, author = {Chervenak, FA and Mcleod-Sordjan, R and Pollet, SL and Bachman, G and Warman, A and Grünebaum, A}, title = {Cesarean delivery on maternal request: the essential role of professional obligations.}, journal = {American journal of obstetrics and gynecology}, volume = {233}, number = {6S}, pages = {S216-S225}, doi = {10.1016/j.ajog.2025.02.039}, pmid = {41485817}, issn = {1097-6868}, mesh = {Humans ; Female ; *Cesarean Section/ethics/psychology ; Pregnancy ; *Informed Consent/ethics ; Beneficence ; Personal Autonomy ; *Patient Preference ; Decision Making ; Obstetrics/ethics ; }, abstract = {Cesarean delivery on maternal request presents an ethical challenge in obstetrics. This comprehensive ethical examination of cesarean delivery on maternal request incorporates emerging evidence on both medical and psychological factors while providing a framework for balancing respect for patient autonomy with professional beneficence-based obligations to optimize maternal and neonatal outcomes. We explore key factors influencing cesarean delivery on maternal request decisions, including cognitive biases, clinical considerations, and the impact of physician self-interest. Major obstetric organizations generally support cesarean delivery on maternal request as an option after appropriate counseling, while emphasizing vaginal delivery as the preferred mode in the absence for indications for cesarean delivery. We propose a systematic approach to informed consent that incorporates trauma-informed care, considers future reproductive plans, and addresses both immediate and long-term implications for mother and child. The framework includes comprehensive discussion of maternal risks (surgical complications, placental disorders in future pregnancies) and fetal considerations (respiratory morbidity, microbiome alterations, and potential long-term health effects). Special attention is given to ensuring consent processes are accessible across varying health literacy levels and cultural backgrounds. The timing of consent discussions is critical, with distinct considerations for antepartum versus intrapartum requests. Quality metrics and financial implications of cesarean delivery on maternal request are examined, highlighting the need for policy reform to better accommodate patient autonomy while maintaining healthcare quality standards. We conclude that while cesarean delivery on maternal request may be ethically permissible, it requires thorough counseling and should not be viewed as a routine option. This analysis provides practical guidance for clinicians navigating cesarean delivery on maternal request requests while upholding professional obligations to optimize maternal and perinatal outcomes.}, } @article {pmid41485679, year = {2026}, author = {Xie, H and Cheng, HS and Ng, JXJ and Zhang, S and Kim, JHS and Tan, SH and Tan, CH and Tan, NS}, title = {A gut-liver lipid flux checkpoint mediates FAHFA protection from MASLD.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {108085}, doi = {10.1016/j.phrs.2025.108085}, pmid = {41485679}, issn = {1096-1186}, abstract = {Pharmacotherapies for metabolic dysfunction-associated steatotic liver disease (MASLD) remain limited. Although resmetirom and semaglutide have approvals for MASH, gut-liver axis options are still needed. Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) offer anti-inflammatory and metabolic benefits but are constrained by poor stability and synthesis complexity. We develop a modular, scalable chemistry platform that installs bioisosteric linkages to generate orally stable, gut-retentive FAHFAs. High-throughput screening identifies lead candidates (12-TAASA, 12-HDTZSA) that selectively inhibit intestinal lipid handling while sparing glucose absorption. In a diet-induced MASLD model, oral dosing reduces weight gain, lowers hepatic triglycerides, improves steatosis histology and liver injury markers, and enhances glycemic control, achieving efficacy comparable to semaglutide. Mechanistically, we identify an intestine-anchored dual-brake mechanism. First, 12-TAASA slows and diminishes gut-to-liver lipid flux in vivo, directly reducing the dietary lipid burden reaching the liver. Second, 12-TAASA and 12-HDTZSA remodel the gut microbiome toward short-chain fatty acid (SCFA)-producing consortia and increase circulating, bacterially derived SCFAs, providing a complementary, microbiota-mediated route to systemic metabolic benefit. Multi-omics integration further implicates a CD44-centered epithelial program, together with allied lipid-handling pathways, as a key intestinal target network governing flux control. These findings position stabilized FAHFAs as gut-localized agents that couple epithelial lipid-uptake restraint with microbiome-derived SCFA signals to reduce gut-to-liver lipid flux, establishing an orally active, dual-action strategy for MASLD.}, } @article {pmid41485632, year = {2026}, author = {Di Bello, A and Scala, A and Gili, R and Falcicchia, R and Bassolino, A and Polidori, S and D'Auria, F and Tortora, G and Bossi, P and Cassano, A}, title = {The Microbiome in Head and Neck Squamous Cell Carcinoma: Biological Drivers, Therapeutic Interactions, and Emerging Clinical Applications.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {105108}, doi = {10.1016/j.critrevonc.2025.105108}, pmid = {41485632}, issn = {1879-0461}, abstract = {Head and neck squamous cell carcinoma (HNSCC) develops within a biologically complex niche shaped by epithelial, immune, environmental, and microbial interactions. Growing evidence indicates that microbial communities influence HNSCC initiation, progression, therapeutic response, and toxicity. This narrative review synthesizes current knowledge on microbiome composition in healthy mucosa, oral potentially malignant disorders, and established HNSCC, emphasizing how dysbiosis characterized by enrichment of periodontitis-associated taxa such as Fusobacterium and Porphyromonas and depletion of protective genera including Corynebacterium and Kingella may drive carcinogenesis through inflammation, genotoxic metabolites, immune modulation, and metabolic alterations. We also examine microbiome-mediated effects on systemic treatments, including chemotherapy, radiotherapy-induced mucositis, and immune checkpoint inhibitor (ICI) response, and review emerging approaches to therapeutically modulate microbial communities. Although several microbial signatures show potential as biomarkers or therapeutic targets, no reproducible microbiome-based tools are yet ready for clinical implementation. Standardized methodologies and prospective interventional studies will be essential to translate these findings into precision oncology for HNSCC.}, } @article {pmid41485602, year = {2026}, author = {Adejumo, S and Lewis, G and Das, P and Lim, CKY and Malas, J and Oli, AN and Allen, JM and Hampton-Marcell, J}, title = {Dietary Protein Source Shapes Gut Microbial Structure and Predicted Functional Potential: A Systematic Integrative Re-analysis Using Machine Learning.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100582}, doi = {10.1016/j.advnut.2025.100582}, pmid = {41485602}, issn = {2156-5376}, abstract = {BACKGROUND: Dietary proteins shape gut microbial ecology, yet the taxonomic and functional consequences of plant- versus animal-based proteins remain poorly defined. Although digestibility and fermentation profiles differ by protein type, a systematic evaluation of how these differences influence microbial diversity, community structure, and metabolic capacity is lacking. This study represents a systematic integrative re-analysis of raw 16S rRNA sequencing datasets derived from independent controlled animal feeding studies.

METHODS: Following PRISMA guidelines, we analyzed 16S rRNA sequencing data from 10 murine studies (n = 187) comparing plant- and animal-protein diets. Alpha diversity was assessed using Shannon, Inverse Simpson, and Chao1 indices, and beta diversity with Aitchison distances. Differentially abundant taxa were identified using LEfSe and class-weighted Random Forest models. Functional potential was inferred with PICRUSt2, and taxon-pathway relationships were explored using correlation and network analyses.

RESULTS: Plant-protein diets increased gut microbial diversity across all alpha diversity metrics and were associated with higher representation of saccharolytic and nitrogen-recycling genera such as Bacteroides, Muribaculaceae, and Allobaculum. Animal-protein diets favored proteolytic taxa, including Clostridium sensu stricto 1 and Colidextribacter. Microbial community structure differed significantly between diets (ANOSIM R = 0.663, p < 0.001). Random Forest models achieved >88% accuracy (AUC = 0.995) in predicting dietary groups, and LEfSe identified consistent discriminating taxa. Functional profiling showed that plant-based diets enriched pathways linked to short-chain fatty acid and aromatic amino acid metabolism, whereas animal-based diets favored sulfur- and branched-chain amino acid-associated pathways. Network analysis identified Muribaculaceae as a plant-associated hub and Lactobacillus as an animal-associated hub.

CONCLUSION: Dietary protein source significantly influences gut microbiota composition and functional potential in mice. Plant- and animal-based proteins generate distinct metabolic signatures with implications for nitrogen cycling, sulfur metabolism, and microbial ecology. Future controlled dietary studies that harmonize protein source with other macronutrient variables are needed to isolate protein-specific effects.

STATEMENT OF SIGNIFICANCE: This study presents the first standardized systematic integrative re-analysis of murine protein-intervention microbiome datasets, integrating taxonomic, machine learning, and predicted functional profiling to identify robust microbial and metabolic signatures that differentiate plant- from animal-based protein diets. By harmonizing raw sequencing data across diverse experimental contexts, this work clarifies foundational ecological responses to protein source and provides mechanistic hypotheses to guide future controlled nutrition and microbiome research.}, } @article {pmid41485542, year = {2026}, author = {Allani, M and Nath, G and Juyal, G and Chandra Joshi, M and Tiwari, V}, title = {Fecal Microbiota Transplantation Attenuates Neuropathic Pain in Rats via Gut Microbiota-Mediated Immunomodulation of Ion Channels and Nociceptors.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108275}, doi = {10.1016/j.micpath.2026.108275}, pmid = {41485542}, issn = {1096-1208}, abstract = {INTRODUCTION: Neuropathic pain, resulting from somatosensory nervous system damage, presents significant treatment challenges due to limited effectiveness and adverse side effects of current therapies. Emerging evidence highlights the gut microbiome's potential role in pain regulation, yet the specific microbial species and mechanisms underlying chronic neuropathic pain remain largely unexplored.

OBJECTIVES: This study aimed to determine the relationship between gut microbiota and neuropathic pain using fecal microbiota transplantation (FMT) in rats with chronic constriction injury (CCI). Additionally, it sought to identify microbial species associated with pain modulation.

METHODS: CCI was performed in wildtype and antibiotic-treated pseudo-germ-free (PGF) rats. FMT was performed using fecal matter slurry from healthy (hFMT) and CCI-dysbiotic (dFMT) donors, transplanted into nerve-injured and healthy rats, respectively. Pain-related behaviors were assessed and microbial composition was analysed via 16sRNA sequencing. Western blot and RT-PCR assays were conducted on dorsal root ganglion (DRG) and spinal cord tissues.

RESULTS: CCI induced gut microbial dysbiosis, characterized by increased Proteobacteria and Fusobacteriota and decreased Actinobacteria. hFMT from healthy rats alleviated mechanical, thermal, and cold hyperalgesia but did not reverse mechanical allodynia in CCI rats. Conversely, dFMT from CCI rats induced pain-like hypersensitivity in healthy rats, mimicking nerve injury effects. Correlation analysis identified microbial species linked to pain modulation: Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger were associated with reduced pain behaviors, while Pasteurellaceae bacterium, Bacillus sp., and Staphylococcus arlettae were linked to nerve injury-induced dysbiosis. hFMT restored claudin-5 and anti-inflammatory markers TGF-β and IL-10 while downregulating pain-related proteins TRPM8, Nav 1.8, Nav 1.7, and TRPA1 in CCI rats. In contrast, dFMT promoted neuroinflammation by increasing IBA1, TNF-α, and IL-1β, leading to microglial activation in healthy rats.

CONCLUSION: Our findings demonstrate that the composition of gut bacteria influences pain-like behaviors through nerve injury-induced microbial dysbiosis, operating in a bidirectional manner. Additionally, the study suggests that a cocktail of Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger could serve as a promising alternative for managing neuropathic pain.}, } @article {pmid41485494, year = {2026}, author = {Miyachi, H and Shibata, R and Javornik Cregeen, SJ and Surathu, A and Sijaric, M and Espinola, JA and Sullivan, AF and Mansbach, JM and Camargo, CA and Zhu, Z}, title = {Interactions between host genetics and gut microbiome influence susceptibility to childhood asthma and lung function.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.12.1005}, pmid = {41485494}, issn = {1097-6825}, abstract = {BACKGROUND: The gut microbiome is thought to influence risk of childhood allergic diseases; however, data on species-level links to childhood asthma and lung function are limited, and the role of host genetics in the gut-lung axis remains unclear.

METHODS: In a multicenter cross-sectional study of children with a history of bronchiolitis, from the 35[th] Multicenter Airway Research Collaboration, we performed shotgun metagenomic profiling of stool samples at age 6 years and examined associations of gut microbiome with prevalent asthma and lung function. We also calculated polygenic risk scores (PRS) of asthma and lung function to investigate the interaction between host genetics and gut microbiome on these traits.

RESULTS: In the 300 children included for this study, three bacterial species (e.g., Bacteroides vulgatus, Eisenbergiella massiliensis, Butyricimonas virosa) were differentially associated with FEV1, and four bacterial species were differentially associated with FEV1/FVC (e.g., Bifidobacterium longum) (MaAsLin: FDR<0.25). Furthermore, host genetics-gut microbiome interaction analysis showed association of B.vulgatus (FDR=0.037) and Bacteroides uniformis (FDR=0.037) with FEV1/FVC among children with high FEV1/FVC PRS. Additionally, Ruminococcus bromii (FDR=0.067) and Alistipes indistinctus (FDR=0.13) were suggested to have protective associations with asthma, specifically in children with high asthma PRS, indicating that host genetics can modulate the effect of gut microbiome on these respiratory outcomes.

CONCLUSION: By applying the metagenomic approach to a multicenter cohort of children with a history of bronchiolitis during infancy, this study suggests potential interplay of host genetics with gut microbiome, and their integrated relationship with childhood asthma and lung function.}, } @article {pmid41485339, year = {2025}, author = {Zhang, X and Chen, H and Liu, P and Zhou, Y and Li, J and Lee, HK and Miao, X and Huang, Z}, title = {Impact of lactational per- and polyfluoroalkyl substances exposure on infant gut microbiota and potential mediating effects on infant neurodevelopment.}, journal = {Journal of hazardous materials}, volume = {502}, number = {}, pages = {140959}, doi = {10.1016/j.jhazmat.2025.140959}, pmid = {41485339}, issn = {1873-3336}, abstract = {Exposure to per- and polyfluorinated substances (PFAS) is associated with adverse maternal and infant health effects, particularly undesirable birth outcomes. Whether PFAS affects neurodevelopmental trajectories remains unknown. This longitudinal study enrolled 114 mother-infant pairs, analyzing longitudinally collected human milk and infant fecal samples at 0.5, 1, and 3 months postpartum. Infant neurodevelopment was assessed using the Ages & Stages Questionnaires Third Edition and the Social-Emotional at 6 months of age. Increasing concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), 2-(N-Methylperfluorooctanesulfonamido) acetic acid and PFAS mixture overall in human milk were associated with significantly lower scores in communication, gross motor, fine motor, problem solving, and personal-social domains. Moreover, long-chain perfluoroalkyl carboxylic acids and PFOS disrupted the establishment of the early infant gut microbiome, resulting in increased relative abundances of Klebsiella variicola, Enterococcus faecium, Clostridium perfringens, and Veillonella atypica. During this developmental period, perfluorononanoic acid (PFNA), PFOS, and its substitute perfluoro2-((6-chlorohexyl) oxy) ethane sulfonic acid also decreased the abundance of Bifidobacterium breve and Streptococcus. Mediation analysis further revealed that Clostridium perfringens mediated 13 % of ΣPFAS exposure's effect on fine motor and Streptococcus mediated 11 % of PFOS exposure's effect on gross motor deficits. These findings establish gut microbiota as a mechanistic link between lactational PFAS exposure and neurodevelopmental delays, identifying the microbiota as a potential therapeutic target.}, } @article {pmid41485298, year = {2026}, author = {Chopra, C and Kukkar, D and Kaur, H}, title = {A 16S rRNA-based meta-analysis of gut microbiota in diabetic nephropathy using QIIME2 and publicly available NGS datasets.}, journal = {Computational biology and chemistry}, volume = {121}, number = {}, pages = {108876}, doi = {10.1016/j.compbiolchem.2026.108876}, pmid = {41485298}, issn = {1476-928X}, abstract = {Gut microbial profiles can differ significantly between diabetic nephropathy (DN), diabetic patients, and healthy controls (HCs). The exact microbial taxa involved in DN progression is yet to be fully characterized. Therefore, this study aims to compare the gut microbiota od DN patients with diabetic and healthy individuals. Accordingly, this study executes a pioneering metanalytical view using the publicly available datasets (National centre for biotechnology information) to evaluate DN associated variation in gut-microbiota diversity. We hypothesize that the DN patients should have a smaller number of beneficial microbes along with a greater fraction of pathogenic microbial composition relative to the other two groups. Specifically, this report utilizes quantitative insights into microbial ecology 2 (QIIME2) platform to identify an association between gut microbiota composition and DN advancement. This novelty provides distinctive nature to our work in comparison to the broader diabetes microbiome studies. Our study enables comprehensive taxonomic profiling, differential abundance testing, and alpha and beta diversity analyses across multiple studies. A total of six studies were included, comprising 684 samples from both DN patients and HCs. Post quality control check, these samples were processed using QIIME2 platform for taxonomic profiling and diversity analysis to characterize microbial dysbiosis in DN patients in relation to other two groups. Alpha diversity indicates insignificant trend towards reduction of microbial diversity as observed using the Kruskal-Wallis test, Shannon index, Observed features (richness), and Faith's PD analysis (p > 0.05). Additionally, beta diversity analyses revealed a trend toward microbial richness in DN compared to diabetic individuals and HCs, though differences were statically insignificant (P > 0.05). Taxonomic profiling showed a depletion of beneficial genera (e.g., Faecalibacterium, Roseburia, and Bifidobacterium) with false discovery rate (FDR)-adjusted p < 0.05. Contrarily, pathogenic and pro-inflammatory taxa including Escherichia-Shigella, Enterococcus, and Klebsiella showed higher abundance in the DN group (FDR-adjusted p < 0.05). These compositional shifts highlight pronounced gut dysbiosis during the transition from diabetes to DN, suggesting a potential association between gut-kidney axis.}, } @article {pmid41485185, year = {2026}, author = {Mao, C and Zhang, K and Tursunay, M and Ji, J and Li, X}, title = {Responses of gut microbial community and metabolic function to disposable face mask of Zophobas atratus larvae.}, journal = {Advanced biotechnology}, volume = {4}, number = {1}, pages = {1}, pmid = {41485185}, issn = {2948-2801}, support = {E5290504//the "First Action Plan for Attracting Talents" of the Chinese Academy of Sciences-Category B/ ; }, abstract = {With the prevalence of epidemics, disposable face masks have been used in large quantities and has caused global environmental pollution concern. The gut microbiome of Zophobas atratus larvae showed great potential for plastic degradation. In a preliminary study, the larval gut microbiome could degrade masks, which has not been previously reported. This study validated the ability of the gut microbiome to degrade masks. Functional microbiomes and metabolic pathways associated with the degradation of masks were also analyzed. Our findings confirmed that the larvae have high masks-degrading ability with a consumption of 60 ± 0.04 mg/d (dry mass by per 50 larvae), which is gut microbiome-dependent. At the genus level, Hafnia and Corynebaterium were highly abundant and contributed to masks degradation. The degrading metabolites were then identified, of which 46 were significantly upregulated. Steroid hormone biosynthesis and the cytochrome P450 pathway may be linked to DFM (PP) oxidation and degradation. Finally, Stenotrophomonas sp. strain M212 with a masks-degrading ability was screened from these functional microorganisms, further establishing the role of the gut microbiome.}, } @article {pmid41485141, year = {2026}, author = {Koch, TNM and Siu, KK and Falkinham, JO and Honda, JR}, title = {Methods to reduce environmental nontuberculous mycobacteria exposure: revisiting the recent literature.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/1040841X.2025.2610213}, pmid = {41485141}, issn = {1549-7828}, abstract = {The incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease (LD) cases are rising, with diagnosis and treatment proving difficult. With the preponderance of viable NTM in both natural and engineered environments, the understood route of human infection is through environmental exposures. In an effort to decrease the occurrence of NTM LD, methods to reduce environmental NTM exposures are of great interest to people with infection and the clinical community. In 2013, coauthor Falkinham summarized methods known at the time to reduce exposure to LD-causing Mycobacterium avium. The objective of this current review was to perform an updated PubMed, Web of Science, and Google Scholar literature search spanning 2014-2025 for newly reported methods and newer studies that expand on known mitigation strategies. In total, 31 articles were found. Among these new reports that posed new or improved methods to reduce environmental NTM exposure, risk assessment remains limited underscoring the need for more research in this area. We propose a feasible solution may be to revisit the "healthy home" concept and to consider the engineered environmental microbiome interactions when designing future homes.}, } @article {pmid41484966, year = {2026}, author = {Fu, R and Liang, XJ and Yang, WM and Li, R and Shi, YR and Guo, L and Yu, H and Chen, YH and Wang, HN}, title = {Gut microbial signatures in schizophrenia: exploring archaea, fungi, and bacteria.}, journal = {BMC psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12888-025-07721-3}, pmid = {41484966}, issn = {1471-244X}, support = {LHJJ24YF06//Interdisciplinary Integration Project of Xijing hospital/ ; 82201679//National Natural Science Foundation of China/ ; 82330043//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Gut microbial, mainly bacterial dysbiosis, has been demonstrated in patients with schizophrenia (SCH). However, the signatures and differences of minority gut microbiota in SCH, such as archaea and fungi, have been poorly addressed.

METHODS: We obtained stool samples from 61 SCH patients and 69 healthy controls (HC), and analyzed the compositional and functional alterations of gut archaea, fungi, and bacteria using metagenomic shotgun sequencing (MSS). Additionally, we developed potential biomarkers to distinguish SCH from HC.

RESULTS: SCH patients showed significantly lower archaeal α-diversity compared with that of HC. Whereas there were significant differences between SCH and HC in β-diversity at the species level of archaea, fungi and bacteria. Meanwhile, the functional differences between the two groups were concentrated in glucose, lipid and amino acid metabolic pathways. Furthermore, we established potential diagnostic archaeal (9 species, AUC = 0.73), fungal (8 species, AUC = 0.69), and bacterial (22 species, AUC = 0.74) microbiomes for differentiating SCH patients from HC.

CONCLUSIONS: This study describes a more comprehensive understanding of abnormal gut microbiome in SCH and might provide candidate targets for the development of a microbe-based diagnosis for SCH.

TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000032118, registration date: 2020/04/20.}, } @article {pmid41484954, year = {2026}, author = {Martins, P and Cartaxana, P and Cruz, S}, title = {Microbiome characterization of the sea slugs Elysia viridis and Placida dendritica: insights into potential roles in kleptoplasty.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04573-5}, pmid = {41484954}, issn = {1471-2180}, support = {949880/ERC_/European Research Council/International ; 949880/ERC_/European Research Council/International ; CEECIND/01434/2018//Fundação para a Ciência e a Tecnologia/ ; 2020.03278.CEECIND//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {BACKGROUND: Kleptoplasty is the process by which functional chloroplasts from algae food sources are sequestered and retained by a host organism. Some sacoglossan sea slugs display this ability, enabling them to survive extended periods of food shortage, as they can obtain organic compounds from photosynthesis. While research has focused on the mechanisms underlying chloroplast retention and functionality, the contribution of the microbiome to kleptoplasty in these photosynthetic sea slugs is largely unexplored. In this study, we assessed the bacterial communities of Elysia viridis and Placida dendritica, two photosynthetic sacoglossan species that share the same habitat and macroalga food source, but exhibit distinct abilities to retain chloroplasts.

RESULTS: High-throughput 16S rRNA gene sequencing revealed highly significant differences in bacterial community composition between E. viridis and P. dendritica. The sea slug E. viridis hosted a smaller and more specialized bacterial community, while P. dendritica supported a larger, more diverse, and generalist microbiome. Bacteroidota and Actinomycetota were the most dominant phyla in E. viridis (~ 92% of the total sequence reads), while Pseudomonadota (former Proteobacteria) was the prevalent phylum in P. dendritica (~ 66% of the total sequence reads). The dominance analysis revealed that one particularly dominant ZOTU, comprising 224,282 sequence reads (32.5% of total), was found exclusively in E. viridis that exhibits long-term retention of functional chloroplasts. According to BLAST search results, this ZOTU was related to the genus Fulvibacter (Flavobacteriaceae family), known for producing carotenoid-type pigments. These bacteria were not present in the microbiome of P. dendritica that shows short-term, non-functional, chloroplast retention.

CONCLUSION: This study provides novel insights into the microbial communities associated with photosynthetic sea slugs, highlighting significant differences in bacterial composition between E. viridis and P. dendritica. The identification of carotenoid-producing bacteria in E. viridis suggests a possible role in oxidative stress mitigation, and opens new perspectives on the relevance of the microbiome in supporting kleptoplasty. Further research is needed to characterize the functional contributions of bacterial taxa to chloroplast acquisition and maintenance in photosynthetic sea slugs.}, } @article {pmid41484934, year = {2026}, author = {Gouka, L and Serra I Melendez, C and Vardazaryan, N and Nor Nielsen, K and Riber, L and Hestbjerg Hansen, L and Raaijmakers, JM and Seidl, MF and Melkonian, C and Cordovez, V}, title = {Genomic insights into adaptative traits of phyllosphere yeasts.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-025-00839-7}, pmid = {41484934}, issn = {2524-6372}, support = {Grant NNF19SA0059348//Novo Nordisk Fonden/ ; Grant OCENW.XS23.3.113//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; Grant NWO/OCW 024.004.014//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; 24AA-IF0651//higher education and science committee MESCS RA PhD Support Program/ ; }, abstract = {BACKGROUND: Yeasts are ubiquitous microorganisms thriving in diverse environments. They are prevalent members of the phyllosphere microbiome, but genomic studies of plant-associated yeasts remain limited.

RESULTS: We established a taxonomically diverse yeast culture collection from flag leaves of field-grown wheat. This collection captured between 48-56% of the genus-level diversity detected by ITS amplicon sequencing conducted over two consecutive years, including the core members Aureobasidium, Dioszegia, Filobasidium, Papiliotrema, Sporobolomyces, and Vishniacozyma. De novo sequencing of 96 high-quality genomes from this collection, representing 14 yeast genera, and comparative genomics revealed specific signatures associated with life in the phyllosphere, the aboveground part of the plant. These adaptive traits encompass enriched carbohydrate metabolism, secondary metabolite biosynthetic pathways, and pectin degradation. The substantially smaller genomes of the phyllosphere yeast genera Candida and Metschnikowia suggest niche specialization via prioritizing metabolic pathways that are essential for survival in the nutrient-limited phyllosphere.

CONCLUSIONS: This study represents a significant advancement in our understanding of the diverse and largely unknown genomic traits of environmental yeasts and their adaptation to life in the phyllosphere environment. Our findings highlight their untapped functional potential for biotechnological applications in sustainable crop production.}, } @article {pmid41484864, year = {2026}, author = {Kwak, EJ and Song, H and Baek, YS and Kum, KY and Kim, JM}, title = {Oral microbiome-based evaluation of periodontal treatment responses in individuals with special health care needs: a longitudinal study.}, journal = {BMC oral health}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12903-025-07587-7}, pmid = {41484864}, issn = {1472-6831}, support = {08-2022-0019//Seoul National University Dental Hospital/ ; }, } @article {pmid41484626, year = {2026}, author = {Zhai, Z and Li, X and Shang, S and Ma, S and Liang, X and Yin, S and Wu, M and Yu, J and Song, Q and Chen, D}, title = {Intratumoral microbiota and metabolites: dual roles in cancer progression and therapeutic opportunities.}, journal = {Cell communication and signaling : CCS}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12964-025-02623-z}, pmid = {41484626}, issn = {1478-811X}, abstract = {Microorganisms play critical roles in tumor development, diagnosis, and treatment. In recent years, the newfound understanding of microorganisms in cancer tissues has sparked a renewed enthusiasm and research interest. The intratumoral microbes and metabolites have been discovered to interact with tumor cells to exert tumor-promoting or tumor-suppressing effects. Intratumoral microorganisms and their metabolites can alter tumor metabolism, activate key signaling pathways, regulate anti-tumor immunity, and affect tumor metastasis or recurrence. Additionally, intratumoral microbiota has emerged as promising predictive biomarkers for both diagnosis and prognosis of cancer patients. Intratumoral microorganisms and metabolites also have a substantial impact on tumor treatment by influencing therapeutic efficacies of immunotherapy, chemotherapy and radiotherapy. Intratumoral microbes can also serve as carriers to transport anti-tumor drugs, directly modulating intratumoral microecology and intervening in the carcinogenic pathway. However, the current research on the understanding of intratumoral microbiome and their metabolites is still limited and warrants more in-depth exploration. In this review, we extensively explore the structure and role of the intratumoral microbiota and metabolites in different cancer types, summarize the potential role in tumor diagnosis and prognosis, and provide recent advances of clinical implications for cancer treatment. (Source: Created with https://www.biorender.com/).}, } @article {pmid41484525, year = {2026}, author = {Papazoglou, AS and Stefanaki, AS and Linos, D}, title = {Gut Microbiome Care as a Gateway to Mental Well-being and Theological Restoration.}, journal = {Journal of religion and health}, volume = {}, number = {}, pages = {}, pmid = {41484525}, issn = {1573-6571}, abstract = {Recent research has highlighted the profound connection between the gut microbiome and overall human health, particularly its impact on mental well-being. The potential of "psychobiotic" interventions to foster resilience and emotional stability is especially promising. Methodologically, this article offers a philosophical-theological exploration that interprets current microbiome research in dialog with Christian theological sources, emphasizing how human-microbe symbiosis shapes both mental health and theological understandings of the human person. The intricate relationship between the microbiome, mental health, and brain function, in turn, affects spirituality and challenges anthropocentric notions of human identity. Certain anthropological and theological perspectives suggest that the gut microbiome can be viewed as a divine gift that enhances human flourishing through symbiosis. Within this framework, the human person appears as a holobiont-a composite of body, soul, and microbial life-created for communion with God and others. As steward and priest of creation, the human-holobiont is called to actively participate in the divine work of creation and redemption through relational communion with others, including fellow humans, the natural environment, and the microbiota. Integrating scientific insights with theological reflection, this article proposes that microbiome care contributes not only to mental well-being but also to spiritual restoration and ecological ethics. A non-egocentric eco-Christological ethic could thus honor microbiome care as integral to human personhood and divine relationship, fostering harmony between humanity, creation, and the divine.}, } @article {pmid41484454, year = {2026}, author = {Ibrahim, M and Khalil, AM and Attia, H and Alseekh, S and Mohamed, AF and El-Yamany, MF}, title = {Gut Microbiome-Sphingolipid Metabolism-Brain Axis Interactions: Neuroprotective Effects of Amitriptyline as Functional Inhibitor of Acid Sphingomyelinase in a Mouse Model of Tauopathy.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {21}, number = {1}, pages = {3}, pmid = {41484454}, issn = {1557-1904}, mesh = {Animals ; *Sphingomyelin Phosphodiesterase/antagonists & inhibitors/metabolism ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Amitriptyline/pharmacology/therapeutic use ; Mice, Transgenic ; *Tauopathies/metabolism/drug therapy ; *Brain/drug effects/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Sphingolipids/metabolism ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; }, abstract = {Tauopathies are neurodegenerative diseases characterized by accumulation of hyperphosphorylated tau protein (P-tau). The gut microbiota (GM) is symbiotic with the host and altered in neurodegenerative diseases. Amitriptyline (AMI) is a functional inhibitor of acid sphingomyelinase (ASM) which is abnormally highly expressed in brains of Alzheimer patients. Little data is known about the role of colonic ASM in management of tauopathy. Therefore, the aim of this study was to investigate the role of AMI on reversing gut dysbiosis, ceramide levels, colonic inflammation and intestinal barrier disruption in tauopathy through the bidirectional gut-brain axis. P301S transgenic mice were administered AMI for 35 days. Colonic ASM, ceramides, inflammation and membrane integrity were assessed besides fecal microbiome analysis and serum lipopolysaccharides to assess intestinal membrane disruption. Levels of hippocampal P-tau, protein phosphatase 2 A and neurogenesis were assessed along with cognitive behavior. AMI treatment significantly reduced colonic ASM, ceramide levels, increased abundance of Harryflintia, Dubosiella, and Parasutterella and decreased abundance of Lactobacillus, Lachnoclostridium, Oscillibacter, Oscillospiracea UCG-003, Colidextribacter, Roseburia, Butyricicoccus, and Sphingomondales. In contrast, P301S mice displayed an altered GM profile with enriched Firmicutes and Clostridia, and low proportions of Bacteroidota- a phylum associated with intestinal barrier protection-, and Ruminococcaceae. Also, AMI treatment decreased inflammation and restored colonic membrane integrity with subsequent decrease in serum lipopolysaccharides, P-tau in hippocampus and improvement in cognitive behaviour and neurogenesis. The current results indicate that AMI has neuroprotective effects against tauopathy through modulation of ASM activity, associated ceramide levels, GM composition, colonic inflammation and membrane integrity through bidirectional gut-brain axis.}, } @article {pmid41484402, year = {2026}, author = {González, R and Castelló-Sanjuán, M and Romoli, O and Blanc, H and Kobayashi, H and Nigg, J and Saleh, MC}, title = {Microbiome composition modulates the lethal outcome of Drosophila A virus infection.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00018-025-06042-8}, pmid = {41484402}, issn = {1420-9071}, support = {ANR-23-CE15-0038-01//Agence Nationale de la Recherche/ ; ANR-10-LABX-62-IBEID//Agence Nationale de la Recherche/ ; 101024099//H2020 Marie Skłodowska-Curie Actions/ ; }, abstract = {Host-associated microbiomes can strongly influence viral infection outcomes, yet how minor variations in commensal bacterial composition modulate viral pathogenesis remain poorly understood. Here, we used Drosophila melanogaster to investigate how bacterial microbiome composition affects pathogenesis of enteric RNA viruses. Lactiplantibacillus plantarum supplementation increased bacterial microbiome diversity without altering total bacterial load, while Acetobacter pomorum supplementation had minimal impact on the bacterial microbiome. L. plantarum-enriched flies exhibited an additional ~ 15% reduction in lifespan from Drosophila A virus (DAV) infection despite showing reduced viral protein accumulation and similar viral RNA levels. The reduction in tolerance to viral infection required live bacteria and was observed only for DAV, as no change in mortality was observed with Nora virus or Drosophila C virus infections. Mechanistic investigations revealed that tolerance reduction occurs independently of transcriptional immune responses, as DAV-infected flies showed similar transcriptional profiles regardless of bacterial microbiome composition. Intestinal barrier function assays demonstrated that a large number of L. plantarum-supplemented flies died before developing signs of gut barrier disruption, suggesting that extra-intestinal mechanisms contribute to mortality; this interpretation is further supported by similar levels of intestinal damage markers observed in virus-infected flies under both microbiome conditions. Viral genomic sequencing ruled out microbiome-driven selection of more pathogenic viral variants, as no adaptive mutations were observed between microbiome conditions that could account for the differential pathogenesis. These findings describe how subtle shifts in microbiome composition modulate viral infection outcomes through pathways that operate independently of canonical immune responses, viral evolution, and intestinal damage.}, } @article {pmid41484272, year = {2026}, author = {Liu, X and Zou, Y and Jin, C and Wang, Y and Zhang, J and Yan, M and Xie, Y and Ding, M and Wang, K and Liu, L and Ding, C and Chen, X}, title = {Viral infections are associated with apical periodontitis: A meta-analysis of prevalence, clinical symptoms, and lesion sizes across 31 clinical studies.}, journal = {Clinical oral investigations}, volume = {30}, number = {1}, pages = {37}, pmid = {41484272}, issn = {1436-3771}, support = {HB2023093//Top Talent Support Program for young and middle-aged people of Wuxi Health Committee/ ; A20210056//Health and Science Project of Hangzhou/ ; 2023WJC034//Hangzhou Biological Medicine and Health Industry Development Support Science and Technology Project/ ; 2021WJCY131//Hangzhou Biological Medicine and Health Industry Development Support Science and Technology Project/ ; 2024ZL724//Zhejiang Science and Technology Program of Chinese Medicine/ ; 20211231Y028//Guided Project of Science and Technology of Hangzhou/ ; }, mesh = {Humans ; *Periapical Periodontitis/virology/epidemiology/pathology ; Prevalence ; *Virus Diseases/complications/epidemiology ; }, abstract = {OBJECTIVE: Bacteria and viruses are components of the oral microbiome and are linked to various oral diseases. Clinical observations indicate a higher prevalence of apical periodontitis (AP) during viral epidemics. However, research on this association is limited. This meta-analysis aimed to explore the relationship between viral infections and AP.

METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified through systematic database searches, and data were extracted for eligible studies. Three validated quality assessment tools were used to ensure rigor. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to quantify the strength of the association.

RESULTS: Out of 427 screened records, 31 studies comprising 1,341,636 participants met the inclusion criteria. The meta-analysis revealed that the prevalence of AP was 2.78 times higher in patients with viral infections compared to controls (95% CI = 1.88-4.12, p < 0.001). Infected individuals demonstrated more severe clinical symptoms (OR = 3.49, 95% CI = 2.07-5.90, p < 0.001) and significantly larger periapical lesions (OR = 3.84, 95% CI = 1.08-13.67, p < 0.05).

CONCLUSIONS: The evidence suggests a significant association between viral infections and AP, particularly in cases of viral co-infections.

CLINICAL RELEVANCE: These findings suggest that evaluating viral infections, particularly herpesviruses, could inform the clinical management of AP. However, further research is required to establish causality.}, } @article {pmid41484074, year = {2026}, author = {de Molon, RS and Vernal, R and Oliveira, GE and Steffens, JP and Ervolino, E and Theodoro, LH and van den Beucken, JJJP and Tetradis, S}, title = {Inflammatory bone loss and signaling pathways in periodontitis: mechanistic insights and emerging therapeutic strategies.}, journal = {Bone research}, volume = {14}, number = {1}, pages = {1}, pmid = {41484074}, issn = {2095-4700}, mesh = {Humans ; *Periodontitis/pathology/metabolism/therapy/complications ; *Signal Transduction ; Animals ; *Inflammation/pathology ; Osteoclasts/pathology/metabolism ; *Bone Resorption/pathology/metabolism ; Osteogenesis ; }, abstract = {Bone resorption is a vital physiological process that enables skeletal remodeling, maintenance, and adaptation to mechanical forces throughout life. While tightly regulated under the physiological state, its dysregulation contributes to pathological conditions such as osteoporosis, rheumatoid arthritis, and periodontitis. Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome, leading to the progressive breakdown of the periodontal ligament, cementum, and alveolar bone and ultimately resulting in tooth loss. This review outlines the molecular and cellular mechanisms underlying periodontitis, focusing on osteoclastogenesis, the differentiation and activation of osteoclasts, the primary mediators of bone resorption. Key transcriptional regulators, including NFATc1, c-Fos, and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase (MAPK), Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), Nuclear Factor Kappa B (NF-κB), and Phosphoinositide 3-kinase (PI3K)/Akt, to elucidate their roles in the initiation and progression of periodontal bone loss. These pathways orchestrate the inflammatory response and osteoclast activity, underscoring their relevance in periodontitis and other osteolytic conditions. Hallmark features of periodontitis, including chronic inflammation, immune dysregulation, and tissue destruction are highlighted, with emphasis on current and emerging therapeutic strategies targeting these molecular pathways. Special attention is given to small molecules, biologics, and natural compounds that have the potential to modulate key signaling pathways. Although advances in understanding these mechanisms have identified promising therapeutic targets, translation into effective clinical interventions remains challenging. Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.}, } @article {pmid41484033, year = {2026}, author = {An, Y and E, P}, title = {Oral butyrate in IBD: From enterotype stratification to a multi-omic and long-term clinical dialogue.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2025.12.020}, pmid = {41484033}, issn = {1878-3562}, } @article {pmid41484024, year = {2025}, author = {Abuqwider, J and Pasolli, E and Scidà, G and Corrado, A and Vitale, M and De Filippis, F and Ercolini, D and Annuzzi, G and Rivellese, AA and Bozzetto, L}, title = {Gut microbiome profiles and associated functional pathways are linked to Mediterranean diet adherence and blood glucose control in adults with type 1 diabetes mellitus.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {}, number = {}, pages = {104487}, doi = {10.1016/j.numecd.2025.104487}, pmid = {41484024}, issn = {1590-3729}, abstract = {BACKGROUND AND AIMS: The Mediterranean diet (MD) has been associated with better glycaemic control in children with type 1 diabetes mellitus (T1DM) and favourable microbiome profiles in healthy individuals. However, it remains unclear whether MD adherence is associated with glycaemic control via microbiome. This study examined the relationships among MD adherence, gut microbiome, and glycaemic control in adults with T1DM and assessed the microbiome's ability to predict clinical and dietary outcomes.

METHODS AND RESULTS: In a cross-sectional study of 253 adults with T1DM, dietary intake was assessed using the EPIC food frequency questionnaire, and MD adherence was measured using the rMED score. Participants were stratified by adherence level (low, medium, high). Glycaemic control was evaluated using HbA1c and CGM metrics. Shotgun metagenomic sequencing of stool samples (n = 103) assessed the gut microbiome. Statistical analyses included ANOVA, PERMANOVA, LEfSe, and machine learning modeling. Higher MD adherence was associated with lower HbA1c levels (7.1 % vs 7.7 %; p < 0.001), greater time in range (67.0 % vs 59.4 %; p-trend = 0.03), and higher HDL cholesterol (1.62 vs 1.39 mmol/L; p = 0.01). High MD adherence was linked to a greater abundance of bacterial species such as Faecalibacterium prausnitzii. Both high MD adherence and lower HbA1c were associated with distinct microbiome functional pathways. Microbiome-based machine learning models predicted dietary patterns and clinical metrics.

CONCLUSIONS: In adults with T1DM, greater MD adherence is associated with better glycaemic control and a favourable gut microbiome. Specific microbial pathways may underlie these associations. Integrating diet and microbiome data supports personalized care. The study was registered at ClinicalTrials.gov with the identifier NCT05936242.}, } @article {pmid41483804, year = {2026}, author = {Psarrakis, C and Tziolos, NR and Matzarakis, V and Kumar, V and Stylianakis, E and Sidiropoulou, C and Tasouli, E and Iliopoulou, K and Samarkos, M and Metallidis, S and Georgiadou, S and Akinosoglou, K and Bolanou, A and Hatziagelaki, E and Kostaki, A and Panagopoulos, P and Toutouzas, K and Milionis, H and Adamis, G and Poulakou, G and Lada, M and Skoutelis, A and Alexiou, Z and Symbardi, S and Chrysos, G and Netea, MG and Giamarellos-Bourboulis, EJ}, title = {A randomized controlled trial of precision bezlotoxumab treatment for Clostridioides difficile infection.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102533}, doi = {10.1016/j.xcrm.2025.102533}, pmid = {41483804}, issn = {2666-3791}, abstract = {Early risk recognition for organ dysfunction and death by Clostridioides difficile infection (CDI) is an unmet need. A prediction score is developed in the BEYOND study (ClinicalTrials.gov; NCT02573571, NCT04725123, and NCT05304715). At the first stage, using 153 patients and 150 comparators, the BEYOND score was developed integrating hemoglobin; blood urea; blood interleukin-8; carriage of G alleles of rs2091172; and presence of Terrisporobacter glycolicus, Enterococcus avium, and Anaerovorax odorimutans in the stool. The score had 84.6% sensitivity and 95.8% specificity for unfavorable outcomes. At the second stage, a double-blind randomized controlled trial was performed, and 44 patients at high-risk by BEYOND score were treated with standard-of-care plus Bezlotoxumab or placebo. The primary endpoint was the incidence of organ dysfunction, CDI relapse, and/or death. This endpoint was met in 72.7% of patients in the placebo arm and 31.8% in the Bezlotoxumab arm (p = 0.015). Results suggest that BEYOND score can detect early risk in patients with CDI.}, } @article {pmid41483682, year = {2026}, author = {Viglino, J and Perea, L and Garcia-Nuñez, M and Rodrigo-Troyano, A and Torrego, A and Domínguez-Alvarez, M and Villar, J and Carrizosa, X and Quero, S and Gabaldon, T and Willis, JR and Saus, E and Gea, J and Santos, S and Camps, P and Agustí, A and Monso, E and Sibila, O and Faner, R}, title = {Characterisation of the gut-lung axis microbiome in clinically stable patients with chronic obstructive pulmonary disease.}, journal = {EBioMedicine}, volume = {123}, number = {}, pages = {106099}, doi = {10.1016/j.ebiom.2025.106099}, pmid = {41483682}, issn = {2352-3964}, abstract = {BACKGROUND: Airway and gut dysbiosis have been reported in Chronic Obstructive Pulmonary Disease (COPD); however, their relationship and association with clinical features remain poorly understood. We aimed to characterise the lung and gut microbiome in patients with stable COPD and controls.

METHODS: Prospective, multicentre, longitudinal and controlled study of n = 60 stable patients with COPD and n = 30 controls. In them, we analysed 16S rRNA-seq in oropharyngeal (OP) swabs, sputum, bronchoalveolar lavage fluid (BALF) and stool. Weighted gene co-expression network analysis (WGCNA) was employed in each sample type to identify modules of co-abundant bacteria associated with clinical traits.

FINDINGS: We found that the microbiome in airway and stool samples was highly dissimilar both in patients and controls, with 0.37% of this diversity associated to COPD. The microbiome taxa associated with COPD in OP swabs and sputum were highly similar, but different from BALF, suggesting that OP swabs can be a surrogate sample of sputum. Finally, using WGCNA, we identified: (a) 5 modules in OP swabs and 3 in sputum associated with FEV1, but some of them were also associated with exacerbations, dyspnoea and inhaled steroid (ICS) use; (b) In BALF 4 modules associated with FEV1 and dyspnoea, and 2 modules with ICS; and, finally, (c) in stool, 1 module related to FEV1, 1 to exacerbations and 3 with ICS.

INTERPRETATION: The gut and lung microbiomes in patients with COPD are distinct, but both clinically relevant as both present bacterial associations with airflow limitation, exacerbation history, and ICS use.

FUNDING: ISC-III PI24/00476. FRPA.2014, ICREA-2024.}, } @article {pmid41483516, year = {2025}, author = {Li, Z and Li, J and Shen, J and Zeng, Q and Lü, Y and Zheng, Y and Nie, H and Su, S}, title = {Tetracycline-induced alterations of gut microbiota and metabolism exacerbate imidacloprid susceptibility in honey bees (Apis mellifera).}, journal = {Journal of hazardous materials}, volume = {502}, number = {}, pages = {140996}, doi = {10.1016/j.jhazmat.2025.140996}, pmid = {41483516}, issn = {1873-3336}, abstract = {The honey bee (Apis mellifera) plays a vital role in global pollination, yet its health is increasingly threatened by multiple environmental stressors. Among these, the molecular interactions between gut microbiota disruption and pesticide exposure remains insufficiently understood. Here, we showed that tetracycline-induced gut microbiota dysbiosis significantly increased bee susceptibility to imidacloprid, leading to premature mortality. Microbiota-depleted bees also exhibited higher mortality under imidacloprid stress, confirming the protective role of a stable gut community. Taxonomic and functional analysis revealed pronounced shifts in bacterial composition, notably the reduction of Gilliamella and Bartonella and the enrichment of Lactobacillus and Commensalibacter, accompanied by broad perturbations in amino acid and carbohydrate metabolism in dysbiotic bees exposed to imidacloprid. Key metabolites with antioxidant and protective functions, including alanyl-glutamine, serotonin, and shikimic acid, were markedly reduced in the gut microbiota dysbiosis-imidacloprid group and correlated with changes in core bacterial taxa. Consistently, immune, detoxification, and nutritional genes were downregulated in bees with disturbed microbiota, indicating weakened antioxidant defense and metabolic capacity. Notably, dietary supplementation with alanyl-glutamine mitigated imidacloprid-induced mortality in honey bees, suggesting that restoring microbiota-derived metabolic functions could enhance host resilience towards imidacloprid toxicity. These findings provide direct evidence that gut microbiota integrity is critical for mitigating imidacloprid stress, and that disturbances in microbial balance heighten honey bee vulnerability to imidacloprid. This work underscores the ecological risk of combined antibiotic-pesticide exposure and emphasizes the microbiome's role as a key mediator of pollinator resilience.}, } @article {pmid41483182, year = {2026}, author = {Caviedes-Triana, K and Vivero-Gómez, R and Duque-Granda, D and Junca, H and Cadavid-Restrepo, G and Moreno-Herrera, CX}, title = {Structure and Diversity of the Microbiome in Amazonian Sand Flies: Insights into Vector-Microbe Interactions.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-025-02663-5}, pmid = {41483182}, issn = {1432-184X}, support = {Scholarship Program of Ministerio de Ciencia, Tecnología e Innovación, Call 15, for Human Capital Development in the context of the Bicentennial and the 2021-2022 Biennial Plan.//Ministerio de Ciencia, Tecnología e Innovación/ ; Hermes 57545//Universidad Nacional de Colombia/ ; }, abstract = {This study uses high-throughput sequencing of the 16 S rRNA gene and specific PCR to analyze the microbiome and identify secondary endosymbionts in sand flies from the Amazon region, important vectors of parasitic and viral diseases. Specimens of Psychodopygus, Trichophoromyia, Nyssomyia, Trichopygomyia and Brumptomyia were collected and analyzed. The results revealed that the richness, diversity, and composition of the microbiome are influenced by several factors, such as insect species specific composition, and insect sex. The core microbiome community was represented by 18 genera, with Novosphingobium, Cutibacterium, Methylobacterium and Staphylococcus being the most prevalent. The highest diversity at the genus level was observed in sand flies of epidemiological relevance as Psychodopygus and Nyssomyia, dominated by Novosphingobium (66.5%), Cutibacterium (29.4%) and Methylobacterium (20.4%), while in non-vectors such as Trichophoromyia, Delftia predominated (59.9%). Endosymbiont analysis showed a high prevalence of Cardinium (20%) and Wolbachia (33%), as well as the presence of Spiroplasma, Arsenophonus and Rickettsia. In addition, some bacterial genera related to the inhibition of parasite development, which have entomopathogenic activity and are involved in the degradation of insecticides were identified. Our results are relevant and contribute to the knowledge of the characterization of the microbiome and the endosymbionts in leishmaniasis vectors in the Amazon region and show promise for improving vector management, highlighting the importance of investigating their interaction with pathogens and their impact on vector biology.}, } @article {pmid41482938, year = {2026}, author = {Jin, N and Chen, Y and Luo, H and Su, Y and Weng, Y and Lin, X and Zheng, T and Li, B and Liu, T and Chen, J}, title = {Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation.}, journal = {Drug delivery}, volume = {33}, number = {1}, pages = {2610532}, doi = {10.1080/10717544.2025.2610532}, pmid = {41482938}, issn = {1521-0464}, mesh = {Animals ; *Curcumin/administration & dosage/pharmacology/chemistry ; *Psoriasis/drug therapy/microbiology/therapy ; Mice ; *Microbiota/drug effects ; Disease Models, Animal ; Imiquimod ; *Skin/microbiology/drug effects ; *Aptamers, Nucleotide/administration & dosage/chemistry ; Recurrence ; Mice, Inbred BALB C ; Silicon Dioxide/chemistry ; Interleukin-17/metabolism ; Male ; Female ; Blue Light ; }, abstract = {The recurrence following the discontinuation of medication is a formidable challenge in managing psoriasis. Changes in the microbiome accompany the onset of psoriasis relapse, highlighting a potential therapeutic modality. To evaluate the superiority of the topical administration of aptamer-functionalized curcumin mesoporous silica (Apt-GA+Cur@μmS) plus blue light (BL) in restoring dysbiosis and intervening in recurrence in a murine model, a psoriasis relapse murine model with double imiquimod induction was established. With a BL-responsive shell, Apt-GA+Cur@μmS released curcumin (Cur) to assist BL to improve the preventative and therapeutic effects in the psoriasis relapse murine model, as evidenced by the psoriasis area and severity index, histology, splenic index, and dorsal IL-17A level. We also observed a negative correlation between splenic nitric oxide (NO) levels and the splenic index, indicating a possible mechanism by which Apt-GA+Cur@μmS&BL may function in the treatment of splenomegaly. Treatment with Apt-GA+Cur@μmS&BL exhibited a higher alpha diversity than the model group, with levels similar to those of healthy mice, indicating that this combination could adjust the composition of the dorsal microbiome to a healthier state. A reduction in the combined relative abundance of Staphylococcus, Streptococcus, and Corynebacterium as well as restoration of dysbiosis was also verified through 16S rDNA gene sequencing in vivo. Collectively, BL and Apt-GA+Cur@μmS cotherapy alleviates psoriasiform lesions in a double imiquimod-induced murine model by inhibiting IL-17A and increasing splenic NO. Additionally, this cotherapy restores the eubiosis of the dorsal lesions. Thus, it is a promising and innovative therapeutic modality for psoriasis inflammation alleviation and recurrence intervention.}, } @article {pmid41482665, year = {2026}, author = {Trischler, R and Müller, V}, title = {Formate as electron carrier in the gut acetogen Blautia luti: a model for electron transfer in the gut microbiome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609406}, doi = {10.1080/19490976.2025.2609406}, pmid = {41482665}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; *Formates/metabolism ; Humans ; Electron Transport ; *Clostridiales/metabolism/genetics ; Fermentation ; Formate Dehydrogenases/metabolism/genetics ; Acetates/metabolism ; Succinic Acid/metabolism ; Glucose/metabolism ; Bacterial Proteins/metabolism/genetics ; }, abstract = {Species of the genus Blautia are commonly found in the human gut and are known to be beneficial for the human well-being. However, only little is known about the physiology and the specific role of Blautia species in the human gut. In this study, we investigated the heterotrophic metabolism of the formate dehydrogenase lacking gut acetogen Blautia luti. We identified acetate, succinate, lactate, formate, and hydrogen as end products of sugar fermentation. Interestingly, formate is produced by the pyruvate-formate lyase reaction and used as electron acceptor in the Wood-Ljungdahl pathway of CO2 fixation. Thus, formate connects the oxidative branch of glucose metabolism with the reductive branch. The use of formate as an intraspecies electron carrier seems to be common in gut acetogens. This study highlights the role of formate as electron carrier in the gut microbiome and improves our understanding of the physiology of Blautia species in the human gut. It also introduces B. luti as potential candidate for biotechnological applications due to the production of highly desired succinate.}, } @article {pmid41482646, year = {2026}, author = {Levine, J and Thomas, SC and Xu, F and Isbiroglu, A and Zanganeh, R and Barazani, L and Vardhan, M and Hwang, S and Persaud, JK and Thakor, N and Joseph, S and Trasande, L and Saxena, D}, title = {Microbial signature of pediatric Crohn's disease: Differentiation from functional gastrointestinal disorders and relationship with increased disease activity.}, journal = {Physiological reports}, volume = {14}, number = {1}, pages = {e70665}, pmid = {41482646}, issn = {2051-817X}, support = {1911-03329//Leona M. and Harry B. Helmsley Charitable Trust (Helmsley)/ ; }, mesh = {Humans ; *Crohn Disease/microbiology/diagnosis ; Male ; Female ; Child ; *Gastrointestinal Microbiome ; Feces/microbiology ; Adolescent ; Bacteria/classification/genetics ; *Gastrointestinal Diseases/microbiology/diagnosis ; }, abstract = {The prevalence and incidence of Crohn's disease (CD) in pediatric populations have been steadily increasing. Growing evidence suggests that gut microbiomal community differences play a critical role in the pathogenesis of CD. Additionally, the clinical course of patients with CD is unpredictable, making treatment decisions challenging. We investigated the fecal microbiome of newly diagnosed, treatment-naïve pediatric CD patients (n = 43) compared to age- and sex-matched controls with other functional gastrointestinal disorders (n = 139). We also correlated microbial changes with CD disease activity, measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Our results showed that microbial richness and diversity were significantly lower in CD patients. Furthermore, taxonomic analysis revealed an enrichment in pro-inflammatory bacteria (Fusobacteria and Proteobacteria) and depletion in favorable bacteria (Firmicutes and Verrucomicrobia). Higher PCDAI scores were linked to the enrichment of genera harboring pro-inflammatory taxa (Hungatella and Veillonella) and decreased abundance of genera harboring protective taxa (Lachnospiraceae). Our study underscores the potential of fecal microbiome profiling as an effective tool for understanding CD pathogenesis, identifying microbial biomarkers, and predicting disease activity for treatment response. This, in turn, can help to improve personalized treatment and management strategies in pediatric CD.}, } @article {pmid41482560, year = {2026}, author = {Chakaroun, RM and Pradhan, M and Björnson, E and Arvidsson, D and Fridolfsson, J and Gummesson, A and Schoeler, M and Mitteregger, M and Smith, GJ and Larsson, I and Börjesson, M and Blüher, M and Uhlén, M and Stumvoll, M and Bergström, G and Tremaroli, V and Bäckhed, F}, title = {Multi-omic definition of metabolic obesity through adipose tissue-microbiome interactions.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41482560}, issn = {1546-170X}, support = {2017.0026//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2017.0026//Diabetesfonden (Stiftelsen Svenska Diabetesförbundets Forskningsfond)/ ; 20210366//Hjärt-Lungfonden (Swedish Heart-Lung Foundation)/ ; 20240882//Hjärt-Lungfonden (Swedish Heart-Lung Foundation)/ ; NNF15OC0016798//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF21OC0070298//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF24OC0092455//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 17CVD01//Fondation Leducq/ ; ERC-2022-ADG 101096705//Fondation Leducq/ ; 2019-01599//Vetenskapsrådet (Swedish Research Council)/ ; EXC3105/1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; EXC3105/1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Obesity's metabolic heterogeneity is not fully captured by body mass index (BMI). Here we show that deep multi-omics phenotyping of 1,408 individuals defines a metabolome-informed obesity metric (metBMI) that captures adipose tissue-related dysfunction across organ systems. In an external cohort (n = 466), metBMI explained 52% of BMI variance and more accurately reflected adiposity than other omics models. Individuals with higher-than-expected metBMI had 2-5-fold higher odds of fatty liver disease, diabetes, severe visceral fat accumulation and attenuation, insulin resistance, hyperinsulinemia and inflammation and, in bariatric surgery (n = 75), achieved 30% less weight loss. This obesogenic signature aligned with reduced microbiome richness, altered ecology and functional potential. A 66-metabolite panel retained 38.6% explanatory power, with 90% covarying with the microbiome. Mediation analysis revealed a bidirectional, metabolite-centered host-microbiome axis, mediated by lipids, amino acids and diet-derived metabolites. These findings define an adipose-linked, microbiome-connected metabolic signature that outperforms BMI in stratifying cardiometabolic risk and guiding precision interventions.}, } @article {pmid41482527, year = {2026}, author = {Riaz, N and Alban, TJ and Haddad, RI and Saul, M and Makarov, V and Zhu, Y and Cohen, EEW and Ferris, RL and Chang, PM and Lin, JC and Psyrri, A and Parthasarathy, PB and Novaj, A and Gawali, M and Hoen, D and Hamilton, P and Silver, NL and Juric, I and Chawla, D and Gradissimo, A and Ko, J and McGrail, DJ and Davis, CB and Lee, NY and Chan, TA}, title = {Tumor ecosystem and microbiome features associated with efficacy and resistance to avelumab plus chemoradiotherapy in head and neck cancer.}, journal = {Nature cancer}, volume = {}, number = {}, pages = {}, pmid = {41482527}, issn = {2662-1347}, abstract = {Immune checkpoint blockade-based multimodal therapy is widely used across oncology; yet drivers of resistance in most cancer types are not well understood. Here, we comprehensively characterized the tumor genome, microenvironment and microbiome in a phase 3 international randomized trial (NCT02952586) to identify factors that shape outcomes to anti-PD-L1 avelumab plus standard-of-care chemoradiotherapy versus placebo/chemoradiotherapy in individuals with locally advanced head and neck cancer. Patients receiving avelumab whose tumors contained distinct immunologic and genetic features had superior outcomes compared to those receiving placebo. By contrast, patients with increased myeloid/neutrophil activities had worse outcomes with avelumab than those treated with placebo. Strikingly, these tumors possessed telltale intratumoral bacteria, elevated tumor-associated neutrophils, high systemic neutrophil-to-lymphocyte ratios and suppressed adaptive immunity. We define tumor ecosystems associated with benefit to chemoimmunotherapy. Our data demonstrate how intratumoral bacteria affect immune checkpoint blockade response within a randomized trial. These discoveries enhance our understanding of combination immunotherapy, provide a useful multiomic resource and identify unanticipated interactions that may guide future therapeutic strategies.}, } @article {pmid41482480, year = {2026}, author = {McKenzie, J and Carter, C and Jackson, MM and Singanayagam, A and Shah, A}, title = {Mechanisms driving immunopathogenesis of viral exacerbations in chronic respiratory disease.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thorax-2024-222169}, pmid = {41482480}, issn = {1468-3296}, abstract = {BACKGROUND: Exacerbations are major causes of morbidity in individuals with chronic respiratory diseases such as chronic obstructive pulmonary disease, asthma and bronchiectasis. Increasing evidence implicates respiratory viruses as predominant triggers, though the underlying immunopathogenic mechanisms remain poorly understood.

NARRATIVE: This review synthesises current knowledge on the interplay between viral pathogens at the airway epithelial barrier, including structural and immunological mechanisms that may dysregulate antiviral immunity in chronic respiratory diseases. Furthermore, we discuss how perturbations in the respiratory microbiome, characterised by reduced microbial diversity, can modulate host antiviral immune defences.

CONCLUSIONS: Collectively, these interconnected factors create a permissive environment predisposing to viral infection and exacerbations in chronic respiratory diseases. Understanding the complex interactions between airway structure, interferon-mediated antiviral responses, inflammation and microbiota is essential for developing targeted therapies to effectively manage virus-induced exacerbations and reduce disease burden.}, } @article {pmid41482458, year = {2026}, author = {Zhou, CB and Zhao, LC and Qin, Y and Yu, J and Li, W and Feng, Q and Tong, X and Abuduaini, R and Lu, SY and Tang, H and Zhang, YX and Cui, Y and Xiao, L and Song, LH and Ni, LK and Wu, K and Zhong, H and Jiang, YC and Zou, Y and Leng, XX and Wang, M and Zhao, WY and Wang, CJ and Liu, Q and Zhang, JQ and Hu, C and Chen, YX and Yao, YF and Zhu, S and Fang, JY}, title = {Streptococcus anginosus-derived methionine promotes gastric cancer progression.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336966}, pmid = {41482458}, issn = {1468-3288}, abstract = {BACKGROUND: Streptococcus anginosus has been linked with an increasing risk of gastric cancer (GC) and recognised as a signature for GC screening.

OBJECTIVE: To investigate the promotional effect of S. anginosus in terms of its metabolic interactions with the host.

DESIGN: We used the functional profiles of shotgun metagenomic sequencing from stools to detect bioactive molecules relevant to S. anginosus. In vivo and in vitro experiments were used to validate the facilitation of S. anginosus to GC progression. S. anginosus clinical strains were isolated and cultivated from cancerous tissues to verify its promotion of GC via methionine production. S. anginosus ΔmetE mutant strains were constructed to confirm the critical role of metE in methionine biosynthesis.

RESULTS: We verified S. anginosus facilitated GC progression in vivo and in vitro. Our functional analysis of metagenomes revealed a significant enrichment of bacterial methionine biosynthesis pathways in GC patients with high S. anginosus abundance. Methionine, identified here as one of the primary microbial metabolites derived from S. anginosus, contributed to GC progression in humans and mice. S. anginosus strains from cancerous tissues were found to promote GC via methionine production. We further observed a higher abundance and prevalence of metE gene in cancer stool metagenomes. By constructing an S. anginosus ΔmetE mutant strain, we confirmed the critical role of metE in methionine biosynthesis.

CONCLUSION: Our results elucidate the role of S. anginosus-derived methionine in GC progression, shedding light on intricate metabolic interplay between S. anginosus and host.}, } @article {pmid41482415, year = {2026}, author = {Tomuța, RA and Gîtea, MF and Ghitea, MC and Ghitea, EC and Ghitea, TC and Banica, F}, title = {Nutritional Assessment of Pesticide-associated Metabolic Stress in Plant-based Diets.}, journal = {In vivo (Athens, Greece)}, volume = {40}, number = {1}, pages = {136-150}, pmid = {41482415}, issn = {1791-7549}, mesh = {Humans ; Oxidative Stress/drug effects ; Male ; Female ; *Pesticides/adverse effects/toxicity ; Biomarkers ; Adult ; *Nutrition Assessment ; Middle Aged ; Metabolomics/methods ; *Stress, Physiological/drug effects ; Fruit/chemistry ; Vegetables/chemistry ; Diet, Plant-Based ; }, abstract = {BACKGROUND/AIM: Chronic low-dose pesticide exposure through high fruit and vegetable consumption is an underappreciated risk factor for metabolic dysfunction. While plant-based diets provide antioxidants and polyphenols, co-exposure to pesticide residues and heavy metals may induce subtle but clinically relevant biochemical disruptions.

MATERIALS AND METHODS: We analyzed the detailed metabolomic organic acid profiles from 26 individuals reporting high intake of conventionally grown fruits and vegetables. Dietary modeling was performed to estimate daily polyphenol intake, while metabolomic data were evaluated for markers of detoxification stress, oxidative damage, mitochondrial function, gut dysbiosis, and heavy metal burden.

RESULTS: Both profiles revealed reproducible patterns of metabolic disturbance, including elevated methylmalonic acid, formiminoglutamic acid, and xanthurenic acid (suggestive of methylation and B-vitamin deficits); increased lipid peroxides and 8-OHdG (indicative of systemic oxidative stress); raised Krebs cycle intermediates and β-hydroxybutyrate (suggesting mitochondrial dysfunction); mild to moderate dysbiosis markers and evidence of fungal overgrowth; and elevated mercury levels exceeding reference thresholds. Despite estimated high polyphenol intake (2.5-3.5 g/day), antioxidant biomarkers remained elevated, supporting the hypothesis of pesticide-induced oxidative burden.

CONCLUSION: These findings suggest that chronic dietary pesticide exposure - even at regulatory-compliant levels - may produce a consistent metabolomic signature, particularly when at least five different pesticide, herbicide, or fungicide residues are simultaneously detected, highlighting the potential for cumulative biological effects characterized by oxidative stress, detoxification pathway strain, gut microbiome disruption, and mitochondrial impairment. This underscores the need for integrated dietary strategies to reduce contaminant intake and highlights the importance of further cohort studies to clarify health impacts and guide nutritional interventions.}, } @article {pmid41482260, year = {2025}, author = {Ticinesi, A and Zuliani, G and Spaggiari, R and Volpato, S and Maggi, S and Franceschi, C}, title = {The social microbiome of older people.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {103008}, doi = {10.1016/j.arr.2025.103008}, pmid = {41482260}, issn = {1872-9649}, abstract = {The human gut microbiome (GM) is increasingly recognized as one of the main systems influencing the aging trajectory. Age-related dysbiosis, with imbalance between symbionts and pathobionts, can in fact fuel chronic inflammation (inflammaging) and promote frailty. In older individuals, GM composition is characterized by marked inter-individual variability and consistently influenced by environmental exposures. Studies conducted in animals and closed human communities suggest that social contacts are associated with horizontal transmission of commensal bacteria, enhancing biodiversity and preventing dysbiosis. Recent studies also suggest transmission of intestinal commensal bacteria from animals to humans sharing the same household. Bacterial populations residing on environmental surfaces may also have an influence on GM composition. In this framework, impoverishment of social relationships in older individuals may not be only associated with cognitive and emotional disengagement, but also with unfavorable changes in GM composition, driven by isolation and top-down neuromodulation of intestinal function. In fact, studies conducted during forced social distancing in the COVID-19 pandemic show GM changes pointing towards dysbiosis. Therefore, the detrimental consequences of social isolation for health outcomes of older individuals, including frailty progression towards disability, could be at least partly mediated by GM dysbiosis. Conversely, interventions aimed at restoring sociality, including animal-assisted activities, could expose older individuals to a range of novel bacterial species helping to counteract GM dysbiosis. This perspective article critically discusses the concept of social microbiome, its possible relevance for maintenance of good health in human beings, and its implications for the care of older patients.}, } @article {pmid41482235, year = {2025}, author = {Chambial, P and Thakur, N and Kumar, U and Gupta, S}, title = {The Mediating Role of the Gut Microbiome in the Nutritional Prevention of Cancer.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101301}, doi = {10.1016/j.tjnut.2025.101301}, pmid = {41482235}, issn = {1541-6100}, abstract = {The concept of food as medicine is gaining renewed importance in oncology, with growing recognition that diet is not only supportive care but a mechanistically informed intervention for cancer treatment. However, the biological basis linking nutrition to cancer outcomes has remained incomplete until recent advances positioned the gut microbiome as the missing link. Recent research has highlighted the gut microbiome as a key mediator, acting as a biochemical and immunological bridge that transforms dietary compounds into metabolites, influencing inflammation, immune function, and carcinogenesis. This perspective shifts nutrition from a supportive measure to an active, evidence-based strategy in cancer prevention. In this review, we highlight how specific foods, nutrients, and microbial consortia contribute to anti-cancer effects, while also identifying research gaps related to causality, multi-omics integration, and the need to account for global dietary and genetic diversity.}, } @article {pmid41482230, year = {2025}, author = {Goand, UK and Paudel, D and Koehle, AM and Hao, F and Nguyen, LV and Yalavarthi, G and Tian, S and Rajakaruna, S and Robert, CEM and da Silva, IV and Chassaing, B and Patterson, AD and Castro, R and Singh, V}, title = {Invited: Longitudinal assessment of diets with varying carbohydrate-to-fat ratios and fiber supplementation on immunometabolic markers, liver function, and gut microbiome.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101285}, doi = {10.1016/j.tjnut.2025.101285}, pmid = {41482230}, issn = {1541-6100}, abstract = {The proportions of macronutrients and fiber in the diet influence host metabolism and the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear how early shifts in immune, metabolic and liver function markers occur upon consuming diets with markedly different proportions of carbohydrates and fats such as the ketogenic diet (KD) and the high-carbohydrate diet (HCD) and whether these diets exert differential effects on these markers under lean and obese conditions. Moreover, the potential for prebiotic fiber supplementation to alter or mitigate the metabolic consequences of the KD has not been established. To address these questions, we conducted longitudinal assessments at 2-, 4-, 8-, and 16-weeks post-intervention in lean C57BL/6 mice, which revealed that diets rich in fat (high fat (HFD) and KD) induced obesity and hyperglycemia compared to the baseline chow diet. KD resulted in nutritional ketosis as early as two-weeks post-feeding; however, it impaired metabolic and liver function starting from week 2. Following the 16-week intervention, we observed that the fat-rich diets (HFD & KD), but not the HCD, promoted hepatic steatosis, inflammation, and fibrosis, as assessed by [1]H-NMR, quantitative PCR, and histology, respectively. Next, we found that incorporating inulin into the KD (KD-F) partly mitigated the adverse immunometabolic effects of the KD. In the HFD-induced obesity cohort, intervention with HCD and KD-F improved immunometabolic and liver function markers. The HCD showed the most pronounced benefits as early as two weeks following the diet switch. Microbiome analysis revealed reduced bacterial richness across all experimental diets (HCD, KD, and KD-F) compared to standard chow. Collectively, the present study highlights that high fat intake, but not high-carbohydrate consumption negatively impacts metabolic and liver health in lean mice. The incorporation of dietary fiber into a KD may enhance its metabolic effects while preserving the therapeutic benefits of ketogenesis.}, } @article {pmid41481471, year = {2026}, author = {Regan, MD and Chiang, E and Grahn, M and Tonelli, M and Assadi-Porter, FM and Suen, G and Carey, HV}, title = {Host-microbiome mutualism drives urea carbon salvage and acetogenesis during hibernation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {1}, pages = {e2518978123}, doi = {10.1073/pnas.2518978123}, pmid = {41481471}, issn = {1091-6490}, support = {IOS-1558044//NSF (NSF)/ ; P41GM136463//HHS | NIH (NIH)/ ; DGE-1747503//NSF | NSF Graduate Research Fellowship Program (GRFP)/ ; RGPIN-2021-03109//Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; 21HLSRM06//Canadian Space Agency (CSA)/ ; }, mesh = {Animals ; *Hibernation/physiology ; *Urea/metabolism ; *Sciuridae/microbiology/physiology/metabolism ; *Carbon/metabolism ; *Acetates/metabolism ; *Gastrointestinal Microbiome/physiology ; *Symbiosis/physiology ; Acetic Acid/metabolism ; Fatty Acids, Volatile/metabolism ; *Host Microbial Interactions/physiology ; }, abstract = {Hibernation is a seasonal survival strategy employed by certain mammals that, through torpor use, reduces overall energy expenditure and permits long-term fasting. Although fasting solves the challenge of winter food scarcity, it also removes dietary carbon, a critical biomolecular building block. Here, we demonstrate a process of urea carbon salvage (UCS) in hibernating 13-lined ground squirrels, whereby urea carbon is reclaimed through gut microbial ureolysis and used in reductive acetogenesis to produce acetate, a short-chain fatty acid (SCFA) of major value to the host and its gut microbiota. We find that urea carbon incorporation into acetate is more efficient during hibernation than the summer active season and that while both host and gut microbes oxidize acetate for energy supply throughout the year, the host's ability to absorb and oxidize acetate is highest during hibernation. Metagenomic analysis of the gut microbiome indicates that genes involved in the degradation of gut mucins, an abundant endogenous nutrient, are retained during hibernation. The hydrogen disposal associated with reductive acetogenesis from urea carbon helps facilitate this mucin degradation by providing a luminal environment that sustains fermentation, thereby generating SCFAs and other metabolites usable by both the host and its gut microbes. Our findings introduce UCS as a mechanism that enables hibernating squirrels and their gut microbes to exploit two key endogenous nutrient sources-urea and mucins-in the resource-limited hibernation season.}, } @article {pmid41481427, year = {2026}, author = {Wang, J and Zi, F and Liu, W and Liu, C and Zhang, Z and Kong, L and Xu, X and Wei, J and Chen, T and Li, J}, title = {Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609455}, doi = {10.1080/19490976.2025.2609455}, pmid = {41481427}, issn = {1949-0984}, mesh = {*Clostridium butyricum/physiology/metabolism ; Animals ; *Multiple Myeloma/microbiology/therapy/metabolism/pathology ; Humans ; *Gastrointestinal Microbiome/physiology ; Mice ; Phosphatidylinositol 3-Kinases/metabolism/genetics ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Bone Marrow/metabolism/pathology ; Signal Transduction ; Tumor Microenvironment ; Dysbiosis/microbiology ; Female ; Th17 Cells/immunology ; }, abstract = {Emerging evidence reveals a strong connection between the gut microbiota and cancer. However, the exact role of gut microbiota dysbiosis in multiple myeloma (MM) is poorly understood, and the therapeutic potential of microbiota-targeted interventions represents a promising strategy that demands urgent mechanistic and translational investigation. First, we conducted a comprehensive microbiome-metabolite analysis between MM patients and healthy individuals. The result revealed a marked compositional difference characterized by reduced abundances of butyrate-producing bacteria and diminished butyrate levels in the MM cohort. Subsequent fecal microbiota transplantation demonstrated that the gut microbiota critically modulates MM progression, with healthy donor-derived microbiota reducing the tumor burden and concomitantly elevating serum butyrate. Furthermore, through function-based culturomics screening, Clostridium butyricum (C. butyricum) was identified as a key butyrate-producing specialist. C. butyricum or its metabolite butyrate significantly reduced the systemic tumor burden in 5TGM1 mice. Notably, C. butyricum and butyrate alleviated bone marrow inflammation and osteolytic lesions by suppressing Th17 cells and IL-17 levels in the bone marrow. Moreover, cellular assays and transcriptome sequencing further revealed that butyrate could induce MM cells' apoptosis via HDAC inhibition-mediated upregulation of PPARγ, leading to sequential suppression of the PI3K/AKT pathway and antiapoptotic BCL-2 expression. This apoptotic signaling cascade was reversed by PPARγ antagonism. The direct antitumor effect was further confirmed in M-NSG mice. Our research systematically verifies the specific role of the gut microbiota in MM and provides the first evidence of the immune and molecular mechanisms by which C. butyricum alleviates MM progression, offering preclinical support for probiotic-based therapies against MM.}, } @article {pmid41481332, year = {2026}, author = {Wall, H and Ivarsson, E and Sun, L and Boyner, M and Naghizadeh, M and Dalgaard, TS and Wattrang, E}, title = {Early access to feed, water and Neurospora intermedia in broiler starter diet (part II) - caecal microbiota, antibody production and blood leukocyte counts.}, journal = {British poultry science}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/00071668.2025.2595642}, pmid = {41481332}, issn = {1466-1799}, abstract = {1. This study examined the effects of providing feed and water immediately post hatch in combination with inclusion of Neurospora intermedia biomass in chick starter diet, as a source of protein and bioactive compounds. Variables monitored were caecal microbiota, total levels of IgY, specific antibody responses to vaccination and blood leukocyte counts.2. Ross 308 chicks were subjected to two hatching treatments - immediate access to feed and water, or delayed access at 48 h. In addition, three starter diets were fed until d 10: a control diet (C), a diet with inclusion of 10% N. intermedia (N) or diet N followed by diet C (NC).3. Chicks were vaccinated against avian pneumovirus (APV) and focal birds were repeatedly blood sampled for quantification of total IgY and antibodies specific to APV in serum. Birds fed starter diet C were sampled for measures of blood leukocyte counts. Caecal microbiota were studied in birds sacrificed on d 5, 9 and 43, respectively.4. With age, microbial richness in caeca increased and there was a shift in composition, but no effects of hatching treatment or starter diet were observed.5. Neither the starter diet nor the hatching treatment affected the total IgY in serum or specific antibody responses to APV vaccination. Late-fed chicks had a significant decrease in the total amount of IgY in serum from d 2 to d 8, likely a consequence of dehydration at d 2. Early feeding did not affect any of the leukocyte populations monitored.6. In conclusion, there were no effects of early feeding or inclusion of N. intermedia on gut microbiome or the immune traits monitored. However, the absence of adverse effects of a starter diet with the fungal biomass suggested that N. intermedia is a source of high-quality protein.}, } @article {pmid41481156, year = {2026}, author = {Jones, EV and Wang, Y and Wei, W and Reed, JC and Chaudhari, SN and Li, DK and Boursier, J and Lang, S and Demir, M and Diehl, AM and Allegretti, AS and Schnabl, B and Chung, RT and Devlin, AS}, title = {Bile salt hydrolase activity as a rational target for MASLD therapy.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2608437}, doi = {10.1080/19490976.2025.2608437}, pmid = {41481156}, issn = {1949-0984}, mesh = {Humans ; Bile Acids and Salts/metabolism ; *Amidohydrolases/metabolism/antagonists & inhibitors/genetics ; Feces/microbiology/chemistry ; Gastrointestinal Microbiome/drug effects ; *Bacteria/enzymology/isolation & purification/genetics/classification/drug effects ; Male ; Female ; Middle Aged ; Bacterial Proteins/metabolism/antagonists & inhibitors/genetics ; Enzyme Inhibitors/pharmacology ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease in the United States, yet therapeutic options remain limited. Emerging evidence implicates the gut‒liver axis and intestinal permeability in disease pathogenesis. Previous studies in animal models and human cell culture indicated that bile salt hydrolases (BSHs), which are gut bacterial enzymes that deconjugate host-derived bile acids, damage intestinal barrier integrity and cause liver damage through the generation of unconjugated bile acids (UBAs). However, the relevance of these findings to MASLD patients is unknown. Here, we demonstrate that BSH activity is elevated in fecal samples from MASLD patients with advanced liver fibrosis and correlates with reduced fecal bile acid levels, which is consistent with a proposed model of increased intestinal permeability during MASLD progression. Through anaerobic culturing and activity-guided screening, we identify diverse BSH-active bacteria from patient fecal samples, suggesting broad microbial contributions to bile acid deconjugation in MASLD patients. Importantly, small-molecule BSH inhibitors suppressed BSH activity in both fecal communities and monocultures from MASLD patients without affecting bacterial viability. These findings indicate that BSH activity is a microbial function associated with MASLD progression and suggest that BSH inhibitors could be developed as a microbiome-targeted strategy for MASLD treatment.}, } @article {pmid41480755, year = {2026}, author = {Lorsch, ZS and Liddle, RA}, title = {Mechanisms and clinical implications of gut-brain interactions.}, journal = {The Journal of clinical investigation}, volume = {136}, number = {1}, pages = {}, pmid = {41480755}, issn = {1558-8238}, mesh = {Humans ; Animals ; *Brain/metabolism ; *Gastrointestinal Microbiome ; *Brain-Gut Axis ; Glucagon-Like Peptide-1 Receptor ; Obesity/metabolism ; Irritable Bowel Syndrome/metabolism/physiopathology ; Glucagon-Like Peptide-1 Receptor Agonists ; }, abstract = {Connections between the digestive system and the brain have been postulated for over 2000 years. Despite this, only recently have specific mechanisms of gut-brain interaction been identified. Due in large part to increased interest in the microbiome, the wide use of incretin-based therapies (i.e., glucagon-like peptide 1 [GLP-1] receptor agonists), technological advancements, increased understanding of neuroimmunology, and the identification of a direct enteroendocrine cell-neural circuit, research in the past 10 years has made it abundantly clear that the gut-brain connection plays a role both in clinical disease as well as the actions of therapeutics. In this Review, we describe mechanisms by which the gut and brain communicate and highlight human and animal studies that implicate changes in gut-brain communication in disease states in gastroenterology, neurology, psychiatry, and endocrinology. Furthermore, we define how GLP-1 receptor agonists for obesity and guanylyl cyclase C agonists for irritable bowel syndrome leverage gut-brain mechanisms to improve patient outcomes. This Review illustrates the critical nature of gut-brain communication in human disease and the potential to target gut-brain pathways for therapeutic benefit.}, } @article {pmid41480620, year = {2025}, author = {Rodriguez, MT and Olmstead, SJ and McLaurin, KA and Mactutus, CF and Booze, RM}, title = {S-Equol: a novel therapeutic for HIV-1-associated gastrointestinal dysbiosis.}, journal = {NeuroImmune pharmacology and therapeutics}, volume = {4}, number = {4}, pages = {325-337}, pmid = {41480620}, issn = {2750-6665}, abstract = {OBJECTIVE: HIV-1 infection affects approximately 38.4 million people around the world. The advent of combination anti-retroviral therapy (cART) has greatly improved the quality of life of infected individuals; however, roughly 50 % of these individuals will still experience HIV-1-associated neurocognitive disorders (HAND). Additionally, the gastrointestinal microbiome has been reported to be dysbiotic in HIV-1 infected individuals, regardless of adherence to cART. Current research has pointed to the gut-brain-microbiota axis as a potential target to treat both cognitive deficits and microbial changes. The present study investigated S-Equol (SE) as a potential therapeutic for HAND by modulating the gastrointestinal microbiome.

METHODS: The study included 21 HIV-1 Tg rats and 21 F344 control animals to test the effect 0.2 mg SE has on cocaine-maintained responding on a PR schedule of reinforcement.

RESULTS: Gastrointestinal microbiome alterations between genotypes were found at the phylum and genus level, regardless of treatment group, and SE treatment had both main effects and interactions with genotype. Prevotella_UCG_001 was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes.

CONCLUSIONS: SE may provide a novel adjuvant treatment in addition to cART for HIV-1-associated dysbiosis and associated neurocognitive dysfunction.}, } @article {pmid41480617, year = {2025}, author = {Abu, YF and Tao, J and Jayakumar, A and Hussain, H and Paidas, M and Roy, S}, title = {Maternal opioid use is associated with altered placental bacterial DNA and activation of immune-apoptotic pathways.}, journal = {NeuroImmune pharmacology and therapeutics}, volume = {4}, number = {4}, pages = {353-362}, pmid = {41480617}, issn = {2750-6665}, abstract = {OBJECTIVES: Opioid use during pregnancy is associated with adverse perinatal outcomes, but its effects on placental biology are not well understood. Because the placenta plays a vital role in fetal development and immune regulation, we examined how maternal opioid exposure influences microbial DNA signatures and immune gene expression in the placenta.

METHODS: Placentas from opioid-exposed and control C57 BL/6 female mice were analyzed through 16S rRNA gene sequencing, bulk RNA sequencing and pathway enrichment analysis.

RESULTS: Opioid-exposed placentas showed altered microbial DNA profiles, including increased α-diversity and enrichment of Staphylococcus spp. Transcriptomic analysis revealed 357 differentially expressed genes, emphasizing immune pathways, including dendritic cell-NK cell crosstalk, immunogenic cell death, and cytokine storm signaling. STAT3 signaling and heparan sulfate biosynthesis were downregulated. Pathways related to apoptosis, cytotoxicity, and neonatal death were upregulated.

CONCLUSIONS: Maternal opioid exposure may disrupt placental microbial and immune environments, potentially leading to structural compromise through immune-mediated cellular apoptosis.}, } @article {pmid41360887, year = {2025}, author = {Le Lay, A and Brial, F and Rouch, C and Shao, X and Bourgey, M and Sonomura, K and Ou, H and Ghezzal, S and Vincent, M and Rugard, M and Audouze, K and Ragoussis, J and Matsuda, F and Bourque, G and Grundberg, E and Lathrop, M and Magnan, C and Gauguier, D}, title = {Gastrectomy promoted diabetes remission involves the molecular clock and epigenetic mechanisms in a rat model of lean type 2 diabetes.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {96}, pmid = {41360887}, issn = {2045-2322}, support = {DIABETOMARKERS//Institut National de la Santé et de la Recherche Médicale/ ; EpiTriO, ANR-15-EPIG-0002-05//Agence Nationale de la Recherche/ ; }, abstract = {UNLABELLED: Bariatric surgery results in type 2 diabetes (T2D) improvement. To identify mechanisms associated with gastrectomy-promoted T2D remission in lean individuals, we performed pathophysiological, behavioural and molecular (liver transcriptome, metabolome and lipidome) investigations in the Goto-Kakizaki (GK) model of spontaneously-occurring non-obese T2D following vertical sleeve gastrectomy (VSG) or sham operation. VSG resulted in sustained reduction in hyperglycemia and changes in nycthemeral feeding patterns and activity. Liver transcriptome and lipidome profiling pointed to changes in the expression of genes involved in inflammation, PPAR signalling and fatty acid metabolism, and in the regulation of phosphatidylcholine and lysophosphatidylethanolamine classes. Deeper analysis revealed altered expression of genes involved in histone methylation and co-ordinately differential transcription of key regulators of the molecular clock (Clock, Arntl/Bmal1, Per1, Per2, Per3). In addition to previously reported changes in bile acid metabolism and gut microbiome in this model of VSG, our findings underline the multiple biological mechanisms associated with diabetes remission following VSG and suggest a contribution of chronobiology and epigenetic processes in the long-term therapeutic consequences of VSG in the context of polygenic non-obese T2D.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-29273-y.}, } @article {pmid41480369, year = {2025}, author = {Qin, S and Guo, S and Tan, X and Li, K and Huang, J}, title = {Research progress of gut microbiota and its metabolites in polycystic ovary syndrome.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1700191}, pmid = {41480369}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Female ; Animals ; }, abstract = {Polycystic ovary syndrome (PCOS) ranks among the most widespread endocrine and metabolic conditions affecting women of childbearing age, but its specific pathogenesis remains unknown. More and more evidence indicates that PCOS may be a complex polymorphic disease, influenced by epigenetic and environmental factors, including diet and lifestyle. This review focuses on the role of the gut microbiota and its metabolites in PCOS, a topic that has gained significant attention recently due to the established link between the gut microbiome and metabolic disorders.}, } @article {pmid41480316, year = {2025}, author = {Majeed, AA and Butt, AS}, title = {Gut microbiota: An overlooked target in dyslipidemia management.}, journal = {World journal of gastroenterology}, volume = {31}, number = {48}, pages = {113178}, pmid = {41480316}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology/immunology ; *Dyslipidemias/therapy/microbiology/metabolism ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Lipid Metabolism ; Cardiovascular Diseases/prevention & control ; Bile Acids and Salts/metabolism ; Circadian Rhythm ; }, abstract = {With the global rise in sedentary lifestyles, obesity, and unhealthy dietary patterns, dyslipidemia has emerged as a leading modifiable risk factor for atherosclerotic cardiovascular disease. Beyond host genetics and diet, the gut microbiota has gained recognition as a critical regulator of lipid homeostasis through mechanisms involving bile acid metabolism, short-chain fatty acid signaling, and microbial modulation of inflammation. Lv et al provide a comprehensive synthesis of the diet microbe-lipid axis and therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation. In this correspondence, we expand on their framework by highlighting underexplored yet clinically relevant dimensions, including circadian rhythm alignment, pharmacotherapy microbe crosstalk, population-specific microbial signatures, and functional microbial phenotyping. Addressing these overlooked aspects could accelerate the translation of microbiome science into precision dyslipidemia management, with the potential to improve cardiovascular outcomes worldwide.}, } @article {pmid41480270, year = {2025}, author = {Bustos-Caparros, E and Viver, T and Gago, JF and Venter, SN and Bosch, R and Konstantinidis, KT and Rodriguez-R, LM and Rossello-Mora, R}, title = {Uneven sequencing (coverage) depth can bias microbial intraspecies diversity estimates and how to account for it.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf228}, pmid = {41480270}, issn = {2730-6151}, abstract = {An unbiased and accurate estimation of intraspecies diversity, i.e. the extent of genetic diversity within species (or microdiversity), is crucial for clinical and environmental microbiome studies. Although it is well appreciated that sequencing depth (or coverage depth) below 10X can provide biased estimates of microdiversity, typically underestimating diversity due to the random sampling of alleles, there is a widely accepted convention that microdiversity estimates tend to be relatively stable at sequencing depth exceeding 10X. Therefore, discarding species with <10X or rarefying to 10-20X sequencing depth are generally used to compare microdiversity among taxa and samples. Our findings showed that these biases may persist even at depth levels above 50-200X for all popular sequencing platforms, including Illumina, PacBio, and Oxford Nanopore. The biases mostly, but not always, represent an underestimation of diversity and were attributable to the incomplete recovery of Single Nucleotide Variants (SNVs) at lower sequencing depth levels. To address this issue, we recommend using rarefaction-based approaches to standardize data at least 50X, and ideally at 200X sequencing depth, which reduces differences between observed and expected microdiversity values to <0.5%. Furthermore, the Average Nucleotide Identity of reads (ANIr) metric is significantly less sensitive to sequencing depth variability than nucleotide diversity (π), making it a robust alternative for estimating microdiversity at sequencing depth close or exceeding 10X, without a need to rarefying data. Therefore, the sequencing depth thresholds proposed herein provide a more standardized framework for direct comparisons of microdiversity across samples and studies.}, } @article {pmid41480268, year = {2025}, author = {Wang, Y and Lejoly, JDM and Berlinches de Gea, A and van den Elsen, S and Veen, GFC and Geisen, S}, title = {Protist size-dependent shifts of bacterial communities can reduce litter decomposition.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf231}, pmid = {41480268}, issn = {2730-6151}, abstract = {Microbial-mediated litter decomposition drives carbon and nutrient cycling. This process can be top-down regulated by microbiome predators, particularly the diverse protists. Size has been suggested to determine predation impacts, but how protists of different size categories affect microbial-mediated litter decomposition remains unknown. Using a litter decomposition experiment with three protist size categories, we investigated protist size-dependent effects on microbial-driven litter decomposition. We found that protists of the large-size category created more structurally similar bacterial communities compared to the no-protist control. These protists of the large size category also reduced litter mass loss by 40%, while increasing microbial respiration by 17% compared to the no-protist control after five weeks of decomposition. In contrast, protists of the small-size category and protists of the medium-size category had no measurable impact on bacterial communities, litter mass loss, or microbial respiration. Random forest analysis identified Streptomyces as a major contributor to litter mass loss (explained 8% of litter mass), while the potential protist symbionts Taonella and Reyranella explained 8% and 6% of microbial respiration, respectively. These likely predation-resistant bacterial taxa were primarily enriched by protists of the large-size category. Our results indicate that protists, especially large ones, can alter litter decomposition by shaping microbiome composition. Future studies on litter decomposition and carbon cycling should incorporate protists and their traits, particularly size, to enhance our understanding of global carbon and nutrient cycling.}, } @article {pmid41480266, year = {2025}, author = {Li, HR and Wang, ZQ and Zhang, XY and Ullah, Y and Yuan, R and Zhao, JY and Xu, X and Luo, X and Zhang, W}, title = {Oral microbiome is related to lepidopteran herbivore performance by lignin degradation.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf229}, pmid = {41480266}, issn = {2730-6151}, abstract = {Microorganisms associated with insects play crucial roles in mediating the host plant adaptation of their insect hosts. Although oral microbiota are the primary interface with ingested plant material, we still poorly understand their diversity, their function, and their ecological relationship with insect performance. Here, we investigated the diversity and function of the oral microbiota in two generalist lepidopteran pests (Spodoptera litura and Spodoptera frugiperda) feeding across three host plants (bok choy, peanut, and maize). Plant species significantly influenced the diversity and composition of oral microbiota in both S. litura and S. frugiperda. Oral microbial communities from insects feeding on bok choy exhibited significantly higher Sobs richness and Shannon diversity compared to those with peanut or maize plants. Community-level analysis revealed overlapping enriched oral taxa-including Brevibacterium, Staphylococcus, Microbacterium, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Brachybacterium, and Rhodococcus-that were enriched in both insect species when consuming bok choy. In contrast, they accumulated distinct bacterial taxa emerged when feeding on peanut and maize. Microbial ligninolysis capacity within the oral microbiota showed positive associations with leaf lignin content and herbivore performance. This functional trait primarily associated with Brevibacterium and Rhodococcus taxa. Accordingly, two isolated strains, Brevibacterium sedimins OS20 and Rhodococcus sp. OS5 demonstrated effective lignin degradation capacity, achieving 41.01% and 17.62% lignin loss in litter, respectively, after 60 days in microcosm experiments. Overall, host plants shape the diversity and composition of insect oral microbiota. Crucially, microbial ligninolysis capacity and leaf lignin content positively correlated with herbivore performance. This study provides novel insights into the function of oral microbiota in plant-insect interactions, potentially informing the complex multitrophic relationships underlying coevolutionary dynamics.}, } @article {pmid41480264, year = {2025}, author = {Kok, PJR and Urbaniak, M}, title = {Lost paradise-anthropogenic pressure alters microbial functional diversity in an endangered endemic toad-habitat system.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf239}, pmid = {41480264}, issn = {2730-6151}, abstract = {Tourism-driven human activity is increasingly disrupting fragile and once-pristine ecosystems worldwide, as evidenced by coral reef degradation in the Great Barrier Reef, vegetation loss in the Himalayas, and, as demonstrated in this study, microbial shifts in isolated highland habitats such as tepui summits. Integrating field-based ecological, microbiological, and conservation perspectives, this study provides novel insights into how anthropogenic disturbance-particularly tourism-affects microbial functional diversity across interconnected environmental (soil) and host-associated (amphibian skin and faeces) compartments in a globally unique and poorly studied highland ecosystem, the summit of Roraima-tepui in Venezuela. Our results provide clear evidence that anthropogenic disturbance on the summit of Roraima-tepui reduces microbial functional diversity-by 59% in soil and by 21% and 14% in the skin and faecal microbiomes of the (near)endemic toad Oreophrynella quelchii, respectively-compared to pristine sites. Our findings raise significant concern, as alterations in microbial composition and functions could disrupt host immunity and disease resistance in this unique, insular, and ecologically fragile ecosystem, particularly given the recent detection of anthropogenic pathogen incursion in amphibian communities. Our results stress the need to better understand the link between the observed shift in the skin microbiome's functional profiles in O. quelchii at summit sites most impacted by tourism and the recent emergence of the fungal pathogen Batrachochytrium dendrobatidis in the same environmental context. Our findings underscore the urgent need to mitigate human-induced pressures threatening the ecological integrity of the summit of Roraima-tepui, one of the world's most fragile and irreplaceable montane habitats.}, } @article {pmid41480259, year = {2025}, author = {Bachtiar, E and Bachtiar, BM and Tahapary, DL and Fath, T and Theodora, CF and Haerani, N and Shahab, SN and Soeroso, Y and Wildan, A and Runtu, FMJG and Tadjoedin, FM and Ayuningtyas, D}, title = {Salivary microbiome and periodontopathogen/denitrifying bacteria associated with gingivitis and periodontitis in people with type 2-diabetes.}, journal = {F1000Research}, volume = {14}, number = {}, pages = {297}, pmid = {41480259}, issn = {2046-1402}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/complications ; *Saliva/microbiology ; *Periodontitis/microbiology/complications ; *Microbiota ; *Gingivitis/microbiology/complications ; Adult ; Male ; Female ; *Bacteria/metabolism/genetics ; Young Adult ; Nitrites/metabolism ; Nitrates/metabolism ; }, abstract = {BACKGROUND: Despite diabetes mellitus and periodontal diseases are mutually exclusive, little is known about particular types of bacteria that may have exacerbated the development of diabetics' periodontal inflammation. The purpose of this study was to descriptively characterize and explore the differences in the salivary microbiomes of individuals with type 2 diabetes (20-40 years old) who had gingivitis or periodontitis to those who did not. Additionally, we evaluated the descriptive relationship between the relative abundance of periodontopathogens and nitrate-reducing bacteria in their salivary microbiome.

METHODS: Saliva was collected from all participants. Genomic DNA was isolated and pooled in equimolar quantities from all individuals within each group to create three pooled libraries: type 2 diabetes (T2DM) patients without periodontal disease (G1), T2DM patients with gingivitis (G2), and T2DM patients with periodontitis (G3). Sequencing was performed using Oxford Nanopore MinION Technology. The relative abundance and bacterial diversity were measured using bioinformatic methods, and all analyses of sequencing data were strictly descriptive and exploratory. Salivary nitrite/nitrate concentrations were measured on individual, un-pooled samples.

RESULTS: The salivary microbiota among people with type 2 diabetes and periodontal disease (G2; G3) was observed to have greater bacterial diversity and abundance than that of patients without periodontal disease (G1), according to descriptive alpha-diversity analysis. The G3 group exhibited the largest relative abundance of Porphyromonas gingivalis, a key periodontopathogen. Descriptive analysis also suggested that periodontopathic bacteria and nitrate-reducing bacteria have different community structures across the groups. Furthermore, comparison of individual salivary samples showed that nitrite/nitrate concentration was significantly lower in the G3 group compared to the G1 group (p< 0.05).

CONCLUSION: Results of this exploratory study suggest that the relationship between periodontopathic and denitrifying bacteria in the salivary microbiome varies among those with type 2 diabetes mellitus who also have gingivitis or periodontitis. These distinct microbial features observed may be microbiological characteristics associated with the progression of periodontal disease in this population, warranting further validation as potential indicators for early management.}, } @article {pmid41480207, year = {2025}, author = {Song, S and Xu, LS and Wang, LQ and Zhou, X and Jiang, X and Li, CP}, title = {Tumor-resident microorganisms as clinical biomarkers in primary liver cancer: A systematic review of current evidence.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {12}, pages = {112936}, pmid = {41480207}, issn = {1948-5204}, abstract = {BACKGROUND: Hepatic malignancies represent the sixth most prevalent cancer globally, with emerging evidence revealing that intratumoral microbes actively modulate carcinogenesis through immunomodulation and metabolic reprogramming. Recent high-throughput sequencing technologies have identified taxonomically diverse microbial communities within tumor tissues, challenging traditional sterility paradigms. Germ-free mouse models have established causal relationships between gut microbiota and hepatocarcinogenesis. However, comprehensive evaluation of intratumoral microbiota as clinical biomarkers remains limited, necessitating systematic analysis of their diagnostic, prognostic, and therapeutic applications in hepatic malignancies.

AIM: To systematically analyze intratumoral microbes as biomarkers for hepatic malignancies diagnosis, prognosis, and treatment response.

METHODS: We conducted a systematic literature search in PubMed from inception to July 2025 using keywords combining hepatic malignancies, intratumoral microbiota, and biomarkers. Inclusion criteria encompassed human studies examining intratumoral microbial communities with biomarker applications. Exclusion criteria included animal-only studies, reviews, and research focusing solely on gut microbiota. Data extraction focused on diagnostic accuracy, prognostic significance, therapeutic predictions, and underlying mechanisms. Study quality was assessed using Newcastle-Ottawa Scale, with scores ≥ 7 indicating high quality.

RESULTS: Twenty studies (sample sizes: 18-925 patients) examining hepatocellular carcinoma (80%) and intrahepatic cholangiocarcinoma (20%) were included. All studies achieved Newcastle-Ottawa Scale scores ≥ 6, with 60% scoring the maximum 9 points, indicating moderate-to-high quality. Studies predominantly employed 16S rRNA sequencing (100%) targeting V3-V4 regions, with complementary validation techniques including fluorescence in situ hybridization, quantitative PCR, and immunohistochemistry. Specific bacterial taxa demonstrated exceptional diagnostic accuracy [area under the curve (AUC) > 0.9] for tumor discrimination. Notably, Bacilli showed AUC = 0.943 in validation cohorts. Microbial diversity and specific genera (Methylobacterium, Akkermansia, Intestinimonas) showed consistent prognostic associations with survival outcomes, though relationships varied across cancer subtypes. Advanced risk stratification models incorporating multiple bacterial biomarkers showed independent predictive capacity through multivariable Cox regression. Mechanistic investigations revealed microbe-mediated oncogenic pathway activation, particularly NF-κB signaling, immune modulation through M2 macrophage polarization, and drug resistance mechanisms via autophagy regulation. Germ-free mouse models established causal relationships, demonstrating that specific bacterial communities, particularly Klebsiella pneumoniae, can autonomously initiate hepatocarcinogenesis through TLR4-dependent pathways.

CONCLUSION: Intratumoral microbes represent promising clinical biomarkers for hepatic malignancies across diagnostic, prognostic, and therapeutic applications. While standardization and multicenter validation remain essential prerequisites, mechanistic evidence from human and experimental studies positions microbiome-based biomarkers at the threshold of clinical translation.}, } @article {pmid41480165, year = {2025}, author = {Madarasz, B and Balazs, MA and Palfi, E and Konczos, J and Toth, A and Szentmartoni, G and Herold, Z and Dank, M}, title = {Ultra-processed foods and dietary habits of oncology patients: Risk factor or survival strategy.}, journal = {World journal of clinical oncology}, volume = {16}, number = {12}, pages = {111372}, pmid = {41480165}, issn = {2218-4333}, abstract = {The consumption of ultra-processed foods (UPFs) is continuously increasing, and there is growing evidence that these foods contribute to the development and progression of cancer. For oncology patients alone, maintaining nutritional status is crucial for tolerating treatments and improving survival. The aim of this paper is to review the role of UPFs in the diet of oncology patients, highlighting their potential health-damaging effects (e.g., increased inflammation, microbiome disruption, nutrient deficiencies) and potential benefits (e.g., easy accessibility, high energy content, specially formulated nutritional supplements) particularly in the context of addressing the energy and nutrient needs and nutritional challenges of patients experiencing cancer-related cachexia or anorexia. Using a literature review, we examine how the UPFs can impact oncology patients' health, supporting the quality of life and clinical outcomes of oncology patients.}, } @article {pmid41480161, year = {2025}, author = {Ansari, S and Ahmed, N}, title = {Pathogenicity of Helicobacter pylori-associated gastric cancer.}, journal = {World journal of clinical oncology}, volume = {16}, number = {12}, pages = {110909}, pmid = {41480161}, issn = {2218-4333}, abstract = {Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and ranks among the top five most common malignancies. Helicobacter pylori (H. pylori) infection is recognized as the primary risk factor, although gastric carcinogenesis also reflects complex interactions among bacterial virulence factors, host genetics, and the gastric microbiome. H. pylori harbors well-characterized proteins such as CagA, VacA, BabA, and SabA that enable persistent infection and fuel tumor initiation. Recent high-quality evidence from randomized trials and meta-analyses provide strong support that H. pylori eradication therapy substantially reduces cancer risk-even in those with established precancerous lesions such as intestinal metaplasia or dysplasia. Additionally, emerging research indicate that H. pylori may influence the tumor immune microenvironment, such as through altering programmed death ligand 1 expression-which could affect immunotherapy outcomes. This review presents a cohesive and updated perspective on H. pylori-driven GC, summarizing bacterial virulence, host predispositions, microbiome interactions, epigenetic changes like DNA repair gene methylation, and evolving therapeutic implications, all while illuminating current scientific debates and emerging directions.}, } @article {pmid41480121, year = {2025}, author = {Wang, Y and Wu, J and Wang, Y and Jiang, W and Wang, D and Zhao, J and Qin, X and Yuan, Y and Zhang, H and Wang, J and Zhen, J and Du, Y and Mu, X and Li, L and Wang, T and Zou, L and Fang, X and Sun, B and Li, H}, title = {Respiratory Microbiome in Elderly Patients on Prolonged Mechanical Ventilation: A Prospective Multi-Center Observational Study.}, journal = {Clinical interventions in aging}, volume = {20}, number = {}, pages = {2705-2716}, pmid = {41480121}, issn = {1178-1998}, mesh = {Humans ; Aged ; Male ; Female ; Prospective Studies ; *Pneumonia, Ventilator-Associated/microbiology/virology ; *Microbiota ; *Respiration, Artificial/adverse effects ; Aged, 80 and over ; Klebsiella pneumoniae/genetics/isolation & purification ; }, abstract = {PURPOSE: The purpose of this study was to explore dynamic changes of respiratory microbiome in elderly patients undergoing prolonged mechanical ventilation (PMV) by isothermal microfluidic amplification chip technology (IAMC).

METHODS: The study enrolled patients in six general hospitals in Beijing. Patients who developed Ventilator-associated pneumonia (VAP) within the observation period were enrolled in the VAP group, while those without VAP were categorized in non-VAP group. The study adopted IAMC technology to dynamically monitor the differences in the detection rates of bacteria, fungi, and viruses in the two groups. The conventional microbiological tests (CMT) were performed to clarify the correlation between KPC and drug resistance phenotype of K. pneumoniae.

RESULTS: Among 218 patients, 78 were diagnosed with VAP. The pulmonary microbiota composition of patients without VAP was relatively stable. Compared with the non-VAP group, the detection rates of Enterococcus faecalis, Epstein-Barr virus, and Herpes simplex virus were significantly increased in the VAP group, whereas those of Haemophilus influenzae and Serratia marcescens were significantly reduced. In the VAP group, the detection rates of Enterococcus faecalis and Epstein-Barr virus were higher after the occurrence of VAP than before. A high correlation was observed between the KPC genotype of K. pneumoniae and its resistance phenotype.

CONCLUSION: Viruses and Gut microbes might be closely related to the development of VAP in elderly undergoing PMV. The detection of the KPC gene of K. pneumoniae can guide antibiotic selection, and IAMC can aid in quickly identifying pathogens and facilitate targeted treatment.

ChiCTR2100051343.}, } @article {pmid41480114, year = {2025}, author = {Robayo-Cuevas, C and Junca, H and Uribe, S and Gómez-Palacio, A}, title = {Detection of endosymbiotic, environmental, and potential bacterial pathogens in diverse mosquito taxa from Colombian tropical forests using RNAseq.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1727830}, pmid = {41480114}, issn = {1664-302X}, abstract = {INTRODUCTION: Mosquitoes of the subfamily Culicinae transmit pathogens of major medical and veterinary importance, particularly in tropical regions where urbanization and ecological change promote arbovirus circulation. In Colombia, rural Culicinae species are diverse and harbor microbiomes that may influence vector competence, yet their bacterial communities remain poorly characterized.

METHODS: We characterized the bacterial microbiota of multiple Culicinae species and morphotypes collected from two rural localities in Antioquia, Colombia, using an integrated metagenomic approach. Ribosomal 16S rRNA sequences were extracted from total RNA-seq datasets to infer bacterial community composition and assess α- and β-diversity. Diversity metrics (Chao1 and Shannon indices), Discriminant Analysis of Principal Components (DAPC), and Bray-Curtis ordination were used to evaluate community structure. In parallel, de novo assembled contigs were taxonomically annotated against the NCBI NR bacterial database to obtain complementary taxonomic and functional insights.

RESULTS: Culex morphotypes exhibited the highest richness and evenness, whereas Aedes and Trichoprosopon showed lower diversity. Ordination and DAPC analyses revealed partial clustering by species and tribe. Both the 16S and assembly-based analyses showed complex bacterial assemblages dominated by Wolbachia (up to 60% of reads in several Aedes and Culex morphotypes), followed by environmental genera such as Pseudomonas and Acinetobacter (10-20%). Lower-abundance taxa of medical and veterinary importance-including Salmonella, Borrelia, and Clostridium (<5%)-were also detected. Bacterial community structure differed among mosquito species; Aedes albopictus was enriched in lactic acid bacteria, while Culex morphotypes exhibited broader environmental and endosymbiotic profiles.

DISCUSSION: This study provides the first comprehensive metagenomic description of bacterial communities associated with rural Culicinae mosquitoes in Colombia. The predominance of symbionts such as Wolbachia and Spiroplasma, coupled with distinct bacterial signatures among host species, highlights the ecological complexity of these microbiomes and their potential relevance for microbiome-based strategies in sustainable arboviral disease management.}, } @article {pmid41480112, year = {2025}, author = {Fu, J and Bu, G and Aimaier, S and Yang, Y and Bao, Z and Wulasihan, M}, title = {Sex-specific association between gut Faecalibacterium prausnitzii and hypertension in male individuals.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1683587}, pmid = {41480112}, issn = {1664-302X}, abstract = {OBJECTIVE: While gut microbiota (GM) dysbiosis has been implicated in hypertension, the sexassociated microbial signatures and their underlying mechanisms remain poorly understood, particularly in populations living in unique geographical and climatic conditions.

DESIGN: Through an integrated approach combining 16S rRNA sequencing, shotgun metagenomics, and serum metabolomics, we systematically investigated the sex-associated characteristics of the gut microbiota in hypertension among a cohort of 200 participants from Xinjiang.

METHODS: An initial cohort analysis identified Faecalibacterium as a male-associated biomarker for hypertension. Subsequent species-level characterization revealed that Faecalibacterium prausnitzii (F. prausnitzii) showed significant negative correlations with systolic blood pressure (SBP). This male-specific association was consistently observed across both 16S rRNA sequencing and shotgun metagenomic datasets. Then, our integrated analysis suggested a potential pathway through which F. prausnitzii may be linked to systolic blood pressure in male individuals, with N-phenylacetylglutamine (PAGln) identified as a potential mediating metabolite.

CONCLUSION: Our study establishes a microbe-metabolite-clinical trait axis in the pathophysiology of sex-associated hypertension and significantly advances our understanding of sex-driven host-microbe interactions.}, } @article {pmid41480103, year = {2025}, author = {Jobert, L and Vicheth, V and Czernic, P and Suong, M and Béna, G and Moulin, L}, title = {Rhizosphere legacy of leaf-diseased rice and its impact on next generation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1677271}, pmid = {41480103}, issn = {1664-302X}, abstract = {Plants interact continuously with the surrounding soil microbiota, shaping and being shaped by these communities over time, termed as the plant-soil feedback (PSF). As a result, plants can leave a biological imprint in the soil that affects the performance of subsequent plants, a phenomenon termed the soil-borne legacy. In this study, we investigated how the rhizosphere microbiota of rice plants exhibiting (or not) foliar disease symptoms in a Cambodian field was modified and influenced subsequent generation of plants. Based on a visual assessment of foliar symptoms, we collected and mixed the rhizospheres of plants classified as "diseased" or "healthy," respectively. These mixed rhizospheres were then used to sow new rice plants in controlled conditions, which were subsequently challenged with Xanthomonas oryzae pv. oryzae. Phenotypic analyses revealed that plants grown in the rhizosphere microbiota collected from diseased field plants were smaller, yet displayed smaller symptoms to foliar pathogens compared to those grown in the microbiota of healthy plants. Amplicon sequencing of roots and rhizospheres from field samples confirmed that diseased and healthy plants harbored distinct microbial communities. A dysbiotic rhizosphere was found to be present in leaf-diseased plants, in contrast to healthy ones. These differences were also detectable in the composite rhizosphere mixes, and persisted in the rhizospheres of a new generation of rice plants grown in these soils. This suggests a microbiota-driven legacy, wherein the health status of the previous generation shapes the microbial environment and influences plant phenotype in terms of growth and defense. Our results support the idea that leaf-diseased plants condition their rhizosphere microbiota thus influencing plant phenotype in the next generation. Understanding the impact of disease-induced microbial legacy on next generation plant phenotype is crucial for developing microbiome-based crop protection strategies.}, } @article {pmid41480099, year = {2025}, author = {Chen, Y and Li, X and Huang, R and Zhang, F and Ma, C}, title = {Changes in soil microbial community structure during the transformation from native soil to alfalfa cultivation soil in the Kunlun Mountain sand area, Xinjiang, China.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1702974}, pmid = {41480099}, issn = {1664-302X}, abstract = {Alfalfa cultivation is widely regarded as an effective biological approach for improving desertified and degraded soils. However, it remains unclear how this effect unfolds in high-altitude desert environments and how soil and plant microbiomes assemble when native soil (NS) host plants are replaced. In this study, we tested whether converting NS to alfalfa-cultivated soil (CS) affected the composition of soil microbial communities and changed microbial diversity. Specifically, alfalfa cultivation reshaped core microbial components, increasing beneficial bacteria such as Arthrobacter and Pseudomonas, potentially enhancing nutrient cycling and plant growth, while reducing certain decomposers (e.g., Bacteroides). Results indicated that alfalfa cultivation improved NS quality, and with longer planting time, promoted the recovery and homogenization of soil microbial diversity. This process was accompanied by the replenishment or exclusion of soil microorganisms. Soil organic matter and pH were identified as key drivers of microbial community change. Across 541 bacterial OTUs and 56 fungal OTUs were shared across NS, CS, and alfalfa rhizosphere soil (RS), this core microbiome accounted for a large proportion of reads (bacteria: 28.70%, fungi: 40.37%). Microbial network structure and interactions were more complex NS and RS than in CS, with bacterial interactions more pronounced than fungal ones. Overall, the transition from NS to CS via alfalfa planting positively affected local microbial diversity, and RS assembly was shaped by both recruitment and dispersal. This research highlights the potential of alfalfa to restore high-altitude desertified ecosystems by strengthening microbially mediated soil fertility and biogeochemical cycling, offering insights for sustainable land management in arid regions.}, } @article {pmid41479870, year = {2025}, author = {Ghosh, N and Sinha, K}, title = {Guardians within: Cross-talk between the gut microbiome and host immune system.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {4}, pages = {111245}, pmid = {41479870}, issn = {2150-5330}, abstract = {The gut microbiome, a complex ecosystem of trillions of microorganisms, plays a crucial role in immune system regulation and overall health. This review explores the intricate cross-talk between the gut microbiota and the host immune system, emphasizing how microbial communities shape immune cell differentiation, modulate inflammatory responses, and contribute to immune homeostasis. Key interactions between innate and adaptive immune cells - including macrophages, dendritic cells, natural killer cells, innate Lymphoid cells, T cells, and B cells - and gut microbiota-derived metabolites such as short-chain fatty acids are discussed. The role of commensal bacteria in neonatal immune system development, mucosal barrier integrity, and systemic immunity is highlighted, along with implications for autoimmune diseases, inflammatory conditions, and cancer immunotherapy. Recent advances in metagenomics, metabolomics, and single-cell sequencing have provided deeper insights into the microbiota-immune axis, opening new avenues for microbiome-based therapeutic strategies. Understanding these interactions paves the way for novel interventions targeting immune-mediated diseases and optimizing health through microbiome modulation.}, } @article {pmid41479867, year = {2025}, author = {Priyanka, P and Khullar, S and Singh, M and Morya, AK and Sharma, B and Periasamy, B and Moharana, B and Morya, R}, title = {Role of gut microbiomes in different ocular pathologies: A systematic review.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {4}, pages = {113488}, pmid = {41479867}, issn = {2150-5330}, abstract = {BACKGROUND: The gut microbiome is integral to human health, with emerging research underscoring its potential impact on ocular health through the gut-eye axis. Various ocular disorders, such as dry eye syndrome, retinal vascular diseases, macular degeneration, and glaucoma, may be influenced by gut dysbiosis, which could significantly contribute to their development and progression.

AIM: To evaluate the influence of the gut microbiome on the pathogenesis and progression of various ocular diseases.

METHODS: An extensive search of the scientific literature was undertaken by adhering to Preferred Reporting Items for Systematic Reviews & Meta-Analyses standards, using PubMed (MEDLINE), Scopus, EMBASE, and the Cochrane Library as sources to locate studies addressing the relationship between the gut microbiome and human health. To capture all relevant publications, search terms were systematically applied across these major databases, without limiting the search by language or publication date. Inclusion criteria covered randomized controlled trials, non-randomized controlled trial, prospective studies, cross-sectional studies, and case-control studies. Out of the 3077 articles, 36 full texts were included in the review.

RESULTS: Ocular health appears to be shaped by the gut microbial community through mechanisms such as immune regulation, preservation of the blood-retinal barrier, and the generation of protective metabolites. Disturbances in this microbial balance can provoke measurable alterations in host immunity, providing a plausible immunopathogenic pathway that connects intestinal dysbiosis with eye disease. Both laboratory models and early human data suggest that targeted interventions, including prebiotics, probiotics, synbiotics, and faecal microbiota transfer, hold therapeutic potential.

CONCLUSION: The gut-eye relationship reflects a multifaceted interaction in which the intestinal microbiome contributes to ocular health through complex biological pathways. Integrating microbiome assessments into diagnostic methods can revolutionize disease management through early detection and targeted interventions. Further, randomised controlled clinical trials are necessary for ocular diseases to prove causal relationships.}, } @article {pmid41479866, year = {2025}, author = {Dutta, AK and Vishruth, S and Kovi, SL and Dadhich, P and Polavarapu, J and Abraham, D}, title = {Gut microbiota as a potential predictor of therapeutic response in adults with Crohn's disease: A systematic review.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {4}, pages = {112961}, pmid = {41479866}, issn = {2150-5330}, abstract = {BACKGROUND: Various therapeutic options are available for the treatment of Crohn's disease (CD). About 30%-40% patients experience primary non-response, and 20%-30% secondary loss of response to biological therapy. Predicting therapeutic response is challenging and an area of active research. Gut microbiota has emerged as an important player in the pathogenesis of CD and also appears to be a promising biomarker for predicting therapeutic response.

AIM: To systematically review the literature on the current status of gut microbiota as a tool to predict response to treatment in adults with CD.

METHODS: We searched the literature database (PubMed, Scopus, and Cochrane database) from inception to August 2025. We screened for studies reporting on adult patients with CD receiving biologic or immunomodulator therapies, with baseline microbiome analyses performed prior to treatment. Papers reporting on baseline gut microbiota as a predictor of therapeutic response were finally included. The utility of bacterial diversity, microbial community structure, and the role of specific operational taxonomic units as biomarkers of therapeutic response was reviewed. The results were grouped based on the bacterial parameters studied and presented in separate tables. The quality of the included studies was assessed using the MINORS criteria. The review was registered prospectively in PROSPERO.

RESULTS: After applying the selection criteria, sixteen studies were included in this systematic review. The majority of the papers were from Europe and the United States. All except two papers assessed gut bacterial population using 16S rRNA gene sequencing. Ten of the sixteen studies were of high quality. Among the sixteen studies included, most identified an association between microbial taxa and treatment response, while the relation with alpha-diversity was inconsistent. The functional characteristics were reported in only four studies and were found to be useful. The best prediction was achieved when microbial characteristics were combined with clinical and other parameters, with area under the curve values up to 0.96.

CONCLUSION: The overall results suggest good performance of microbial parameters as a novel biomarker of therapeutic response. However, there are variations across individual studies, probably related to the methodology of assessing microbial communities and the therapeutic agent used. Future multicenter studies integrating microbial, clinical, and metabolomic data are warranted to develop predictive models for personalized therapy in CD.}, } @article {pmid41479772, year = {2025}, author = {Jiang, C and Ma, J and Mu, J and Fu, Y and Zhao, Y and You, Y and Cui, Z and Guo, C}, title = {Biological relationship between Parkinson's disease and gallstone disease.}, journal = {Neuroprotection (Chichester, England)}, volume = {3}, number = {4}, pages = {322-335}, pmid = {41479772}, issn = {2770-730X}, abstract = {Compelling evidence indicates a significant connection between dysfunction of the gastrointestinal tract, the gut microbiome, and Parkinson's disease (PD), which aligns with the notion of the "gut-brain axis". While the exact mechanisms involved in gut-brain interactions are still not fully understood, the high incidence of gastrointestinal symptoms during the early stages of PD aids in the development of diagnostic biomarkers and prospective disease-modifying therapies. Importantly, a number of studies have revealed a possible association between gallstone disease (GD) and PD; nevertheless, the exploration of diverse risk factors and the theory suggesting that the onset of PD might be associated with GD requires further investigation. This review aims to explore the evidence that connects alterations in GD with PD, emphasizing mechanisms that promote gut dysbiosis, the gut-brain connection, changes in lipid profiles, genetic and dietary influences, as well as neuroinflammation. Furthermore, we assess the potential implementation of innovative therapeutic strategies, including probiotic treatments and gut microbiota transplantation, in patients with PD. Although the evidence supports an association between PD and GD, causality remains to be established. Prospective cohort studies are needed to determine whether gallstones represent a prodromal marker or a causal risk factor for PD, and to validate these pathways as novel diagnostic and therapeutic targets for PD.}, } @article {pmid41479668, year = {2025}, author = {Vázquez-Frias, R and Vinderola, G and Abreu Y Abreu, AT and Angulo, D and Giler-Párraga, N and Ladino, L and Ortiz, C and Pereira, S and Bustamante, JP}, title = {Postbiotics in pediatric clinical practice: position paper from Special Group of Latin American Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN).}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1716791}, pmid = {41479668}, issn = {2296-861X}, abstract = {Postbiotics, defined by the ISAPP as preparations of inanimate microorganisms and/or their components that confer health benefits, represent a promising category of microbiome-derived solutions. This position paper highlights their clinical relevance, particularly in pediatrics, while addressing key aspects of definition, safety, quality, and strain-level specificity. Evidence supports the use of Lactobacillus LB -including L. fermentum CNCM I-2998 and L. delbrueckii subsp. lactis CNCM I-4831- in reducing the duration and severity of acute diarrhea in children. Other strains, such as Bifidobacterium breve C50, Streptococcus thermophilus 065, Lacticaseibacillus paracasei CBA L74, Lactiplantibacillus plantarum LPL28, and Ligilactobacillus salivarius AP-32, show promise in preventing infections, supporting oral health, and modulating immune responses. Additional postbiotics, including Limosilactobacillus reuteri DSM 17648, expand their potential into metabolic and gastrointestinal disorders. Collectively, postbiotics emerge as clinically valuable interventions, bridging science and medical practice.}, } @article {pmid41479564, year = {2025}, author = {N Kukaev, E and Tokareva, AO and Krogh-Jensen, OA and Lenyushkina, AA and Starodubtseva, NL}, title = {Gut Microbiota and Short-Chain Fatty Acids in the Pathogenesis of Necrotizing Enterocolitis in Very Preterm Infants.}, journal = {Acta naturae}, volume = {17}, number = {4}, pages = {38-51}, pmid = {41479564}, issn = {2075-8251}, abstract = {The development of a symbiotic gut ecosystem is a crucial step in postnatal adaptation. The gut microbiome of very preterm infants is characterized by an overall instability, reduced microbial diversity, and a predominance of Gram-negative Proteobacteria, all factors associated with an increased risk of necrotizing enterocolitis (NEC). Short-chain fatty acids (SCFAs) are the key bacterial metabolites that are essential for maintaining intestinal homeostasis, supporting immune development, enhancing intestinal barrier integrity, and reducing inflammation. This review examines the role of gut microbiota and SCFAs in neonatal NEC, with a focus on potential diagnostic and therapeutic strategies. Clinical studies have consistently demonstrated a significant decrease in total SCFA levels and individual bacterial metabolites in preterm infants with NEC. This finding has been corroborated by various experimental models. Clarification of the role of SCFAs in NEC pathogenesis, determination of their diagnostic utility, and assessment of the feasibility of developing comprehensive pro- and postbiotic formulations require multi-center, multi-omics investigations that include a large cohort of very preterm infants.}, } @article {pmid41479542, year = {2025}, author = {Nath, S and Weyrich, LS and Guzzo, G and Hedges, J and Tamrakar, M and Kapellas, K and Jamieson, L}, title = {The sociobiome-oral microbiome mediates dental caries among Indigenous Australians.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1721183}, pmid = {41479542}, issn = {2235-2988}, mesh = {Humans ; *Dental Caries/microbiology/epidemiology ; Saliva/microbiology ; *Microbiota ; Female ; Male ; Adult ; Cross-Sectional Studies ; Australia/epidemiology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Young Adult ; Socioeconomic Factors ; Dental Plaque/microbiology ; Aged ; Adolescent ; *Mouth/microbiology ; Oral Health ; Bacteria/classification/genetics ; }, abstract = {BACKGROUND: The sociobiome refers to the social and socioeconomic conditions that shape human microbial communities, linking structural inequities to biological changes in the microbiome. The aim of this study was to examine how individual and neighbourhood socioeconomic status (SES) are associated with the oral microbiota and dental caries in Indigenous Australian adults.

METHODS: This cross-sectional study involved 100 Indigenous Australian participants aged ≥ 18 years and was embedded within a decolonising, community-based participatory research framework. Demographic, socioeconomic, and oral health behaviour data were collected, followed by a dental examination and collection of saliva and plaque samples. The samples were analysed using 16S rRNA amplicon sequencing, and alpha and beta diversity, redundancy analysis, and differential abundance analysis were conducted. Mediation models were used to examine associations between income (Healthcare card ownership), education (≤ secondary), the oral microbiome, and dental caries.

RESULTS: The microbiome analyses showed saliva had higher alpha diversity (p < 0.01), and beta diversity was significantly different between saliva and plaque (adonis p < 0.001). In saliva, alpha diversity was lower with advancing age, secondary education, income, Healthcare card ownership, and dental caries presence. Beta diversity in saliva microbiome composition showed a stronger association with SES than plaque, with income source (R²=3.8%, p < 0.01), education (R²=2.0%, p < 0.01), and dental caries (R²=2.2%, p < 0.01). Differential abundance analysis showed that the Rikenellaceae RC9 gut group, F0058, Fillifactor, and Treponema were elevated in the low-SES and caries groups. Mediation analysis showed that 75% of the impact of low income on caries was mediated via microbiome shifts, compared with 21% for education, highlighting the strong role of oral microbiome alterations in SES-driven caries risk.

CONCLUSION: Socioeconomic disadvantage is associated with variations in the oral microbiome, and these microbial patterns may explain the link between lower income and dental health caries. Saliva may serve as a sensitive biomarker of socioeconomic gradients in oral health. These findings support integrated approaches that address structural determinants of disadvantage alongside microbiome-informed preventive strategies when tackling oral health inequities in Indigenous populations.}, } @article {pmid41479540, year = {2025}, author = {Kong, Z and He, Y and Xue, J and Chen, Z and Gui, Y and Wu, J and Chen, X}, title = {Plant growth-promoting bacteria (PGPB) inoculants enhance the bacterial network connectivity more than non-PGPB in heavy metal-contaminated soil.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1717976}, pmid = {41479540}, issn = {1664-462X}, abstract = {Optimizing the performance of plant growth-promoting bacteria (PGPB) inoculants in phytoremediation requires a deeper understanding of their interactions with the indigenous soil microbiome. However, current knowledge is particularly limited regarding how PGPB versus non-PGPB inoculants interact with indigenous microbes and establish colonization persistence in the rhizosphere. In this study, we employed amplicon sequencing to compare the impacts of PGPB versus non-PGPB inoculants on the indigenous rhizosphere and bulk soil microbiome of Indian mustard in heavy metal-contaminated soil, and their interactions within the indigenous bacterial networks. Our results showed that both PGPB and non-PGPB inoculants significantly altered the composition and diversity of the rhizosphere microbiome. However, only PGPB inoculants enhanced the complexity and stability of bacterial co-occurrence networks. PGPB inoculants not only maintained rhizosphere persistence but also actively integrated into the network, enhancing associations with indigenous bacterial taxa. Notably, they established enhanced co-occurrence associations with native bacterial taxa characterized as potential PGPB, including Lysinimonas, Sinomonas, Nocardioides, Actinoalloteichus, Amycolatopsis, Bradyrhizobium, Novosphingobium etc., and these interactions were predominantly positive. These findings highlight the important role of PGPB versus non-PGPB inoculants in reshaping the rhizosphere microbiome under heavy metal stress, indicating a potential approach for improving phytoremediation efficiency by fostering a more resilient and cooperative soil microbiome.}, } @article {pmid41479529, year = {2025}, author = {Punnuri, SM and Thudi, M and Mir, RR}, title = {Editorial: Genetics and genomics of emerging and multifactorial stresses affecting plant survival and associated plant microbiomes.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1738816}, pmid = {41479529}, issn = {1664-462X}, } @article {pmid41479404, year = {2025}, author = {Wang, D and Yu, L and Lu, Q and Han, M and Wang, B and Peng, X and Yue, M and Li, Y}, title = {Oral pretreatment with Escherichia coli Nissle 1917 enhances the host's defense against influenza A virus infection.}, journal = {mLife}, volume = {4}, number = {6}, pages = {666-682}, pmid = {41479404}, issn = {2770-100X}, abstract = {Influenza A viruses (IAVs) pose a significant threat to global health, causing annual epidemics and occasional pandemics with substantial morbidity and mortality. Despite the availability of vaccines and antiviral therapies, the development of novel preventive and therapeutic strategies remains a critical research focus. In this study, we evaluated the protective effects of orally administering Escherichia coli Nissle 1917 in IAV-infected mice and elucidated its mechanisms of action by analyzing cecal microbiota and plasm metabolome profiles. Oral administration of E. coli Nissle 1917 alleviated respiratory symptoms, reduced weight loss, and mitigated pathological injury in mice infected with H9N2 or H1N1 IAV. These protective effects were mediated through the modulation of gut microbiota diversity, which increased the abundance of Bacteroides and Akkermansia, correlating with elevated pipecolic acid levels and ultimately aiding in defense against IAV infection in mice. Notably, we identified that the circulating metabolic molecule pipecolic acid plays a significant role in fighting IAV infection. Our findings suggest the potential usefulness of E. coli Nissle 1917 or pipecolic acid in influenza prevention.}, } @article {pmid41479117, year = {2026}, author = {Attar, R and Hamid, A and Dar, LS and Normakhamatov, N and Farooqi, AA}, title = {Silhouette of Probiotics in the Regulation of miRNAs and lncRNAs in Carcinogenesis and Metastasis: Is It a Silver Lining or a Cross to Bear.}, journal = {Experientia supplementum (2012)}, volume = {115}, number = {}, pages = {243-251}, pmid = {41479117}, issn = {1664-431X}, mesh = {*Probiotics/therapeutic use ; *RNA, Long Noncoding/genetics ; Humans ; Animals ; *MicroRNAs/genetics ; *Carcinogenesis/genetics/drug effects ; *Neoplasms/genetics/pathology/microbiology ; Neoplasm Metastasis ; Gene Expression Regulation, Neoplastic/drug effects ; }, abstract = {Cancer is a genomically complex and multifaceted disease. Wealth of information distilled through decades of high-throughput research has revealed a broad spectrum of oncogenic signaling cascades, immunological evasion, and drug resistance, which play a steering role in carcinogenesis and metastasis. Noncoding RNAs have also emerged as key players in the regulation of multiple stages of cancer progression and metastatic spread of cancer cells to secondary sites. The concept of probiotics has started to gain limelight due to its ability to pharmacologically modulate the host microbiome and the immunological responses. The genomics era has provided impetus for the discovery and characterization of bacterial probiotic effector molecules that stimulate specific responses. We have witnessed an exponential increase in the seminal studies which provided proof-of-concept about the mechanistic regulation of cell signaling pathways and noncoding RNAs by probiotics. These exciting and groundbreaking studies ignited an outburst of data generated using several "omics" technologies. In this chapter, we have provided a summary of seminal studies associated with the anticancer and antimetastatic role of probiotics in animal models. However, circumstantial evidence has also underlined tumor-promoting role of probiotics in animal model studies. Therefore, there is a need to scrupulously reinterpret the existing pieces of evidence related to conflicting data about pro-tumorigenic and tumor-inhibitory roles of probiotics. We also critically summarized how probiotics modulated noncoding RNAs to prevent/inhibit cancer progression. Surprisingly, probiotics-mediated regulation of noncoding RNAs has not been comprehensively explored in different cancers. In accordance with this approach, in-depth analysis of target long noncoding RNAs and circular RNAs by probiotics will allow the researchers to develop near-to-complete signaling landscape to reap the full benefits of the medicinal significance of probiotics.}, } @article {pmid41316248, year = {2025}, author = {Wang, L and Wang, L and Liu, M and Yuan, Q and Cheng, L and Chen, H and Mao, S and Li, S and Yan, Q and Xing, G and Zheng, N}, title = {Characterization of the gut virome in patients with nonalcoholic fatty liver disease.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {6}, pmid = {41316248}, issn = {1479-5876}, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with complex gut microbiome involvement. While bacterial dysbiosis in NAFLD has been widely studied, the role of the gut virome remains largely unexplored.

METHODS: We profiled gut viral communities from 90 NAFLD patients and 90 non-NAFLD controls using whole-metagenome shotgun sequencing. Viral taxonomic composition, host associations, and functional gene repertoires were analyzed. Serum metabolomic data were integrated to assess virus–metabolite interactions, and random forest models were constructed to evaluate the diagnostic potential of viral signatures.

RESULTS: Overall viral diversity showed no significant differences between NAFLD and controls, but subtle compositional shifts were detected at the vOTU level, with 105 viruses enriched in NAFLD and 185 in non-NAFLD individuals. NAFLD-enriched phages primarily targeted Bacteroides, whereas non-NAFLD-enriched phages were associated with beneficial genera such as Faecalibacterium, Oscillibacter, and Prevotella. Functional annotation revealed a reorganization of viral gene repertoires: genes involved in DNA recombination and horizontal transfer (e.g. int, recD) were depleted, while those related to host interaction and stress response (e.g. xerD, dnaK, hipB) were enriched in NAFLD, indicating enhanced viral persistence and host communication. Serum metabolomic profiling identified 8 differential metabolites, and correlation analysis linked specific vOTUs with altered metabolic pathways. A random forest model based on viral features achieved an AUC of 0.758, outperforming the bacterial model, while integration of viral and bacterial features further improved prediction (AUC = 0.837).

CONCLUSION: The gut virome in NAFLD undergoes compositional and functional remodeling characterized by a shift toward host-adaptive, metabolically interactive viral communities. These viral alterations are closely associated with host metabolic changes and demonstrate strong diagnostic potential. Our findings highlight the virome as an overlooked yet critical component of the gut ecosystem in NAFLD pathogenesis and as a promising source of noninvasive biomarkers for disease prediction and monitoring.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07443-w.}, } @article {pmid41479039, year = {2026}, author = {Elbrashy, MM and Farouk, S and Hamdy, NM and Metwally, H and Bader El Din, NG}, title = {Unlocking the Epigenetic Landscape of Colorectal Cancer: A Step Toward Epigenetics to Precision.}, journal = {Sub-cellular biochemistry}, volume = {114}, number = {}, pages = {183-236}, pmid = {41479039}, issn = {0306-0225}, mesh = {Humans ; *Colorectal Neoplasms/genetics/pathology/metabolism ; *Epigenesis, Genetic ; *DNA Methylation ; *Gene Expression Regulation, Neoplastic ; MicroRNAs/genetics/metabolism ; Biomarkers, Tumor/genetics ; Precision Medicine ; }, abstract = {Epigenetic modifications function as central controllers of gene expression in cancer, coordinating crucial cellular activities that trigger the initiation and progression of the tumor, besides their importance in therapeutic response. These modifications can control the gene expression without changing the sequence of DNA. In colorectal cancer (CRC), these alterations involving DNA methylation, histone modifications, chromatin rearrangement, and noncoding ribonucleic acids play a significant role in the pathogenesis of CRC. Abnormal DNA methylation silences the tumor suppressor genes, meanwhile leading to the instability of the genome via reduction of the whole methylation. Specific methylation signatures, such as CpG islands, help in categorizing the subtypes of the tumor and predicting the clinical outcomes. In addition, histone-modifying enzymes, including enhancer of zeste homolog 2 and histone deacetylases, are frequently uncontrolled in cancer, leading to alterations in gene expression. Moreover, small regulatory ribonucleic acids such as microRNA-21 and microRNA-143 contribute to the complex networks that regulate cell survival and growth. Collectively, these epigenetic alterations trigger the transition from benign growth to malignant cancer by continuously suppressing crucial genes. Furthermore, the epigenetic markers can be detected in blood and stool specimens, offering promising tools for the early detection of cancer. The major obstacle in cancer treatment is the resistance to chemotherapy drugs, which is mainly caused by epigenetic modifications in cancer cells. Therefore, the new therapeutic ways target the modifications that occur in DNA methylation and histone, mostly in conjunction with conventional therapies. As the metabolites produced by the gut microbiome can alter the host epigenetics, they can promote cancer development. Promising technologies help in the concise proofreading of epigenetic marks, and advanced single-cell analysis is paving the way for personalized treatment approaches. This cutting-edge knowledge of epigenetic regulation mechanisms offers new prospects for enhancing diagnosis, prognosis, and targeted therapies in colorectal cancer.}, } @article {pmid41479037, year = {2026}, author = {El-Daly, SM and Fayed, B and Talaat, RM and Gouhar, SA and Fahmy, CA and El-Jawad, AMA and Hamdy, NM and Abd Elmageed, ZY}, title = {The Intricate Interplay of Noncoding RNAs and the Gut Microbiome in Gastrointestinal and Endocrine-Related Cancers.}, journal = {Sub-cellular biochemistry}, volume = {114}, number = {}, pages = {61-121}, pmid = {41479037}, issn = {0306-0225}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Gastrointestinal Neoplasms/microbiology/genetics/pathology/metabolism ; *RNA, Untranslated/genetics/metabolism ; *Endocrine Gland Neoplasms/microbiology/genetics/metabolism/pathology ; Dysbiosis/microbiology/genetics ; Animals ; }, abstract = {The human gut microbiome and noncoding RNAs (ncRNAs) represent interconnected regulatory networks that profoundly influence cancer development, particularly in gastrointestinal and endocrine-related malignancies. This chapter delineates the intricate interplay of microbiome-ncRNA crosstalk in the context of gastrointestinal and endocrine-related cancers.The chapter begins with a comprehensive overview of the taxonomic and functional landscape of the healthy adult gut microbiome. The gut microbiome, comprising trillions of microorganisms, plays a crucial role in endocrine regulation through hormone metabolism, synthesis of bioactive compounds, and modulation of immune responses, thereby establishing a critical crosstalk with the host endocrine system. Dysbiosis, or microbial imbalance, has been linked to endocrine dysfunction and the pathogenesis of various diseases, including gastrointestinal and endocrine-related cancers.We then elucidate the classifications of noncoding RNAs and their function as key molecular regulators in cellular communication, gene expression, and disease progression. NcRNAs contribute significantly to the development and progression of endocrine-related malignancies. The intricate crosstalk between the gut microbiome and host ncRNAs demonstrates how gut dysbiosis can disrupt host ncRNA expression patterns, thereby affecting oncogenic pathways, immune surveillance, and metabolic reprogramming linked to tumor initiation, progression, and metastasis. Conversely, host-derived ncRNAs, secreted into the gut lumen, can directly shape microbial gene expression. In this section, we explore how dysregulation of this axis contributes to carcinogenesis through the promotion of chronic inflammation, epithelial barrier dysfunction, and oncogenic signaling. Therapeutic strategies targeting this interplay, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, are introduced in the context of restoring microbial balance.This comprehensive chapter provides crucial insights into the molecular mechanisms governing microbiome-ncRNA interactions and their implications for cancer biology, offering new perspectives for therapeutic interventions in gastrointestinal and endocrine-related malignancies.}, } @article {pmid41478928, year = {2026}, author = {de Brito, CB and de Amorim-Santos, BM and Souza, DG}, title = {Handling and Experimentation with Germ-Free Mice.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2993}, number = {}, pages = {1-8}, pmid = {41478928}, issn = {1940-6029}, mesh = {Animals ; *Germ-Free Life ; Mice ; *Gastrointestinal Microbiome ; }, abstract = {Immediately after birth, mammals are largely colonized by microorganisms, with the gastrointestinal tract being the most commonly colonized organ. Over the years, several studies have shown that the intestinal microbiota is important for various physiological functions of the host. Gnotobiotic animal models are frequently used to better understand how the microbiota influences health and disease scenarios. Among gnotobiotic models, germ-free (GF) animals were first used in 1895, but it was not until 60 years later that germ-free colonies were suitable for large-scale experiments. The use of GF mice is an interesting and rich tool for studying the microbiome. However, their maintenance is a complex process that needs to be done carefully. In this chapter, we describe step by step how to manage and manipulate the gut microbiota of GF mice.}, } @article {pmid41478687, year = {2026}, author = {Wang, G and Liu, Y and Ma, F and Qiu, W}, title = {Insights into meat-microbiome interactions: from community assembly to meat spoilage.}, journal = {Food microbiology}, volume = {136}, number = {}, pages = {105010}, doi = {10.1016/j.fm.2025.105010}, pmid = {41478687}, issn = {1095-9998}, mesh = {*Meat/microbiology ; *Microbiota ; Animals ; *Bacteria/classification/genetics/isolation & purification/metabolism ; Food Microbiology ; Microbial Interactions ; Ecosystem ; }, abstract = {Meat spoilage represents a critical challenge in food security and sustainability. Although extensive research has characterized meat microbiota composition and identified specific spoilage organisms, comprehensive understanding of the complex ecological dynamics within meat microbiomes remains limited. This review critically examines current knowledge of meat-associated microbiomes by applying an ecological perspective to address four key questions: the functional roles assigned to microorganisms during community assembly, microbial colonization and adaptation mechanisms in meat ecosystems, nutrient utilization patterns driving metabolic activities and ecological interactions, and microbial interaction effects on community ecology and functional outcomes. Through systematic exploration of these questions, we reveal that meat spoilage is determined by community dynamics and functional activities of entire microbial ecosystems rather than individual species alone. Our analysis identifies critical research gaps including inadequate understanding of core and keystone taxa contributions, limited exploration of microbial interactions, and insufficient integration of multi-omics approaches with ecological modeling. Based on these findings, future practical applications should focus on ecology-guided preservatives that target key spoilage pathways and predictive models integrating metabolic fluxes with environmental parameters. This comprehensive paradigm shift from composition-focused to function-oriented research will enhance theoretical understanding and provide practical insights for more effective spoilage control in the food industry.}, } @article {pmid41478678, year = {2026}, author = {Wang, Y and He, L and Hu, X and Guan, Y and Chen, X and Du, J and Chen, J and Ma, C and Ye, L}, title = {Metagenomic and culture-based genomics reveal virulence and resistance risks in Manila clam microbiomes.}, journal = {Food microbiology}, volume = {136}, number = {}, pages = {105001}, doi = {10.1016/j.fm.2025.105001}, pmid = {41478678}, issn = {1095-9998}, mesh = {Animals ; *Bivalvia/microbiology ; Metagenomics ; *Bacteria/genetics/isolation & purification/pathogenicity/drug effects/classification ; *Microbiota ; Virulence Factors/genetics ; Anti-Bacterial Agents/pharmacology ; Virulence ; Genomics ; *Drug Resistance, Bacterial ; Vibrio/genetics/pathogenicity/isolation & purification/drug effects ; Shellfish/microbiology ; Phylogeny ; }, abstract = {Bivalves are important aquaculture products whose safety is shaped by their microbiomes. Here, we present the first comprehensive characterization of Manila clam (Ruditapes philippinarum) microbiomes using both shotgun metagenomics (6 clams) and culture-based genomics (169 isolates, 40 draft genomes), integrating community, functional, and antimicrobial resistance profiling. Communities were dominated by Proteobacteria (99.3-99.9 %), with Pseudoalteromonas and Vibrio collectively accounting for 74.9-99.7 % and showing strong inverse correlations, defining Pseudoalteromonas-dominated, Vibrio-dominated, and mixed states. Species richness ranged from 22 to 180 per sample. Recognized human pathogens occurred at low abundance (<0.3 %), including Vibrio parahaemolyticus, Vibrio alginolyticus, and Photobacterium damselae, while opportunistic vibrios expanded in some clams (e.g., Vibrio cyclitrophicus 57.9 %). We reconstructed 34 high-quality MAGs, seven resolved to species (Pseudoalteromonas tetraodonis, V. cyclitrophicus, Shewanella aquimarina), alongside unclassified lineages. Metagenomes encoded 14 virulence-factor categories with 2281 subtypes, and isolate genomes added 93 further subtypes, including high-virulence loci in Escherichia coli and type III secretion genes in V. parahaemolyticus. Resistomes spanned 18 antibiotic classes with 511 subtypes; isolates contributed 22 additional antibiotic resistance genes(ARGs), including extended-spectrum β-lactamases (blaCTX-M-102) and blaNDM-1. Four carbapenemase-producing isolates (three Shewanella algae, one V. parahaemolyticus) carried blaNDM-1 on IncC plasmids, with the V. parahaemolyticus plasmid transferable to E. coli. Two P. tetraodonis MAGs encoded RiPP-like and terpene biosynthetic clusters plus phage-defense systems, consistent with Vibrio suppression. These findings demonstrate that clam microbiomes fluctuate between protective (Pseudoalteromonas) and pathogenic (Vibrio-Shewanella) states, providing a first integrated framework for assessing microbial risk, antimicrobial resistance, and food safety interventions in bivalve aquaculture.}, } @article {pmid41478594, year = {2025}, author = {Lee, DY and Liu, J and Lee, SJ and Lamichhane, G and Swayze, A and Zhang, G and Kim, TY and Egan, JM and Kim, Y}, title = {Bioconverted red ginseng protects liver functions and alters insulin homeostasis-associated gut microbiome composition in aged mice.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101310}, doi = {10.1016/j.tjnut.2025.101310}, pmid = {41478594}, issn = {1541-6100}, abstract = {BACKGROUND: Aging is associated with progressive functional deteriorations that affect the metabolic dysfunction in the liver and the alteration of the gut microbial environment. Red ginseng (RG) is one of the widely investigated ginseng products known for its anti-aging properties, derived from its unique bioactive compounds known as ginsenosides.

OBJECTIVE: This study aimed to discover the potential anti-aging effects of bioconverted red ginseng (BRG), a new RG product applied with enzymatic treatments, using an aged mouse model.

METHODS: Two different interventional regimes were employed: oral gavage administration and ad libitum intervention. For oral gavage study, 9-week-old (Young) and 18-month-old (Old) mice were orally injected with either distilled water or 300 mg/kg BRG for 4 weeks (n = 10 per group). For ad libitum study, 19-month-old mice were fed with a normal chow diet (NCD), NCD with 150 mg/kg BRG (BRG-Low; NCD+BRGL), or NCD with 300 mg/kg BRG (BRG-High; NCD+BRGH) for 14 weeks (n = 9-10 per group). Liver tissues were harvested from each group for RNA sequencing, immunoblotting, and mRNA expression analyses. Fecal samples were collected and 16S rRNA sequencing was conducted to profile gut microbiome composition.

RESULTS: The 4-week BRG administration provided potential modulations in hepatic gene expression profiling in terms of mitigating age-driven liver cholestasis, as well as positive alterations in the gut microbial structure and composition. Moreover, the 14-week BRG supplementation protected insulin homeostasis through activating the hepatic protein kinase B (AKT)/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway and inhibiting glycogen synthase kinase (GSK)-3β in aged mice. In the meantime, BRG consumption altered insulin homeostasis-related microbiome structures by not only reducing the Firmicute/Bacteroidetes (F/B) ratio and relative abundance of opportunistic taxa, including Erysipelotrichaceae, but also increasing the enrichment of commensal bacteria, such as Muribaculaceae.

CONCLUSIONS: Taken together, this study highlights that BRG could be a promising anti-aging functional food substance by maintaining insulin homeostasis and the gut microbial equilibrium.}, } @article {pmid41478407, year = {2025}, author = {Ribeiro, BE and Schmukler de Lima, I and Cristina da Silva E Souza, K and Bittencourt Rosas, SL and Santana, PT and Amaral, G and Machado, JC and Pereira de Oliveira, R and Leal, C and Thompson, C and Thompson, F and Lima Castelo-Branco, MT and Coutinho-Silva, R and Pereira de Souza, HS}, title = {The P2X7 receptor promotes intestinal fibrosis by modulating the gut microbiota and the inflammasome.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101718}, doi = {10.1016/j.jcmgh.2025.101718}, pmid = {41478407}, issn = {2352-345X}, abstract = {BACKGROUND AND AIMS: Considering the role of the P2X7 receptor in intestinal inflammation, we examined its potential involvement in fibrosis development.

METHODS: Colonic biopsies from patients with inflammatory bowel disease (IBD) were analyzed via double immunofluorescence under confocal microscopy. Colon fibroblasts were used to analyze P2X7 receptor modulation and chemotaxis. Experimental chronic colitis was induced with three cycles of oral dextran sodium sulfate (DSS) treatment in P2X7[+/+] and P2X7[-/-] mice. The mice were evaluated via follow-up video endoscopy with an endoluminal ultrasound biomicroscopic (eUBM) system, histological scoring, immunohistochemistry, cytokine measurement in colon explants, gene expression analysis of P2X7 signaling targets via qRT‒PCR, and microbiome composition analysis.

RESULTS: Colocalization studies revealed a greater density of P2X7[+]/α-SMA[+] cells in colon sections from patients than in those from controls, especially in patients with Crohn's disease (p<0.05). Activation of the ATP-P2X7 pathway in human fibroblasts increased cell migration, calcium influx, and collagen production. Video colonoscopy with the eUBM system revealed significantly more inflammation, with greater wall thickness and stiffness, in P2X7[+/+]- mice than in P2X7[-/-] and P2X7[+/+] mice treated with A740003 (a P2X7-selective inhibitor). P2X7[+/+] mice exhibited increased caspase-1 and NLRP3 expression, as well as NF-κB and ERK activation, accompanied by decreased PPARγ expression. In the supernatants of colon explants, TNF-α, IL-1β, IFN-γ, TGF-β, IL-10, and collagen production were increased in P2X7[+/+] mice. Various microbial changes were observed in P2X7[-/-] and P2X7[+/+] mice.

CONCLUSION: Regulatory mechanisms downstream of P2X7, combined with signals from a dysbiotic microbiota, activate intracellular signaling pathways and the inflammasome, leading to intestinal inflammation and promoting fibrogenesis.}, } @article {pmid41478323, year = {2025}, author = {Li, R and Liu, S and Zhang, H and Huang, X and Qian, W and Han, D and Wang, F and Feng, Z and Zhang, T and Lin, H and Li, H}, title = {Prevotella copri leads to colonic barrier dysfunction via the succinate receptor 1-FoxM1-IL-6 axis.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {}, number = {}, pages = {120099}, doi = {10.1016/j.bbamcr.2025.120099}, pmid = {41478323}, issn = {1879-2596}, abstract = {Prevotella copri, a key commensal bacterium in the human gut microbiome, exhibits both positive and negative abundance correlations with various disorders. Although multiple studies have suggested an association between P. copri and intestinal pathologies, the mechanistic basis remains elusive. In this study, we examined P. copri's effects on colonic physiology in healthy mice, revealing its capacity to compromise intestinal barrier integrity. This was demonstrated through downregulation of colonic tight junction proteins (Occludin and ZO-1) and elevated serum levels of gut permeability markers (LPS and D-LA). We identified succinate as the primary microbial metabolite mediating P. copri's barrier-disrupting effects, with succinate receptor 1 (SUCNR1) being essential for this pathological process. Notably, both P. copri colonization and succinate administration activated the IL-6-STAT3 signaling pathway, leading to transcriptional suppression of the tight junction-related gene, Occludin. Through mechanistic studies, we identified Forkhead box M1 (FoxM1) as a crucial transcription factor regulating P. copri- or succinate-induced Il-6 expression. Clinical relevance was established through human cohort analyses showing significant positive correlations between fecal succinate levels and plasma markers of gut permeability. These findings elucidate a novel mechanistic pathway through which P. copri impairs colonic function, suggesting therapeutic potential in colitis through strategies targeting either P. copri abundance or microbial succinate production.}, } @article {pmid41478268, year = {2025}, author = {Chen, J and Xu, J and Xu, J and Xu, F and Gong, F and Xiao, P and Ma, H and Zhang, Q and Feng, J and Min, Y}, title = {Gut microbiota-derived propionic acid mitigates age-related albumen quality deterioration by modulating magnum functions.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106357}, doi = {10.1016/j.psj.2025.106357}, pmid = {41478268}, issn = {1525-3171}, abstract = {The declined albumen quality during the late laying phase is associated with age-related magnum dysfunction, in which to the roles of gut microbiota is unclear. This study aimed to elucidate the relationship between gut microbiota and magnum function, and its impact on albumen quality. Hy-Line Brown layers at peak (30 wk) and late (70 wk) laying phases were compared to assess age-related changes in albumen quality, magnum function, and gut microbiota. Fecal microbiota transplantation (FMT) from peak- to late-phase hens was conducted to assess functional effects. Microbiome and metabolome analyses were then integrated to identify key bacterial taxa and metabolites. The role of the leading candidate metabolite was further validated through dietary supplementation. Results showed that late-phase hens exhibited significant reductions in albumen height, magnum mucosal fold height, and tubular gland diameter (P < 0.05), alongside gut microbial dysbiosis. FMT from peak-phase donors effectively reversed age-related declines in magnum histomorphology and albumen height in late-phase hens. It also up-regulated the expression of barrier function genes (Claudin-1, ZO-2, MUC2, AGR2) and magnum secretory markers (OVOA), while down-regulating pro-inflammatory cytokines (IL-4, IFN-γ) (P < 0.05). Microbial analysis identified Anaerotruncus as the only genus consistently enriched following FMT and positively correlated with improved albumen height and magnum morphology. Metabolomic analysis revealed that propionic acid was the top metabolite associated with Anaerotruncus abundance. Crucially, dietary supplementation with sodium propionate recapitulated the key benefits of FMT. In summary, our findings revealed a gut microbiota-oviduct axis through which microbiota from peak-laying hens ameliorate age-related magnum decline and improve albumen quality in aging hens.}, } @article {pmid41478129, year = {2025}, author = {Baharaghdam, S and Karimi, S and Farahani, ME and Aghebati-Maleki, L and Yousefi, M}, title = {Endometrial immune profile: A predictor of pregnancy success.}, journal = {Reproductive biology}, volume = {26}, number = {1}, pages = {101174}, doi = {10.1016/j.repbio.2025.101174}, pmid = {41478129}, issn = {2300-732X}, abstract = {The likelihood of a successful pregnancy is influenced by a set of variables that influence endometrial receptivity, including hormonal, genetic, metabolic, age, lifestyle, and immunological factors. Among these, the endometrial immune profile has received particular attention as a critical actor of implantation and embryo tolerance. Dynamic fluctuations in immune cell populations-such as macrophages, dendritic cells, uterine natural killer cells, and regulatory T cells-across the menstrual cycle might significantly affect the endometrium's capacity to support successful implantation. Recent evidence highlights that disruptions in the quantity, phenotype, or function of these immune cells contribute to impaired endometrial receptivity in infertility-related disorders, including recurrent implantation failure, recurrent pregnancy loss, endometriosis, and polycystic ovary syndrome. This review provides a comprehensive assessment of immune cell composition and function in the healthy endometrium compared to pathological conditions, emphasizing how immune dysregulation may impair pregnancy. Furthermore, we evaluate both current and emerging diagnostic modalities-from immunohistochemistry and flow cytometry to high-resolution single-cell transcriptomics-and endometrial microbiome impact on immune profiling that enables more precise characterization of immune profile dysregulation, alongside established and investigational therapies, with particular attention to their efficacy and mechanistic rationale. By integrating these insights, a clinically oriented framework can be provided to guide the development of personalized diagnostic algorithms and targeted immune-based therapies that, ultimately, could lead to improved implantation rates and live birth outcomes in individuals facing infertility disorders with immunological causes.}, } @article {pmid41478124, year = {2025}, author = {Xing, W and Gai, X and Cheng, X and Fang, Z and Chen, G}, title = {Rhizosphere microbiome drives Betula luminifera adaptation to antimony mining sites through functional traits and transcriptional reprogramming.}, journal = {Journal of hazardous materials}, volume = {501}, number = {}, pages = {140972}, doi = {10.1016/j.jhazmat.2025.140972}, pmid = {41478124}, issn = {1873-3336}, abstract = {Rhizosphere microbiome are pivotal for plant adaptation to extreme environments. However, the regulatory mechanisms underlying their control of the ecological adaptation of native woody plants in mining areas remain unclear. Here, we integrated metagenomic and transcriptomic analyses to elucidate how the rhizosphere microbiome facilitates Betula luminifera adaptation to antimony (Sb) mining sites. Under sterile conditions, B. luminifera from mining sites prioritized shoot growth, whereas control-origin seedlings favored root development. Microbial inoculation mitigated this growth dichotomy, balancing above- and belowground biomass allocation. Notably, B. luminifera from control sites upregulated antioxidant biosynthesis genes (α- and β-tocopherol pathways), while B. luminifera from mining sites enhanced lignin synthesis under Sb stress. After inoculation with rhizosphere microbiome from the mining-site, genes related to Sb/As resistance (ACR3, arsB/C) and soil nutrient cycle (narG, phnM) were significantly enriched in the rhizosphere of B. luminifera, which were contributed by Proteobacteria and Actinobacteria. Transcriptional profiling revealed that microbial inoculation triggered systemic upregulation of phytohormone-related genes (auxin, cytokinin, abscisic acid), enhancing stress resilience and growth. These findings unveil a synergistic plant-microbe adaptation mechanism in Sb polluted soils in mining sites, highlighting microbial-mediated trait trade-offs and transcriptional plasticity as drivers of ecological success in extreme environments.}, } @article {pmid41477949, year = {2025}, author = {Li, W and Song, X and Wang, Y and Wen, D and Zhou, Y and Zhang, D}, title = {Iron-manganese inputs shape the coupling between deposit morphology and microbiome during the early-stage corrosion on cement mortar-lined pipe walls under drinking-water conditions.}, journal = {Journal of environmental management}, volume = {398}, number = {}, pages = {128468}, doi = {10.1016/j.jenvman.2025.128468}, pmid = {41477949}, issn = {1095-8630}, abstract = {Maintaining water quality in drinking water distribution systems (DWDSs) requires resilient pipe-wall interfaces, yet the build-up of iron (Fe) and manganese (Mn), the most common metals in DWDSs, often initiates deposit growth and triggers discoloration events. However, the physicochemical impacts of early Fe-Mn deposition on pipe-wall surfaces have not been systematically elucidated. To elucidate their mechanistic role in the onset of scale development, self-designed electrodes were employed to monitor the electrochemical behavior of cement mortar-lined pipe surfaces under controlled Fe-Mn dosing (50-200 μg/L Fe with 10 μg/L Mn). Results showed that a dosing condition of 100 μg/L Fe with 10 μg/L Mn produced compact and adherent deposits with high charge-transfer resistance (Rct = 1.33 × 10[6] Ω) and low corrosion current density (icor = 3.68 × 10[-5] mA/cm[2]). This condition was attributed to cohesive biofilms dominated by Pseudomonas with co-dominant Hydrogenophaga and Sphingomonas, which, through assimilation-centered carbon and nitrogen pathways, secreted abundant extracellular polymeric substances, associated with minimized particulate metal accumulation in bulk water. In contrast, excessive Fe input (200 μg/L) generated scale-like, metal-oxide-bearing deposits accompanied by elevated Fe-Al contents, reduced Rct = 2.97 × 10[5] Ω, higher icor = 1.70 × 10[-4] mA/cm[2] and metabolically diverse but weakly coordinated microbial communities. These results demonstrate that Fe-Mn-regulated morphology-microbiome coupling shapes early-stage corrosion behavior and that appropriate Fe-Mn levels are essential for promoting stable deposits and supporting long-term drinking-water safety.}, } @article {pmid41477864, year = {2026}, author = {Favela, A and Kent, AD and Sible, CN and Flint-Garcia, S and Klimasmith, IM and Mujjabi, C and Raglin, SS and Below, FE and Bohn, MO}, title = {Lost and found: Rediscovering microbiome-associated phenotypes that reshape agricultural sustainability.}, journal = {Science advances}, volume = {12}, number = {1}, pages = {eaed3360}, pmid = {41477864}, issn = {2375-2548}, mesh = {*Microbiota ; Phenotype ; *Agriculture/methods ; *Zea mays/microbiology/genetics/growth & development ; Rhizosphere ; Soil Microbiology ; Plant Roots/microbiology ; Crops, Agricultural/microbiology ; Nitrogen/metabolism ; Nitrification ; }, abstract = {Modern agriculture faces an urgent need to improve nutrient use efficiency while reducing environmental impacts. Here, we show that ancestral traits controlling rhizosphere microbiome functions can be reintroduced into elite maize through targeted teosinte introgressions. Using near-isogenic lines, we mapped microbiome-associated phenotypes (MAPs) derived from teosinte that suppress nitrification and denitrification-key microbial processes contributing to nitrogen loss. These introgressions altered root exudate chemistry, resulting in distinct microbial assemblies and enhanced nitrogen retention. We identified candidate loci and exudate metabolites responsible for suppressive activity and demonstrated their functional effects in vitro. These findings reveal a genetic and biochemical basis for rewilding microbiome-mediated ecosystem services in crops, offering a scalable path toward sustainable nutrient management in global agriculture.}, } @article {pmid41477781, year = {2025}, author = {Garashchenko, NE and Smurova, NE and Semenova, NV and Belkova, NL and Nemchenko, UM and Klimenko, ES and Zugeeva, RE and Kolesnikov, SI and Madaeva, IM and Kolesnikova, LI}, title = {[Gut microbiome and sleep disturbances in menopause.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {38}, number = {4}, pages = {562-570}, pmid = {41477781}, issn = {1561-9125}, mesh = {Humans ; Female ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Menopause/physiology ; *Sleep Wake Disorders/microbiology/diagnosis/physiopathology ; Surveys and Questionnaires ; Sleep Quality ; }, abstract = {The paper presents the results of the gut microbiota study in menopausal women with sleep disorders based on different assessments of sleep quality. The study involved 96 menopausal women. Sleep quality was assessed using three questionnaires: the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale. The qualitative and quantitative composition of the microbiota was assessed using microbiological and molecular genetic methods. In the group with sleep disorders (according to PSQI), molecular genetic analysis of the microbiome revealed an increased content of Enterococcus spp. (p=0,03), Clostridium perfringens (p=0,01), and Shigella spp. (p=0,04). Compared to the control, with moderate sleep disorders (according to the ISI questionnaire), the content of Clostridium perfringens was increased (p=0,02). According to the Epworth scale, a higher content of Bifidobacterium spp. (p=0,04), Prevotella spp. (p=0,02) and Eubacterium rectale (p=0,04) was noted in the group with excessive daytime sleepiness compared to the control. Thus, in menopausal women, the composition and structure of the gut microbiota are associated with sleep disorders.}, } @article {pmid41477766, year = {2025}, author = {Mirji, G and Bhat, SA and El Sayed, M and Reiser, SK and Gavara, SP and Ye, Y and Miyamoto, T and Zhang, W and Vogel, P and Cassel, J and Liu, Q and Goldman, AR and Kossenkov, A and Zhang, N and Shinde, RS}, title = {Aromatic microbial metabolite hippuric acid enhances inflammatory responses in macrophages via TLR-MyD88 signaling and lipid remodeling.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116749}, doi = {10.1016/j.celrep.2025.116749}, pmid = {41477766}, issn = {2211-1247}, abstract = {The gut microbiome produces diverse metabolites shaping immunity, yet their pro-inflammatory potential remains unclear. Using untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics, we identified hippuric acid-an aromatic, microbe-derived metabolite-as a potent enhancer of inflammatory responses during Escherichia coli infection. Hippuric acid administration heightened inflammation, activated innate immune cells, and reduced survival in infected mice. In vitro, hippuric acid selectively potentiated M1-like (lipopolysaccharide [LPS] or LPS+interferon gamma [IFNγ]) macrophage pro-inflammatory responses but had no effect on M2-like (interleukin [IL]-4) polarization. It enhanced responses to myeloid differentiation primary response 88 (MyD88)-dependent Toll-like receptor (TLR) ligands but not TRIF-, STING-, or NOD2-mediated stimuli. Genetic deletion of MyD88 abolished hippuric-acid-induced pro-inflammatory responses. Transcriptomic and lipidomic analyses revealed increased cholesterol biosynthesis and lipid accumulation, while reducing cellular cholesterol blunted the pro-inflammatory effects of hippuric acid. Notably, hippuric acid also enhanced pro-inflammatory responses in human macrophages, and its elevated levels correlated with sepsis mortality, linking microbial metabolism, lipid remodeling, and innate immunity.}, } @article {pmid41477725, year = {2026}, author = {Chan, NSL and Cross, C and Prestidge, CA and Wardill, HR and Bowen, J and Joyce, P}, title = {The resilient microbiome: how baseline gut microbial composition influences response to cancer treatment.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/1040841X.2025.2610215}, pmid = {41477725}, issn = {1549-7828}, abstract = {The human gut microbiome is increasingly recognized as a key modulator of health and disease, with growing evidence supporting its influence on responses to cancer therapy. An important aspect of this relationship is gut microbial resilience, defined as the ability of the microbiome to recover its ecological equilibrium following disruption. Individual variations in microbial composition significantly influence resilience and, consequently, personalized responses to cancer treatments. However, the underlying functional characteristics of a resilient microbiome remain incompletely understood. Identifying specific microbial profiles with greater resilience to cancer therapies could improve the ability to predict treatment responses and mitigate adverse events. However, despite growing interest, a lack of longitudinal and mechanistic studies currently limits their clinical translation. This review examines current literature on gut microbiome compositions and individual treatment response to cancer therapy, with a focus on microbial features linked to resilience which could enable prediction of adverse response. While the use of microbial metabolites as predictive biomarkers (e.g. short-chain fatty acids and bile acids) is promising, further longitudinal and interventional studies are essential to support clinical application. Establishing specific microbial and metabolite profiles that promote resilience is essential to advance this emerging field of personalized gut-microbiome therapy.}, } @article {pmid41477720, year = {2025}, author = {Kurnosov, AS and Linde, NN and Molodtsova, PA and Glazunova, EV and Moskalenko, AM and Sheptulina, AF and Bodunova, NA and Zlobovskaya, OA}, title = {[Comparative Evaluation of DNA Extraction Methods from Fecal Samples: Statistical Analysis of Commercial Kits and Laboratory Protocols Using Real-Time PCR Data].}, journal = {Molekuliarnaia biologiia}, volume = {59}, number = {6}, pages = {1002-1021}, doi = {10.7868/S3034555325060104}, pmid = {41477720}, issn = {0026-8984}, mesh = {*Feces/microbiology/chemistry ; Humans ; *DNA, Bacterial/isolation & purification/genetics ; *Real-Time Polymerase Chain Reaction/methods ; *Gastrointestinal Microbiome/genetics ; Reagent Kits, Diagnostic ; *Gram-Negative Bacteria/genetics/isolation & purification ; *Gram-Positive Bacteria/genetics/isolation & purification ; }, abstract = {The emergence of new data on the association between the composition of the intestinal microbiota and various human diseases has generated increasing interest in microbiome research. In this context, selection of the DNA extraction method represents a critical stage in the design of the experiment, significantly affecting the reliability and reproducibility of results. This study presents a comparative analysis of 12 DNA extraction methods, including nine commercial kits and three laboratory protocols. We evaluated the taxonomic representation, including Gram-positive (Lactobacillaceae, Coprococcus spp., Streptococcus sp., Clostridium leptum) and Gram-negative bacteria (Enterobacteriaceae, Akkermansia muciniphila, Fusobacterium nucleatum, Bacteroides fragilis). The extraction efficiency was assessed by the DNA yield, expressed in GE/pL of eluate or in GE/-µL of feces, as well as by the frequency of low-abundance taxa loss. Clustering of the methods according to the type of lysis was demonstrated: mechanical lysis provided stable and high DNA yields, particularly for Gram-positive bacteria, while chemical and enzymatic methods showed lower efficiency. We determined that the lysis type and pre-processing of intact fecal samples are the key factors affecting the DNA extraction efficiency and preservation of the native taxonomic profile. The best results were demonstrated by the QIAamp® PowerFecal® Pro DNA Kit (Qiagen) and the combination of AmpliTest UniProb + AmpliTest RIBO-prep kits (Center for Strategic Planning, Federal Medical-Biological Agency, Russia), both of which outperformed other methods in terms of DNA yield. The QIAamp® Fast DNA Stool Mini Kit (Qiagen) showed minimal losses of low-abundance taxa. These findings can be used for the standardization of gut microbiota DNA extraction methodologies and the development of domestic protocols.}, } @article {pmid41477712, year = {2025}, author = {Glazunova, EV and Kurnosov, AS and Molodtsova, PA and Moskalenko, AM and Makarov, VV and Zlobovskaya, OA}, title = {[Gut Microbiota in Colorectal Cancer Carcinogenesis: The Evolution of Hypotheses].}, journal = {Molekuliarnaia biologiia}, volume = {59}, number = {6}, pages = {891-908}, doi = {10.7868/S3034555325060029}, pmid = {41477712}, issn = {0026-8984}, mesh = {*Colorectal Neoplasms/microbiology/pathology ; Humans ; *Gastrointestinal Microbiome ; *Carcinogenesis/pathology/genetics ; Animals ; *Dysbiosis/microbiology ; }, abstract = {Colorectal cancer remains one of the leading causes of cancer-related mortality, highlighting the importance of optimizing approaches for its early diagnosis and therapy. One promising area in this field is the investigation of the role of the gut microbiome in the initiation and progression of colorectal cancer. This review examines three principal hypotheses explaining the contribution of microbiota to carcinogenesis: the "Alpha-bug", the "Keystone pathogen", and the "Driver-Passenger" models. We analyze data on the mechanisms of microbiota-tumor cells interactions, including the induction of inflammation, genotoxicity, and disruption of the intestinal barrier function. Findings are also presented indicating that certain microorganisms previously considered markers of the advanced stages may possess pro-oncogenic properties, thereby refining existing carcinogenesis models. Overall, the data suggest that the microbiota and its dysbiotic alterations can be considered potential targets for colorectal cancer diagnosis and therapy.}, } @article {pmid41477689, year = {2026}, author = {Chen, F and Sun, T and Song, H}, title = {Advances in Chemically Modified Polysaccharides with Enhanced Hypoglycemic Bioactivity.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c08511}, pmid = {41477689}, issn = {1520-5118}, abstract = {Polysaccharides are natural biopolymers with diverse bioactivities, but their clinical use in diabetes is restricted by poor solubility and bioavailability. Chemical modification provides an effective strategy to optimize polysaccharide structures, thereby enhancing their physicochemical properties and biological functions. This review summarized major chemical modification methods, focusing on introducing functional groups to sites such as hydroxyl, carboxyl, aldehyde, and amino groups. These modifications influence molecular weight distribution, monosaccharide composition, glycosidic linkage, solubility, and thermal stability, thereby modulating biological activities. Enhanced hypoglycemic effects of chemically modified polysaccharides were extensively discussed, emphasizing mechanisms such as suppression of digestive enzyme activities and the prevention of advanced glycation end-product generation, improvement of oxidative stress, improvement of gut microbiome and maintenance of gut health, and anti-inflammatory actions. This review underscored the potential of chemically modified polysaccharides as functional antidiabetic agents and advocated for further mechanistic studies and scalable, environmentally friendly modification techniques to advance their applications.}, } @article {pmid41477501, year = {2025}, author = {Govindharaj, GP and Choudhary, JS and Panda, RM and Basana-Gowda, G and Annamalai, M and Patil, N and Khan, RM and Banra, S and Srivastava, K and Mohapatra, SD}, title = {Bacterial communities in Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) showed significant variation among the developmental stages with functional diversity.}, journal = {Heliyon}, volume = {11}, number = {4}, pages = {e42776}, pmid = {41477501}, issn = {2405-8440}, abstract = {Nilaparvata lugens, a major rice pest, hosts an essential microbiome, yet its dynamic changes across developmental stages remain poorly understood. This study analyzed the bacterial community across developmental stages using V3-V4 amplicon sequences of 16S rRNA gene. The microbiome was classified into 20 phyla, 38 classes, 77 orders, 155 families, and 273 genera, with Proteobacteria, Firmicutes, and Bacteroidetes dominating phyla. Families Morganellaceae, Enterobacteriaceae, and Moraxellaceae were prevalent across all stages, while Anaplamataceae was dominant in all the developmental stages except males. Key genera included Arsenophonous (5 %), Bacillus (5 %), and Acinetobacter (3 %), with Wolbachia (11 %) abundant in all developmental stages except in males. The shared operational taxonomic units (OTUs) between the developmental stages of N. lugens were only 40 OTUs, and higher unique OTUs were found in the late instar stage (89 OTUs), and the lowest unique OTUs were found at the male stage (64 OTUs). Functional prediction indicated roles in carbohydrate, amino acid, and energy metabolism, as well as membrane transport, signaling, DNA replication and repair. These findings highlight stage-specific microbiome variations, laying the foundation for microbiome-based pest management techniques.}, } @article {pmid41477359, year = {2025}, author = {Lee, YR and Park, JH and Yoo, HH and Choi, I and Park, HY}, title = {Standardization of Fecal Metabolomics Using Microbiome Preservation Kits: Implications for Multiomics Integration.}, journal = {International journal of analytical chemistry}, volume = {2025}, number = {}, pages = {8551545}, pmid = {41477359}, issn = {1687-8760}, abstract = {With the advancement of multiomics technologies and cohort study designs, integrative omics research is increasingly applied to human health and nutrition. However, optimal storage and preprocessing of labile biological samples, particularly feces, remain challenging. In this study, we systematically evaluated three normalization methods-wet weight, dry weight, and protein quantification-for quantitative metabolomic profiling of fecal samples, using 41 metabolites. Fresh fecal samples from three healthy individuals showed high reproducibility, with 24 metabolites exhibiting a coefficient of variation (CV) below 30 for both wet and dry weight normalization. Fecal samples from 20 obese patients collected using the OMNIgene·GUT kit demonstrated improved reproducibility with wet weight normalization (20 metabolites, CV < 30) and protein quantification normalization (19 metabolites, CV < 30), whereas dry weight normalization yielded no metabolites meeting the CV < 30 criterion. Direct analysis of the kit solution without a drying step further enhanced chromatographic clarity, highlighting practical considerations for large-scale studies. Overall, wet weight normalization consistently minimized variation across sample types, providing a robust and standardized framework for fecal metabolite profiling. These findings demonstrate that the OMNIgene·GUT kit is compatible with broad-spectrum metabolomic analyses and support its integration into multiomics workflows. By establishing reproducible normalization protocols, this study provides the foundation for accurate, comparable, and scalable fecal metabolomics in both clinical and nutritional research settings.}, } @article {pmid41477198, year = {2025}, author = {Feng, X and Song, W and Ren, X and Xu, Z and Li, C and Feng, M and Wang, N}, title = {Microbial influences on HPV infection and cervical carcinogenesis: emerging evidence from the vaginal microbiome.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1733315}, pmid = {41477198}, issn = {1664-302X}, abstract = {Microbial communities play a vital role in the human defense system, existing symbiotically with us, contributing to metabolic processes, and strengthening immune defenses against pathogens. A diverse bacterial population in the vagina contributes to maintaining dynamic homeostasis, with their interactions playing a critical role in determining health or disease status. The balanced vaginal microbiota, dominated by Lactobacilli, helps maintain vaginal pH, converts glycogen to lactic acid, and produces bacteriocins and hydrogen peroxide (H2O2), all contributing to its protective functions. On the other hand, an abnormal vaginal microbial composition, characterized by a decrease in beneficial microorganisms, heightens the risk of gynecological diseases such as bacterial vaginosis (BV), sexually transmitted infections, human papillomavirus (HPV) infections, and cervical cancer due to persistent infections. Variation in microbial composition is influenced by factors such as racial background, ethnicity, pregnancy, hormonal fluctuations, sexual behavior, personal hygiene practices, and various physiological conditions. This review aims to offer a detailed overview of the existing literature, focusing on the complex interplay between vaginal microbiota and gynecological conditions such as HPV infection. Our goal is to provide valuable insights that can inform future clinical strategies and interventions.}, } @article {pmid41477061, year = {2025}, author = {Zhong, D and Sun, Y and Zhao, L and Hu, Z and Li, G and Li, H and Xie, Z}, title = {Interplay between aging and metabolic diseases: from molecular mechanisms to therapeutic horizons.}, journal = {Medical review (2021)}, volume = {5}, number = {6}, pages = {477-489}, pmid = {41477061}, issn = {2749-9642}, abstract = {Aging and metabolic diseases are intricately linked through bidirectional molecular mechanisms that foster a harmful cycle of physiological decline. This cycle is driven by several key factors, including altered nutrient sensing, mitochondrial dysfunction, cellular senescence, chronic inflammation, epigenetic modifications, circadian rhythm disruptions, and imbalances in the gut microbiota. Emerging interventions targeting this aging-metabolism axis hold significant promise for extending healthspan. These approaches include the use of pharmacological mimetics, senolytics, multi-omics strategies, and microbiome modulation, all of which aim to restore metabolic homeostasis and mitigate age-related pathologies. However, several challenges remain in translating these strategies into clinical practice. These include the need for tissue-specific targeting, ensuring the long-term safety of interventions, and addressing socioeconomic disparities in healthcare access. Future research efforts are focusing on integrating multi-omic technologies, organoid and human cellular models, and developing equitable precision medicine frameworks. These initiatives aim to extend healthspan and reduce the global impact of aging-related metabolic diseases.}, } @article {pmid41477025, year = {2025}, author = {Miao, H and Wang, Z and Chen, S and Wang, J and Ma, H and Liu, Y and Yang, H and Guo, Z and Wang, J and Cui, P}, title = {Application of machine learning in the discovery of antimicrobial peptides: exploring their potential for ulcerative colitis therapy.}, journal = {eGastroenterology}, volume = {3}, number = {4}, pages = {e100253}, pmid = {41477025}, issn = {2976-7296}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease with complex aetiology and limited treatment options. Antimicrobial peptides (AMPs), as endogenous immune effectors, have recently emerged as promising therapeutic agents in UC. However, systematic identification and functional evaluation of AMPs remain underexplored. We aimed to discover novel AMPs with potential therapeutic efficacy in UC by leveraging machine learning-based prediction and validating their impact in an experimental colitis model.

METHODS: We established a machine learning-driven pipeline to predict candidate AMPs based on their structural and functional features. Top-ranked peptides were synthesised and subjected to in vitro antibacterial assays and proteolytic stability tests. Their therapeutic potential was evaluated using a dextran sulfate sodium (DSS)-induced colitis mouse model, assessing clinical indicators, histopathology, inflammatory markers and gut microbiota alterations. Metagenomic and metabolomic analyses provided insights into microbial community dynamics and metabolic pathways. To probe the role of gut microbes in AMP-mediated gut homeostasis, we conducted Akkermansia (A.) muciniphila replenishment experiments.

RESULTS: Several AMPs identified by machine learning exhibited potent antimicrobial activity and resistance to proteolytic degradation. In vivo, AMP administration ameliorated DSS-induced colitis symptoms, including body weight loss, Disease Activity Index and histological damage. Treatment also modulated the gut microbiome, increasing the abundance of A. muciniphila and restoring microbial balance. Functional metagenomic profiling revealed enrichment of genes involved in mucosal barrier protection and immunoregulation. These findings were supported by improved inflammatory cytokine profiles and enhanced epithelial integrity.

CONCLUSIONS: Our findings demonstrate that machine learning-guided discovery of AMPs is a viable approach to identify promising therapeutic agents for UC. By integrating multi-omics analyses, we reveal potential microbiota-mediated mechanisms underlying AMP efficacy. These insights provide a strong foundation for advancing AMP-based strategies in UC management.}, } @article {pmid41476963, year = {2025}, author = {Ma, S and Zheng, L and Zhuang, X and Wang, M and Zou, Y}, title = {Pathogenic mechanisms and therapeutic potential of the microbiome in premature ovarian insufficiency.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1734367}, pmid = {41476963}, issn = {1664-3224}, mesh = {Humans ; *Primary Ovarian Insufficiency/therapy/microbiology/metabolism/etiology ; Female ; Animals ; *Microbiota ; Ovary/metabolism/microbiology ; Probiotics/therapeutic use ; }, abstract = {The postponement of childbearing age has become a global issue. Factors such as increased work pressures on women and environmental changes have led to a rising incidence and younger onset of premature ovarian insufficiency (POI). POI not only impacts patients' reproductive function but also heightens the risk of depression, anxiety, cognitive decline, premature mortality, osteoporosis, and cardiovascular disease. Exploring effective prevention and treatment strategies for POI can slow ovarian ageing and safeguard female reproductive health. Microbiome research confirms that most human tissues and organs form dynamic, interactive systems with symbiotic microbes that play a crucial role in female reproductive function. Previous studies on the microbiome and female reproductive health have rarely focused on POI. The proposed 'Microbiota-Ovary Axis' aims to establish an integrated regulatory framework. This theoretical model systematically elucidates how microbial signals influence ovarian function through four core pathways: the hypothalamic-pituitary-ovarian (HPO) axis, metabolism and endocrine regulation, immunoregulation, and oxidative stress. Evaluating the efficacy of dietary modifications, probiotics, and microbiota transplantation in animal models and preliminary clinical studies will establish a robust theoretical foundation for developing microbiota-targeted innovative diagnostic and therapeutic strategies for POI, thereby enhancing reproductive health throughout the female lifespan.}, } @article {pmid41476768, year = {2025}, author = {Dommer, AC and Amaro, RE and Prather, KA}, title = {Understanding Aerosol-Mediated Disease Transmission.}, journal = {ACS central science}, volume = {11}, number = {12}, pages = {2319-2328}, pmid = {41476768}, issn = {2374-7943}, abstract = {This Outlook aims to update the longstanding treatment of airborne disease transmission through an interdisciplinary lens combining biology, surface chemistry, and aerosol physics, drawing parallels between environmental and human-generated infectious aerosols and examining their effects on human and ecosystem health. By recasting the lung surface as a dynamic interface akin to the ocean surface, this Outlook illustrates the importance of a multidisciplinary approach to elucidate the mechanisms of disease transmission at a depth that enables practical mitigation strategies. The urgency of this analysis is motivated by the evolving nature of airborne pathogens of concern, such as SARS-CoV-2 and influenza, and the global impact of dynamic environments on the poorly understood airborne microbiome.}, } @article {pmid41476253, year = {2025}, author = {Kvitne, KE and Zuffa, S and Charron-Lamoureux, V and Mohanty, I and Patan, A and Mannochio-Russo, H and Zemlin, J and Burnett, LA and Zhang, LS and Cecala, MC and Ersoz, C and Connelly, JA and Halasa, N and Nicholson, M and Dorrestein, PC and Tsunoda, SM and Markle, J}, title = {Fecal microbial and metabolic signatures in children with very early onset inflammatory bowel disease.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00899-0}, pmid = {41476253}, issn = {2055-5008}, support = {5P30HD106451-03//NICHD/NIH/ ; 5P30HD106451-03//NICHD/NIH/ ; 5P30HD106451-03//NICHD/NIH/ ; P50HD106463/HD/NICHD NIH HHS/United States ; }, abstract = {Very early onset inflammatory bowel disease (VEO-IBD) is a clinically distinct form of IBD manifesting in children before the age of six years. Disease in these children is especially severe and often refractory to treatment. While previous studies have investigated changes in the fecal microbiome and metabolome in adult and pediatric IBD, insights in VEO-IBD remain limited. This multi-omics analysis reveals changes in the fecal microbiome and metabolome in children diagnosed with VEO-IBD compared with age- and sexmatched healthy controls. Untargeted metabolomics analysis identified a depletion of short-chain N-acyl lipids and an enrichment of dipeptides, tripeptides, and oxo bile acids in children with VEO-IBD. Differential abundance analysis of 16S rRNA sequencing data showed lower abundance of beneficial bacteria such as Bifidobacterium and Blautia, and higher abundance of Lachnospira, Veillonella, and Bacteroides in VEO-IBD. Multi-omics integration revealed associations between the altered gut microbiome composition and metabolic dysregulation, specifically for the N-acyl lipids. This study offers unique insight into fecal microbial and metabolic signatures in VEO-IBD, paving the way for a better understanding of disease patterns and thereby more effective treatment strategies.}, } @article {pmid41476057, year = {2025}, author = {Wu, Y and Wong, O and Chen, S and Wang, Y and Lu, W and Cheung, CP and Ching, JYL and Cheong, PK and Chan, S and Leung, P and Chan, FKL and Su, Q and Ng, SC}, title = {Distinct diet-microbiome associations in autism spectrum disorder.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-67711-7}, pmid = {41476057}, issn = {2041-1723}, abstract = {Autism spectrum disorder (ASD) is linked to both altered gut microbiota and unhealthy diets; however, the mechanistic connections remain elusive. In this study, we conducted a systematic analysis of fecal microbiome metagenomic data, paired with granular dietary assessments and phenotypic profiles, across a cohort of 818 children (462 with ASD, 356 without ASD; mean age = 8.4 years; 27.3% female). By integrating dietary indices, nutrient intake, and food additive exposures, we uncovered ASD-specific linkages to the microbiome. Poor dietary quality correlated with aggregated core autistic symptoms, gastrointestinal complications, and atypical eating behaviors. Notably, children with ASD exhibited a more pronounced diet-microbiome interaction network compared to neurotypical peers, suggesting heightened microbial sensitivity to nutritional inputs. Furthermore, synthetic emulsifiers-specifically polysorbate-80 and carrageenan-were associated with disrupted microbial connectivity in ASD, a phenomenon attenuated in neurotypical children. Our findings elucidate the mechanistic links between dietary factors-particularly synthetic food additives-and microbiome dysregulation in ASD, urging a re-evaluation of dietary guidelines for ASD populations and laying the groundwork for personalized nutritional strategies.}, } @article {pmid41475989, year = {2025}, author = {Liu, YH and Peng, P and Hung, WC and Wu, PH and Kao, CY and Wu, PY and Huang, JC and Chen, SC and Kuo, CH}, title = {Gut microbiota profiles by LDL-C target achievement in statin-treated patients: A cross-sectional study.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {}, number = {}, pages = {104465}, doi = {10.1016/j.numecd.2025.104465}, pmid = {41475989}, issn = {1590-3729}, abstract = {BACKGROUND AND AIMS: Hyperlipidemia is linked to gut microbiota alterations, but the impact of statins on the gut microbiome remains unclear, especially concerning different low-density lipoprotein cholesterol (LDL-C) targets. This study explores gut microbiome changes in chronic disease patients under varying LDL-C targets with statin therapy.

METHODS AND RESULTS: A total of 125 patients (77 males and 48 females) diagnosed with chronic diseases, specifically diabetes mellitus (87 %), hypertension (74 %), and chronic kidney disease (48 %), were recruited. Fecal samples were collected from the participants to analyze the composition of the gut microbiota using Illumina sequencing of the 16S ribosomal ribonucleic acid gene. The patients were divided into two groups according to LDL-C level, including 57 patients in the LDL-C target-achieved group (LDL-C < 70 mg/dL), and 68 in the LDL-C target-not-achieved group (LDL-C ≥ 70 mg/dL). There were no significant differences in microbial species diversity (Chao1 index and Shannon index), beta diversity and microbial dysbiosis index between the two groups. However, a distinct microbial community structure was found in the LDL-C target-achieved group, with decreased abundances at the genus level of Barnesiella, Coprococcus 1, Flavonifractor, Odoribacter and Coprobacter.

CONCLUSION: No significant difference in alpha diversity, beta diversity, and microbial dysbiosis index were found between the LDL-C target-achieved and target-not-achieved groups. However, the LDL-C target-achieved group was associated with a significant reduction in short-chain fatty acid-producing bacteria, including taxa Barnesiella, Coprococcus 1, Flavonifractor and Odoribacter.}, } @article {pmid41475718, year = {2026}, author = {Zavagna, L and Alfano, A and Bianchi, M and Di Meo, C and Fusco, A and Esin, S and Batoni, G and Donnarumma, G and Schiraldi, C and Danti, S}, title = {Gellan gum electrohydrodynamic microencapsulation of probiotics for intestine-targeted delivery.}, journal = {Carbohydrate polymers}, volume = {375}, number = {}, pages = {124742}, doi = {10.1016/j.carbpol.2025.124742}, pmid = {41475718}, issn = {1879-1344}, mesh = {*Probiotics/chemistry/pharmacology/administration & dosage ; *Polysaccharides, Bacterial/chemistry ; Humans ; Caco-2 Cells ; Limosilactobacillus fermentum/chemistry ; Drug Compounding/methods ; Escherichia coli/drug effects ; Intestines/microbiology ; Particle Size ; *Anti-Bacterial Agents/pharmacology/chemistry ; Microspheres ; Drug Delivery Systems ; Hydrogen-Ion Concentration ; }, abstract = {Microencapsulation is a promising strategy to improve time-stability, viability and targeted delivery of probiotics, thus enhancing their beneficial roles in the intestine. However, areas of improvement persist, including optimal viability protection during storage and gastrointestinal (GI) transit, control over encapsulation and targeted release. Due to pH-responsiveness, gellan gum (GG) could be ideal to face some of these criticalities. In this study, we set-up a robust electrohydrodynamic (EHD) microdripping process to produce GG microparticles (GGMs) encapsulating Limolactobacillus fermentum. By varying GG concentration, flow rate and applied voltage, the optimized EHD parameters led to highly monodisperse microbeads with controlled morphology. Successful encapsulation of L. fermentum in GGMs was obtained at concentrations of 10[6] CFU/mL and 10[9] CFU/mL, leading to 300 ± 40 μm and 450 ± 100 μm particle sizes, with encapsulation efficiency of 94 ± 6 % and 99 ± 1 %, respectively. GGMs demonstrated post-encapsulation probiotic viability with lactic acid production. Freeze-dried formulations were lasting under storage until 3 months and resulted stable under GI-simulated conditions. Their bioactive properties were demonstrated by antimicrobial efficacy against Escherichia coli and enhanced defensin expression in Caco-2 intestinal cells. Overall, EHD microdripping was a versatile and robust platform useful in functional foods and gut microbiome engineering.}, } @article {pmid41475684, year = {2025}, author = {Yamoah, JAA and Kwofie, KD and Akorli, J and Ladzekpo, D and Kawada, H and Boateng, KY and Beyuo, J and Keleve, A and Danquah, JB and Tawiah-Mensah, C and Ansah-Owusu, J and Dadzie, SK and Wallace, PA and Tsuji, N and Hatta, T}, title = {Beyond the usual suspects: Uncovering less-recognized pathogenic bacteria in Ghanaian blood-feeding Amblyomma variegatum ticks using 16S rRNA amplicon sequencing.}, journal = {Parasitology international}, volume = {112}, number = {}, pages = {103228}, doi = {10.1016/j.parint.2025.103228}, pmid = {41475684}, issn = {1873-0329}, abstract = {Ticks are important vectors of bacterial pathogens affecting both human and animal health. In Ghana, Amblyomma variegatum is the predominant cattle-infesting tick, yet most studies have focused on a limited range of well-characterized pathogens, potentially overlooking a broader diversity of less-recognized, emerging, or opportunistic bacteria. In this study, we used 16S rRNA amplicon sequencing to characterize the bacteriome of partially blood-fed Am. variegatum ticks, with emphasis on underexplored taxa. As ticks were blood-fed at the time of collection, some detected microorganisms may represent transient, host-derived bacteria rather than endogenous tick microbiota; therefore, findings should also be interpreted within the context of xenosurveillance. Partially-fed ticks were collected from cattle across three ecological zones within Ghana's Greater Accra Region. 11 Am. variegatum ticks, confirmed through both morphological and molecular analyses, were subjected to high-throughput sequencing, and bacterial diversity and composition were analysed using established bioinformatics tools. Sequencing generated over 1.75 million high-quality reads and 3172 amplicon sequence variants. Five dominant bacterial phyla were detected, with Actinomycetota and Bacillota being the most abundant. While Rickettsia spp. were prevalent in some samples, Anaplasma and Coxiella, two commonly studied tick-borne bacteria, were not detected. Several less-recognized or opportunistic species, including multidrug-resistant Corynebacterium resistens and bovine-associated Porphyromonas levii, were identified at high relative abundance. These findings suggest that Am. variegatum may harbor a broader range of bacterial taxa than previously recognized. Incorporating such neglected microorganisms into a One Health tick-surveillance framework may improve disease risk assessment and guide public and animal health interventions in the region.}, } @article {pmid41475679, year = {2025}, author = {Morel, C and Li, R and Luces, CF and Brougham, MFH and Pascual-Gazquez, JF and Iniesta, RR and Torquati, L}, title = {Interventions targeting the gut microbiome to improve cancer treatment outcomes and their gastrointestinal side effects: a systematic review and meta-analysis.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101300}, doi = {10.1016/j.tjnut.2025.101300}, pmid = {41475679}, issn = {1541-6100}, abstract = {BACKGROUND: Improvements in cancer treatment are essential to reduce premature mortality. Emerging evidence highlights the role of the gut microbiome (GM) in influencing treatment responses and modulating gastrointestinal adverse events (GIAEs). Because cancer therapy disrupts GM composition, restoring gut health may help mitigate side effects and support gut-associated immunity.

OBJECTIVE: This study aims to systematically evaluate and assess the effectiveness of GM interventions on the occurrence of GIAEs and clinical responses to cancer treatment.

METHODS: Three databases (PubMed, Web of Science, Cochrane Library) were systematically searched up to February 2025 for studies assessing gut microbiome interventions during cancer treatment. Risk of bias was evaluated using the EPHPP Quality Assessment Tool. Meta-analyses were conducted in Stata 18® using random-effects models to estimate the pooled relative risk of GM interventions on GIAEs (primary outcome) and objective disease response rates (secondary outcome).

RESULTS: Fifty-six studies were included in the systematic review and forty were meta-analysed (n=37 for GIAE outcomes, n=8 for treatment response). GM interventions reduced the overall risk of GIAEs (RR = 0.59, 95% CI = 0.53, 0.65, I[2] = 76.8%; 95% PI = 0.32, 1.08), including diarrhoea, constipation, nausea, and vomiting, but with considerable heterogeneity between studies. There was insufficient evidence to suggest improvements in objective disease response rates (RR = 1.06, 95% CI = 0.93, 1.20; I[2] = 0%; 95% PI = 0.93, 1.20).

CONCLUSION: GM interventions show promise in improving cancer care by reducing GIAEs, though evidence for direct effects on treatment response remains limited. Standardising intervention protocols and outcome reporting in future RCTs is essential to strengthen the evidence base and guide clinical recommendations.

PROSPERO REGISTRATION: Registration number: CRD42023443332 LINK TO PROTOCOL: Https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023443332.}, } @article {pmid41475610, year = {2025}, author = {Xie, Y and Jiang, C and Xu, S and Zhou, H and Wang, P and Yang, Y and Hou, X and Zheng, X and Zhuang, X}, title = {Application and mechanisms of wastewater load regulation for enhanced partial denitrification in constructed wetlands: From microbiome structure to single-cell functional validation.}, journal = {Bioresource technology}, volume = {}, number = {}, pages = {133899}, doi = {10.1016/j.biortech.2025.133899}, pmid = {41475610}, issn = {1873-2976}, abstract = {Achieving robust nitrogen removal in constructed wetlands (CWs) is often hindered by the inhibitory effects of high pollutant loads on microbial activity. This study validates that influent load regulation is a pivotal strategy for engineering a partial denitrification (PD)-dominant microbial ecosystem, effectively overcoming such limitations. Comparing low-load (LL), medium-load (ML), and high-load (HL) conditions, the LL group achieved superior total nitrogen removal (up to 97.11%), outperforming the ML and HL groups by 9.28% and 16.21%, respectively. The underlying mechanism involves the alleviation of free ammonia (FA) inhibition at lower loads, which permitted the enrichment of crucial PD-related genera like Pseudomonas and Flavobacterium. This engineered community structure facilitated the stable production of nitrite, a key substrate that subsequently fueled downstream processes such as anammox and DAMO, thereby creating a synergistic nitrogen removal network. Consequently, our findings confirm that managing influent load is a critical and practical method for engineering a stable, PD-dominant microbial ecosystem to achieve robust and sustainable nitrogen removal in CWs.}, } @article {pmid41475548, year = {2025}, author = {Borgini, S and Pasveer, E and Petre, C and Iorga, BI and Vertommen, D and Remaut, H and Collet, JF and Lauber, F}, title = {Identification of receptor-binding domains of Bacteroidales antibacterial pore-forming toxins.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {111113}, doi = {10.1016/j.jbc.2025.111113}, pmid = {41475548}, issn = {1083-351X}, abstract = {Bacteroidales are abundant Gram-negative bacteria present in the gut microbiota of most animals, including humans, where they carry out vital functions for host health. To thrive in this competitive environment, Bacteroidales use sophisticated weapons to outmatch competitors. Among these, BSAPs (Bacteroidales Secreted Antimicrobial Proteins) represent a novel class of bactericidal pore-forming toxins that are highly specific to their receptor, typically targeting only a single membrane protein or lipopolysaccharide. The molecular determinants conferring this high selectivity remain unknown. In this study, we therefore investigated the model protein BSAP-1 and determined which of its domains is involved in providing receptor specificity. We demonstrate that receptor recognition is entirely driven by the C-terminal domain (CTD) of BSAP-1 using a combination of in vivo competition assays, in vitro protein binding studies and mutational analysis. Specifically, we show that deletion of the CTD abrogates BSAP-1 bactericidal activity by preventing receptor binding, while grafting the CTD to unrelated carrier proteins enables CTD-driven interaction with the BSAP-1 receptor. Combining structural investigation of a BSAP-1-receptor complex with mutational analysis, we unveil that this interaction is driven by electrostatic interactions. Building upon this discovery, we show that BSAPs can be categorized according to the structure of their CTD, suggesting a strong CTD structure/receptor type correlation. In summary, our research demonstrates that BSAP receptor recognition is driven by their CTD and paves the way for future applications.}, } @article {pmid41475542, year = {2025}, author = {Nayak, A and Bera, S and Purohit, S and Jain, CK}, title = {Gut Microbiota Mediated Neuroinflammation in Psychiatric Disorders: Current Perspectives and Challenges.}, journal = {Behavioural brain research}, volume = {}, number = {}, pages = {116019}, doi = {10.1016/j.bbr.2025.116019}, pmid = {41475542}, issn = {1872-7549}, abstract = {Psychiatric disorders remain a major global health concern, with complex diagnostic criteria and a lack of clear biological markers that continue to challenge therapeutic strategies. Current treatment methods, such as psychotherapy, brain stimulation therapy, and pharmacological interventions, often come with their own set of side effects, thus warranting the need to explore alternative approaches. Emerging research highlights the gut brain axis (GBA) and gut microbiota (GM) as key modulators of brain health and disease. Dysbiosis, a disruption in gut microbial composition, can influence blood brain barrier (BBB) integrity, immune signaling, and microbial metabolite production, collectively modulating neuroimmune homeostasis and contributing to the onset of neuroinflammation. While growing preclinical and clinical evidence links altered GM to depression, anxiety, schizophrenia, bipolar disorder (BD), and autism spectrum disorder (ASD), causal relationships remain incompletely defined. This review examines the established and emerging mechanisms connecting the GM to neuroinflammation underlying psychiatric disorders and evaluates current microbiome targeted interventions, such as diet based strategies, probiotics, next generation probiotics (NGPs), and fecal microbiota transplantation (FMT). We also discuss speculative microbiome engineering approaches and highlight translational limitations that must be addressed before clinical implementation. A holistic approach integrating these strategies with conventional psychiatric treatments could facilitate more effective and personalized interventions.}, } @article {pmid41475424, year = {2025}, author = {Ranson, HJ and Ye, Y-S and Petukhova, VZ and Green-Saxena, A and He, R and Sun, J and Godugu, B and Sanchez, LM and Wu, Q and Rowley, DC}, title = {Lipopeptides and antibiotics from a marine Bacillus pumilus mediate a potential "catch and kill" effect on pathogenetic Vibrio parahaemolyticus.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0144025}, doi = {10.1128/msystems.01440-25}, pmid = {41475424}, issn = {2379-5077}, abstract = {UNLABELLED: Bacteria produce a diverse range of specialized metabolites that influence the health and behavior of neighboring cells and, therefore, have potential applications in treating diseases. Deciphering the intended ecological functions of specialized metabolites is challenging due to the small scales at which these interactions occur and the complexity of unraveling simultaneous responses to multiple signals. In this study, we investigated the chemical interactions between two marine bacterial colonies, Vibrio parahaemolyticus PSU5429 and Bacillus pumilus YP001. When the two bacteria were grown in proximity on agar, V. parahaemolyticus exhibited swarming motility toward B. pumilus, but close approach to the B. pumilus colony was impeded by a zone of inhibition. Matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-TOF IMS) suggested that lipopeptides produced by Bacillus induced swarming motility, a finding corroborated by genomic and chemical analyses of YP001. Based on activity and metabolomics guidance, the antibiotic amicoumacin B was found to be responsible for the observed antibiosis, while swarming motility by V. parahaemolyticus was induced by lipopeptides and two lipoamides. In this scenario, lipopeptide production by the Bacillus colony induces the Vibrio colony to swarm toward a lysis zone, resulting in a possible "catch and kill" effect. These results demonstrate the complexity of behaviors and outcomes exhibited by microbes under the simultaneous influence of different allelochemicals, suggesting possible interplays between antibiotics and compounds that induce motility.

IMPORTANCE: Microbes communicate and compete using small molecules, yet linking specific metabolites to visible behaviors is difficult. We combine imaging mass spectrometry, genomics, analytical chemistry, and bioassays to decode an interaction between a marine Bacillus and the pathogen Vibrio parahaemolyticus. Surfactin-like lipopeptides act at a distance to stimulate Vibrio swarming and draw cells toward the colony. Amicoumacin B accumulates at the interface and halts growth, yielding a simple "catch and kill" outcome. This study shows that the spatial localization of natural products shapes microbial behavior on surfaces and provides a general, scalable workflow that maps chemistry to phenotype. Beyond this case, the approach can be applied broadly to understand and, ultimately, tune microbial interactions relevant to marine ecosystems, aquaculture health, and microbiome engineering.}, } @article {pmid41475279, year = {2025}, author = {Singh, G and Ansari, S and Yadav, S and Aran, KR}, title = {Gut microbiota's role in NAFLD- and HBV/HCV-related hepatocellular carcinoma: Mechanisms and therapeutic implications.}, journal = {Microbial pathogenesis}, volume = {211}, number = {}, pages = {108273}, doi = {10.1016/j.micpath.2025.108273}, pmid = {41475279}, issn = {1096-1208}, abstract = {Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally and has been closely linked to chronic liver conditions, such as viral hepatitis and non-alcoholic fatty liver disease. Recent research has demonstrated that the gut microbiota significantly impacts the gut-liver axis, a crucial aspect of the pathophysiology of HCC. This review emphasizes the mechanisms by which gut dysbiosis contributes to liver inflammation, fibrosis, and tumor formation. In NAFLD-related HCC, modification in the microbiota composition facilitates intestinal barrier dysfunction, endotoxemia, and metabolic disturbances. In HCC associated with HBV/HCV, the microbiome modulates immune surveillance and viral persistence. Shared pathogenic pathways, such as LPS-TLR4 signaling, bile acid dysregulation, and immunosuppressive microenvironments, highlight the role of microbial imbalance across varied etiologies. We also discuss how antibiotics, diet, probiotics, and postbiotics influence gut-liver homeostasis, as well as their therapeutic potential in primary and secondary prevention and treatment of HCC. Short-chain fatty acids and valeric acid are examples of postbiotics with anti-inflammatory and pro-apoptotic anti-IBD effects, while fecal microbiota transplantation and dietary modulation have shown potential in improving outcomes. The review also identifies significant research gaps, particularly in establishing causality, understanding intrahepatic metastasis, and investigating the roles of the fungal and viral microbiome (mycobiome and virome). Finally, the incorporation of microbiome-based interventions into clinical practice could represent an effective future strategy for risk stratification, prevention, and adjuvant therapy of HCC. Future studies focusing on longitudinal analysis, mechanistic validation, and multi-kingdom profiling are essential for translating microbiome research into effective clinical applications.}, } @article {pmid41475232, year = {2025}, author = {Lehmann, K and Arachchige, DE and Lehmann, R and Overholt, WA and Küsel, K and Totsche, KU}, title = {Neglected but pivotal: Complex matter dynamics in the aeration zone contribute to groundwater quality evolution.}, journal = {Water research}, volume = {291}, number = {}, pages = {125287}, doi = {10.1016/j.watres.2025.125287}, pmid = {41475232}, issn = {1879-2448}, abstract = {Fluid and matter dynamics in thick aeration zones of topographic highs are insufficiently understood, particularly in their role for groundwater quality evolution and subsurface ecosystem functioning. We apply novel drainage collectors, installed in sub-horizontal boreholes, to fill the observational gap of bedrock percolates. In the Hainich Critical Zone Exploratory, 20 spatially distributed collectors act as a super-collector for percolates from the highly geodiverse aeration zone, complementing a lysimeter and well network. For over 3 years, we investigated percolate volume, quality, and controlling factors. 65% of the annual percolation flux occurred during winter. Of this, extreme rainfall (33%) and snowmelt events (25%) together accounted for 58%, depending on the recent past of subsurface moisture conditions. Collectors captured 13% of topsoil seepage, with soil thickness, sub-season, slope, and fracture properties as major factors. The mobile percolate inventory showed strong seasonality, driven by weather conditions. The solute signature differed markedly from that of soil seepage, more closely resembling groundwater. Winter high-flows translocated most of the organic carbon and a broad spectrum of mineral particles, up to 160 µm large mineral-organic aggregates, and bioparticles. Bacterial diversity suggests a distinct aeration-zone microbiome adapted to fluctuating habitat conditions, serving as a dispersal source for phreatic communities. Our findings showcase complex dynamics between matter sources, transformations, and sinks. Weather extremes affect the formation and transport of matter through regolith and bedrock. Increasing above- and belowground effects of climate change could thus impair subsurface services, including the provision of high-quality groundwater. We advocate considering thick recharge-area aeration zones as key compartments for subsurface life and for the evolution of groundwater quality.}, } @article {pmid41475022, year = {2025}, author = {Chen, N and Pang, D and Shang, H}, title = {Akkermansia muciniphila: A double-edged sword in life-stage-specific nutritional modulation of Parkinson's disease via the gut-brain axis.}, journal = {Microbiological research}, volume = {305}, number = {}, pages = {128436}, doi = {10.1016/j.micres.2025.128436}, pmid = {41475022}, issn = {1618-0623}, abstract = {The gut mucin specialist Akkermansia muciniphila (A. muciniphila) exhibits a paradoxical duality in PD, showing both positive and negative correlations with motor and non-motor symptoms across distinct PD subtypes. This enigmatic role is further complicated by its dynamic lifespan trajectory: colonizing early life, peaking in adulthood, declining with aging, yet resurging in longevity cohorts. This review synthesizes evidence on A. muciniphila's structural components, its divergent associations with PD phenotypes, and the dietary and host factors shaping its abundance from gestation to senescence. We propose a lifespan-targeted intervention model that strategically modulates A. muciniphila, which could concurrently mitigate PD progression and promote healthy aging. We suggest suppressing its neurotoxic pathways in susceptible individuals while enhancing its beneficial functions in the aging process. Reconciling this microbial Janus face may pave the way for novel microbiome-based precision therapeutics against neurodegeneration.}, } @article {pmid41474788, year = {2025}, author = {Wong, KX and Chen, ST and Ong, JJ and Gan, WY and Abdul Murad, NA and Chong, CW and Ramzi, NH}, title = {Exploring gut microbiome and nutritional status among children with Autism Spectrum Disorder (MY-ASD Microbiome): A study protocol.}, journal = {PloS one}, volume = {20}, number = {12}, pages = {e0338801}, pmid = {41474788}, issn = {1932-6203}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology ; *Gastrointestinal Microbiome ; Child ; Male ; Child, Preschool ; *Nutritional Status ; Case-Control Studies ; Feces/microbiology ; Saliva/microbiology ; Malaysia ; Female ; }, abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by persistent deficits in social communication and the presence of restricted, repetitive behaviours or interests. Previous literature has identified a link between the gut and ASD; however, the underlying mechanisms remain unclear. Gut microbiota dysbiosis has been extensively reported in cohort studies of ASD, and specific microbial metabolites or by-products may serve as potential biomarkers for ASD. Additionally, children with ASD often exhibit food refusal, have a limited food repertoire and display a tendency to consume the same foods frequently; thus, these behaviours increase their risk of malnutrition (over-nutrition or under-nutrition) compared to typically developing (TD) healthy children. This study primarily aims to identify oral and gut microbiota among children with ASD and TD healthy children. The secondary aim is to determine the associations between oral and gut microbiota with nutritional status among children with ASD. The findings will enhance understanding of the aetiology of ASD and inform early intervention strategies to mitigate disease severity and early identification of malnutrition in genetically at-risk children.

METHODS AND ANALYSIS: This observational, age-matched, case-control study is conducted in Malaysia among 40 male children with ASD and age-matched with 40 TD healthy controls aged 4-10 years. The dependent variables include the microbiota profile, identified through metagenomic sequencing analysis of saliva and faecal samples, and autism severity, assessed through validated questionnaires. Independent variables include nutritional status, determined through Subjective Global Nutrition Assessment (SGNA), anthropometry and dietary measurements, gastrointestinal symptoms, eating behaviour, behavioural profile, and sleep quality. Data collection is expected to be completed by June 2026. The study nature may limit causality establishment. Analyses will use chi-square/ANOVA for group comparisons, SparCC for microbiota correlations, and mixed-effects logistic regression to model associations.

CONCLUSION: This study advances understanding of ASD-related microbiota, guiding personalised nutrition and precision healthcare in Malaysia.}, } @article {pmid41474687, year = {2025}, author = {Abulaiti, A and Yu, H and Ma, J and Wuji, A and Chi, H}, title = {Advancement on the Association between Gut Microbiota and Autism Spectrum Disorder in Children.}, journal = {Annals of nutrition & metabolism}, volume = {}, number = {}, pages = {1-24}, doi = {10.1159/000549716}, pmid = {41474687}, issn = {1421-9697}, abstract = {Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interaction, communication, and the presence of restricted, repetitive behaviors. The rising global prevalence of ASD suggests a multifactorial etiology involving genetic, environmental, and neurodevelopmental factors. This review explores the establishment of the early-life microbiome, highlighting rapid microbial colonization from maternal and environmental sources. Emerging evidence indicates that delivery mode and infant feeding practices may influence ASD susceptibility. Although the concept of a sterile intrauterine environment remains debated, its investigation is valuable. The bidirectional "microbiota-gut-brain axis" has emerged as a critical pathway linking gut microbiota and brain function, offering potential therapeutic targets for ASD. Dietary patterns in children with ASD are often characterized by selectivity and restriction, which may disrupt gut microbiota composition and exacerbate gastrointestinal symptoms, thereby increasing ASD risk. Nutritional interventions and early behavioral therapies are thus essential. The gluten-free, casein-free (GFCF) diet remains controversial, with inconsistent evidence regarding its efficacy. Probiotic supplementation shows strain-specific effects, necessitating rigorous evaluation before clinical application. Given the heterogeneity of ASD, pharmacological treatments have shown limited universal efficacy. This review provides a comprehensive analysis of the interplay between diet, gastrointestinal symptoms, and ASD, evaluates the gut-brain axis as a mechanistic framework, and assesses the therapeutic potential of microbial interventions, including probiotics, prebiotics, and fecal microbiota transplantation (FMT). While promising findings have emerged, further well-designed clinical studies are needed to elucidate the complex etiology of ASD and validate therapeutic strategies.}, } @article {pmid41474588, year = {2025}, author = {Rattanapitoon, NK and Thanchonnang, C and Rattanapitoon, SK}, title = {Exploring the gut-biliary microbiome axis in Opisthorchis viverrini-associated cholangiocarcinoma: An overlooked pathogenic interface.}, journal = {Journal of cancer research and therapeutics}, volume = {21}, number = {7}, pages = {1464-1465}, doi = {10.4103/jcrt.jcrt_1012_25}, pmid = {41474588}, issn = {1998-4138}, } @article {pmid41474487, year = {2025}, author = {Mukhanbetzhanov, N and Zhetkenev, S and Vinogradova, E and Sergazy, S and Jarmukhanov, Z and Issilbayeva, A and Kossumov, A and Kassenova, A and Mukhametuly, B and Kenessarin, M and Zhumadilov, K and Stepanenko, V and Bogacheva, V and Petukhov, A and Sato, H and Endo, S and Fujimoto, N and Hoshi, M}, title = {Multicompartmental analysis of microbiome alterations under radiation stress.}, journal = {AMB Express}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13568-025-02002-4}, pmid = {41474487}, issn = {2191-0855}, support = {(Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; (Grant No. AP09057915)//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, } @article {pmid41474484, year = {2025}, author = {Kinkpe, L and Solomon, AI and Niu, Y and Goswami, N and Ikele, CM and Hu, D and Abdessan, R and Zhigang, H and Xia, W}, title = {A guide to network analysis, multi-omics integration, and applications in livestock microbiome research.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {1}, pages = {17}, pmid = {41474484}, issn = {1573-0972}, support = {2023YFD1300300//National Key Research and Development Program of China/ ; (CARS-42-2)//China Agriculture Research System of MOF and MARA/ ; }, mesh = {Animals ; *Livestock/microbiology ; *Gastrointestinal Microbiome ; *Genomics/methods ; *Microbiota ; Computational Biology/methods ; Machine Learning ; Multiomics ; }, abstract = {The function of the livestock gut microbiome in driving animal growth, health, and methane emissions is controlled by networks of interactions among microbes. A major challenge is to move beyond simply listing microbial members to understanding these interaction networks, which determine how the community functions as a whole. This review synthesizes how network analysis, combined with multi-omics data, can meet this challenge. We focus on the critical task of identifying keystone species, the disproportionately influential microbes that direct processes like fiber digestion and immune function, yet are often missed by standard surveys. We evaluate a progression of methods, from identifying correlated species to building models that integrate genomic, metabolic, and host data. This integration is key to separating true ecological relationships from statistical noise and to linking microbial presence to function. We highlight how computational techniques like metabolic modeling and machine learning are turning networks into predictive tools. Finally, we outline the path forward: field-ready studies that track microbiomes over time, the development of livestock-specific metabolic models, and analytical standards that will allow research to translate into practical strategies. The goal is to provide a framework for using network science to actively manage the microbiome, enhancing sustainable livestock production.}, } @article {pmid41474336, year = {2025}, author = {Vazquez-Munoz, R and Ranjan, A and Bertolini, M and Thompson, A and Mosharaf Ghahfarokhy, P and Harnden, A and Nobile, CJ and Sobue, T and Vera-Licona, P and Dongari-Bagtzoglou, A}, title = {Enterococcus faecalis induces H2O2-mediated epithelial cell death and enhances Candida albicans virulence in oropharyngeal candidiasis.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0082225}, doi = {10.1128/msphere.00822-25}, pmid = {41474336}, issn = {2379-5042}, abstract = {UNLABELLED: In immunosuppressed humans with oropharyngeal candidiasis (OPC) and in mice with experimental OPC, Candida albicans infection is associated with a bacterial imbalance characterized by significantly reduced oral microbiome diversity and the expansion of enterococcal and streptococcal species, which may exacerbate oral mucosal pathology. In this study, we applied an unbiased genome-wide transcriptomic profiling approach to shed further mechanistic light on the role of indigenous enterococcal communities in mucosal infection in a mouse model of cancer chemotherapy-associated OPC. Transcriptomic profiling of tongue tissues revealed a wide-ranging, barrier-compromising molecular activity of resident enterococci that explains the previously observed attenuation of fungal mucosal invasion with antibiotic treatment in this mouse model. Mechanistically, we validated the pathogenic potential of resident bacteria by showing that enterococci isolated from mice with OPC produce hydrogen peroxide (H2O2) and induce oral epithelial cell death through apoptosis and necrosis in vitro. We also discovered that C. albicans increased enterococcal H2O2 production. These findings uncover a novel mechanism of pathogenic synergy between C. albicans and Enterococcus faecalis, which may be responsible for increased epithelial barrier damage and mucosal invasion by C. albicans hyphae during cancer chemotherapy.

IMPORTANCE: Chemotherapy-induced mucosal barrier injury and immune suppression increase susceptibility to oropharyngeal candidiasis (OPC), a debilitating fungal infection. Our study uncovers a previously unknown pathogenic interaction between Candida albicans and Enterococcus faecalis, by showing that indigenous enterococci produce H2O2, which contributes to oral epithelial cell death during fungal infection. By integrating transcriptomics with functional assays, we demonstrate that enterococci compromise epithelial integrity independently of fungal burdens, highlighting the role of the bacterial microbiota in driving tissue damage. These findings emphasize the need to consider bacterial-fungal interactions in managing OPC and suggest that targeting the microbial crosstalk could be a promising adjunctive strategy in immunocompromised hosts.}, } @article {pmid41474178, year = {2025}, author = {Yang, XG and Yan, YW and Zhang, XX and Su, Y and Chen, MX and Li, XY}, title = {Decoding Plant-Microbe Interactions through the Kiwifruit Microbiome in Bacterial Canker Disease.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c12587}, pmid = {41474178}, issn = {1520-5118}, abstract = {Numerous communities of bacteria, fungi, viruses, and other microorganisms live inside plants and colonize their internal and external tissues, having a significant impact on the health and functionality of the plants. Studies on infection specific microbiome interactions remain restricted in spite of broad studies of plant microbiome interactions. An excellent model for examining these interactions is kiwifruit bacterial canker (KBC), which is caused by Pseudomonas syringae pv actinidiae (Psa). The present understanding of Psa pathogenicity and kiwifruit-associated microbiomes in various ecological niches is summarized in this review with a focus on their dual functions of either promoting or suppressing disease. We identify important microbial taxa and interaction mechanisms that serve as ecological leverage points for KBC control mediated by the microbiome by incorporating recent findings. This perspective advances the conceptual shift from pathogen elimination to microbiome balance restoration, offering new insights into sustainable KBC management.}, } @article {pmid41473794, year = {2025}, author = {Han, EJ and Ganley, JG and Winner, CB and An, JS and Seyedsayamdost, MR}, title = {Tetracycline Antibiotics Induce Biosynthesis of Pro-Inflammatory Metabolites in the Immunobiotic Bacteroides dorei.}, journal = {ACS central science}, volume = {11}, number = {12}, pages = {2421-2432}, pmid = {41473794}, issn = {2374-7943}, abstract = {The human gut microbiome consists of diverse microbes that communicate through small molecules. Numerous recent studies have demonstrated links between gut microbiota and host physiological processes; however, the underlying metabolites remain elusive in part because laboratory conditions do not replicate the native environment of these bacteria. Herein, we focused on Bacteroides dorei, a predominant and representative member of human gut microbiota, to interrogate the chemical composition and possible biological functions of its secondary metabolome. Using UPLC-MS-guided high-throughput elicitor screening (HiTES), we examined how the metabolome of this commensal bacterium responds to hundreds of FDA-approved drug molecules that the host may intake. We identified low-dose tetracyclines as pleiotropic inducers of the B. dorei secondary metabolome, leading to the identification and structural elucidation of six serine-glycine dipeptide lipids, named doreamides A-F, and two 6-N-acyladenosines. The induced doreamides and N-acyladenosines exhibited pro-inflammatory activities, upregulating tumor necrosis factor α (TNFα), interleukin (IL)-1β, IL-6, and IL-10 in macrophages. Doreamides also triggered production of cathelicidin, which inhibits the growth of multiple bacteria tested but not B. dorei. Our results show that low-dose antibiotics can perturb the secondary metabolome of gut bacteria, and that these induced metabolites can exert immunomodulatory effects and restructure the microbiome.}, } @article {pmid41473772, year = {2025}, author = {Wang, T and Cao, H and Ma, S and Wang, Z and Liu, H and Zhang, H and Wang, Q}, title = {Periodontal disease and gastric and colorectal cancers: mechanisms and therapeutic perspectives.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1699738}, pmid = {41473772}, issn = {2235-2988}, mesh = {Humans ; *Colorectal Neoplasms/therapy/epidemiology/prevention & control/etiology ; *Periodontal Diseases/complications/therapy/epidemiology ; *Stomach Neoplasms/therapy/epidemiology/prevention & control/etiology ; }, abstract = {Periodontal disease (PD) is one of the most prevalent chronic oral diseases globally, characterized by chronic inflammatory responses in the gingiva and supporting periodontal tissues. Recent epidemiological and mechanistic studies have indicated that PD not only adversely affects oral health but is also significantly associated with gastric and colorectal cancers. This article reviews the potential link between PD and these gastrointestinal malignancies, exploring the underlying pathogenic mechanisms and potential strategies for preventing and treating gastric and colorectal cancers through the management of PD. Periodontal health management may represent an adjunct avenue for the prevention and control of gastrointestinal cancers; however, high-quality longitudinal and interventional studies are needed to clarify causality.}, } @article {pmid41473771, year = {2025}, author = {Mao, X and Hu, X and Fang, J}, title = {Gut microbiota-metabolite interactions in drug-induced liver injury: mechanisms, biomarkers, and therapeutic perspectives.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1737234}, pmid = {41473771}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Chemical and Drug Induced Liver Injury/microbiology/metabolism/therapy ; Biomarkers/metabolism ; Dysbiosis ; Animals ; Liver/metabolism ; }, abstract = {Drug-induced liver injury (DILI) remains a major obstacle in clinical pharmacotherapy and a leading cause of acute liver failure and drug withdrawal worldwide. Conventional mechanistic models centered on hepatic xenobiotic metabolism, oxidative stress, and immune injury cannot fully account for the substantial interindividual variability and the unpredictable nature of idiosyncratic DILI. Increasing evidence shows that the gut microbiota and its metabolites critically shape hepatic susceptibility through modulation of drug metabolism, inflammatory signaling, and intestinal barrier integrity. This review summarizes current understanding of the gut-liver axis in DILI pathogenesis, with a focus on microbial enzymes such as β-glucuronidase that reactivate detoxified drug conjugates, microbial dysbiosis that disrupts bile acid homeostasis, and depletion of short chain fatty acids and indole derivatives that normally support epithelial defenses and immunologic tolerance. Drug-specific microbial patterns are discussed, including acetaminophen, amoxicillin-clavulanate, anti-tuberculosis regimens, and immune checkpoint inhibitors. We introduce the concept of metabotype-dependent hepatotoxicity, which emphasizes that individual microbial metabolic profiles influence DILI risk. Advances in metagenomics, metabolomics, and integrative multi-omics enable the identification of microbial biomarkers and functional pathways associated with DILI susceptibility. Emerging therapeutic strategies include restoration of microbial homeostasis, selective inhibition of microbial enzymes, and supplementation of hepatoprotective metabolites. Finally, we outline key challenges and future directions toward translating microbiome-based insights into clinical prediction and precision prevention of DILI. Importantly, this review integrates microbial metabolic functions with precision hepatology concepts, highlighting how metabotype-driven variability can be leveraged for individualized DILI risk assessment.}, } @article {pmid41473770, year = {2025}, author = {Machado, A and Foschi, C and Liao, Q and Xiao, B and Marangoni, A}, title = {Editorial: Advances in vaginal microbiome and metabolite research: genetics, evolution, and clinical perspectives.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1755233}, pmid = {41473770}, issn = {2235-2988}, } @article {pmid41473686, year = {2025}, author = {Yao, X and Zou, X and Cao, B}, title = {The Human Respiratory Virome in Health and Disease: Interactions, Dysbiosis, and Methodological Challenges.}, journal = {Advanced genetics (Hoboken, N.J.)}, volume = {6}, number = {4}, pages = {e00022}, pmid = {41473686}, issn = {2641-6573}, abstract = {The human respiratory virome is an underexplored component of the microbiome that includes diverse DNA and RNA viruses such as eukaryotic viruses, bacteriophages, and archaeal viruses. Recent advances in metagenomics have revealed the complexity and dynamic nature of the human respiratory virome, which interacts closely with the host and the bacterial microbiome to influence respiratory health and disease. In healthy individuals, the virome is characterized by low biomass and high temporal variability, with Anelloviruses predominant in the upper airways, whereas Streptococcus phages and herpesviruses are most commonly detected in the lower airways. Common respiratory viruses, such as respiratory syncytial virus, human rhinovirus, and influenza A virus, can persist after acute infection and modulate host immunity. The respiratory virome also plays a significant role in chronic respiratory diseases. Despite its importance, research on the respiratory virome is hampered by technical challenges, including low viral abundance and limited reference databases. This review summarizes current understanding of the composition and determinants of the respiratory virome in healthy individuals, describes its interactions with the host and respiratory microbiota, including the potential modulatory roles of bacteriophages, outlines virome alterations in respiratory diseases, examines methodological challenges, and highlights potential clinical applications and future research directions.}, } @article {pmid41473682, year = {2025}, author = {Fu, X and Wu, F and Liu, X}, title = {Bio-Archive of Cultural Heritage Microbiomes for Sustainable Conservation in the Multi-Omics Era.}, journal = {Advanced genetics (Hoboken, N.J.)}, volume = {6}, number = {4}, pages = {e00046}, pmid = {41473682}, issn = {2641-6573}, abstract = {Cultural heritage sites are commonly exposed to outdoor environments, resulting in severe damage to heritage objects from biotic and abiotic processes. Control of outdoor environments is impossible for heritage conservation, and we cannot prevent the abiotic processes. However, a variety of mitigation management can be developed for biotic damage, such as microbial colonization and biodeterioration. Over the past few decades, both conventional cultivation-dependent and modern cultivation-independent techniques have been employed to elucidate the microbiomes associated with the biodeterioration of cultural heritage. However, many studies are limited to segmentary analyses or simply stop at examining the community composition of the microbiomes, lacking solid evidence of microbial metabolism and biochemical reactions between microorganisms and heritage materials to support the core microbiomes associated with the biodeterioration. Here, we recommend thoroughly exploring the benefits of more advanced multi-omics techniques for analyzing cultural heritage microbiomes. We propose establishing a professional open-access database to standardize analytical procedures, integrating both culture-dependent and culture-independent approaches, and bio-archive valuable information on the core microbiomes, including their biodeterioration mechanisms, timelines, causes, and environmental conditions. This bio-archive of cultural heritage microbiomes will empower conservators and researchers worldwide to develop evidence-based, sustainable approaches for cultural heritage conservation under environmental change.}, } @article {pmid41473651, year = {2025}, author = {Damoulaki, E and Sioutis, D and Sarli, V and Trakakis, E and Mastorakos, G and Katoulis, A and Kastrinakis, K and Koratzanis, C and Machairiotis, N and Panagopoulos, P and Christodoulaki, C}, title = {Polycystic Ovary Syndrome-Associated Acne: The Interplay of Hyperandrogenism, Insulin Resistance, and Therapeutic Strategies.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e98103}, pmid = {41473651}, issn = {2168-8184}, abstract = {Acne vulgaris is one of the most prevalent dermatologic disorders in adolescent and adult women. Beyond classic pathogenic factors, such as sebaceous hypersecretion, follicular hyperkeratinization, Cutibacterium acnes overgrowth, and inflammation, endocrine drivers are pivotal. Polycystic ovary syndrome (PCOS) is common across reproductive ages and frequently presents with dermatologic manifestations, notably acne, through mechanisms dominated by hyperandrogenism and compounded by insulin resistance (IR). This narrative review synthesizes current evidence linking PCOS with acne, explains the interrelated roles of hyperandrogenism and IR, and outlines evidence-based management strategies tailored to women with PCOS. The Rotterdam diagnostic framework remains the globally favored standard for PCOS, emphasizing combinations of oligo-/anovulation, clinical/biochemical hyperandrogenism, and polycystic ovarian morphology. PCOS pathophysiology involves dysregulation of the hypothalamic-pituitary-ovarian axis with increased gonadotropin-releasing hormone pulsatility, elevated luteinizing hormone, and suppression of follicle-stimulating hormone, promoting thecal androgen excess and impaired folliculogenesis. IR, prevalent in PCOS, augments ovarian/adrenal androgen synthesis and lowers sex hormone-binding globulin levels, increasing free testosterone and sebum production; IGF-1 signaling further amplifies sebogenesis and follicular hyperkeratinization. Emerging data implicate genetic/epigenetic determinants, endocrine-disrupting chemicals, gut microbiome dysbiosis, and endoplasmic reticulum stress as modulators of the PCOS-acne phenotype. Epidemiologic studies and meta-analyses report higher acne prevalence and severity in PCOS, particularly among adolescents. First-line therapy includes combined oral contraceptive pills with antiandrogenic progestins; spironolactone is an effective adjunct. Where indicated, metformin addresses IR and may improve acne and ovulatory function. Judicious use of standard acne modalities such as topical retinoids, benzoyl peroxide, and oral/topical antibiotics remains essential; oral isotretinoin is reserved for refractory disease with careful risk management. PCOS-associated acne reflects converging endocrine and metabolic disturbances. Integrating androgen-targeted therapy, IR mitigation, and guideline-based acne care provides the most durable control. Future research should refine phenotype-directed treatment and clarify the contributions of microbiome, environmental exposures, and cellular stress pathways.}, } @article {pmid41473600, year = {2025}, author = {Zhang, Z and Chang, C and Xiao, L and Su, H and Lyu, Y and Zhao, J and Chen, J and Gou, K and Zhou, J and Wang, C and Zhu, X and Fu, S and Lu, M and Shi, L}, title = {The Neuroimmune Axis in Atopic Dermatitis: From Pathogenic Mechanisms to Targeted Neuroimmunotherapy.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {18079-18113}, pmid = {41473600}, issn = {1178-7031}, abstract = {Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which intense pruritus and eczematous lesions arise from tightly coupled disturbances of the nervous and immune systems. Emerging evidence indicates that a dysregulated neuroimmune axis-as reflected by peripheral neuronal sensitization, epidermal barrier dysfunction, and central itch processing-plays a central role in disease onset, persistence, and clinical heterogeneity. In this review, we synthesize current knowledge on the neuroimmune mechanisms that drive AD, focusing on how cytokines such as IL-31, IL-4/IL-13, TSLP and IL-33, together with neuropeptides including substance P, CGRP and VIP, establish self-reinforcing itch-scratch and inflammation loops at the level of the skin and the central nervous system. We then highlight recent multi-omics and systems biology approaches, including single-cell and spatial transcriptomics, neuroimaging, and microbiome profiling, that have reshaped the understanding of neuroimmune "neighbourhoods" and the gut-skin-brain axis in AD. Building on these mechanistic insights, we summarize key neuroimmune biomarkers-such as NGF, IL-31, TARC/CCL17, S100 proteins, barrier-related lipids, neurofunctional readouts from fMRI, and microbial signatures-and discuss their potential for improving diagnosis, patient stratification, and treatment monitoring within a precision medicine framework. Finally, we review established and emerging neuroimmune-targeted therapies, including IL-4/IL-13 and IL-31 pathway inhibitors, JAK inhibitors, OX40/OX40L-directed biologics, TRP and NK1R antagonists, phototherapy, and microbiome-based interventions, with a particular emphasis on biomarker-guided sequencing and combination strategies. Overall, we propose that positioning the neuroimmune axis at the core of AD pathogenesis provides a conceptual basis for developing stratified, durable, and patient-centred neuroimmunotherapy, while also outlining the remaining challenges regarding clinical validation of biomarkers, long-term safety, accessibility, and implementation across diverse patient populations.}, } @article {pmid41473328, year = {2025}, author = {Primov, K and Scott, C and Huzar, A and Peterson, C and Kirkpatrick, M and Matz, M}, title = {Acropora millepora 's microbiome is predicted by algal symbionts, host genetics, and environment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.15.694400}, pmid = {41473328}, issn = {2692-8205}, abstract = {The coral microbiome is a critical component of coral health and resilience, yet it is unclear what factors drive coral microbiome composition, especially within the context of coral bleaching. Here, we use whole genome sequencing data combined with a machine learning approach (RDAforest) to assess predictors of the microbiome in 208 colonies of Acropora millepora from 12 reef sites in the Central Great Barrier Reef during a 2016 bleaching event. We characterized microbiome variation using k-mers. While some environmental variables, such as chlorophyll seasonal range and maximum degree heating weeks, were associated with microbiome composition, we find that host genetics and dominant photosymbionts were more powerful predictors. In contrast, bleaching score had negligible predictive power. The coral's microbiome therefore correlates with dominant photosymbiont identity even during a bleaching event. The association of the microbiome with the environment suggests that the coral microbiome can serve as a proxy for environmental variation when environment cannot be measured directly, which may be especially useful in ancient DNA studies.}, } @article {pmid41473293, year = {2025}, author = {Estrada, KB and Azamar, KMM and Wang, C and Sudi, SD and Friday-Saunders, K and Márquez, V and Quintanilla-Carvajal, MX and Acosta-González, A and Conde-Martinez, N and Porras, AM and Alviña, K}, title = {Supplementation with a Limosilactobacillus fermentum K73 synbiotic modulates gut microbiota function and behavior in gnotobiotic mice transplanted with microbiota from children diagnosed with autism spectrum disorder.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.16.694732}, pmid = {41473293}, issn = {2692-8205}, abstract = {BACKGROUND: Gut dysbiosis has been implicated in numerous pathological conditions, including neurodevelopmental and neurodegenerative disorders. Recently, dietary interventions targeted at restoring microbial balance have therefore gained attention as potential therapeutic strategies. We recently demonstrated that an encapsulated synbiotic containing high-oleic palm oil and Limosilactobacillus fermentum K73 can modulate the metabolic activity and composition of human-derived gut microbiota in an in vitro batch bioreactor. Here, we extended this work through an in vivo supplementation pilot study using gnotobiotic mice colonized with gut microbiota from Colombian pediatric patients diagnosed with autism spectrum disorder (ASD) or age-matched neurotypical (NT) donors. Behavioral assessments and analyses of gut microbiota composition and function were performed before and after synbiotic supplementation.

RESULTS: First, we found that the gut microbiota from Colombian ASD patients exhibited significantly reduced richness relative to NT donors, consistent with reports from other geographical regions, and displayed distinct compositional features unique to this population. Humanization of the gnotobiotic mice with this donor microbiota was successful, with murine gut communities reflecting features of their corresponding donor microbiota. Notably, synbiotic supplementation induced significant increases in the abundance of beneficial taxa and the production of short chain fatty acids that were more pronounced in mice colonized with ASD-derived microbiota, with concurrent behavioral changes associated with beneficial modulation of gut microbiota.

CONCLUSIONS: Overall, we provide evidence that supports synbiotic supplementation as a viable strategy to positively modulate gut microbiome in conditions of dysbiosis. Our study also expands the body of knowledge of gut microbiome to understudied populations such as Latin America.}, } @article {pmid41473253, year = {2025}, author = {Wagner, ES and Oliphant, K and D'Souza, M and Cruz-Ayala, W and Azzam, RK and Andrews, B and Claud, EC}, title = {Fecal Microbiome and Bile Acid Profiles Differ in Preterm Infants with Parenteral Nutrition-associated Cholestasis.}, journal = {Journal of clinical and translational hepatology}, volume = {13}, number = {12}, pages = {1036-1045}, pmid = {41473253}, issn = {2310-8819}, abstract = {BACKGROUND AND AIMS: Parenteral nutrition (PN)-associated cholestasis (PNAC) is frequently diagnosed in premature infants; however, not all PN-exposed infants develop PNAC. We propose that, in premature infants receiving PN and varying amounts of enteral feeds, differences in the gut microbiome and fecal bile acid content are associated with PNAC development. This study aimed to examine the fecal microbiome and bile acid content of premature infants on PN to determine if there is a relationship with the development of PNAC.

METHODS: Twenty-two preterm infants had serial bilirubin measurements and fecal samples collected during their neonatal intensive care unit admission. Fecal samples underwent 16S rRNA gene sequencing and bile acid analysis. Binomial regression, adjusting for postmenstrual age with feed amount as a moderator, was used to assess the impact of the fecal microbiome and bile acids on PNAC development.

RESULTS: Cholestatic patients (n = 11) had greater PN and antibiotic exposure (p = 0.020; p = 0.010) and longer neonatal intensive care unit stays (p = 0.0038) than non-cholestatic patients. Microbiome richness was higher in non-cholestatic infants (p < 2E-16), with no difference in β diversity (p = 1.0). Cholestatic infants had a significantly higher abundance of Proteobacteria and Fusobacteriota and a lower abundance of Bacteroidota (p < 2E-16). Akkermansia was abundant in all infants on low feeds; as feed volume increased, Akkermansia abundance significantly increased in non-cholestatic infants (p < 2E-16). Bile acid analysis demonstrated significantly lower deoxycholic acid concentrations in cholestatic infants (p < 2E-16). Metagenomic analysis revealed an increase in Proteobacteria requiring augmented stress responses in non-cholestatic infants.

CONCLUSIONS: This is the first study to directly explore the relationship between PNAC susceptibility, the microbiome, and fecal bile acids in preterm infants. The microbiome and bile acid patterns identified here may inform the development of targeted therapeutics for this vulnerable population.}, } @article {pmid41473248, year = {2025}, author = {Zhang, Y and Cao, J and Wang, Y and Fan, X and Deng, R and Mi, J}, title = {Effects of fecal microbiota transplantation on glycemic and lipid profiles in overweight or obese patients with metabolic disorders: a systematic review and meta-analysis.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1737543}, pmid = {41473248}, issn = {1664-2392}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Obesity/therapy/blood/complications ; *Metabolic Diseases/therapy/blood ; *Overweight/therapy/blood ; *Lipids/blood ; *Blood Glucose/metabolism ; Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Lipid Metabolism ; }, abstract = {UNLABELLED: Obesity and its associated metabolic disorders (such as type 2 diabetes, metabolic syndrome, and NAFLD/MASLD) represent a global health challenge. Fecal microbiota transplantation (FMT), as a therapy regulating the gut microbiome, has demonstrated inconsistent clinical efficacy. This systematic review aims to evaluate the impact of FMT on key indicators of glucose and lipid metabolism in overweight/obese adults with metabolic diseases. We systematically searched PubMed, Embase, Cochrane, and Web of Science databases up to September 28, 2025, to identify randomized controlled trials evaluating FMT for obesity and metabolic disorders. Data were pooled using a random-effects model, with primary outcomes being changes in BMI, HOMA-IR, and HbA1c relative to baseline. A total of 11 RCTs (320 participants) were included. The primary analysis showed that FMT intervention demonstrated a trend toward improvement in the primary outcome measures, BMI (MD: -0.65, p = 0.070) and HOMA-IR (MD: -0.64, p = 0.062), but these trends did not reach statistical significance. There was no significant effect on HbA1c (MD: 0.06, p = 0.742). However, this negative conclusion based on the conventional assumption (Corr = 0.5) exhibited high instability: sensitivity analysis revealed that FMT's improvement effects on BMI became statistically significant (p = 0.010) when the correlation coefficient (Corr) used to estimate the standard deviation of change was adjusted to 0.75. Furthermore, meta-regression analysis revealed that treatment regimen, follow-up duration, and patient baseline characteristics were significantly associated with HbA1c efficacy. Based on the current "low" certainty evidence, the overall improvement of metabolic parameters in overweight or obese patients with metabolic diseases following FMT did not reach statistical significance in the primary analysis. However, the robustness of this negative finding is limited, exhibiting high sensitivity to statistical hypotheses and likely being significantly confounded by methodological factors (e.g., administration protocols) and donor variability. Consequently, the true efficacy of FMT for treating systemic metabolic disorders remains uncertain. Future trials should shift toward precision medicine, prioritizing the standardization of donor selection and optimization of administration protocols.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251172011, identifier CRD420251172011.}, } @article {pmid41473189, year = {2025}, author = {Duysburgh, C and Verstrepen, L and Van Meulebroek, L and Marzorati, M}, title = {Tributyrin (CoreBiome[®]) enhances butyrate levels and modulates the gut microbiota, barrier function, and immune response in vitro.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1712993}, pmid = {41473189}, issn = {2296-861X}, abstract = {BACKGROUND/OBJECTIVES: Oral butyrate is unstable during upper gastrointestinal tract (GIT) transit and very little reaches the colon. Tributyrin, a butyrate precursor, resists gastric acid and is converted to butyrate by pancreatic lipases. This study aimed to quantify tributyrin stability during upper GIT passage and to uncover the effects of tributyrin supplementation on the human gut microbiome and cellular responses.

METHODS: In vitro upper GIT simulations were used to evaluate the stability of a capsule and softgel formulation of tributyrin (CoreBiome[®]). The effects of tributyrin supplementation on the human gut microbiome and cellular responses were evaluated using the Simulator of the Human Intestinal Microbial Environment (SHIME[®]) model and Caco-2/THP1 co-cultures.

RESULTS: The upper GIT simulations showed that 40.9 and 48.7% of the tributyrin dose administered via the capsule or softgel, respectively, was hydrolyzed to butyrate in the small intestine; 59.1 and 51.3% remained stable and was available to enter the colon. Using the SHIME[®] model, it was shown that 3 weeks of daily tributyrin supplementation increased butyrate levels and enhanced the abundance of several bacterial species, including Bifidobacterium spp. and Akkermansia mucinophila. Metabolic impacts on the gut microbiome were also observed. Assessment of cellular responses revealed that tributyrin fermentation had a protective effect on the intestinal barrier and exerted immunomodulatory properties.

CONCLUSION: Enhanced butyrate concentrations and beneficial impacts on the gut microbial community composition were observed in an in vitro simulation of the human intestinal environment, suggesting that tributyrin could be considered as a solid alternative to butyrate supplementation.}, } @article {pmid41472866, year = {2025}, author = {Namasivayam, S and Romero-Soto, HN and Bacorn, M and Perez-Chaparro, PJ and Burns, AS and Mistry, S and Brandes, N and Chong, A and Cooper, G and LaCroix, IS and LaPoint, P and Banks, K and Chen, Q and Patel, A and Mueller, NT and Dominguez-Bello, MG and Maxwell, GL and Levy, S and Schwarz, B and Belkaid, Y and Hourigan, SK}, title = {The pioneering gut microbiome acquired via different delivery modes in neonates shapes distinct immune and metabolic environments.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.09.30.25337005}, pmid = {41472866}, abstract = {BACKGROUND: Cesarean section (CS) delivery is associated with an increased risk of inflammatory diseases, hypothesized to be driven by differences in the microbiome acquired at birth compared to vaginally delivered (VD) infants. How delivery mode associated differences in initial colonizers directly modulate early life immune education and metabolic development is poorly understood.

OBJECTIVE: First, to investigate how differences in pioneering colonizers associated with delivery mode directly modulate early life immune education and metabolic programming. Second, to examine the effect of vaginal seeding, an intervention aimed to restore the microbiome of CS infants to a VD state.

DESIGN: Germ-free mice were colonized with transitional stool from VD, CS or CS-delivered and vaginally seeded neonates. Immune cell populations, serum immunoglobulin levels, and fecal microbiome and metabolome profiles were analyzed.

RESULTS: Mice colonized with stool from VD neonates displayed increased numbers of myeloid cells at barrier tissues, whereas CS microbiome colonized mice exhibited decreased Th1/Th2 ratios and increased serum IgE levels. Key amino-acid pathways including tryptophan metabolism, riboflavin co-enzymes and carbohydrate metabolites were significantly enriched in the murine VD fecal metabolome and correlate with the increased abundance of Escherichia typically observed in the VD microbiome. Mice colonized with stool from CS neonates who received vaginal seeding, resulted in increased regulatory T cells and serum IgA in mice, suggesting potential benefits of vaginal seeding.

CONCLUSION: Collectively, our studies demonstrate the ability of pioneering colonizers to set the immune and metabolic tone that could have long-lasting effects and provide avenues for microbiome-mediated interventions.}, } @article {pmid41472856, year = {2025}, author = {Qi, C and Zhang, Y and Qing, W and Chen, R and Zhou, Z and Liu, Y and Chen, E and Chen, W and , and Zhou, H and Chen, M}, title = {Nationwide profiling of vaginal microbiota in Chinese women reveals age-dependent shifts and predictive biomarkers for reproductive health.}, journal = {iMeta}, volume = {4}, number = {6}, pages = {e70088}, pmid = {41472856}, issn = {2770-596X}, abstract = {The vaginal microbiome is central to reproductive health, yet large-scale studies in East Asian populations remain scarce. Here, we characterized the vaginal microbiota of 6423 Chinese women of reproductive age across 18 provinces and assessed associations with 33 host factors. We observed a striking compositional transition around age 40, marked by declining Lactobacillus crispatus and enrichment of dysbiosis-associated taxa including Gardnerella vaginalis, independent of lifestyle or sociodemographic influences. Sexual behavior, contraceptive use, and educational attainment emerged as key determinants of community structure, differentially shaping Lactobacillus crispatus and Lactobacillus iners. Despite these associations, host factors explained less than 2% of overall variation, highlighting the resilience and individuality of the vaginal microbiome. To quantify vaginal health, we derived a microbiome balance score, validated it in external cohorts, and demonstrated its predictive power for incident bacterial vaginosis and sexually transmitted infections. Our findings establish a national-scale reference for the vaginal microbiome in Chinese women, reveal a midlife inflection point in microbial composition, and introduce a clinically actionable metric for risk stratification. These insights advance mechanistic understanding of host-microbiome interactions and inform strategies for precision interventions to preserve vaginal health.}, } @article {pmid41472855, year = {2025}, author = {Wu, D and Wang, AJ and Bu, DC and Sun, YY and Li, CH and Hong, YM and Zhang, S and Chen, SY and Zhou, JA and Zhang, TY and Yu, MH and Ma, YJ and Wang, XL and Xu, J and He, W and Heeschen, C and Chen, JF and Mao, WJ and Ding, H and Wu, WJ and Zhao, Y and Wang, H and Liu, NN}, title = {The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma.}, journal = {iMeta}, volume = {4}, number = {6}, pages = {e70090}, pmid = {41472855}, issn = {2770-596X}, abstract = {The intratumoral microbiome is an emerging hallmark of cancer, yet its multi-kingdom host-microbiome ecosystem in colorectal cancer (CRC) remains poorly characterized. Here, we conducted an integrated analysis using deep shotgun metagenomics and proteomics on 185 tissue samples, including adenoma (A), paired tumor (T), and para-tumor (P). We identified 4057 bacterial, 61 fungal, 108 archaeal, and 374 viral species in tissues and revealed distinct intratumor microbiota dysbiosis, indicating a CRC-specific multi-kingdom microbial ecosystem. Proteomic profiling uncovered four CRC subtypes (C1-C4), each with unique clinical prognoses and molecular signatures. We further discovered that host-microbiome interactions are dynamically reorganized during carcinogenesis, where different microbial taxa converge on common host pathways through distinct proteins. Leveraging this interplay, we identified 14 multi-kingdom microbial and 8 protein markers that strongly distinguished A from T samples (area under the receiver operating characteristic curve (AUROC) = 0.962), with external validation in two independent datasets (AUROC = 0.920 and 0.735). Moreover, we constructed an early- versus advanced-stage classifier using 8 microbial and 4 protein markers, which demonstrated high diagnostic accuracy (AUROC = 0.926) and was validated externally (AUROC = 0.659-0.744). Functional validation in patient-derived organoids and murine allograft models confirmed that enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum promoted tumor growth by activating Wnt/β-catenin and NF-κB signaling pathways, corroborating the functional potential of these biomarkers. Together, these findings reveal dynamic host-microbiome interactions at the protein level, tracing the transition from adenoma to carcinoma and offering potential diagnostic and therapeutic targets for CRC.}, } @article {pmid41472853, year = {2025}, author = {Xu, J and Hu, P and Liu, M and Zhang, W and Xie, K}, title = {Cultivar-specific preference of bacterial communities and host immune receptor kinase modulate the outcomes of rice-microbiota interactions.}, journal = {iMeta}, volume = {4}, number = {6}, pages = {e70098}, pmid = {41472853}, issn = {2770-596X}, abstract = {Deciphering how plant-microbiota interactions achieve beneficial outcomes for crops will provide innovative strategies for sustainable agriculture. Here, we dissected rice-microbiota dynamics using a tailored gnotobiotic cultivation system that models the semiaquatic environment in a paddy field. Inoculation with native soil microbiota resulted in root-growth-promotion (RGP) and root-growth-inhibition (RGI) phenomena in different cultivars. This preference persisted in a simplified synthetic community and individual bacterial strains, indicating that cultivar-specific growth promotion is an intrinsic property of microbial inocula. Though stochastic process dominated the assembly of root microbiome in gnotobiotic cultivation, absolute quantification revealed that imbalance of detrimental and beneficial bacterial loads in roots correlated with RGP or RGI outcomes in different rice cultivars. From the host perspective, genetic screening identified that receptor-like kinase mutants, including OsFLS2 (FLAGELLIN-SENSITIVE 2), inverted microbiota functionality, converting RGP to RGI. In particular, over 4534 rice genes responded to microbiota inoculation and 46.1% of them were reprogrammed in osfls2 mutants, demonstrating the prominent regulatory role of OsFLS2 in rice-microbiota signaling. On the basis of these results, we propose that the rice-microbiota relationships are gated by cultivar-specific preferences of the bacterial microbiota and host immune receptor kinase, which provides a useful framework for crop microbiome engineering in the future.}, } @article {pmid41472849, year = {2025}, author = {Xiao, Z and Ding, K and Guo, X and Zhao, Y and Li, X and Jiang, D and Zhu, D and Chen, Q and Jong, MC and Graham, DW and Li, G and Zhu, YG}, title = {Soil-borne legacy facilitates the dissemination of antibiotic resistance genes in soil-plant continua.}, journal = {iMeta}, volume = {4}, number = {6}, pages = {e70094}, pmid = {41472849}, issn = {2770-596X}, abstract = {Antimicrobial resistance (AMR) disseminates throughout the soil-plant continuum via complex microbial interactions. Plants shape root- and leaf-associated microbiomes that sustain plant health; however, soil-borne legacies-enriched with antibiotic-producing microbes and resistance genes-govern AMR dynamics across agroecosystems. Using 16S rRNA gene sequencing, shotgun metagenomics, and high-throughput quantitative PCR, we profiled antibiotic resistance genes (ARGs), mobile genetic elements, and virulence factor genes across bulk soil, rhizosphere, phyllosphere, and root endosphere within soil-tomato and soil-strawberry continua. Recurrent bacterial wilt amplified the resistome, particularly polypeptide resistance genes, thereby establishing the rhizosphere as a major hotspot of ARG accumulation. Multidrug-resistant Ralstonia solanacearum (R. solanacearum) strains acted as major ARG reservoirs, harboring resistance determinants on both chromosomes and megaplasmids. Collectively, these findings demonstrate that pathogen-driven restructuring of the plant microbiome accelerates ARG dissemination, establishing soil-borne diseases as critical amplifiers of AMR across agricultural ecosystems.}, } @article {pmid41472817, year = {2025}, author = {Zhao, Z and Mao, Z and He, D and Wang, H and Wu, Q}, title = {Host specificity and uniqueness of shell microbiome in freshwater mollusks.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1702047}, pmid = {41472817}, issn = {1664-302X}, abstract = {INTRODUCTION: Mollusk shells represent a major substrate for the colonization of microbial communities and the functioning of aquatic ecosystems. However, our knowledge of the shell microbiome is very limited.

METHODS: Here, we selected Bellamya aeruginosa and Corbicula fluminea as two types of snails and clams, respectively, to explore their shell epiphytic bacteria by 16S amplicon sequencing.

RESULTS: We found different shell bacterial communities between snails and clams, which were also distinct from those in the surrounding environment. Source tracking analysis indicated that snail-shell bacteria were mostly derived from sediments, whereas clamshells originated from tissues. There was a site-specific difference in the shell bacteria within the habitat. Temporal variation in clamshell bacteria was observed, but not in snail shells, which corresponds to their source dynamics in the water column and stable surface sediment bacterial communities, respectively. The genus Nitrospira is mostly enriched in shell bacteria, particularly in eutrophic lakes. Taxa related to carbon, nitrogen, and sulfur cycling were recognized as the keystone species in the co-occurrence network associated with the shell surface. Our results demonstrate that mollusk shells represent a unique ecological niche for microbiomes in aquatic ecosystems and may serve as hotspots for biogeochemical cycling.}, } @article {pmid41472812, year = {2025}, author = {Xie, X and Tao, H and Li, Y and Feng, X and Li, K and Zhang, Z and Yan, J and Wang, X}, title = {Microbial fertilizer for improving maize yield, straw decomposition and soil microbiome structure.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1670118}, pmid = {41472812}, issn = {1664-302X}, abstract = {Microbial fertilizers represent a promising strategy to sustainably produce crops by enhancing the biological function of soil and availability of nutrients. However, there is a lack of study on their performance across diverse agroecological zones. In this study, we conducted a 3-year, two-site field experiment to assess the effects of a composite microbial fertilizer (Bacillus subtilis and Trichoderma harzianum) on the yield of maize (Zea mays), soil properties, straw degradation, and composition of the microbial community. The results showed that the microbial fertilizer treatment (MF) increased the yield of maize by 11.4 and 6.9% in Qingfeng Country (QF) and Xun Country (Xun), China, respectively, compared to normal chemical fertilizer (CF). These gains coincided with an enhanced straw degradation rate (SDR; +8.4-8.6%) and a tendency toward higher available phosphorus (AP; +15.4-19.7%), alongside shifts in bacterial and fungal composition. High-throughput sequencing revealed that Proteobacteria, Actinobacteriota, Acidobacteriota, and Chloroflexi dominated the bacterial communities at both sites, whereas the fungal communities were mainly composed of Sordariomycetes, Dothideomycetes, and Eurotiomycetes-taxa whose abundances displayed pronounced site specificity. Application of the microbial fertilizer was associated with higher relative abundance of Acidobacteriota by 22.7% (QF) and 60.8% (Xun) and that of Sordariomycetes by 13.7% (QF) and 30.9% (Xun), underscoring its strong, selective impact on the dominant bacterial and fungal assemblages. These regional differences underscore the influence of site-specific microbial assemblages on the performance of fertilizer. Partial least squares path modeling supported a plausible pathway in which changes in community structure and straw decomposition are linked to improved soil nutrient status, which in turn predicted yield (β = 0.846, R [2] = 0.715). Together, the field data indicate that microbial fertilizers may act through multi-step, microbiome-associated pathways, with success depending on compatibility with native microbial assemblages and environmental context.}, } @article {pmid41472811, year = {2025}, author = {Liao, J and Duan, L and Wang, G and Yu, S and Shen, X and Jiang, M and Shen, K and Singla, RK and Shen, B and Zhou, Y}, title = {Gut microbiome associated with melanin deposition by supporting energy metabolism in Sichuan mountainous black-bone chickens.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1682376}, pmid = {41472811}, issn = {1664-302X}, abstract = {INTRODUCTION: Variation in melanin deposition profoundly influences the economic value of Sichuan mountainous black-boned chickens; however, the contribution of the gut microbiome in modulating this process remains poorly understood. This study aimed to characterize the gut microbiome in Sichuan mountainous black-boned chickens with distinct skin color brightness (quantified by colorimeter) and to explore its association with melanin deposition.

METHODS: Cecal microbiota composition was profiled using 16S rRNA sequencing in dark-skinned (BlackD) and light-skinned (BlackL) groups. Serum metabolic profiles were determined via untargeted metabolomics. Differential abundance of bacterial genera was assessed, followed by pathway enrichment analysis (KEGG and MetaCyc). Associations between microbiome, metabolites, and melanin-related pathways were evaluated.

RESULTS: The BlackD group exhibited higher alpha diversity and significant alterations in 10 bacterial genera (primarily linked to short-chain fatty acid metabolism and melanin-related metabolites) compared to the BlackL group. Pathway enrichment showed upregulation of energy metabolism-related KEGG pathways (AMPK signaling, insulin signaling, thyroid hormone signaling) and MetaCyc pathways in BlackD. Untargeted serum metabolomics revealed elevated melanin-related metabolites in BlackD, including L-Tyrosine, L-DOPA, and Dopaquinone. Gut microbiome and serum metabolite profiles in BlackD were strongly correlated with enhanced energy metabolism.

DISCUSSION: The gut microbiome may influence melanin deposition by modulating host metabolic activity, with microbiome-derived metabolites supporting the high energy demands of melanocyte activity. These findings uncover a potential mechanism linking microbial composition to phenotypic variation in melanin deposition.}, } @article {pmid41472810, year = {2025}, author = {Lan, B and Liang, Y and Zhou, Z and Liu, J}, title = {Gut microbiome dysbiosis implicates the gut-bone axis in Modic changes: a metagenomic case-control study.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1702357}, pmid = {41472810}, issn = {1664-302X}, abstract = {INTRODUCTION: Modic changes (MCs) are vertebral endplate lesions strongly associated with discogenic low back pain (LBP), though their pathogenesis remains poorly understood. Emerging evidence implicates gut microbial dysbiosis in systemic inflammation and musculoskeletal disorders, yet its potential role in MCs has not been investigated. This study aimed to characterize the gut microbiome in patients with MCs and identify microbial and metabolic features linked to disease severity.

METHODS: In a case-control study, shotgun metagenomic sequencing was performed on fecal samples from 31 patients with MCs (16 Type 1, 15 Type 2) and 25 age- and sex-matched healthy controls. Microbial community structure was assessed via alpha and beta diversity analyses. Differential taxa and predictive biomarkers were identified using linear discriminant analysis effect size (LEfSe) and Random Forest modeling. Functional potential was evaluated via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Associations between microbial features and clinical markers (C-reactive protein [CRP], Pfirrmann grade) were also examined.

RESULTS: Patients with MCs showed significantly reduced gut microbial alpha diversity compared to controls (Chao1 index: p = 0.005; Shannon index: p = 0.034; Simpson index: p = 0.042), with the most pronounced reduction in Type 1 MCs. Beta diversity analysis revealed distinct microbial communities between groups (PERMANOVA, p = 0.001). Key discriminative taxa included unclassified_Parabacteroides (AUC = 0.895) and Bacteroides uniformis (AUC = 0.889). Metabolic pathway analysis identified 52 differentially abundant pathways, with significant enrichment of quorum sensing (p < 0.001) and glycerolipid metabolism (p < 0.001) in MC patients, both strongly correlated with elevated CRP and higher Pfirrmann grade (p < 0.001).

DISCUSSION: Gut microbial dysbiosis is associated with MCs, marked by reduced diversity, specific bacterial biomarkers, and altered metabolic pathways related to inflammation and tissue degeneration. These results suggest a potential role of the gut-bone axis in MC pathogenesis and highlight novel targets for diagnostic and therapeutic strategies in LBP.}, } @article {pmid41472807, year = {2025}, author = {Zhang, Q and Ding, L and Xie, X and Ru, L and Li, Q and Yao, C and Solkner, J and Jiang, R}, title = {Third-generation sequencing reveals the spatial variation of microbial composition of airborne bacteria in an intensive dairy farm.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1688472}, pmid = {41472807}, issn = {1664-302X}, abstract = {INTRODUCTION: The intensification of livestock farming has led to increased bacterial bioaerosol emissions, posing potential health risks to both animals and humans. This study aimed to investigate the bacterial community composition, abundance, diversity, and variation in different functional zones of cattle farms to assess their impact on public health and environmental quality.

METHODS: We employed third-generation sequencing on the PacBio platform to analyze 16S ribosomal RNA (rRNA) sequences from air samples, identifying a diverse range of bacterial phyla, including Proteobacteria, Firmicutes, Verrucomicrobia, Bacteroidetes, Fusobacteria, Actinobacteria, Deinococcus-Thermus, Cyanobacteria, and Acidobacteria. The phylogenetic tree was built using the microbiome abundance of these samples.

RESULTS: Notably, Firmicutes and Proteobacteria were predominantly enriched in the samples, with genera such as Staphylococcus, Acinetobacter, Enterococcus, and Bacillus, and the family Enterobacteriaceae, which was unknown, being particularly abundant. These bacteria are known to be associated with various infections and chronic diseases. Correlation and canonical correspondence analysis (CCA) revealed that environmental factors, particularly ultraviolet (UV) radiation and global horizontal irradiance (GHI), significantly influence microbial species distribution, with R [2] values of 0.774 (p < 0.05) and 0.769 (p < 0.05), respectively. We further calculated the alpha and beta diversity of microbiome in these samples and observed that fermenting manure (F1), fresh manure (X2), and piled-up manure after fermentation (D3) samples have the highest alpha diversity, while PC1 from beta diversity, that is, weighted principal coordinates analysis (PCoA), explained 32.66% of the variance in the data. Interestingly, the relative abundance of the Kocuria genus was significantly different between the waste management area (FW) and the milking parlor (NT) (t-test, p < 0.013).

DISCUSSION: Our findings underscore the importance of understanding the complex microbial ecosystems in livestock farming environments and highlight the need for targeted interventions to mitigate public health risks associated with bacterial bioaerosols.}, } @article {pmid41472804, year = {2025}, author = {Zhao, R and Liu, P and Wu, Y and Bi, H and He, J and Zhang, J and Qu, Y and Chen, X and Chen, Z}, title = {Triclocarban exposure at environmentally relevant concentrations perturbs the gut microbiota and metabolic profile in Rana taihangensis (Anura, Ranidae) tadpoles.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1740880}, pmid = {41472804}, issn = {1664-302X}, abstract = {INTRODUCTION: The antibacterial agent triclocarban (TCC) poses a significant threat to aquatic ecosystems and its impact on amphibians remain poorly understood.

METHODS: Here, we investigated its acute and chronic effects on Rana taihangensis tadpoles at environmentally relevant concentrations (i.e., 5, 15 and 45 μg/L) using an integrated approach combining morphology, gut microbiome, and non-targeted metabolomic analyses.

RESULTS AND DISCUSSION: The acute toxicity tests for 96 h revealed that TCC had a lethal concentration (LC50) value of 169.863 μg/L for R. taihangensis tadpoles. Chronic exposure resulted in reduced body condition score across all the three TCC-treated groups compared to the control. Gut microbiome analysis revealed that TCC exposure significantly altered the community composition at both phylum (e.g., Pseudomonadota and Fusobacteriota) and genus (e.g., Cetobacterium and Citrobacter) levels. In addition, several metabolites (e.g., 20-carboxy-leukotriene B4, 11b-PGF2a, and leukotriene E4) associated with immune response and neural signaling were significantly perturbed in TCC-exposed tadpoles. Interestingly, correlation analysis indicated a significant relationship between specific metabolite changes and shifts in gut microbiota. Overall, our findings demonstrated that TCC exposure adversely affects the growth indexes, gut microbial composition and metabolites in R. taihangensis tadpoles, and the present study will provide new insights into the ecotoxicological risks of TCC and enhance the understanding of its mechanisms of toxicity in aquatic organisms.}, } @article {pmid41472773, year = {2025}, author = {Charoenwai, O and Tanpichai, P and Sukkarun, P and Jeon, HJ and Kim, B and Han, JE and Piamsomboon, P}, title = {Emergence of decapod hepanhamaparvovirus genotype V and its co-infection with Enterocytozoon hepatopenaei in cultured Penaeus vannamei in Thailand: Evidence from epidemiological, pathogenicity, and microbiome analyses.}, journal = {Veterinary world}, volume = {18}, number = {11}, pages = {3496-3508}, pmid = {41472773}, issn = {0972-8988}, abstract = {BACKGROUND AND AIM: Growth retardation syndrome in cultured Penaeus vannamei has been associated with Enterocytozoon hepatopenaei (EHP) and a recently identified decapod hepanhamaparvovirus (DHPV) genotype V. However, data on its prevalence, pathogenicity, and interaction with the shrimp hepatopancreatic microbiome in Thailand remain limited. This study aimed to determine the incidence and co-infection rate of DHPV genotype V with EHP, evaluate its pathogenic potential, and explore microbiome alterations associated with infection.

MATERIALS AND METHODS: Between 2022 and 2023, 1,270 shrimp from 127 grow-out ponds across 46 farms in eastern Thailand and post-larvae 12 from five hatcheries in the south were screened for DHPV and EHP by polymerase chain reaction. Six representative isolates underwent phylogenetic analysis based on non-structural protein 1 (NS1) and NS2 genes. Pathogenicity was evaluated by immersion challenge bioassays in specific pathogen-free P. vannamei. Hepatopancreatic microbiomes of naturally infected and healthy shrimp were compared using 16S ribosomal RNA gene sequencing and Quantitative Insights Into Microbial Ecology 2-based analysis.

RESULTS: DHPV was detected in 54.33% (69/127) of ponds and 4% (1/25) of hatchery tanks. Co-infection with EHP occurred in 40.16% of ponds. Phylogenetic analysis showed 97.99%-98.82% similarity with DHPV genotype V from South Korea, confirming transboundary genetic relatedness. Experimental infection caused low mortality (20%) but resulted in viral replication (10[1]-10[3] copies/μL) and characteristic intranuclear inclusion bodies in hepatopancreatic cells. DHPV-infected shrimp exhibited distinct microbiome profiles with elevated Firmicutes, Planctomycetota, and Actinobacteriota abundances, supporting a pathobiome shift during infection.

CONCLUSION: This is the first report of DHPV genotype V in P. vannamei from Thailand and its frequent co-infection with EHP. Despite its low experimental virulence, the widespread occurrence and microbiome dysbiosis suggest that it may have subclinical impacts that could exacerbate growth retardation. Routine molecular screening in hatcheries and farms, coupled with integrated viral-microbiome surveillance, is essential for sustainable aquaculture biosecurity and aligns with the United Nations Sustainable Development Goal 14 (Life Below Water) by promoting resilient aquatic food systems.}, } @article {pmid41472726, year = {2025}, author = {Jani, CT and Edwards, K and Bhanushali, C and Zheng, X and Salazar, AS and Lopes, G and Watson, DC}, title = {Leveraging beneficial microbiome-immune interactions via probiotic use in cancer immunotherapy.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1713382}, pmid = {41472726}, issn = {1664-3224}, mesh = {*Probiotics/therapeutic use ; Humans ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {The gut microbiome is a critical regulator of systemic immunity and a major modulator of response to cancer immunotherapy with immune checkpoint inhibitors (ICIs). However, the clinical implementation of microbiome-inspired therapies that leverage these associations have proven challenging. Probiotics-live microorganisms thought to confer health benefits as part of food or food supplements-have gained increasing attention as readily testable, low-toxicity agents with potential of favorably influencing host-microbiome-immune interactions in the context of cancer immunotherapy. In this review, we critically evaluate the growing body of evidence supporting the role of probiotics in enhancing ICI efficacy and summarize published and ongoing clinical trials formally testing their role as adjuncts to cancer immunotherapy. Probiotics have been shown in preclinical murine models to exert immunomodulatory effects, including activation and maturation of dendritic cells, enhancement of MHC-I-mediated antigen presentation, modulation of cytokine profiles, and promotion of pro-inflammatory macrophage polarization. Probiotics also regulate adaptive immunity via microbial metabolites such as short-chain fatty acids (SCFAs), inosine, and tryptophan derivatives that support effector T cell activation and reduce T cell exhaustion. Cross-reactivity between microbial and tumor-associated antigens (molecular mimicry) further underscores the potential of probiotic strains to stimulate antitumor responses. In these models, supplementation with specific bacterial strains such as Bifidobacterium spp., Lactobacillus spp., Clostridium butyricum, and Akkermansia muciniphila enhanced ICI responses across tumor types including melanoma, lung cancer, and colorectal cancer. These findings are in part supported by early-phase clinical studies and retrospective cohorts, particularly in lung and renal cancers, where probiotic use has been associated with improved progression-free and overall survival. However, most clinical data are observational, and the field lacks standardized probiotic formulations and dosing protocols. To transition probiotics from food supplements to clinically validated immunotherapy adjuncts, rigorous mechanistic, translational, and clinical studies are necessary. These approaches have the potential to define mechanism-of-action, identify immunologically active strains, and inform rational clinical trial design. With careful development, probiotics hold promise as cost-effective, scalable, and personalized tools to optimize the efficacy and safety of cancer immunotherapy.}, } @article {pmid41472687, year = {2025}, author = {Loke, P and Smith, A and Kiwanuka, K and Pessenda, G and Rahmberg, A and Flynn, J and Herbert, R and Brenchley, J}, title = {Hematological Consequences of Environmental Change During Dewilding of Rhesus Macaques.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-7767375/v1}, pmid = {41472687}, issn = {2693-5015}, abstract = {The environment shapes immune system development and the regulation of inflammatory responses, which may affect the prevalence of immune mediated inflammatory diseases. However, the hematological consequences of a major environmental change, such as those experienced during migration, remain poorly understood. Here, we used cellular and molecular approaches to assess the immunological consequences in rhesus macaques as they transitioned from an outdoor provisioned environment to an indoor laboratory facility in a process we term 'dewilding.' Dewilding led to a sharp decrease in neutrophils and increased lymphocytes in the peripheral blood, a skewing toward a proinflammatory TH1 response, and increased T cell activation. Concurrently, we observed changes in the microbiome, with fungal abundance decreasing while bacterial abundance increased during dewilding. In the bone marrow, we observed increased granulopoiesis, reduced lymphocytes, and reduced hematopoietic stem cells and progenitors, with their shift toward less committed progenitor states. Single-cell nuclear RNA sequencing of the bone marrow revealed increased erythrocyte progenitors in the bone marrow during dewilding, with upregulation of genes involved in hemoglobin control and erythropoiesis. Notably, the vaccination response against measles varied based on vaccination period during the dewilding process. Together, our findings illustrate how dewilding alters immune homeostasis, with implications for understanding immune adaptation in migrants from rural to urban environments and for optimizing immunization strategies during environmental change.}, } @article {pmid41472620, year = {2025}, author = {Zhang, D and Xu, X and Zhang, Z}, title = {Effect of Social Rank on Gut Microbes and Their Metabolites of Greater Long-Tailed Hamsters (Tscherskia triton).}, journal = {Integrative zoology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1749-4877.70049}, pmid = {41472620}, issn = {1749-4877}, support = {RZ2300002832//Hainan University research start-up fund project/ ; }, abstract = {Although the effects of social rank on behavior and physiology are well established, their relationship with gut microbiota is not yet fully understood. We investigated how social rank affects physiological responses, gut microbiota, and metabolites in the greater long-tailed hamster (Tscherskia triton), a naturally solitary rodent. Dominant male hamsters displayed a "high-vigilance, metabolically activated" phenotype, characterized by increased aggression, elevated serum corticosterone (CORT) and serotonin (5-HT) levels, and activation of the paraventricular nucleus, a key regulator of the hypothalamic-pituitary-adrenal axis. In contrast, subordinates exhibited lower CORT and 5-HT levels, with increased activation of the arcuate nucleus (ARC), suggesting a more energy-conserving and stress-resilient phenotype. Social rank strongly shaped gut microbiota and metabolic output: dominants were enriched in energy-harvesting taxa (e.g., Limosilactobacillus and Alistipes) and had higher fecal queuine levels, a metabolite derived from gut microbiota. Conversely, subordinates were enriched in immunomodulatory taxa (e.g., Faecalibacterium and Butyrivibrio). These findings suggest that dominance in solitary species may be supported by coordinated host-microbiome interactions, which meet high energetic demands while maintaining stress resilience. This provides a novel framework for understanding the gut-brain-microbiome axis in social dominance.}, } @article {pmid41472585, year = {2025}, author = {Orhan, F and Bektaş, M and Bariş, Ö}, title = {Elucidating environmental reservoir of antimicrobial resistance - a phenotypic characterization of gut microbiota from aquatic coleoptera in a low-anthropogenic impact zone.}, journal = {Annals of agricultural and environmental medicine : AAEM}, volume = {32}, number = {4}, pages = {504-510}, doi = {10.26444/aaem/210421}, pmid = {41472585}, issn = {1898-2263}, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Microbial Sensitivity Tests ; *Gastrointestinal Microbiome/drug effects ; *Coleoptera/microbiology ; *Bacteria/drug effects/isolation & purification/genetics/classification ; *Drug Resistance, Bacterial ; Turkey ; *Gram-Negative Bacteria/drug effects/isolation & purification/genetics ; Drug Resistance, Multiple, Bacterial ; }, abstract = {INTRODUCTION AND OBJECTIVE: This study investigated the antibiotic resistance of bacterial isolates obtained from the gut microbiota of certain insects (Coleoptera: Hydrophilidae and Helophoridae), which were collected from aquatic areas in Erzurum Province, Türkiye. This area is characterised by a low level of human impact, thereby providing a unique opportunity to investigate the baseline microbial diversity and ecological roles within relatively pristine aquatic environments.

MATERIAL AND METHODS: The antimicrobial susceptibility of the isolates was assessed using disc diffusion and minimum inhibitory concentration (MIC) methods. The analysis encompassed 30 Gram-negative bacteria belonging to the genera Aeromonas, Acinetobacter, Vibrio, Pseudomonas, Escherichia and Yersinia.

RESULTS: The results indicated that the most resistant bacteria were Aeromonas, Pseudomonas and Acinetobacter, while enteric bacteria demonstrated greater sensitivity. It is noteworthy that nitrofurantoin, a commonly used antibiotic for treating urinary tract infections, exhibited the highest level of resistance among the antibiotics tested by disc diffusion, followed by cephalosporins and penicillins.

CONCLUSIONS: The MIC testing with DKGM and NF kits demonstrated high resistance to cephalosporins, sulfonamides, polymyxins and monobactams. Furthermore, two multidrug-resistant (MDR) isolates exhibited resistance to at least two antibiotic classes. These findings underscore the necessity for expanded antimicrobial resistance surveillance beyond clinical settings, extending into environmental samples, and contributing to ongoing research on resistance mechanisms.}, } @article {pmid41472545, year = {2026}, author = {Chen, W and Lai, X and Tang, X and Ye, Q and Zhang, C and Yang, Y and Wang, Z and Li, M and Wang, Z and Li, Z and Yuan, C and Zhang, X and Li, L and Wang, B and Wang, R and Yan, Y}, title = {Dysbiosis in Acne Vulgaris and Hidradenitis Suppurativa: A Comparative Microbiome Analysis.}, journal = {Experimental dermatology}, volume = {35}, number = {1}, pages = {e70198}, doi = {10.1111/exd.70198}, pmid = {41472545}, issn = {1600-0625}, support = {82073471//National Natural Science Foundation of China/ ; CFH-2022-2-4043//Capital's Funds for Health Improvement and Research/ ; }, mesh = {Humans ; *Hidradenitis Suppurativa/microbiology ; *Acne Vulgaris/microbiology ; *Dysbiosis/microbiology ; Male ; Female ; Adult ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Skin/microbiology ; Young Adult ; Mouth Mucosa/microbiology ; Case-Control Studies ; Feces/microbiology ; Gastrointestinal Microbiome ; Adolescent ; }, abstract = {Acne and hidradenitis suppurativa (HS) are inflammatory disorders of the pilosebaceous unit that exhibit distinct clinical manifestations, indicating that they likely differ in their underlying pathophysiology. Microbial dysbiosis is implicated in both diseases, yet direct comparisons using unified methods and analyses incorporating the oral microbiome are lacking. In this study, we collected lesional and nonlesional skin, buccal mucosa and faecal samples from 28 HS patients, 29 acne patients and 40 healthy controls, and profiled microbial communities using 16S rRNA V3-V4 sequencing with qPCR validation. HS lesions showed a pronounced enrichment of anaerobic Gram-negative taxa, including Prevotella, Porphyromonas and Fusobacterium, whereas acne lesions were dominated by Cutibacterium and Pseudomonas. Oral microbiome diversity was increased in both diseases, with HS showing distinct enrichment of Prevotella and Veillonella. HS patients also exhibited reduced gut microbial diversity. Correlation analyses revealed coordinated microbial alterations across the oral-gut-skin axis, and qPCR confirmed elevated concentrations of key anaerobes in HS. By directly comparing acne and HS across multiple anatomical sites, our study helps differentiate general inflammatory microbiome changes from those more specific to HS. The findings also suggest a potential oral-gut-skin microbial axis that may contribute to the chronic and destructive phenotype of HS, providing insights that could inform future microbiome-targeted therapeutic approaches.}, } @article {pmid41472301, year = {2025}, author = {Yagi, K and Ethridge, AD and Asai, N and Malinczak, CA and Arzola Martinez, L and Rasky, AJ and Morris, SB and Falkowski, NR and Fonseca, W and Huffnagle, GB and Lukacs, NW}, title = {Changes in Microbiome Correspond with Diminished Lung Pathophysiology Following Early-Life Respiratory Syncytial Virus Infection or Antibiotic Treatment: Microbiome Following RSV Infection.}, journal = {Viruses}, volume = {17}, number = {12}, pages = {}, pmid = {41472301}, issn = {1999-4915}, mesh = {*Respiratory Syncytial Virus Infections/microbiology/physiopathology/drug therapy/virology ; Animals ; *Lung/physiopathology/microbiology/virology/drug effects ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Mice ; Mice, Inbred BALB C ; Dysbiosis ; *Microbiota/drug effects ; Gastrointestinal Microbiome/drug effects ; Animals, Newborn ; Disease Models, Animal ; Ampicillin/pharmacology ; Respiratory Syncytial Viruses ; Humans ; Female ; }, abstract = {Early-life respiratory syncytial virus (EL-RSV) infection has been implicated in long-term pulmonary disease in children. In these studies, neonatal BALB/c mice were infected at day 7 of life, leading to >35% losses in critical lung function, airway mucus metaplasia, and transcriptional hallmarks of mucus hypersecretion four weeks after RSV infection. While EL-RSV minimally reshaped the resident lung microbiota, it led to significant gut dysbiosis, including a long-term reduction of Proteobacteria that can be a source of protective metabolites related to barrier and immune function. Subsequent studies assessing whether a common infant antibiotic (ampicillin) could mitigate EL-RSV-induced lung alterations revealed further severe gut microbiome alterations and, on its own, later in life, recapitulated the full spectrum of RSV-associated alterations in lung function. Metagenomic inference showed that both RSV and ampicillin administered during early life reduced biosynthetic pathways for microbiome-derived metabolites, which are known to reinforce tight junctions, regulate inflammation, and preserve extracellular matrix elasticity. The shared loss of these metabolic programs provides a mechanistic bridge linking distinct early-life exposures to the microbiome changes and airway mechanical deficits later in life. Collectively, the data suggest that RSV and/or antibiotic-triggered gut dysbiosis is the primary insult that likely promotes improper lung maturation/repair through a metabolite-mediated mechanism and may suggest metabolite restoration as a strategy to promote proper developmental lung function.}, } @article {pmid41472294, year = {2025}, author = {Mandal, E and Noirungsee, N and Disayathanoowat, T and Kil, EJ}, title = {TSWV Infection Differentially Reshapes the Symbiotic Microbiome of Two Frankliniella Thrips Species.}, journal = {Viruses}, volume = {17}, number = {12}, pages = {}, pmid = {41472294}, issn = {1999-4915}, support = {0//Gyeongkuk National University/ ; }, mesh = {*Thysanoptera/microbiology/virology ; Animals ; *Symbiosis ; *Microbiota ; *Tospovirus/physiology ; Serratia/genetics ; Bacteria/classification/genetics/isolation & purification ; Insect Vectors/virology/microbiology ; Metagenomics ; Plant Diseases/virology ; Wolbachia/genetics ; }, abstract = {Vectoring tomato spotted wilt virus (TSWV) by two well-known thrips species, Frankliniella occidentalis Pergande and F. intonsa Trybom (Thysanoptera: Thripidae), is facilitated in different ways. Symbiotic bacteria positively influence thrips fitness, but the interaction between these bacteria and tospovirus inside the thrips' body remains unknown. Metagenomic profiling of symbionts in nonviruliferous and viruliferous Frankliniella thrips was performed to elucidate the interactions between symbiotic bacteria and the virus. A total of 97 operational taxonomic units (OTUs) were identified by profiling the microbes, where Proteobacteria was the most abundant phylum, with a high richness in Serratia spp. F. occidentalis showed lower variation in bacterial diversity between nonviruliferous and viruliferous treatments than F. intonsa. RT-qPCR validation for Serratia and Escherichia revealed opposite abundance patterns between the two thrips species. In contrast, Enterobacteriaceae and Pantoea showed similar patterns with higher abundance in nonviruliferous conditions. Wolbachia was detected exclusively in F. intonsa, with a higher bacterial titer in the viruliferous sample. Our findings suggest that TSWV association may influence the abundance of different bacterial symbionts within the thrips' body, potentially via induction of antimicrobial peptides in response to viral invasion, and to our knowledge this is the first report addressing this tripartite interaction. These findings improve our understanding of how virus-symbiont association contributes to thrips vector competence.}, } @article {pmid41472213, year = {2025}, author = {Abdelbary, ER and Ramadan, M and Amin, IA and Abd-Elsamea, FS and Elsaghier, AM and Abd-Alrahman, EA and Ozbak, HA and Hemeg, HA and Almutawif, YA and Zakai, SA and Abdelrahman, AA and Salah, M}, title = {Early-Life Demographic Factors Shape Gut Microbiome Patterns Associated with Rotavirus Gastroenteritis Severity.}, journal = {Viruses}, volume = {17}, number = {12}, pages = {}, doi = {10.3390/v17121542}, pmid = {41472213}, issn = {1999-4915}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Gastroenteritis/microbiology/virology/epidemiology ; *Rotavirus Infections/microbiology/epidemiology/virology ; Infant ; Female ; Male ; Case-Control Studies ; Infant, Newborn ; Severity of Illness Index ; RNA, Ribosomal, 16S/genetics ; Rotavirus ; Bacteria/classification/genetics/isolation & purification ; Feces/microbiology ; Sociodemographic Factors ; }, abstract = {BACKGROUND: Rotavirus gastroenteritis (RVGE) remains a leading cause of severe infant diarrhea worldwide, with growing evidence supporting the role of the gut microbiome in modulating the disease. However, the interplay between early-life demographic factors, the gut microbiome, and their combined impact on RVGE clinical severity remains inadequately characterized, particularly in specific geographic populations.

AIM: We aimed to investigate how demographic determinants shape gut microbiome composition and function in RVGE and how these features relate to clinical severity.

METHODS: In our comprehensive case-control study of 165 infants (120 RVGE cases and 45 healthy controls, aged 0-12 months), we utilized 16S rRNA sequencing combined with advanced statistical modeling and machine learning to investigate how demographic factors influence microbiome composition and clinical outcomes.

RESULTS: RVGE cases exhibited significantly reduced bacterial diversity (Kruskal-Wallis, Static = 14.85, p < 0.001) and distinct patterns, with community structure most strongly associated with dehydration severity (PERMANOVA; R[2] = 0.15, p < 0.001). Substantial taxonomic alterations were identified characterized by depletion of beneficial commensals including Akkermansia (LDA score = 3.8, p < 0.001), Faecalibacterium (Random Forest AUC = 0.82, p < 0.001), and Bifidobacterium (r = -0.42 with breastfeeding, p < 0.001), alongside enrichment of inflammation-associated taxa such as Escherichia-Shigella (WBC; r = 0.49, p < 0.001, and CRP; r = 0.56, p < 0.001), Streptococcus (LDA score = 4.2, p < 0.001), and Staphylococcus. Proteobacteria was the top potential biomarker of severe outcomes (Random Forest AUC = 0.85), with abundance positively correlated with systemic inflammation (CRP: r = 0.51, p = 0.003). Functional predictions revealed increased lipopolysaccharide biosynthesis (ko00540) and reduced butanoate metabolism (ko00650, p < 0.001) in severe disease. Importantly, demographic factors significantly modulated clinical outcomes: cesarean-delivered, formula-fed infants presented the most dysbiotic profiles and experienced 3.2-fold longer hospitalization (95% CI: 1.8-5.6, p < 0.001) than vaginally delivered, breastfed infants did.

CONCLUSIONS: Collectively, these findings demonstrate that early-life demographic factors potentially shape the gut microbiome composition and function, may influence RVGE severity and recovery trajectories, thus providing candidate biomarkers for risk stratification and identifying targets for microbiota-based interventions.}, } @article {pmid41472186, year = {2025}, author = {Lu, Y and Li, Z and Yang, Z and Zhu, R and Yan, M and Liu, Z and Liu, M and Wang, Y and Wang, J and Wang, Q and Liu, J and Zhang, C and Wang, X and Cui, H}, title = {Effects of Combined Oregano Essential Oil and Macleaya cordata Extract on Growth, Antioxidant Capacity, Immune Function, and Fecal Microbiota in Broilers.}, journal = {Veterinary sciences}, volume = {12}, number = {12}, pages = {}, pmid = {41472186}, issn = {2306-7381}, support = {YJ2023038;246Z6604G;HBCT2024270204;CARS-41-13;KY2024006//This research was funded by the special project of introducing talents for scientific research in Hebei Agricultural University;Central government guided local science and technology development fund projects;Hebei Agriculture Research System;China Agricu/ ; }, abstract = {With the growing demand for antibiotic-free and sustainable poultry production, plant-derived antimicrobials have emerged as promising alternatives. However, a systematic understanding of the combined effects of oregano essential oil (OEO) and Macleaya cordata extract (MCE) on the broiler gut microbiome remains lacking. This study employed an integrated "structure-function-phenotype" framework to investigate the individual and combined (OMS) effects of OEO and MCE on gut microecological remodeling and its coupling with host growth, metabolic, and immune phenotypes. A total of 960 one-day-old broiler chicks were individually weighed and then randomly allocated to four treatments using body-weight-stratified randomization, with 6 replicate pens per treatment and 40 birds per pen, to ensure similar initial body weight across groups. Over a 42-day trial, we evaluated growth performance, serum biochemistry, antioxidant status, and immune parameters. Compared to the control, the OMS treatment significantly enhanced average daily feed intake (ADFI) and average daily gain (ADG), increased serum total protein (TP), and decreased blood urea nitrogen (BUN), triglycerides (TG), total cholesterol (TC), and alkaline phosphatase (ALP). However, the feed-to-gain ratio (F/G) was also higher in the OMS group, indicating that the improvement in growth rate did not translate into enhanced feed efficiency but was primarily driven by increased feed consumption. OMS also improved overall antioxidant capacity and key enzyme activities, elevated immunoglobulin levels, and reduced pro-inflammatory cytokines. Notably, OMS maintained Lactobacillus dominance, enriched Bacteroides, Enterococcus, and Butyricicoccus, and reduced Escherichia-Shigella. Functional predictions via PICRUSt2 suggested enhanced metabolic pathways related to antioxidant and immune functions; however, these results represent inference-based predictions and should be interpreted cautiously. Overall, the combination of OEO and MCE exerted synergistic benefits on growth, physiological health, and gut microbiota, supporting its potential as a phytogenic strategy for antibiotic-free broiler production.}, } @article {pmid41472081, year = {2025}, author = {Urga, and Wang, X and Wei, H and Zhao, G}, title = {Mechanisms and Applications of Gastrointestinal Microbiota-Metabolite Interactions in Ruminants: A Review.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472081}, issn = {2076-2607}, support = {2025YJRC077//Research Foundation for Advanced Talents of InnerMongolia Normal University/ ; }, abstract = {The gastrointestinal microbiota of ruminants constitutes a complex invisible organ, which converts plant fibers into volatile fatty acids (VFAs) and microbial protein through fermentation, serving as the primary energy and protein sources for the host. While substantial progress has been made in characterizing this system, critical gaps remain in understanding causal mechanisms and translating knowledge into scalable interventions. This review systematically synthesizes current knowledge on the composition, function, and metabolite profiles of gastrointestinal microbial communities in ruminants, with emphasis on interaction mechanisms, methodological advances, and intervention strategies. We highlight persistent challenges, including the uncultured majority of microbes, causal inference limitations, and translational bottlenecks. The review further evaluates strategies for targeted microbiome modulation aimed at improving production performance and reducing environmental emissions. Finally, we propose integrated research priorities for developing efficient, low-carbon, and sustainable ruminant production systems.}, } @article {pmid41472077, year = {2025}, author = {Xu, L and Long, K and Zhang, Y and Zhou, G and Liu, J}, title = {Responses of Soil Microbial Communities and Anthracnose Dynamics to Different Planting Patterns in Dalbergia odorifera.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472077}, issn = {2076-2607}, abstract = {Anthracnose is one of the major diseases affecting Dalbergia odorifera T. Chen. However, the soil microbial mechanisms underlying D. odorifera responses to anthracnose remain largely unexplored. This study investigated three planting systems: a Dalbergia odorifera monoculture (J); a mixed plantation of D. odorifera and Pterocarpus macrocarpus (JD); and a composite mixed plantation of D. odorifera, P. macrocarpus, and Clinacanthus nutans (JDY). Using amplicon sequencing technology for soil microbial analysis and combining soil physical and chemical properties with disease severity, we comprehensively analyzed changes in soil microbial community structure and function across different planting modes. The results showed that the diverse mixed mode (JD, JDY) significantly improved soil physicochemical properties and promoted soil nutrient cycling. Redundancy analysis (RDA) indicated that soil organic matter (SOM) and disease severity, quantified by the area under the disease progress curve (AUDPC), were the primary environmental drivers of microbial community variation. Genera positively correlated with SOM and negatively correlated with AUDPC were significantly enriched in JDY and JD, whereas genera showing opposite relationships were predominantly enriched in J. Functional predictions revealed enhanced nutrient-cycling capacities in JD and JDY, with JDY uniquely harboring functional groups such as Arbuscular Mycorrhizal, Epiphyte, and Lichenized taxa. In contrast, microbial functions in the J plantation were mainly limited to environmental amelioration. Co-occurrence network analysis further showed that as planting patterns shifted from J to JDY, microbial communities evolved from competition-dominated networks to cooperative defensive networks, integrating efficient decomposition with strong pathogen suppression potential. The study demonstrates that complex mixed planting systems regulate soil properties, enhance the enrichment of key functional microbial taxa, reshape community structure and function, and ultimately enable ecological control of anthracnose disease. This study provides new perspectives and theoretical foundations for ecological disease management in plantations of rare tree species and for microbiome-based ecological immunization strategies.}, } @article {pmid41472044, year = {2025}, author = {Hu, C and Wu, Y and Li, Z and Wang, Z and Huang, F and Fan, Z and Peng, M}, title = {Ecological Modulation of Soil Microbial Communities by Fertilization Regimes: Insights from Castor Bean Cake, Chemical Fertilizers, and Organic Fertilizer.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472044}, issn = {2076-2607}, support = {S202510517029//Student Innovation and Entrepreneurship Training Program of Hubei Minzu University/ ; KYPT012305//Open Fund of Hubei Key Laboratory of Biological Resources Protection and Utilization (Hubei Minzu University)/ ; }, abstract = {Fertilization plays a vital role in replenishing soil nutrients, shaping microbial community composition, and enhancing agricultural productivity. Castor bean cake (CBC) is a nitrogen- and carbon-rich by-product increasingly used as an organic amendment, yet its effects on soil microbiomes remain unclear. Here, we compared CBC with a compound chemical fertilizer (CF) and a manure-based organic fertilizer (OF) across dose gradients using 16S rRNA sequencing and multi-level ecology analyses (α/β diversity, co-occurrence networks, and community assembly models). The results revealed that CBC increased bacterial richness and phylogenetic breadth relative to the unfertilized cultivated control, whereas OF showed dose-dependent declines in richness and CF maintained relatively stable richness with slight reductions in evenness at higher doses. Phylum-level composition shifted strongly with fertilizer identity: Bacillota decreased, whereas Pseudomonadota and Acidobacteriota increased under fertilization, with the largest compositional changes under CBC. CBC strengthened nutrient-enzyme-microbe coupling and generated increasingly complex, highly connected, and robust co-occurrence networks along the dose gradient, outperforming high-dose OF in network complexity and robustness, while OF maintained higher modularity. Null-model partitions (βNTI/RC_bray, NST, NCM, iCAMP) indicated that stochastic processes dominated community assembly across treatments; along the CBC gradient, dispersal limitation decreased from CBC1 to CBC2 and drift remained dominant, indicating increasing stochastic stabilization at moderate-high doses. Together, CBC promoted microbiome recovery and ecological resilience and represents a promising amendment for soil health.}, } @article {pmid41472041, year = {2025}, author = {Sharma, SB and Raverkar, KP and Wani, SP and Bagyaraj, DJ and Kannepalli, A and Kandula, DRW and Mikaelyan, A and Ansari, MA and Stock, SP and Davies, KG and Sharma, R}, title = {Role of the Plant-Microbiome Partnership in Environmentally Harmonious 21st Century Agriculture.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472041}, issn = {2076-2607}, abstract = {The 21st century calls for a paradigm shift in agricultural practices to address the pressing issues of regeneration of soil health, climate change, environmental degradation, sustainability under growing population pressures, and food security challenges. This article reviews the potential of the plant-microbiome approach as a key driver for eco-conscious green farming. The focus is on the diverse roles of microbial communities in close association with plants in improving plant health, crop productivity, and soil ecosystem functions, and in enhancing environmental sustainability, with focus on four key areas: (1) Soil health and fertility through microbial partnerships; (2) Ecosystem sustainability through microbial functions; (3) Plant health, productivity and food security through microbial innovations emphasising the potential of microbial applications (biofertilisers, bioprotectants, and biostimulants) in sustainable agriculture; (4) Standardisation and stewardship in microbial agriculture highlighting the need for standardisation and quality control in microbial product development and use, and the concept of microbial stewardship and its importance in long-term agricultural sustainability. By synthesising current knowledge and identifying future challenges, this review underscores the transformative potential of the plant-associated microbiome approach in creating resilient, productive, and environmentally harmonious agricultural systems. We highlight current research gaps and future directions, arguing that embracing microbial solutions is not just an option but a necessity for ensuring food security and environmentally benign sustainability in the face of global challenges.}, } @article {pmid41472037, year = {2025}, author = {Aschalew, ND and Liu, J and Liu, Y and Sun, W and Yin, G and Cheng, L and Wang, H and Zhao, W and Zhang, L and Wang, Z and Jiang, H and Wang, T and Qin, G and Zhen, Y and Sun, Z}, title = {Enhancing Sheep Rumen Function, and Growth Performance Through Yeast Culture and Oxalic Acid Supplementation in a Hemicellulose-Based Diet.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472037}, issn = {2076-2607}, support = {20230202075NC//the Scientific and Technological Development Scheme of Jilin Province/ ; 20230202075NC//the Scientific and Technological Development Scheme of Jilin Province/ ; }, abstract = {Yeast culture (YC) is a microbial product that enhances ruminal fiber breakdown and improves nutrient digestion and utilization. Our previous research showed that oxalic acid (OA) is a crucial metabolite in YC that enhances rumen function. This study aimed to investigate the effects of YC, OA, and their combination (YO) on rumen function, growth, and fattening in sheep. Twenty lambs were divided into 4 groups (ctrl, YC, OA, and YO; n = 5 each) and fed a diet supplemented with 2 levels of YC and 2 doses of OA for 60 days in a 2 × 2 factorial design. Growth and fattening performance, rumen microbiome analysis, serum indices and anti-oxidant levels, and metabolomic profiling were performed. Individual supplementation with YC and OA significantly increased the digestibility of dry matter (DM), organic matter (OM), and crude protein (CP) (p < 0.001); neutral detergent fiber (NDF) (p < 0.05); and acid detergent fiber (ADF) (p < 0.001) and their interaction significantly increased dry matter intake (DMI) (p = 0.05). Serum IgA and IgM levels were higher in the supplemented groups (p < 0.05). Serum calcium levels were higher in the OA and YO groups (p < 0.001). The supplemented groups showed significantly higher growth hormone and superoxide dismutase levels (p < 0.05). The longissimus dorsi muscle had higher levels of iron in the OA and YO groups; zinc in the OA, YO, and YC groups (p < 0.01); and selenium in the YC group (p < 0.05). The OA group had a higher total antioxidant capacity. All supplemented groups showed higher bacterial richness and diversity. Ruminococcus, Succinivibrio, and Fibrobacter were positively correlated with the fermentation and digestibility parameters. The supplementation also altered metabolite levels and types in key physiological pathways. In conclusion, this supplementation improved bacterial composition, nutrient digestibility, weight gain, carcass weight and quality, serum indices, antioxidant levels and metabolomic profiles. This suggests potential for the development of dietary supplements for ruminants.}, } @article {pmid41472035, year = {2025}, author = {Mntambo, N and Arumugam, T and Pramchand, A and Pillay, K and Ramsuran, V}, title = {A Review of Global Patterns in Gut Microbiota Composition, Health and Disease: Locating South Africa in the Conversation.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472035}, issn = {2076-2607}, abstract = {The gut microbiota plays an essential role in human health through its contributions to immune regulation, metabolism, pathogen defence and disease susceptibility. Despite this significance, most gut microbiome research remains disproportionately focused on high-income countries, resulting in a limited and underrepresented view of global microbial diversity. This bias is evident in Africa, where populations, including those in South Africa, show unique combinations of genetic variation, dietary patterns and environmental exposures that are insufficiently captured in current datasets but offer opportunities to uncover novel insights into microbial evolution and its influences on health across diverse settings. In response to this gap, this review synthesises global patterns in gut microbiota composition and diversity while situating South African findings within this broader context. We examine evidence across microbial domains, including bacteria, fungi, viruses, archaea, protozoa and helminths, and highlight the impact of dietary transitions and environmental exposures on microbial community structure. Although still emerging, research on the gut microbiome of South African populations consistently reports contrasts between rural and urban populations, with rural groups enriched in fibre-fermenting and anti-inflammatory taxa, whereas urban communities often exhibit reduced diversity and features of dysbiosis linked to Westernisation. However, limited sample sizes, heterogeneous methodologies and absence of multi-omic approaches constrain robust interpretation. These lacunae in current knowledge emphasise the urgent need for large-scale, longitudinal studies that reflect South Africa's demographic and geographic diversity. Strengthening this evidence will not only help identify microbial signatures linked to modifiable lifestyle factors but will also guide nutrition, prevention and screening programmes to improve health in African populations.}, } @article {pmid41472032, year = {2025}, author = {Li, M and Chen, P and Liu, C and Wang, S and Zhang, H and Li, J and Karrow, NA and Mao, Y and Yang, Z}, title = {Gut Microbiome and Metabolome Signatures Associated with Heat Tolerance in Dairy Cows.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472032}, issn = {2076-2607}, support = {2022YFF1001200//National Key Research and Development Program of China/ ; BK20241934//Natural Science Foundation of Jiangsu Province/ ; 32172686//National Natural Science Foundation of China/ ; }, abstract = {Heat stress significantly impairs dairy cow health and productivity, highlighting the need to understand the gut microbiome-metabolite interactions that contribute to heat tolerance. Here, we integrated metagenomic sequencing and untargeted metabolomics in twelve holstein cows selected from a previously phenotyped herd of 120 individuals, including six heat-tolerant (HT) and six heat-sensitive (HS) cows identified using entropy-weighted TOPSIS scoring. HT cows were enriched in genera such as Faecalimonas and UBA737, which were functionally linked to pathways of energy and lipid metabolism, whereas, HS cows harbored taxa associated with bacterial lipopolysaccharide and glycosphingolipid biosynthesis. A total of 135 metabolites were differentially abundant between groups. Among them, glycerol 2-phosphate and 24(28)-dehydroergosterol showed perfect classification performance (AUC = 1.000), and were mainly involved in membrane lipid remodeling and redox regulation. Integrated analysis revealed coordinated microbial-metabolite networks, exemplified by the Faecalimonas-LysoPS (16:0/0:0) and UBA737-Glycerol 2-phosphate axes, suggesting functional coupling between microbial composition and metabolic adaptation. Together, these findings demonstrate that HT cows harbor gut microbiota and metabolites favoring energy balance, membrane remodeling, and oxidative stress resilience, while HS cows display stress-related metabolic patterns. This study elucidates the microbial-metabolic mechanisms underlying thermal resilience and highlights potential biomarkers and metabolic pathways that could be applied in heat-tolerance breeding and precision management of dairy cattle.}, } @article {pmid41472025, year = {2025}, author = {Yun, Y and Ying, Y and Sun, J and Zhao, J and Wang, W and Kang, B}, title = {Effects of Adding Astragali Radix and Inulae Radix on Fermentation Quality, Nutrient Preservation, and Microbial Community in Barley Silage.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472025}, issn = {2076-2607}, support = {Science and Technology Project from Inner Mongolia//2021GG0068/ ; Ordos Science and Technology Program//2022EEDSKJXM002/ ; }, abstract = {Chinese herbal medicine (CHM) residues represent a promising and sustainable category of silage additives, with the potential to modulate fermentation and enhance nutrient preservation. This study investigated the effects of two CHMs, Astragalus membranaceus L. (Astragali Radix, AR) and Inula helenium L. (Inulae Radix, IR), on the fermentation profile, nutritional composition, and bacterial community structure in barley silage. The forage was ensiled without additive (control, CK), or with 1% or 2% (w/w) of AR or IR for 75 days. The results showed that all additive treatments significantly improved fermentation quality, as evidenced by lower pH and reduced ammonia-nitrogen (NH3-N) content compared to CK. The 2% IR treatment was most effective in promoting homolactic fermentation, yielding the highest lactic acid content and lactic acid-to-acetic acid ratio. Nutritionally, additives significantly increased dry matter, starch, and water-soluble carbohydrates, while decreasing neutral and acid detergent fiber contents. High-throughput sequencing of the 16S rRNA gene revealed that both herbal additives profoundly reshaped the microbial community. They suppressed undesirable bacteria and significantly enriched beneficial Lactobacillus species. Principal component analysis confirmed a distinct separation in microbial community structure between control and treated silages. These findings underscore the potential of these herbal residues as natural modulators of the silage microbiome for improved forage conservation.}, } @article {pmid41471992, year = {2025}, author = {Wang, J and Li, D and Lu, D and Chen, C and Zhang, Q and Fu, R and Huang, F}, title = {Differential Assembly of Rhizosphere Microbiome and Metabolome in Rice with Contrasting Resistance to Blast Disease.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471992}, issn = {2076-2607}, support = {SCCXTD-2024-SD-4 & SCCXTD-2024-SD-8//Sichuan Rice Innovation Team Project/ ; 2021YFYZ0021//Sichuan Provincial Science and Technology Planning Project/ ; 5+1QYGG002//Sichuan Academy of Agricultural Sciences Financial Guidance Fund Project/ ; }, abstract = {Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases threatening global rice production. Although host resistance represents a sustainable control strategy, the underlying mechanisms mediated by the rhizosphere microbiome remain poorly understood. In this study, we selected four rice varieties with varying resistance to blast and demonstrated, through an integrated approach of 16S rRNA/ITS amplicon sequencing, untargeted metabolomics, and soil physicochemical analysis, that the rice genotype reprograms the genotype-root exudate-rhizosphere microbiome system. Results showed that the resistant variety P104 significantly decreased the soil pH while increasing the contents of total nitrogen, ammonium nitrogen, and nitrate nitrogen. On the other hand, the susceptible variety P302 exhibited higher pH and available phosphorus content. Furthermore, the rhizosphere of P104 was enriched with specific beneficial microbes such as Desulfobacterota, Ascomycota, and Pseudeurotium, and activated defense-related metabolic pathways including cysteine and methionine metabolism and phenylpropanoid biosynthesis. In contrast, susceptible varieties showed reduced bacterial diversity and fostered a microecological environment more conducive to pathogen proliferation. Our findings indicate that blast-resistant rice genotypes are associated with a protective rhizosphere microbiome, potentially mediated by alterations in root metabolism, thereby suppressing pathogen establishment. These insights elucidate the underground mechanisms of blast resistance and highlight the potential of microbiome-assisted breeding for sustainable crop protection.}, } @article {pmid41471991, year = {2025}, author = {Qiao, S and Wang, Z and Zhang, R and Wang, Y and Wang, C and Gao, G and Pan, J}, title = {Microbial Community Analysis and Environmental Association in Cave 6 of the Yungang Grottoes.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471991}, issn = {2076-2607}, abstract = {The Yungang Grottoes, a World Heritage Site, face biodeterioration risks. This study analyzed microbial communities in five microenvironments within Cave 6 using high-throughput sequencing (16S/18S rRNA). Communities showed high microenvironment specificity. Ascomycota and Proteobacteria dominated fungi and bacteria, respectively. Areas near the lighting window, with high external interaction, showed the highest diversity, while red pigment areas, likely under heavy metal stress, had the lowest diversity. Human-associated microbes (e.g., Escherichia-Shigella, Malassezia) indicated anthropogenic pollution on statue surfaces. Core microbiome and functional prediction (PICRUSt2) suggested high biodegradation risk in dust accumulation and inter-statue areas, enriched with organic-degrading and acid-producing taxa (e.g., Rubrobacter, Cladosporium). Microbial distribution and function were driven by openness, substrate, and human impact. This study identifies key risk zones and informs targeted conservation strategies for the Yungang Grottoes.}, } @article {pmid41471974, year = {2025}, author = {Tu, Y and Chen, B and Wei, Q and Xu, Y and Peng, Y and Li, Z and Liang, J and Zhuo, L and Zhong, W and Huang, J}, title = {Biochar-Urea Peroxide Composite Particles Alleviate Phenolic Acid Stress in Pogostemon cablin Through Soil Microenvironment Modification.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471974}, issn = {2076-2607}, support = {2023B0202010027//Key-Area Research and Development Program of Guangdong Province/ ; 42177337//National Natural Science Foundation of China/ ; 2022A1515020753//Natural Science Foundation of Guangdong Province/ ; }, abstract = {The continuous-cropping obstacles of Pogostemon cablin (patchouli) is severely constrained by autotoxic phenolic acids accumulated in the rhizosphere soil. Biochar adsorption and chemical oxidation are common remediation strategies; they often fail to simultaneously and efficiently remove phenolic allelochemicals while improving the soil micro-ecological environment. To address this issue, this study developed a novel biochar-urea peroxide composite particle (BC-UP). Batch degradation experiments and electron paramagnetic resonance (EPR) analysis confirmed the synergistic adsorption-oxidation function of BC-UP. A pot experiment demonstrated that application of BC-UP (5.0 g/kg) significantly alleviated phenolic acid stress. Specifically, BC-UP application significantly enhanced shoot biomass by 28.8% and root surface area by 49.3% compared to the phenolic acid-stressed treatment and concurrently reduced the total phenolic acid content in the rhizosphere soil by 37.3%. This growth promotion was accompanied by the enhanced accumulation of key bioactive compounds (volatile oils, pogostone, and patchouli alcohol). BC-UP amendment also improved key soil physicochemical properties (e.g., pH, and organic matter) and enhanced the activities of critical enzymes. Furthermore, BC-UP reshaped the microbial community, notably reducing the fungi-to-bacteria OTU ratio by 49.7% and enriching the relative abundance of Firmicutes and Nitrospirota but suppressing the Ascomycota phylum abundance. Redundancy analysis identified soil sucrase and catalase activity, total phenolic acid content, and Ascomycota abundance as key factors influencing patchouli biomass. In conclusion, BC-UP effectively mitigates phenolic acid stress through combined adsorption and radical oxidation, subsequently improving soil properties and restructuring the rhizosphere microbiome, offering a promising soil remediation strategy for patchouli and other medicinal crops.}, } @article {pmid41471968, year = {2025}, author = {Huang, X and Huang, J and Zhong, CC and Wong, MCS}, title = {Cell-to-Cell and Patient-to-Patient Variability in Antimicrobial Resistance.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471968}, issn = {2076-2607}, abstract = {Antimicrobial resistance (AMR) remains a global health crisis, yet treatment outcomes cannot be explained by resistance genes alone. Increasing evidence highlights the importance of variability at two levels: within bacterial populations and across patients. At the microbial level, cell-to-cell variability including genetic mutations, stochastic gene expression, persister cell formation, heteroresistance, and spatial heterogeneity within biofilms creates phenotypic diversity that allows subsets of bacteria to survive antimicrobial stress. At the host level, patient-to-patient variability including differences in genetic background, immune competence, comorbidities, gut microbiome composition, and pharmacokinetics shapes both susceptibility to resistant infections and the likelihood of treatment success. Together, these dimensions explain why infections with the same pathogen can lead to divergent clinical outcomes. Understanding and integrating both microbial and host variability offers a path toward more precise diagnostics, personalized therapy, and novel strategies to counter AMR.}, } @article {pmid41471964, year = {2025}, author = {Jotic, A and Cirkovic, I and Jovicic, N and Bukurov, B and Krca, N and Savic Vujovic, K}, title = {Biofilm Formation and Its Relationship with the Microbiome in Pediatric Otitis Media.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471964}, issn = {2076-2607}, support = {451-03-65/2025-03/200110//Ministry of Science, Technological Development and Innovation, Republic of Serbia/ ; }, abstract = {Otitis media is among the most common pediatric illnesses globally, constituting a leading cause of antimicrobial prescriptions, recurrent medical consultations, and preventable hearing loss in early childhood. Traditionally regarded as a sterile cavity intermittently invaded by pathogens, the middle ear is now recognized as a dynamic ecological niche influenced by anatomical immaturity of the Eustachian tube, host immune development, and the composition of resident microbial communities. Increasing evidence demonstrates that microbial dysbiosis and the establishment of biofilms are central to the persistence and recurrence of disease. This review synthesizes current knowledge of the pediatric middle ear microbiome, highlighting how commensal organisms contribute to mucosal resilience and colonization resistance, whereas pathogenic bacteria exploit ecological disruption to establish biofilm communities. Biofilm formation provides bacteria with enhanced survival through immune evasion, altered microenvironments, and antibiotic tolerance, thereby transforming acute otitis media into recurrent or chronic states. Furthermore, studies demonstrate how adenoids act as reservoirs of biofilm-forming organisms, seeding the middle ear and perpetuating infection. The emerging ecological perspective emphasizes the limitations of conventional antibiotic-centered management and directs attention toward innovative strategies, including microbiome-preserving interventions, probiotic or live biotherapeutic approaches, and antibiofilm agents. By defining pediatric otitis media as a disorder of disrupted host-microbe equilibrium, future research may pave the way for precision-based preventive and therapeutic strategies aimed at reducing the global burden of this pervasive disease.}, } @article {pmid41471956, year = {2025}, author = {Xue, N and Liu, D and Feng, Q and Zhu, Y and Cheng, C and Wang, F and Su, S and Xu, J and Tao, J}, title = {Comparison of Gut Microbiome Profile of Chickens Infected with Three Eimeria Species Reveals New Insights on Pathogenicity of Avian Coccidia.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471956}, issn = {2076-2607}, support = {No. 31972698 to JT//National Natural Science Foundation of China/ ; }, abstract = {Avian coccidiosis is an intestinal disease caused by Eimeria spp. infection. A deeper understanding of the interaction between host gut microbiota and the Eimeria parasite is crucial for developing alternative therapies to control avian coccidiosis. Here, we used full-length sequencing of 16S ribosomal RNA amplicons to compare changes in the gut microbiota of chickens infected with Eimeria tenella, Eimeria maxima, and Eimeria necatrix, aiming to identify both species-specific and common alterations in gut microbiota at 4 and 10 days post-infection. The result revealed that infection with all three Eimeria species led to a decrease in the abundance of the microbial genera Limosilactobacillus, Streptococcus, Alistipes, Lactobacillus and Phocaeicola, while the abundance of Bacteroides, Escherichia and Ligilactobacillus increased. Escherichia and Enterococcus were most abundant in the jejunum of the E. necatrix-infected group and in the cecum of the E. tenella-infected group, whereas Megamonas abundance was highest in the E. maxima-infected group. LEfSe analysis showed that infection with all three Eimeria species significantly reduced the abundance of 13 bacterial species, including Acetilactobacillus jinshanensis, Bacteroides ndongoniae, Barnesiella viscericola, Christensenella minuta, Enterocloster clostridioformis, Gemella haemolysans_A, Granulicatella adiacens, Lawsonibacter sp000177015, Limosilactobacillus reuteri, Limosilactobacillus reuteri_D, Limosilactobacillus vaginalis_A, Limosilactobacillus caviae, Limosilactobacillus vaginalis. Infection with E. tenella significantly increased the abundance of five bacterial species, including Bacteroides fragilis, Enterococcus cecorum, Helicobacter pylori, Methylovirgula ligni, and Phocaeicola sp900066445. Infection with E. maxima significantly increased the abundance of seven bacterial species, including Clostridioides difficile, Faecalibacterium prausnitzii, Mediterraneibacter torques, Muribaculum intestinale, Mediterraneibacter massiliensis, Phascolarctobacterium faecium, and Phocaeicola plebeius. Infection with E. necatrix significantly increased the abundance of seven bacterial species, including Alistipes sp900290115, Anaerotignum faecicola, Bacteroides fragilis_A, Escherichia coli, Harryflintia acetispora, Pseudoclostridium thermosuccinogenes, and Tidjanibacter inops_A. The results showed that Eimeria infection causes significant species- and time-dependent changes in the gut microbiota of chickens. These findings enhance our understanding of coccidiosis pathogenesis and offer potential targets for developing probiotics.}, } @article {pmid41471952, year = {2025}, author = {Li, TP and Li, HX and Bao, JS and Wang, CH and Wang, KL and Hao, BR and Wang, ZH and Hu, JH and Zhao, LQ}, title = {Geographical Variation in Bacterial Community Diversity and Composition of Corythucha ciliata.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471952}, issn = {2076-2607}, support = {32301594//National Natural Science Foundation of China/ ; 32171803//National Natural Science Foundation of China/ ; }, abstract = {The sycamore lace bug, Corythucha ciliata, a globally invasive pest that damages Platanus spp., harbors a bacterial microbiome that may help it adapt to different geographical environments. However, the geographical differentiation patterns of its bacterial community and the underlying driving mechanisms remain unclear. In this study, we standardized rearing of three C. ciliata populations (collected from Beijing, Lianyungang, and Nanjing) for three generations to reduce immediate environmental interference, then analyzed their bacterial communities via 16S rRNA gene amplicon sequencing. The principal coordinate analysis revealed a significant separation of the bacterial community in the Nanjing population, while the Beijing and Lianyungang populations were more similar. Bacterial alpha diversity followed the gradient of "Nanjing > Lianyungang > Beijing", with the Nanjing population exhibiting significantly higher species richness and evenness than the Beijing population. All three populations shared core bacterial taxa (e.g., phyla Proteobacteria, Bacteroidota; genera Cardinium, Serratia), but their relative abundances differed significantly: Cardinium dominated the Beijing population (50.1%), Serratia dominated the Lianyungang population (45.86%), and the Nanjing population harbored unique dominant genera such as Sphingomonas. For the three target populations, monthly average temperature and wind speed were positively correlated with bacterial diversity, while latitude was negatively correlated (Pearson correlation coefficient: 0.6564 < |r| < 0.7010, p < 0.05). Core bacterial functions (e.g., substance transport) were conserved across populations, whereas differential functions (e.g., detoxification, lipid metabolism) were linked to geographical adaptation. This study confirms the climate-driven geographical differentiation of the C. ciliata bacterial community provides insights into the "insect-microbiome" interactive invasion mechanism that is present here.}, } @article {pmid41471933, year = {2025}, author = {Frizon, L and Rocchetti, TT and Frizon, A and de Alcântara, RJA and de Paiva, CS and Gomes, JÁP}, title = {The Gut Microbiome in Stevens-Johnson Syndrome and Sjögren's Disease: Correlations with Dry Eye.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471933}, issn = {2076-2607}, abstract = {Changes in gut microbial composition may influence mucosal immune responses and contribute to systemic autoimmune manifestations. In this pilot exploratory study, we investigated and compared the gut microbiome in patients with Stevens-Johnson syndrome (SJS), patients with Sjögren's disease (SjD), and healthy controls, using next-generation sequencing (NGS), and assessed correlations with dry eye parameters. The study included 10 patients with SJS matched by age and sex to 10 healthy controls, and 10 patients with SjD matched to an additional set of 10 healthy controls. Dry eye parameters were employed to evaluate dry eye disease (DED). Microbiome profiles were determined using next-generation sequencing of the 16S V3-V4 region and analyzed using the Silva database. The gut microbiome exhibited significant differences in the SJS group, including a reduced Chao1 index (p = 0.01) that was progressively correlated with increased ocular severity and a decrease in Faecalibacterium (p = 0.048) compared to the healthy control group. In the SJS group, strong correlations were observed between increased Christensenellaceae with decreased DED DEWS (Dry Eye Workshop score) (p = 0.04), increased Subdoligranulum with decreased NEI (National Eye Institute) score (p = 0.04), and increased Clostridia and longer TBUT (tear break-up time) (p = 0.009). In contrast, the gut microbiome of SjD patients was similar to that of healthy controls. Patients with SJS exhibited distinct alterations in gut microbial composition, characterized by reduced microbial richness and depletion of Faecalibacterium. Furthermore, a significant association was found between specific bacterial taxa and milder dry eye severity, suggesting a possible link between changes in the gut microbiome and inflammation of the ocular surface.}, } @article {pmid41471929, year = {2025}, author = {Han, D and Zhao, R and Yang, X and Wang, T and Li, Z and Zhu, M and Yang, Q and Qu, Y and Chen, X and Chen, Z}, title = {Comparative Analysis of Environmental and Host-Associated Microbiome in Odorrana schmackeri (Auran: Ranidae): Insights into Tissue-Specific Colonization and Microbial Adaptation.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471929}, issn = {2076-2607}, support = {ZC (Grant no. 32270440), XHC (Grant no. U21A20192) and YFQ (32171498)//National Natural Science Foundation of China/ ; }, abstract = {Amphibian microbial communities are known to be shaped by host physiology and environmental factors, yet the relative roles of sexual dimorphism and tissue specialization remain poorly understood. Using 16S rRNA gene sequencing, we compared the gastrointestinal and integumentary microbiomes of a monomorphic Chinese frog population, Odorrana schmackeri, inhabiting identical montane streams. Our results showed distinct phylogenetic stratification between niches: Proteobacteria dominated both environmental microbiota and O. schmackeri gut and skin microbiotas but with differential sub-phylum specialization. The soil microbiota was dominated by unclassified_Vicinamibacteraceae, the water microbiota was Limnohabitans-dominated, the skin microbiota was dominated by Bordetella, and the gut microbiota was led by Acinetobacter. Alpha diversity analysis revealed significant tissue- and environmental-based divergences but no sexual differentiation, a pattern confirmed by beta diversity assessments showing stronger microbial community separation by tissue and environmental compartmentalization than by sex. Functional metagenomic prediction indicated convergent enrichment of metabolic pathways across host-associated and environmental communities. These results suggest that microbial community structure in O. schmackeri is principally governed by tissue-specific ecological selection pressures rather than host sexual characteristics. Our findings enhance understanding of microbiome assembly rules in vertebrate ectotherms and identify potential connections between microbiota in different ecological niches.}, } @article {pmid41471926, year = {2025}, author = {Presutti, L and Gueningsman, MC and Fredericksen, B and Smith, A and Taylor, R and Tuckett, A and Folsom, C and Wainwright, R and Klena, C and Ericsson, AC and Zapata, I and Brooks, AE}, title = {Exploring the Interplay Between Fatigue and the Oral Microbiome: A Longitudinal Approach.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471926}, issn = {2076-2607}, abstract = {Fatigue is a pervasive burden for emerging medical professionals, often impacted by stress and lifestyle factors, yet insufficiently explained by these aspects alone. Considering the profound immediate and long-term consequences for physician well-being and patient care, exploring the interplay between biological factors, such as the oral microbiome and fatigue, emerges as a critical area of investigation. This exploratory longitudinal study investigates the relationship between oral microbiome diversity and fatigue in first-year medical students across four timepoints, where they provided buccal swabs and completed lifestyle and standardized stress, sleep, and fatigue assessments (PSQI, FAS, PSS). Microbiome analysis was performed using 16S rRNA sequencing and QIIME2-based bioinformatics to identify genus-level profiles and core microbiome composition. Forty-five healthy participants were assessed. Significant increases in fatigue and fluctuations in oral microbiome diversity were observed, with alpha diversity peaking mid-year before declining. Illness frequency and antibiotic use also rose, potentially influencing microbial shifts. These fluctuations may be indicative of an adaptation process where oral microbial diversity adjusts to changes in the subject's environment, which in this case is entering medical school. Despite no clear clustering in biodiversity metrics, associations between fatigue and microbiome richness were noted, suggesting that physiologic fatigue and environmental stressors may contribute to microbial variability. Limitations of the study include a small sample size, attrition, and representativeness of the study population. This study presents a longitudinal baseline that may serve as a reference for future investigations. These findings may support the development of targeted interventions designed to modulate microbial composition as a novel approach to alleviating fatigue.}, } @article {pmid41471906, year = {2025}, author = {Yang, Z and Duan, Y and Wei, R and Yuan, Y and Yan, H and Tang, T and Shang, H}, title = {Rhizosphere Microbiome and Nutrient Fluxes Reveal Subtle Biosafety Signals in Transgenic Cotton.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471906}, issn = {2076-2607}, support = {2023ZD04062//Biological Breeding-Major Projects/ ; 32201828//National Natural Science Foundation of China/ ; 241111114200//Key R&D Program of Henan Province/ ; 2022M722899//China Postdoctoral Science Foundation/ ; 1610162019010101, 1610162023002//Central Public-interest Scientific Institution Basal Research Fund/ ; CB2025C12, CB2024C05//Independent Fund of State Key Laboratory of Cotton Bio-breeding and Integrated Utilization/ ; CAASASTIP-2016-ICR//National Agricultural Science and Technology Innovation Project for CAAS/ ; }, abstract = {Genetically modified crops have transformed agriculture, but their long-term ecological impacts remain incompletely understood. Here we investigate how herbicide-tolerant transgenic cotton affects rhizosphere microbial communities and nutrient cycling over a 28-day growth period using 16S rRNA amplicon sequencing and multivariate analyses. We sampled rhizosphere soil from greenhouse-grown transgenic and wild-type cotton plants at five time points, analyzing microbial diversity, community structure, and nutrient dynamics. Despite initial concerns about transgenic modifications disrupting soil ecosystems, we found no significant differences in microbial α-diversity or β-diversity between genotypes. Only minor, transient changes occurred at the genus level, including <5% shifts in Flavobacterium and Ramlibacter abundance on day 14, alongside brief nutrient flux variations that normalized by day 28. Notably, transgenic plants showed enhanced above-ground biomass accumulation without compromising rhizosphere stability or soil moisture content. These results demonstrate that herbicide-tolerant cotton maintains rhizosphere homeostasis while improving agronomic performance, supporting the environmental safety of this biotechnology for sustainable agricultural intensification.}, } @article {pmid41471878, year = {2025}, author = {Qi, X and Han, Z and Meng, J and Zhao, H and Zhou, M and Wang, M and Kang, S and Shi, Q and Li, H and Lu, F and Zhao, H}, title = {Integrated Metagenomic and Lipidomic Profiling Reveals Dysregulation of Facial Skin Microbiome in Moderate Acne Vulgaris.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471878}, issn = {2076-2607}, support = {32402248//the National Natural Science Foundation of China/ ; No. 24JCQNJC00880//the Natural Science Foundation of Tianjin/ ; }, abstract = {Acne vulgaris is a prevalent chronic inflammatory dermatosis primarily affecting the pilosebaceous units. Current therapeutic approaches often exhibit limited efficacy and high recurrence rates. To investigate the microbiome-related mechanisms of acne vulgaris, facial skin samples from 19 patients with moderate acne and 20 healthy individuals were analyzed using an integrated metagenomic and lipidomic profiling strategy. Metagenomic analysis revealed a significant reduction in microbial diversity (Chao index) in acne-affected skin compared to healthy controls (p < 0.001). The relative abundance of Staphylococcus, particularly Staphylococcus epidermidis, was significantly elevated in acne group (p < 0.05), while Cutibacterium acnes levels remained unchanged. Carbon metabolism pathways were enriched in the acne group (p < 0.05), predominantly driven by Cutibacterium, whereas other enriched metabolic pathways, such as ABC transporters and glycine, serine, and threonine metabolism (p < 0.05), showed a greater contribution from Staphylococcus. Virulence factors enriched in acne samples were primarily offensive in nature and largely attributed to Staphylococcus. Moreover, acne-associated microbiome exhibited a significantly higher prevalence of resistance genes against fluoroquinolones, fosfomycin, and triclosan (p < 0.05). Untargeted lipidomic analysis demonstrated significantly elevated total serum and triglyceride levels, along with a reduction in fatty acid chain length and a higher degree of saturation compared to the healthy group (p < 0.01). Specific triglycerides significantly enriched in the acne group, such as TG (15:0_14:0_16:0) + NH4, exhibited a significant positive correlation with Staphylococcus. This correlation is associated with elevated clinical erythema and melanin indices, suggesting that Staphylococcus is implicated in the development of acne-related inflammation. Additionally, Thermus exhibits negative correlations with acne-associated lipids and inflammatory parameters, potentially exerting a protective role. These findings suggest that Cutibacterium and Staphylococcus play differential yet synergistic roles in acne pathogenesis. The observed skin microbiome dysbiosis and lipid metabolic alterations provide novel insights into the pathophysiology of acne vulgaris, which may inform the development of targeted therapeutic strategies.}, } @article {pmid41471876, year = {2025}, author = {Wang, Y and Gong, L and Gao, Z and Dong, D and Li, X}, title = {Comparative Analysis of Sponge-Associated, Seawater, and Sediment Microbial Communities from Site F Cold Seep in the South China Sea.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471876}, issn = {2076-2607}, support = {42176114//National Natural Science Foundation of China/ ; ZR2023MD100//the Shandong Provincial Natural Science Foundation/ ; CAS-TAX-24-30//Biological Resources Programme, Chinese Academy of Sciences/ ; }, abstract = {Microbial communities at Site F cold seep, ubiquitous in both the environment and the associated fauna, demonstrate clear habitat-specific partitioning. Metagenomic sequencing and binning demonstrated a striking partitioning of microbial taxa at the cold seep: whereas the sponge-associated microbiome was distinctly enriched with specialized sulfur- and methane-oxidizing bacteria that were rare in the environment, it simultaneously exhibited a significantly reduced archaeal content, lower α-diversity, and a simpler overall community structure compared to the sediment and seawater communities. Distinct evolutionary lineages and varying abundances were observed among the microbiomes from seawater, sediment, and sponges. Furthermore, their Metagenome-Assembled Genomes (MAGs) exhibited significant differences in genomic features, including genome size and GC content. The sponge-associated microbiome exhibits lower diversity but maintains a high abundance of key functional genes, particularly those involved in sulfur cycling (e.g., apr, dsr, metZ), indicating enhanced metabolic efficiency in energy conservation and nutrient acquisition. This study reveals that the seawater, sediment, and sponge-associated microbiomes exhibit genome simplification and functional specialization in the cold seep environment, with varying lifestyles driving structural optimization and functional remodeling of the symbiotic microbiomes.}, } @article {pmid41471874, year = {2025}, author = {Song, S and Iino, K and Nakamura, M and Sato, M and Oishi, M and Ito, A and Yokoyama, Y}, title = {Comparative Characterization of Vaginal and Gut Microbiota in Late-Pregnancy Women with or Without Group B Streptococcus Colonization.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471874}, issn = {2076-2607}, support = {JMWH Bayer Grant, 2022//JMWH Bayer Grant/ ; }, abstract = {Group B Streptococcus (GBS) colonization during pregnancy is a major cause of neonatal infection, yet its microbial determinants remain unclear. This pilot study compared the vaginal and gut microbiota of late-pregnancy women with and without GBS colonization to explore potential microbial cues for peripartum risk stratification. Forty-three Japanese pregnant women (GBS-Negative = 34; GBS-Positive = 9) were enrolled at 35-37 weeks of gestation. Vaginal secretions and stool were analyzed by 16S rRNA (V3-V4) sequencing using QIIME 2 with SILVA annotation and community state type (CST) classification. Vaginal communities were mainly Lactobacillus-dominant. GBS-Positive women showed a non-significant tendency toward more L. iners-dominant CST III and fewer L. crispatus-dominant CST I compared with GBS-Negative women. Prevotella, Atopobium, and Gardnerella were significantly enriched in the GBS-Positive group (false discovery rate < 0.05), whereas gut microbial diversity and composition showed no significant differences between groups. Cross-site gut-vagina genus-level correlations were generally weak and non-significant. These findings suggest that, in late pregnancy, GBS colonization is linked to subtle shifts within Lactobacillus-dominant vaginal communities, with more L. iners and bacterial vaginosis-associated genera, rather than global microbiota disruption. The apparent shift from L. crispatus- to L. iners-dominant communities is hypothesis-generating and should be confirmed in larger cohorts.}, } @article {pmid41471873, year = {2025}, author = {Zang, B and Xu, L and Huang, H and Liu, Q and Yao, Y and Li, J and Yang, Y and Zhao, C and Liu, B and Liu, B}, title = {Decoding the Gut Microbiome in Primary Sjögren's Syndrome and Primary Biliary Cholangitis: Shared Dysbiosis, Distinct Patterns, and Associations with Clinical Features.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471873}, issn = {2076-2607}, support = {81671600//National Natural Science Foundation of China/ ; 81241094//National Natural Science Foundation of China/ ; ZR2016HM13 /ZR2023MH066//Natural Science Foundation of Shandong Province/ ; 2024-WJKY160//Qingdao Medical and health scientific research project/ ; }, abstract = {This study aimed to analyze gut microbiome similarities and differences between primary biliary cholangitis (PBC) and primary Sjögren's syndrome (pSS), exploring potential associations with disease pathogenesis. High-throughput sequencing of the 16S rRNA gene was performed on fecal samples from 100 subjects (PBC: 38; pSS: 42; HC: 20) to compare the composition, diversity, and key microbial markers, examining associations with clinical indicators. The gut microbiome of PBC and pSS patients exhibited reduced alpha diversity (p < 0.05) and decreased abundance of the Bacteroides genus (both p < 0.001). While the majority of differentially abundant species were similar in PBC and pSS, unique imbalances were noted: Actinobacteria was elevated in pSS, whereas Proteobacteria was higher in PBC (p < 0.05). At the species level, a higher relative abundance of Ruminococcus torques, Clostridium celatum, and Lactobacillus vaginalis was identified in PBC patients, with positive correlations observed with key clinical indicators such as liver enzymes and TBA. In pSS patients, Faecalibacterium prausnitzii showed a negative correlation with GGT and ALT. Although PBC and pSS shared many similarities in their gut microbiome's composition and diversity, indicating common mechanistic microbial influences on their pathogenicity, distinct microbial profiles correlated with clinical indicators in each disease, highlighting specific microbiome-disease interactions that may underlie their differential pathogenesis.}, } @article {pmid41471872, year = {2025}, author = {Yang, B and Zhong, S and Wang, J and Yu, W}, title = {Dietary Modulation of the Gut Microbiota in Dogs and Cats and Its Role in Disease Management.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471872}, issn = {2076-2607}, support = {No. 20242BAB20315//Natural Science Foundation for Youth of Jiangxi Province/ ; GJJ2200410//The Science and Technology Program of Jiangxi Provincial Department of Education/ ; }, abstract = {Food has a massive influence on the gut microbiota and is one of the most useful therapeutic levers in disease. Recent developments have highlighted how macronutrient balance, food format, and functional ingredients can regulate microbial diversity, metabolism, and host physiology in companion animals such as dogs and cats. This narrative review condenses evidence on the bidirectional gut microbiota-diet connection and on nutritional therapy for gastrointestinal, metabolic, renal, hepatic, and immune-mediated disorders. Protein-based diets including high or hydrolyzed protein, omega-3 acids, fermentative fiber, and probiotics can positively affect microbial composition, stimulate short-chain fatty acid synthesis, and enhance intestinal barrier functions. Conversely, excess fats or refined carbohydrates may cause dysbiosis, inflammation, and metabolic imbalances. Numerous studies have shown that therapeutic nutrition-e.g., low-protein renoprotective, hepatoprotective antioxidants, and allergen-elimination diets-holds enormous potential for treatment. In addition, fecal microbiota transplantation (FMT) can be used as an additive therapy for resistant gastrointestinal illnesses. Despite these developments, constraints remain in terms of standardization, study duration, and species-specific data, especially for cats. This review underscores dietary modification as a clinically actionable tool for microbiota-targeted therapy and calls for integrative, multi-omics research to translate microbiome modulation into precision nutrition for companion animals.}, } @article {pmid41471858, year = {2025}, author = {Long, N and Zuo, Y and Li, J and Yao, R and Yang, Q and Deng, H}, title = {Thuja sutchuenensis Franch. Essential Oil Ameliorates Atopic Dermatitis Symptoms in Mice by Modulating Skin Microbiota Composition and Reducing Inflammation.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471858}, issn = {2076-2607}, support = {zlg2021-cq20211210, zlg2022-cq20220907//National Key Wildlife Conservation Project of Central Forestry Reform and Development Funds/ ; CSTB2024NSCQ-MSX1297//the Chongqing Natural Science Foundation/ ; 25MSZX555//the Sichuan Provincial Administration of Traditional Chinese Medicine/ ; CYZYB24-08//the Chengdu Medical College Natural Science Foundation/ ; }, abstract = {Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by dysregulated immunity, skin barrier dysfunction, and cutaneous microbiome dysbiosis. While current therapies face limitations, Thuja sutchuenensis essential oil (TEO) shows promise due to its multi-target potential. We sought to explore the beneficial effects of TEO and delve into its mechanistic actions in a mouse model of AD. We combined network pharmacology with in vivo validation to evaluate the therapeutic efficacy and mechanisms of TEO in an AD model, and confirmed network-predicted targets in an in vitro inflammatory cell model. In AD mice, TEO alleviated pruritus and epidermal hyperplasia, suppressed systemic IL-4/TNF-α and IgE, and partially normalized serum ALB, LDL-C, and HDL-C. Microbial diversity increased after treatment, although potentially pathogenic taxa (Arthrobacter sp. and Corynebacterium mastitidis) remained enriched. Machine-learning analysis indicated the highest predicted metabolic activity in CK controls, whereas the AD and TEO groups showed elevated pathogenic phenotype scores. Network pharmacology prioritized active compounds [(E)-ligustilide, senkyunolide A, 3-butylisobenzofuran-1(3H)-one, butylated hydroxytoluene, Z-buthlidenephthalide, and β-Myrcene] and core targets (TNF, PTPRC, CCR5, JAK1), implicating T-cell receptor signaling, Staphylococcus aureus infection, and STAT3 pathways. Docking and molecular dynamics supported strong, stable binding of major constituents to JAK1, and Western blotting confirmed TEO-mediated inhibition of the JAK1/STAT3 axis. TEO effectively alleviates atopic dermatitis symptoms by modulating immune responses and enhancing microbial diversity. It targets key signaling pathways, such as JAK1/STAT3, highlighting its potential as a therapeutic option for AD.}, } @article {pmid41471710, year = {2025}, author = {Oliveira, MB and Maurício, AC and Barros, AN and Botelho, C}, title = {Rebalancing the Skin: The Microbiome, Acne Pathogenesis, and the Future of Natural and Synthetic Therapies.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {24}, pages = {}, pmid = {41471710}, issn = {1420-3049}, support = {LA/P/0059/2020//Fundação para a Ciência e Tecnologia/ ; UIDB/00211/2020//Fundação para a Ciência e Tecnologia/ ; UID/04033/2025//Fundação para a Ciência e Tecnologia/ ; }, mesh = {Humans ; *Acne Vulgaris/microbiology/drug therapy/pathology/etiology ; *Microbiota/drug effects ; *Skin/microbiology/drug effects/pathology ; *Biological Products/therapeutic use/pharmacology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Dysbiosis ; Animals ; }, abstract = {The skin serves as a primary interface between the human body and the external environment, functioning both as a protective barrier and as a habitat for a complex and diverse microbiome. These microbial communities contribute to immune regulation, barrier integrity, and defence against pathogens. Disruptions in this equilibrium can precipitate dermatological disorders such as acne vulgaris, which affects millions of adolescents and adults worldwide. This chronic inflammatory disorder of the pilosebaceous unit is driven by microbial dysbiosis, hyperkeratinisation, sebum overproduction, and inflammation. This review synthesizes data from over 100 sources to examine the interplay between the skin microbiome and acne pathogenesis, and to compare synthetic treatments, including retinoids, antibiotics, and hormonal therapies, with natural approaches such as polyphenols, minerals, and resveratrol. The analysis highlights the therapeutic convergence of traditional pharmacology and bioactive natural compounds, proposing microbiome-conscious and sustainable strategies for future acne management.}, } @article {pmid41471248, year = {2025}, author = {Shi, X and Bi, N and Liu, W and Ma, L and Liu, M and Xu, T and Shu, X and Gao, L and Wang, R and Chen, Y and Li, L and Zhu, Y and Li, D}, title = {Identification of Oral Microbiome Biomarkers Associated with Lung Cancer Diagnosis and Radiotherapy Response Prediction.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/pathogens14121294}, pmid = {41471248}, issn = {2076-0817}, support = {NCC202416006//National High Level Hospital Clinical Research Funding and National Cancer Center Climbing Fund/ ; 2023ZD0502100//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, mesh = {Humans ; *Microbiota/genetics ; *Lung Neoplasms/radiotherapy/diagnosis/microbiology ; Male ; Female ; Middle Aged ; *Mouth/microbiology ; RNA, Ribosomal, 16S/genetics ; Aged ; Biomarkers ; *Bacteria/classification/genetics/isolation & purification ; Prognosis ; Biomarkers, Tumor ; }, abstract = {The oral cavity acts as the anatomical gateway to the respiratory tract, sharing both microbiological and pathophysiological links with the lower airways. Although radiotherapy is a cornerstone treatment for lung cancer, reliable oral microbiome biomarkers for predicting patient outcomes remain lacking. We analyzed the oral microbiome of 136 lung cancer patients and 199 healthy controls across discovery and two validation cohorts via 16S rRNA sequencing. Healthy controls exhibited a significantly higher abundance of Streptococcus compared to patients (p = 0.049, p < 0.001, p < 0.001, respectively). The structure of the microbial community exhibited substantial dynamic changes during treatment. Responders showed enrichment of Rothia aeria (p = 0.027) and Prevotella salivae (p = 0.043), associated with prolonged overall survival (OS) and progression-free survival (PFS), whereas non-responders exhibited elevated Porphyromonas endodontalis (p = 0.037) correlating with shorter OS and PFS. According to Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2) analysis, Akkermansia and Alistipes were nearly absent in non-responders, while Desulfovibrio and Moraxella were virtually absent in responders. A diagnostic model based on Streptococcus achieved area under the curve (AUC) values of 0.85 (95% CI: 0.78-0.91) and 0.99 (95% CI: 0.98-1) in the validation cohorts, and a response prediction model incorporating Prevotella salivae and Neisseria oralis yielded an AUC of 0.74 (95% CI: 0.58-0.90). Furthermore, in small cell lung cancer, microbiota richness and diversity were inversely correlated with Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.008, p < 0.001, respectively) and pro-gastrin-releasing peptide (ProGRP) levels (p = 0.065, p = 0.084, respectively). These results demonstrate that lung cancer-associated oral microbiota signatures dynamically reflect therapeutic response and survival outcomes, supporting their potential role as non-invasive biomarkers for diagnosis and prognosis.}, } @article {pmid41471188, year = {2025}, author = {Nikolić, N and Pucar, A and Tomić, U and Petrović, S and Mihailović, Đ and Jovanović, A and Radunović, M}, title = {Oral Microbiota and Carcinogenesis: Exploring the Systemic Impact of Oral Pathogens.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/pathogens14121233}, pmid = {41471188}, issn = {2076-0817}, support = {2019-191//eklund foundation/ ; 451-03-137/2025-03/200129//Ministry of Science, Technological Development and Innovations of the Republic of Serbia/ ; 03-136/2025-03/200129//Ministry of Science, Technological Development and Innovations of the Republic of Serbia/ ; }, mesh = {Humans ; *Mouth/microbiology ; *Microbiota ; *Carcinogenesis ; *Neoplasms/microbiology/etiology ; *Dysbiosis/microbiology/complications ; Fusobacterium nucleatum/pathogenicity ; Animals ; }, abstract = {For decades, cancer risk has been explained mainly by local factors. However, emerging evidence shows that the oral microbiome acts as a systemic modifier of oncogenesis well beyond the head and neck. This review synthesizes clinical and mechanistic data linking dysbiotic oral communities, especially Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, to malignancies across gastrointestinal, respiratory, hepatobiliary, pancreatic, breast, and urogenital systems. We summarize organ-specific associations from saliva, tissue, and stool studies, noting the recurrent enrichment of oral taxa in tumor and peri-tumoral niches of oral, esophageal, gastric, colorectal, lung, pancreatic, liver, bladder, cervical, and breast cancers. Convergent mechanisms include the following: (i) persistent inflammation (lypopolysacharide, gingipains, cytolysins, and collagenases); (ii) direct genotoxicity (acetaldehyde, nitrosation, and CDT); (iii) immune evasion/suppression (TLR/NLR signaling, MDSC recruitment, TAN/TAM polarization, and TIGIT/CEACAM1 checkpoints); and (iv) epigenetic/signaling rewiring (NF-κB, MAPK/ERK, PI3K/AKT, JAK/STAT, WNT/β-catenin, Notch, COX-2, and CpG hypermethylation). Plausible dissemination along an oral-gut-systemic axis, hematogenous, lymphatic, microaspiration, and direct mucosal transfer enables distal effects. While causality is not yet definitive, cumulative data support oral dysbiosis as a clinically relevant cofactor, motivating biomarker-based risk stratification, saliva/stool assays for early detection, and microbiome-targeted interventions (periodontal care, antimicrobials, probiotics, and microbiota modulation) alongside conventional cancer control.}, } @article {pmid41471163, year = {2025}, author = {Ziaka, M}, title = {Targeting Gut-Lung Crosstalk in Acute Respiratory Distress Syndrome: Exploring the Therapeutic Potential of Fecal Microbiota Transplantation.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/pathogens14121206}, pmid = {41471163}, issn = {2076-0817}, mesh = {*Respiratory Distress Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Lung/microbiology/immunology ; Animals ; *Gastrointestinal Tract/microbiology ; }, abstract = {The gastrointestinal (GI) tract contributes significantly to the pathogenesis of acute respiratory distress syndrome (ARDS) by influencing systemic inflammation and sepsis, which are key factors in the development of multiple organ dysfunction syndrome (MODS), while the significant impact of gut microbiota in critically ill patients, including those with sepsis and ARDS, further underscores its importance. The intestinal microbiota is vital to immune system function, responsible for triggering around 80% of immune responses. Therefore, it may be hypothesized that modifying fecal microbiota, such as through fecal microbiota transplantation (FMT), could serve as a valuable therapeutic approach for managing inflammatory diseases like lung injury (LI)/ARDS. Indeed, emerging experimental research suggests that FMT may have beneficial effects in ARDS models by improving inflammation, oxidative stress, LI, and oxygenation. However, well-designed randomized clinical trials in patients with ARDS are still lacking. Our study seeks to examine how therapeutic interventions such as FMT might benefit LI/ARDS patients by exploring the interactions between the gut and lungs in this context.}, } @article {pmid41471117, year = {2025}, author = {Shuvo, MSH and Kim, S and Jo, S and Rahim, MA and Barman, I and Hossain, MS and Yoon, Y and Tajdozian, H and Ahmed, I and Atashi, A and Jeong, G and Suh, HS and You, J and Sung, C and Kim, M and Seo, H and Song, HY}, title = {Flavonifractor plautii as a Next-Generation Probiotic Enhancing the NGP F/P Index in a Simulated Human Gut Microbiome Ecosystem.}, journal = {Pharmaceutics}, volume = {17}, number = {12}, pages = {}, doi = {10.3390/pharmaceutics17121603}, pmid = {41471117}, issn = {1999-4923}, support = {No. RS-2023-00219563//Ministry of Science and ICT/ ; Bio Workforce Training Program//Ministry of Trade, Industry, and Energy/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; }, abstract = {Background/Objectives: Traditionally consumed fermented foods and lactic acid bacteria (LAB)-based products have primarily been investigated for their nutritional and health-promoting benefits as dietary supplements. More recently, research has advanced toward exploring their therapeutic potential in pharmaceutical development. However, reliance on conventional LAB strains despite their established safety and efficacy has led to saturation at the strain level, underscoring the need for next-generation probiotics (NGPs) with novel therapeutic potential. In this context, we identified Flavonifractor plautii from human feces as a candidate NGP and investigated its effects on the human gut microbiota. Methods: Whole-genome sequencing revealed distinct genetic features that supported its uniqueness, and the strain was designated PMC93. A human gut microbial ecosystem simulator was used to administer F. plautii daily for one week, after which microbial community changes were evaluated using 16S rRNA gene-based metagenomic sequencing. Results: The administration did not induce significant changes in alpha or beta diversity, suggesting that F. plautii does not disrupt overall bacterial community structure, thereby supporting its microbial community safety. Taxonomic analysis demonstrated a significant increase in the Firmicutes-to-Proteobacteria ratio (NGP F/P index). The improvement surpassed that of conventional LAB treatments and was consistently maintained under supplementation with commonly encountered pharmaceutical compounds and nutrients. The shift was associated with an increase in short-chain fatty acid (SCFA)-producing beneficial taxa and a decrease in pro-inflammatory and potentially pathogenic groups. Functional outcomes, including elevated SCFA levels and downregulation of inflammation-related gene expression, further corroborated these compositional changes. The strain also demonstrated safety in in vivo models. Conclusions: Collectively, these findings suggest that strain PMC93 is a promising NGP candidate with substantial therapeutic potential for microbiota-associated health and disease modulation, particularly due to its ability to enhance the NGP F/P index.}, } @article {pmid41471111, year = {2025}, author = {Holler, N and Ruseska, I and Schachner-Nedherer, AL and Zimmer, A and Petschacher, C}, title = {Oral Treatment of Obesity by GLP-1 and Its Analogs.}, journal = {Pharmaceutics}, volume = {17}, number = {12}, pages = {}, doi = {10.3390/pharmaceutics17121596}, pmid = {41471111}, issn = {1999-4923}, abstract = {Obesity is a multifaceted disease that significantly increases the risk of various chronic conditions. GLP-1R (co)-agonists first emerged as therapeutics for treatment of type 2 diabetes mellitus and have since become an established drug class for improving glycemic control. The interest in GLP-1 for obesity treatment has surged in 2015 after the approval of Saxenda[®] (liraglutide). To date, GLP-1 analogs are primarily administered by s.c. injection, which poses a significant burden on patient compliance. To address this challenge, research has focused on oral delivery. This review provides a concise overview of the techniques explored to enhance the oral delivery of GLP-1 analogs for the treatment of obesity. Relevant strategies include the following: (1) the use of permeation enhancers to increase gastrointestinal absorption of peptides; (2) micro- and nanocarriers loaded with GLP-1, including targeted delivery systems and general techniques for active drug targeting; (3) GLP-1 gene delivery; and (4) advanced microbiome systems for GLP-1 delivery. The potential for misuse and side-effects of GLP-1 analogs are also discussed.}, } @article {pmid41471101, year = {2025}, author = {Tauser, RG and Vasincu, IM and Iacob, AT and Apotrosoaei, M and Profire, BȘ and Lupascu, FG and Chirliu, OM and Profire, L}, title = {A State-of-the-Art Overview on (Epi)Genomics and Personalized Skin Rejuvenating Strategies.}, journal = {Pharmaceutics}, volume = {17}, number = {12}, pages = {}, doi = {10.3390/pharmaceutics17121585}, pmid = {41471101}, issn = {1999-4923}, abstract = {This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres' recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR's modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways' modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS's modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies.}, } @article {pmid41470907, year = {2025}, author = {Sekikawa, A and Weaver, A and Mroz, K and Heilmann, NZ and Madrid Fuentes, DA and Koltun, KJ and Carlson, LJ and Cattell, KL and Li, M and Li, J and Hughes, TM and Strotmeyer, E and Nindl, B and Cauley, JA}, title = {S-Equol as a Gut-Derived Phytoestrogen Targeting Estrogen Receptor β: A Promising Bioactive Nutrient for Bone Health in Aging Women and Men: A Narrative Review.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243962}, pmid = {41470907}, issn = {2072-6643}, support = {R01 AG074971/AG/NIA NIH HHS/United States ; P30 AG021332/AG/NIA NIH HHS/United States ; P30 AG024827/AG/NIA NIH HHS/United States ; 1S10AG030295-01A1/NH/NIH HHS/United States ; 5UM1TR004929-02/NH/NIH HHS/United States ; }, mesh = {Humans ; *Equol/pharmacology/metabolism ; *Phytoestrogens/pharmacology ; *Estrogen Receptor beta/metabolism/agonists ; Male ; Female ; *Osteoporosis/prevention & control/drug therapy ; Animals ; *Bone and Bones/drug effects/metabolism ; Gastrointestinal Microbiome ; Isoflavones/metabolism ; Bone Density/drug effects ; *Aging ; Aged ; }, abstract = {Background/Objectives: Osteoporosis is highly prevalent and contributes substantially to morbidity and mortality, yet long-term concerns about pharmacologic therapies leave a major treatment gap. Soy isoflavones have been investigated as safer alternatives, but results across trials are inconsistent. A key unresolved issue is the equol-producer phenotype, the gut microbial ability to convert daidzein to S-equol, the most bioactive isoflavone metabolite, which may explain much of this variability. This narrative review synthesizes mechanistic, translational, and clinical evidence to clarify the potential skeletal relevance of S-equol. Methods: Literature was identified through PubMed and Scopus searches (January 2000-October 2025) for experimental, mechanistic, and clinical studies examining S-equol, estrogen receptor β (ERβ), and bone metabolism, with emphasis on equol-producing status, bone strength and bone microarchitecture. Results: S-equol acts as a high-affinity ERβ agonist with antioxidant and anti-inflammatory properties but lacks the carcinogenic or thrombotic risks linked to ERα activation. In estrogen-deficient rodent models, S-equol improves trabecular bone volume by 10-20%, increases trabecular number, and enhances biomechanical strength. These findings align with preclinical evidence demonstrating that S-equol preserves trabecular microarchitecture, enhances bone strength, and reduces bone turnover. A limited number of human trials show reductions in bone resorption by 20% at a daily dose of 10 mg S-equol. In contrast, trials of soy isoflavones in humans have produced inconsistent findings, partly because of substantial variability in equol-producer phenotype among participants and the reliance on dual-energy X-ray absorptiometry, which cannot distinguish trabecular from cortical compartments. Advanced bone imaging and microbiome-informed approaches enable the precise evaluation of S-equol's skeletal effects on trabecular bone and cortical bone, separately. Conclusions: S-equol represents a promising model for "precision nutrition," where microbiome, hormonal, and host factors converge with potential to prevent age-related bone fragility. Rigorous trials that integrate microbiome phenotyping and advanced imaging are needed to validate this approach, translate mechanistic promise into clinical benefit, and better define safety.}, } @article {pmid41470885, year = {2025}, author = {Jung, SH and Hwang, S and Seo, KH and Park, Y and Kim, MJ and Kim, H}, title = {Bioconversion-Based Postbiotics Enhance Muscle Strength and Modulate Gut Microbiota in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243937}, pmid = {41470885}, issn = {2072-6643}, support = {Otoki Ham Taiho Foundation//Otoki Ham Taiho Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Double-Blind Method ; Male ; Adult ; Female ; *Muscle Strength/drug effects ; *Whey Proteins/administration & dosage ; Young Adult ; Feces/microbiology ; Hand Strength ; Healthy Volunteers ; Dietary Supplements ; Biomarkers/blood ; }, abstract = {BACKGROUND: Postbiotics produced by kefir lactic acid bacteria through bioconversion of polyphenol-rich extract and whey protein are emerging as promising modulators of gut microbiota and muscle health. This study investigated whether Lentilactobacillus kefiri DH5-derived postbiotics, prepared with Cucumis melo L. and whey protein (KP, Kefir lactic acid bacteria-derived postbiotics), improve muscle strength and gut microbiota composition in healthy adults.

METHODS: In this 12-week, randomized, double-blind, placebo-controlled trial, participants consumed either KP (6 g/day) or placebo. Handgrip strength, circulating biomarkers, and fecal microbiota profiling (using 16S rRNA sequencing) were analyzed. Correlations between microbial taxa and muscle-related biomarkers were assessed.

RESULTS: KP supplementation significantly increased dominant-hand grip strength and plasma irisin and reduced IL-1β concentrations after 12 weeks, whereas IGF-1, lean mass, and non-dominant grip strength showed no significant changes. Gut microbiota profiling revealed enrichment of Bifidobacterium adolescentis, Latilactobacillus sakei, Lentihominibacter hominis, Mediterraneibacter gnavus, Streptococcus anginosus and Phocaeicola plebeius, with concomitant reductions in Lachnospira eligens, Roseburia inulinivorans, Ruthenibacterium lactatiformans and Vescimonas fastidiosa. Notably, relative abundance of Faecalibacterium prausnitzii was positively correlated with plasma irisin concentration.

CONCLUSIONS: KP supplementation produced a modest within-group improvement in grip strength, potentially through gut-muscle axis modulation involving irisin and anti-inflammation pathways. These preliminary findings suggest that kefir-derived postbiotics may have potential relevance for muscle health.}, } @article {pmid41470864, year = {2025}, author = {Torres-Mejías, J and Arriaza, K and Mena, F and Rivarola, E and Paredes, P and Ahmad, H and López, I and Soza, D and Pino-Villalón, JL and López-Espinoza, MÁ and Duran-Agüero, S and Merellano-Navarro, E}, title = {Body Composition, Microbiome and Physical Activity in Workers Under Intermittent Hypobaric Hypoxia.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243919}, pmid = {41470864}, issn = {2072-6643}, mesh = {Humans ; *Body Composition/physiology ; *Exercise/physiology ; Adult ; Male ; *Gastrointestinal Microbiome/physiology ; *Hypoxia/physiopathology/microbiology ; Nutritional Status ; Energy Metabolism ; Female ; Electric Impedance ; Body Mass Index ; Middle Aged ; Feces/microbiology ; }, abstract = {Background/Objectives: Intermittent hypobaric hypoxia (IHH) induces various physiological and metabolic adaptations. This study aimed to investigate the effects of a seven-day IHH exposure on nutritional status, body composition, gut microbiota, movement intensity, and energy expenditure in 10 workers. Methods: A pre-post comparative design was employed, with measurements taken at the beginning and end of the exposure period. Nutritional status, body composition, and phase angle (PhA) were assessed via bioelectrical impedance analysis (BIA). Gut microbiota composition was analyzed through fecal DNA extraction and qPCR for specific bacterial families. Movement intensity and energy expenditure were monitored using accelerometry. An initial statistical analysis was performed, which included paired t-tests and Wilcoxon signed-rank tests. Results: A significant increase in PhA (mean difference: 0.40; p = 0.0053 for t-test, p = 0.0136 for Wilcoxon) and a significant decrease in BMI (mean difference: -0.38; p = 0.0311 for t-test, p = 0.0546 for Wilcoxon). Conclusions: While the original paper reported no significant changes in nutritional status or body composition, our re-analysis suggests a significant change in BMI. The original paper also reported significant changes in specific gut bacterial families (butyrate-producing bacteria, p = 0.037; Lactobacillus species, p = 0.006). Physical activity levels remained consistently low.}, } @article {pmid41470852, year = {2025}, author = {Stumpf, KA and Green, M and Niu, X and Lu, D and Gan, S and Zhan, X and Maxey, MN and Boren, M and Nayak, SP and Jaleel, S and Brown, LS and Foster, JA and Mirpuri, J}, title = {Gut Microbiome Composition and Variance Are Modified by Degree of Growth Failure in Preterm Infants: A Prospective Study.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243907}, pmid = {41470852}, issn = {2072-6643}, support = {R01 DK121975/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Prospective Studies ; Infant, Newborn ; *Infant, Premature/growth & development ; Feces/microbiology ; Male ; Female ; RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Infant ; Clostridium/isolation & purification ; Gestational Age ; Bifidobacterium/isolation & purification ; *Growth Disorders/microbiology ; Intensive Care Units, Neonatal ; }, abstract = {Background/Objectives: Preterm infants often require increased caloric intake to maintain appropriate growth while in the neonatal intensive care unit (NICU). Emerging evidence suggests that alterations of the gut microbiome may play a role in infant and childhood growth patterns. The fecal microbiome patterns in infants with normal and poor growth patterns were classified in this study. Methods: We conducted a prospective trial of infants of less than 29 weeks' gestation with an embedded case-control analysis of infants with normal or poor growth patterns. Fecal samples were collected weekly from infants on full enteral feeds and analyzed blindly using 16s rRNA next-generation sequencing. The relationship between gut microbial diversity and composition and growth pattern and trajectory were assessed. Results: A total of 115 infants were enrolled in the trial with 263 fecal samples selected from 87 enrolled infants for analysis. In total, 37 samples were available from the normal growth cohort, 56 samples from the poor growth cohort, and 170 samples were available for analysis from the very poor growth cohort. Analysis of relative abundance revealed increased representation of Veillonella, Bifidobacterium, and Clostridium in very poor growth infants compared to normal growth infants. Variation in specific taxa was also found to vary significantly across post-menstrual age depending on the degree of growth failure. Conclusions: Gut microbiome composition and variance was modified by the degree of growth failure in our cohort of preterm infants. Our study adds to the growing body of evidence that alteration of the microbiome is associated with poor growth in preterm infants. This may ultimately represent a therapeutic target for growth failure in preterm infants.}, } @article {pmid41470806, year = {2025}, author = {Black, EG and Bugarcic, A and Lauche, R and El-Omar, E and El-Assaad, F}, title = {The Effects of Kefir on the Human Oral and Gut Microbiome.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243861}, pmid = {41470806}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kefir/microbiology ; *Mouth/microbiology ; Probiotics ; Functional Food ; }, abstract = {Kefir, a fermented probiotic drink made from milk, water, or plant-based ingredients, has gained significant attention as a dietary supplement. Originating from the Caucasus Mountains over three thousand years ago, kefir is believed to harbor a range of health benefits through its ability to alter the composition of microbial niches within the human body. These microbial niches are called microbiomes and encompass the collective community of microbial organisms, their genomes and environment. The modern commercialization of kefir has driven the need for high-quality research into its impact on the human microbiome and associated health outcomes; however, there is currently very limited scientific evidence supporting effects of kefir consumption on the human oral and gut microbiome. High-quality human clinical trials are essential to establish the safety and effectiveness of kefir before it can be advised for use in treating conditions linked to the oral and gut microbiota or metabolic health. This literature review aims to critically analyze recent studies investigating the effect of kefir consumption on the oral and gut microbiome, as well as its potential implications for human health. By examining kefir's effects on these interconnected microbial ecosystems, we can better understand its potential and limitations as a functional food for promoting systemic health.}, } @article {pmid41470796, year = {2025}, author = {Zhu, W and Edirisuriya, P and Ai, Q and Yang, F and Tang, J and Nie, K and Ji, X and Soltanieh, S and Musarrat, M and Alim, MA and Liao, Z and Zhou, K}, title = {C. cochlearium 2316 Ameliorates High-Fat Diet-Induced Obesity and Metabolic Syndrome Risk Factors via Enhanced Energy Expenditure and Glucose Homeostasis.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243848}, pmid = {41470796}, issn = {2072-6643}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Obesity/etiology/metabolism ; *Energy Metabolism/drug effects ; Mice, Inbred C57BL ; *Metabolic Syndrome/etiology/prevention & control ; *Probiotics/pharmacology/administration & dosage ; Mice ; Male ; Homeostasis ; *Blood Glucose/metabolism ; Risk Factors ; Insulin/blood ; Insulin Resistance ; }, abstract = {OBJECTIVES: This study investigated the potential beneficial effects of a probiotic candidate, Clostridium cochlearium 2316, in modulating physiological and metabolic markers in mice with high-fat diet-induced obesity (DIO).

METHODS: C57BL/6 DIO mice were assigned to three groups (ad libitum): standard low-fat control (LF, 10% fat), high-fat diet (HF, 60% fat), and high-fat diet supplemented with approximately one billion CFU/day of CC2316 via daily oral gavage for 16 weeks.

RESULTS: After 16 weeks, the CC group exhibited 17.3% lower body weight gain (p < 0.001) and significant fat mass decrease (p < 0.0001) compared to HF mice. Serum biochemistry showed that CC2316 supplementation resulted in a 27.7% reduction in fasting blood glucose (p < 0.05), a 58.4% reduction in fasting insulin (p < 0.01), and an 89.4% improvement in HOMA-IR score (p < 0.05). Furthermore, serum total cholesterol level decreased dramatically by 40.2% in the CC group (p < 0.001). Despite a higher caloric absorption rate (p < 0.001), CC mice demonstrated a significant beneficial shift in energy expenditure, characterized by an increased basal metabolic rate (p < 0.05), higher energy expenditure (p < 0.05), and an elevated respiratory quotient (RER) (p < 0.05), alongside increased physical activity (p < 0.05).

CONCLUSIONS: This investigation strongly suggests that CC2316 supplementation mitigates the adverse effects of HFD-induced obesity by modulating whole-body energy metabolism, positioning it as a potential aid to lower risk factors associated with metabolic syndrome. The precise mechanisms linking the gut microbiome to altered energy substrate utilization are discussed and suggested for further investigation.}, } @article {pmid41470771, year = {2025}, author = {Polyzou, M and Goules, AV and Tzioufas, AG}, title = {The Role of Nutrition in the Development, Management, and Prevention of Rheumatoid Arthritis: A Comprehensive Review.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243826}, pmid = {41470771}, issn = {2072-6643}, mesh = {Humans ; *Arthritis, Rheumatoid/prevention & control/etiology ; Diet, Mediterranean ; *Diet/adverse effects ; *Nutritional Status ; Risk Factors ; Fatty Acids, Omega-3/administration & dosage ; }, abstract = {Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, with key features being synovial hyperplasia, autoantibody production, and ultimately cartilage and bone destruction. The pathogenesis of rheumatoid arthritis (RA) is not fully understood, but it is estimated that genetic factors account for 50-60% of the risk, with the remainder attributed to environmental factors, including infectious agents, smoking, gut microbiota, and diet. Given that most current clinical trials on RA and nutrition are limited in sample size and duration, there is an unmet need for higher-quality studies in the future, a need that EULAR has already recognized. Objective: This article aims to investigate the impact of diet and nutritional factors on the development, progression, and potential prevention of RA. Specifically, it provides a comprehensive review of certain foods, such as alcohol, gluten, red meat, and saturated and trans fats, and their contribution to the onset and progression of rheumatoid arthritis (RA). In addition, it examines the effect of key anti-inflammatory nutrients in reducing the risk of RA, including olive oil, fatty fish, juices, and certain fruits. Finally, it discusses the potential protective effects of certain dietary patterns, such as the Mediterranean diet (MD) and diets rich in omega-3 polyunsaturated fatty acids (PUFAs). Methods: A comprehensive literature search was conducted in the PubMed/Medline, Science Direct, and Scopus databases (1990-2025). English-language observational studies, clinical trials, and systematic reviews addressing the relationship between diet and dietary patterns and RA were included. Results: High consumption of red and processed meat, saturated and trans fats, sugary drinks, and gluten (in vulnerable individuals) is associated with increased RA risk and greater disease activity, partly through pro-inflammatory pathways and gut dysbiosis. In contrast, regular intake of olive oil, fatty fish rich in omega-3 polyunsaturated fatty acids, fruit juices, cocoa, certain fruits, and vitamin D appears protective and may reduce disease activity and symptom severity. Adherence to anti-inflammatory dietary patterns, particularly the Mediterranean diet and diets rich in omega-3 fatty acids, is consistently associated with a lower incidence of RA, reduced inflammatory markers, and improved clinical outcomes. However, most available studies are limited by small sample sizes, short duration, heterogeneous methodologies, and potential confounding by other lifestyle factors (e.g., smoking, obesity). Conclusions: Although an appropriate diet and dietary habits cannot replace pharmacological therapy, current knowledge supports the inclusion of an anti-inflammatory diet as an adjunct strategy in the prevention and management of RA. The relatively limited studies that have been conducted suggest that high-quality, large-scale, prospective studies are needed to prevent and treat RA. These studies should incorporate genetic, microbiome, and long-term clinical endpoints, so as to establish definitive dietary recommendations and allow for personalized nutritional interventions for patients with RA.}, } @article {pmid41470606, year = {2025}, author = {Karpova, D and Belkina, D and Porotikova, E and Yurchenko, E and Vinogradova, S}, title = {Metagenomic Study of the Grapevine Decline Detected a Cocktail of Fungi Associated with Grapevine Trunk Diseases.}, journal = {Plants (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, pmid = {41470606}, issn = {2223-7747}, support = {23-16-00232//Russian Science Foundation/ ; 00000//Ministry of Education and Science of Russian Federation/ ; }, abstract = {This study analyzed the microbiome of three varieties differing in genotype and technical purpose: Cristal, Riesling, and Avgustin, all exhibiting decline symptoms of unknown etiology. A total of 92 symptomatic and asymptomatic grapevines were analyzed using ITS and 16S rRNA amplicon sequencing and molecular genetic methods. Phytoplasmas and the pathogenic bacteria Xylella fastidiosa and Xylophilus ampelinus were not present in the samples. The decline symptoms were associated with a cocktail of fungal pathogens that cause grapevine trunk diseases. In particular, the analysis revealed the causative agents of Botryosphaeria dieback (Sphaeropsis spp. and Botryosphaeria spp.), fungi associated with the Esca complex (Phaeomoniella spp., Phaeoacremonium spp., Inonotus spp., Seimatosporium spp., Stereum spp., and Cadophora spp.), and the causative agents of Phomopsis dieback (Diaporthe spp.). The symptoms of decline may be increased by several facultative grapevine pathogens that have been identified in microbiome (genera Stemphylium, Alternaria, Aspergillus, Penicillium, Talaromyces, and Fusarium). The metagenomic data of the grapevine microbiome provides opportunities for developing disease control strategies, which is important for the sustainable management of vineyards.}, } @article {pmid41470243, year = {2025}, author = {Kayer, A and Özen, A and Dinleyici, EÇ}, title = {Urinary Microbiota Composition in Treatment-Naïve Bladder Cancer: A Case-Control Study with Tumor Invasiveness Stratification.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470243}, issn = {1648-9144}, support = {2599//Eskişehir Osmangazi University/ ; }, mesh = {Humans ; *Urinary Bladder Neoplasms/microbiology/urine/pathology ; Male ; Female ; Case-Control Studies ; Middle Aged ; Aged ; *Microbiota/physiology ; RNA, Ribosomal, 16S/analysis ; *Urine/microbiology ; Neoplasm Invasiveness ; }, abstract = {Background and Objectives: Emerging evidence suggests that the genitourinary microbiota may influence the development and progression of urological malignancies, including bladder cancer. This study aimed to characterize the urinary microbiota at diagnosis in patients with bladder cancer and compare findings with healthy controls. Materials and Methods: Urine samples were collected from 30 patients with treatment-naïve bladder cancer and 20 age- and sex-matched healthy individuals. Microbiota composition was analyzed using 16S rRNA sequencing, and subgroup comparisons were made between muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Differentially abundant taxa were identified using linear discriminant analysis effect size (LEfSe) with an LDA threshold > 2 and p < 0.05. Results: No significant differences were observed in alpha or beta diversity between patients and controls or between MIBC and NMIBC. At the phylum level, Firmicutes was dominant in both groups but relatively more abundant in bladder cancer cases. Enterococcus was the most abundant genus in the cancer group (35.0%) and especially in MIBC (58.0%), while Lactobacillus was more prevalent in healthy controls (19.8% vs. 9.5%). At the species level, Veillonella dispar was notably enriched in MIBC cases (70.9%) compared to NMIBC (3.9%). LEfSe analysis revealed significant enrichment of Ralstonia, Microbacterium, and Facklamia in patients with bladder cancer, while Parvimonas, Sneathia, Gemella, and Acinetobacter guillouiae were more abundant in controls. Conclusions: These findings highlight preliminary microbiota differences associated with bladder cancer and tumor invasiveness; however, the results are exploratory and larger studies are required to evaluate their diagnostic or clinical relevance.}, } @article {pmid41470224, year = {2025}, author = {Tatarciuc, D and Ghica, DC and Darnea, M and Esanu, IM and Vasluianu, RI and Stamatin, O and Indrei, L and Antohe, M and Lupu, IC and Bobu, L and Dima, AM}, title = {Beyond H. pylori: Re-Examining the Oral Microbiome's Role in Gastric Health and Disease, a Narrative Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470224}, issn = {1648-9144}, mesh = {Humans ; Helicobacter pylori/pathogenicity ; *Helicobacter Infections/complications/microbiology ; *Microbiota/physiology ; Dysbiosis/microbiology/complications ; Oral Health/standards ; Gastritis/microbiology ; Periodontitis/microbiology/complications ; *Mouth/microbiology ; Risk Factors ; }, abstract = {Background: The separation between oral and systemic health is increasingly challenged. Globally prevalent inflammatory diseases such as gastritis, often caused by Helicobacter pylori (H. pylori), and oral pathologies like periodontitis may be interconnected through microbial and inflammatory pathways. Objective: This review synthesizes evidence on the dental-gastric link, examining mechanistic pathways and clinical implications. Methods: A structured literature search identified key studies from 2000 to 2025, prioritizing systematic reviews and high-quality human research. Findings: Three key mechanistic pathways link oral dysbiosis with gastric pathology: (1) the direct translocation of oral pathogens to the stomach, including H. pylori and the broader dysbiotic oral microbiome; (2) the systemic inflammatory spillover from the periodontium, which primes the host immune system and exacerbates gastric inflammation; and (3) ancillary mechanisms such as the disruption of beneficial nitrate-nitrite-nitric oxide metabolism. Epidemiological studies show strong associations, and initial interventional trials indicate periodontal therapy may improve H. pylori eradication rates and reduce recurrence. However, the evidence is tempered by methodological limitations, including profound confounding by shared risk factors (e.g., smoking, socioeconomic status), the challenge of reverse causality, and inconsistent results from interventional studies. Conclusion: While confounding factors require consideration, oral health is a promising modifiable risk factor for gastritis. Interdisciplinary collaboration between dentistry and gastroenterology is essential to advance research and integrate oral care into gastrointestinal disease management.}, } @article {pmid41470214, year = {2025}, author = {Kahraman, T and Ayaz, A}, title = {Dietary Phytonutrients in Fibromyalgia: Integrating Mechanisms, Biomarkers, and Clinical Evidence-A Narrative Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470214}, issn = {1648-9144}, mesh = {Humans ; *Fibromyalgia/diet therapy/physiopathology ; Biomarkers/analysis/blood ; *Phytochemicals/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; }, abstract = {Background and Objectives: Fibromyalgia (FM) is associated with chronic pain, oxidative stress, low-grade inflammation, and disturbances in signalling along the gut-brain axis. These pathways may be modulated by plant-derived phytonutrients. This narrative review summarises mechanistic and clinical evidence on phytonutrient-based strategies in FM. Materials and Methods: Following SANRA guidelines, we searched PubMed, Web of Science, Scopus and ScienceDirect for human and relevant preclinical studies published between 2005 and October 2025 that evaluated phytonutrient-rich dietary patterns or isolated bioactives in relation to FM symptoms or underlying mechanisms. Results: There is a consistent association between FM and increased oxidative damage and reduced antioxidant defences. Adopting plant-based diets, particularly Mediterranean-type and low-FODMAP diets, has been linked to improvements in pain, fatigue, sleep, and gastrointestinal symptoms, as well as modest gains in quality of life. However, the effects on inflammatory markers are conflicting. Trials of selected bioactive compounds, such as coenzyme Q10, curcumin-based formulations, L-carnitine and certain probiotics, suggest beneficial effects on symptoms, whereas others show little or no effect. Studies of the microbiome indicate a loss of butyrate-producing bacteria and altered microbial metabolites. Early dietary or probiotic interventions may partially mitigate these changes to some extent. Preclinical studies have identified SIRT1 as a potential mediator, but there is a lack of human data. Reporting on safety, dosage and formulation is often inadequate. Conclusions: Given the narrative design of this review and the methodological heterogeneity of the included studies, the overall certainty of the evidence cannot be formally graded and should be regarded as limited and heterogeneous. Nevertheless, current data supports phytonutrient-rich, food-based approaches as adjuncts rather than alternatives to standard FM care. Well-designed randomised trials with standardised outcomes and reporting of dose, formulation and relevant biomarkers are needed to identify the most effective strategies and the patient subgroups most likely to benefit.}, } @article {pmid41470154, year = {2025}, author = {Tjiu, JW and Lu, CF}, title = {Oral Probiotics in Acne vulgaris: A Systematic Review and Meta-Analysis of Double-Blind Randomized Clinical Trials.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470154}, issn = {1648-9144}, mesh = {Humans ; *Probiotics/therapeutic use/administration & dosage ; *Acne Vulgaris/therapy/drug therapy ; Randomized Controlled Trials as Topic ; Double-Blind Method ; Administration, Oral ; Adolescent ; }, abstract = {Background and Objectives: Acne vulgaris is a prevalent chronic inflammatory skin condition affecting adolescents and young adults worldwide. Increasing concern regarding antimicrobial resistance has renewed interest in microbiome-modulating therapies, including oral probiotics. This systematic review and meta-analysis evaluated the efficacy and safety of oral probiotic supplementation for acne vulgaris using contemporary random-effects methods. Materials and Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, and ClinicalTrials.gov through November 2025 without language restrictions. Eligible studies were double-blind randomized controlled trials (RCTs) comparing oral probiotics with placebo or standard therapy for ≥4 weeks and reporting quantitative acne severity outcomes. Risk of bias was assessed using RoB 2.0. Standardized mean differences (SMDs) were pooled using restricted maximum likelihood (REML) with Hartung-Knapp adjustment. Heterogeneity was summarized using I[2], τ[2] (95% CI), and 95% prediction intervals. Adverse events were extracted. Results: Three RCTs (n = 231) met eligibility criteria. Pooled analysis suggested a modest reduction in inflammatory lesion counts favoring probiotics (SMD -0.57; 95% CI -0.94 to -0.21), although heterogeneity was substantial (I[2] = 72%; τ[2] = 0.11). The 95% prediction interval (-1.25 to 0.11) indicated that future studies may plausibly observe no meaningful effect. Sensitivity analyses using the DerSimonian-Laird estimator produced comparable results. All trials reported good short-term tolerability with no serious adverse events. Risk of bias was low in two trials and of some concern in one. Certainty of evidence was rated low to moderate. Conclusions: Oral probiotics may modestly reduce acne severity as a generally safe, antibiotic-sparing adjunct; however, the current evidence base is small and heterogeneous, and the certainty of effect remains low-to-moderate. Larger, standardized RCTs are required before firm clinical recommendations can be made. Registration: PROSPERO CRD420251181388. Funding: This research received no external funding.}, } @article {pmid41469665, year = {2025}, author = {Zheng, SH and Li, KZ and Feng, G and Wang, YT and Wang, JN and Li, SQ and Sun, YD}, title = {Gut microbiota reshaping the pancreatic cancer immune microenvironment: new avenues for immunotherapy.}, journal = {Molecular cancer}, volume = {24}, number = {1}, pages = {313}, pmid = {41469665}, issn = {1476-4598}, mesh = {Humans ; *Tumor Microenvironment/immunology ; *Gastrointestinal Microbiome/immunology ; *Pancreatic Neoplasms/therapy/immunology/etiology/pathology/microbiology/metabolism ; *Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Pancreatic cancer remains one of the deadliest malignancies, primarily due to its highly immunosuppressive tumor microenvironment (TME) and poor response to conventional therapies. Increasing evidence highlights the gut microbiota as a pivotal regulator of antitumor immunity, modulating T cell activation, macrophage polarization, and dendritic cell function. Microbial communities and their metabolites can either inhibit or enhance immune surveillance, thereby influencing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs) and CAR-T cell therapy. Approaches including dietary modulation, probiotics, fecal microbiota transplantation (FMT), and microbial metabolite supplementation show promise in restoring immune homeostasis and improving treatment outcomes. Additionally, gut microbiome profiling has emerged as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events. This review summarizes current insights into microbiota-immune interactions in pancreatic cancer, emphasizes microbiome-targeted therapeutic strategies, and explores future opportunities for precision immunotherapy guided by microbial modulation.}, } @article {pmid41469598, year = {2025}, author = {Mbabazi, M and Kateete, DP and Nakazzi, F and Wandera, JN and Mutesi, N and Ocan, M and Biraro, IA and Abaasa, A and Johnson, WE and Wee, B and Muwonge, A}, title = {The impact of tuberculosis and its treatment on the lung and gut microbiota: a global systematic review, meta-analysis, and amplicon-based metagenomic meta-analysis.}, journal = {BMC infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12879-025-12369-1}, pmid = {41469598}, issn = {1471-2334}, } @article {pmid41469399, year = {2025}, author = {Fang, J and Wang, G and Zhang, C and Liu, G and Xu, J and Gao, Y and Guo, Y and Wang, X and Qiu, T}, title = {Conserved genotype-independent rhizobacteria promote maize growth.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00895-4}, pmid = {41469399}, issn = {2055-5008}, support = {TSXM202525//Exploratory Research Project of Beijing Academy of Agriculture and Forestry Sciences/ ; KJCX20251102//Special Program for Creative Ability of Beijing Academy of Agriculture and Forestry Sciences/ ; KJCX20230113//Special Program for Creative Ability of Beijing Academy of Agriculture and Forestry Sciences/ ; }, abstract = {Rhizosphere microbiomes play an essential role in promoting plant growth and health. Although host genotype is known to shape rhizosphere microbial communities, it remains unclear whether core microbial taxa can persist across genetically diverse hosts and contribute to plant performance. Here, we conducted a large-scale analysis of 1005 rhizosphere samples from 335 maize populations to investigate the effects of host genetic variation on rhizosphere microbiota. We observed significant genotype-dependent variation in both bacterial and fungal community diversity and composition. However, community assembly was predominantly governed by stochastic processes, suggesting an evolutionary conservation of rhizosphere microbiota across genotypes. Based on the hypothesis that core microbes may consistently associate with maize independent of genotypes, we identified a core bacterial taxon, ASV245 (Pseudomonas sp.), which was consistently enriched across all maize genotypes. The corresponding strain, designated as WY16, was isolated from maize roots and significantly promoted both stem and root growth by activating maize hormone signaling pathways. These findings highlight the persistence and functional roles of genotype-independent core microbes, deepening our understanding of plant-microbiome interactions and providing new insights for microbiome-based strategies in sustainable agriculture.}, } @article {pmid41469282, year = {2025}, author = {Grover, BT and Docimo, S and Shin, TH and Shope, T and Albaugh, VL and Byers, R and Passerini, H and Northup, CJ and Vosburg, RW}, title = {American Society of Metabolic and Bariatric Surgery review of gut microbiome and alterations related to weight loss treatment, by the Clinical Issues Committee.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.soard.2025.11.021}, pmid = {41469282}, issn = {1878-7533}, abstract = {The gut microbiome is a critical mediator of metabolic health including obesity and type 2 diabetes. Microbial composition variation - driven by diet, genetics, environment, and host physiology - can influence insulin sensitivity, energy absorption, fat storage, and systemic inflammation. Metabolic and bariatric surgery (MBS) is associated with distinct shifts in gut microbiota that may contribute to weight loss and metabolic improvements. Changes in microbial diversity, bile acid metabolism, and enrichment of beneficial taxa have all been linked to favorable metabolic outcomes. Furthermore, the gut microbiome may interact with molecular signaling pathways including glucagon-like peptide-1 signaling. Despite probiotics and prebiotics showing potential modulation of the gut microbiota, their clinical impact on obesity management remains inconsistent. Understanding the complex interplay between MBS, the gut microbiome, and host metabolism may offer novel insights into future therapeutic targets. As the field advances, microbiome-based strategies may enhance procedure selection, improve patient outcomes after MBS, and contribute to more personalized, durable treatment approaches for obesity and its related diseases.}, } @article {pmid41469211, year = {2025}, author = {Munteanu, C and Dhanasekaran, DN}, title = {Obesity as a Systems-Level Driver of Cancer: Mechanisms and Nutritional Reprogramming.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {}, number = {}, pages = {e70075}, doi = {10.1111/obr.70075}, pmid = {41469211}, issn = {1467-789X}, support = {W81XWH-22-1-0415//Department of Defense Ovarian Cancer Research Program Award/ ; P30CA225520//National Cancer Institute of the National Institutes of Health/ ; P30GM154635//National Institutes of General Medical Sciences of the National Institutes of Health/ ; }, abstract = {Obesity has emerged as a global health crisis and a potent driver of cancer incidence and mortality, yet its mechanistic impact on tumor biology remains underappreciated. Far from being a passive risk factor, obesity acts as a systems-level oncogenic stressor, reshaping hormonal signaling, immunometabolism, and epigenetic stability across the body. This review synthesizes current knowledge on the physiological, cellular, and molecular cascades linking obesity to carcinogenesis, with emphasis on chronic inflammation, metabolic reprogramming, tumor microenvironment remodeling, and microbiome dysbiosis. We also examine how dietary patterns modulate these cancer-associated processes, positioning nutrition not merely as a preventive tool but as a programmable interphase with cancer biology through soft epigenetic reprogramming. Emerging frameworks in precision nutritional oncology, driven by nutrigenomics, metabolomics, and patient-specific molecular profiling, offer promising avenues for personalized cancer prevention and metabolic targeting. By integrating epidemiological trends, mechanistic insights, and translational strategies, we propose a paradigm shift: treating obesity not just as a comorbid risk factor but also as a modifiable oncogenic ecosystem-one that can be reprogrammed through informed, individualized precision dietary interventions.}, } @article {pmid41469026, year = {2025}, author = {Yao, L and Solania, A and Luissint, AC and Balana, AT and Zhang, H and Sangaraju, D and Lai, Z and Kuo, J and Storek, KM and Wolan, DW}, title = {The Secreted Metabolite Isopentenyladenine from Faecalibacterium prausnitzii Is Anti-inflammatory with Barrier-Protective Properties.}, journal = {ACS infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsinfecdis.5c00771}, pmid = {41469026}, issn = {2373-8227}, abstract = {Colonic microbiome dysbiosis is correlated with inflammatory bowel disease (IBD), and depletion of the commensal bacterium Faecalibacterium prausnitzii (F. prausnitzii) is routinely observed in the metagenomic analyses of IBD patient microbiome samples. F. prausnitzii is likely beneficial to hosts, as oral administration of F. prausnitzii strain A2-165 has anti-inflammatory properties in murine models of colitis. Previous studies attribute the anti-inflammatory effects of F. prausnitzii A2-165 to production of the short-chain fatty acid butyrate, as well as a secreted protein known as microbial anti-inflammatory molecule (MAM). Here, we verified that oral dosing of strain A2-165 protects against DSS-induced murine colitis and further showed that the aqueous-soluble secreted fraction of overnight cultures from a collection of F. prausnitzii strains inhibits inflammatory signatures, including the activation of the host's NF-κB pathway, production of IL-8, and differentiation of naïve T cells into the TH17 lineage. Our findings against a panel of in vitro assays suggested that the anti-inflammatory responses were attributable to secreted small-molecule or peptide metabolites, as both heat-inactivated and proteinase K-treated F. prausnitzii culture supernatants retained activity. Untargeted and targeted mass spectrometry metabolomics analyses on the soluble anti-inflammatory secretome yielded several unique F. prausnitzii metabolites, including isopentenyladenine. We demonstrated that isopentenyladenine independently modulates host cellular signaling and immune responses and suggest that this newly identified metabolite with human immunomodulatory properties may be useful toward the discovery of IBD-focused therapeutics.}, } @article {pmid41468854, year = {2025}, author = {Chatterjee, S and Basak, C and Basak, G and Karjee, A and Mukherjee, S and Barman, P and Khan, NB and Sarkar, P and Majumdar, S and Chakraborty, R and Barman, C}, title = {Mitigating cadmium-induced stress in Capsicum annuum L. by Pseudomonas aeruginosa strain CD3: Impacts on morpho-physiology, reproductive traits, capsaicin content and soil microbiome.}, journal = {The Science of the total environment}, volume = {1013}, number = {}, pages = {181229}, doi = {10.1016/j.scitotenv.2025.181229}, pmid = {41468854}, issn = {1879-1026}, abstract = {Cadmium (Cd[2+]) contamination poses a major challenge to agricultural productivity and food safety by impairing plant physiology, inducing oxidative stress, and facilitating toxic metal accumulation in plants. Capsicum annuum, a widely cultivated crop, is highly susceptible to heavy metal toxicity, which hampers its growth, reproduction, and physiochemical balance. Although several studies have documented Cd[2+]-induced phytotoxicity in chili, mitigation strategies, particularly involving beneficial microbes, remain underexplored. This study investigates the role of Pseudomonas aeruginosa strain CD3 to alleviate cadmium stress in chili plants under controlled conditions. Morphological, physiological, biochemical, and reproductive traits were analyzed along with rhizospheric microbiome profiling in monsoon and winter seasons. CD3 inoculation significantly enhanced plant height (74.51 %), shoot biomass (73.08 %), relative water content (21.31 %), and antioxidant enzyme activity at 100 ppm Cd[2+] stress in both the season. Reactive oxygen species accumulation was reduced, while photosynthetic pigment content was restored. Our results verify that Cd[2+] severely disrupts chili reproductive biology, while strain CD3 markedly mitigates these effects by improving pollen viability, fruit yield, and seed production. Importantly, this study demonstrates the novel role of CD3 in regulating capsaicin accumulation under Cd[2+] stress, where microbial application alleviated stress-induced capsaicin enrichment. Cd[2+] accumulation was found to be below detectable levels in fruits of CD3-treated plants. Metataxonomic analysis demonstrated that CD3 successfully persisted in the soil, and its central role in the microbial network with strengthened interactions indicated a stabilizing and resilience-enhancing effect under cadmium stress. This research emphasizes the potential of P. aeruginosa strain CD3 as a green, sustainable bioremediation agent to improve crop yield, minimize metal translocation to edible tissues, and stabilize soil integrity in contaminated agricultural soils.}, } @article {pmid41468691, year = {2025}, author = {Leduc, F and Barko, PC and de Souza, CP and Reinhart, JM}, title = {Oral itraconazole may alter the gastrointestinal microbiome in healthy cats.}, journal = {American journal of veterinary research}, volume = {}, number = {}, pages = {1-13}, doi = {10.2460/ajvr.25.09.0338}, pmid = {41468691}, issn = {1943-5681}, abstract = {OBJECTIVE: To determine if and how oral itraconazole alters the gastrointestinal microbiome of cats.

METHODS: This was a single-arm, longitudinal exploratory study performed in a university setting. Healthy cats were administered 5 mg/kg/day of itraconazole solution orally with food during alternating weeks over a 5-week time period. Rectal swabs were collected at 2 time points before treatment and serially during and after treatment over 31 weeks. Bacterial and fungal populations were quantified by 16S and internal transcribed spacer 3 and 4 sequencing, respectively. Changes in α diversity, β diversity, and differential abundance were evaluated over time.

RESULTS: There were no significant changes in bacterial α diversity, β diversity (R2 = 0.0077; P = .550), or relative abundance between the 2 pretreatment time points indicating stable microbial populations before itraconazole exposure in 16 cats. Time was a significant determinant of β diversity during and after itraconazole treatment (R2 = 0.0181; P = .002), and several α-diversity indices significantly decreased in the posttreatment timeframe. Ruminococcus torques (-1.916; 95% CI, -2.971 to -0.861), Acidaminococcus spp (-1.291; 95%, CI -1.866 to -0.716), and Blautia hansenii (-1.475, 95% CI, -2.295 to -0.691) relative abundances were significantly decreased at weeks 1, 5, and 9, respectively. The final fungal internal transcribed spacer dataset only included 5 taxa limiting analysis and interpretation.

CONCLUSIONS: These findings provide preliminary evidence for possible dysbiosis in the feline gastrointestinal tract during itraconazole treatment. However, many changes in differential abundance were small and no longer significant posttreatment.

CLINICAL RELEVANCE: Itraconazole administration might induce gastrointestinal bacterial dysbiosis in cats. Alternate methods for fungal microbiome assessment should be used in future feline studies.}, } @article {pmid41468674, year = {2025}, author = {Feng, W and Ma, R and Guo, Y and Zhang, B and Lan, J and Liu, J and Chen, S}, title = {Rhizosphere metagenomics and metabolomes provide new insights into the relationship between rhizosphere microecology and early bolting of Angelica dahurica.}, journal = {Microbiological research}, volume = {305}, number = {}, pages = {128435}, doi = {10.1016/j.micres.2025.128435}, pmid = {41468674}, issn = {1618-0623}, abstract = {Angelica dahurica is a medicinal and edible plant with a wide range of pharmaceutical and food applications. However, the early bolting, which leads to reduced yield and loss of bioactive constituents, has become a major obstacle to the industrial development of A. dahurica. Rhizosphere microecology affects plant growth and secondary metabolite accumulation, but the association of rhizosphere microecology with the early bolting of A. dahurica is not fully understood. This study integrated metagenomic and metabolomic analyses to systematically characterize the differences in rhizosphere microecology of non-bolting and early bolting A. dahurica plants. Results revealed significant disparities in soil physicochemical properties, root exudate profiles, and microbial community composition between two groups, all of which exhibited correlations with the coumarin compounds content, the primary pharmacologically active constituents of A. dahurica. Integrated analysis suggested that root-derived acyl-homoserine lactone (AHL) quorum-sensing signals, as the primary chemical signals of the prevalent Gram-negative bacteria, may participate in regulating the microbial community structure and soil properties, thereby influencing the bolting and flowering process. This study proposes a potential complex regulatory network of "rhizosphere microbiome - quorum-sensing signals - soil nitrogen cycle - bolting and flowering" linking the rhizosphere microecology to early bolting in A. dahurica, thereby addressing a key knowledge gap in this area. The findings offer a scientific foundation and innovative strategy for the simultaneous prevention of early bolting and quality improvement in A. dahurica through soil microecological management, which is of significant importance for promoting the sustainable commercial development of the A. dahurica industry.}, } @article {pmid41468549, year = {2025}, author = {Ye, L and Wu, Y and Guo, J and Wang, H and Cai, J and Chen, K and Dong, N and Yu, J and Chao, S and Zhou, H and Chen, G and Chen, S and Zhang, R}, title = {Elucidation of population-based bacterial adaptation to antimicrobial treatment by single-cell sequencing analysis of the gut microbiome of a hospital patient.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0163124}, doi = {10.1128/msystems.01631-24}, pmid = {41468549}, issn = {2379-5077}, abstract = {In this study, we used single-cell sequencing to analyze the gut microbiome of an adult male patient with acute cerebral hemorrhage undergoing antibiotic treatment. We identified 92 bacterial species, including 23 Firmicutes and one archaeon from Methanobacteriota, along with 69 unclassified strains. Single-cell sequencing effectively detected bacteria carrying antibiotic resistance genes (ARGs), particularly in unclassified species, and traced the evolution of these genes across diverse bacterial taxa. Notably, the cfr(C) gene was detected in 11 bacterial species following antimicrobial treatment, with mutation patterns characterized in Enterococcus faecalis, Klebsiella pneumoniae, Ruthenibacterium UN-1, and four unclassified species. In total, 29 ARG subtypes across eight types were identified in 13 known, five unknown, and 18 unclassified species, allowing us to trace their evolution routes. In addition, we detected a total of 309 horizontal gene transfer (HGT) events, in which several genes like folE and queE were frequently involved. The products of these genes are known to enhance the ability of the recipient bacterial strains to repair DNA damage and maintain genomic stability, especially following prolonged antibiotic treatment. Comparison between isolated strain genomes (IS-KP1) and single-cell analysis confirmed the presence of at least two K. pneumoniae strains in the patient, with one exhibiting a larger extent of involvement in ARG co-evolution. This strain was found to contain the cfr(C) and fosXCC genes, which were absent in IS-KP1. Klebsiella strains were also found to participate actively in HGT events. In conclusion, the study identified a wide range of ARGs and HGT events within the microbiome. The detection of K. pneumoniae strains with distinct ARG evolution patterns underscores the gut microbiome's adaptability to environmental changes. These findings facilitate the development of novel antimicrobial strategies by fine-tuning the gut microbiome composition.IMPORTANCEThis study highlights the power of single-cell sequencing to unravel the diversity and dynamics of the gut microbiome during antibiotic treatment in a patient with acute cerebral hemorrhage. By identifying antibiotic resistance genes (ARGs) in both known and unclassified bacterial species, we reveal the intricate evolution and horizontal transfer of resistance traits across taxa. The discovery of distinct ARG patterns, including the emergence of the cfr(C) gene in multiple species and its co-evolution in K. pneumoniae, underscores the gut microbiome's adaptability to antimicrobial pressures. These findings provide critical insights into the mechanisms driving resistance dissemination and offer potential pathways for developing precision microbiome-based therapies to combat antibiotic resistance.}, } @article {pmid41468410, year = {2025}, author = {Molina, MA}, title = {From dysbiosis to mechanisms: Why cervicovaginal microbiome-HPV studies must catch up with biology.}, journal = {PLoS pathogens}, volume = {21}, number = {12}, pages = {e1013830}, pmid = {41468410}, issn = {1553-7374}, } @article {pmid41468125, year = {2025}, author = {Kirschen, GW and Gerson, KD}, title = {Performance Characteristics of Current Biomarkers for the Prediction of Spontaneous Preterm Birth.}, journal = {Clinical chemistry}, volume = {72}, number = {1}, pages = {71-81}, doi = {10.1093/clinchem/hvaf141}, pmid = {41468125}, issn = {1530-8561}, mesh = {Humans ; *Premature Birth/diagnosis/metabolism ; *Biomarkers/analysis/blood ; Female ; Pregnancy ; }, abstract = {BACKGROUND: Preterm birth (PTB), or birth occurring before 37 weeks' gestation, remains a significant public health burden, accounting for 10% of live births annually in the United States and incurring substantial healthcare expenditures. Our understanding of the molecular mechanisms underlying spontaneous preterm birth (sPTB) has advanced across the previous 4 decades, yet precise prediction tools and prevention strategies are lacking.

CONTENT: Numerous studies have identified potential anatomical and molecular risk factors for sPTB, including sonographic characteristics of the cervix; maternal serum circulating RNA and proteins; maternal urine metabolic byproducts; cervicovaginal cytokine, microbiome, and metabolome composition; amniotic fluid cytokines; umbilical cord blood leukocyte DNA methylation status; and placental transcriptome profiles. This review focuses on recent developments in sPTB biomarker determination among singleton gestations.

SUMMARY: Herein, we synthesize and evaluate the test characteristics of candidate biomarkers of sPTB, concluding that no single biomarker can accurately predict sPTB. However, several individual or combined panels of biomolecules, including some commercially available, carry clinically significant predictive information. These biomarkers include cervical ultrasonography, the ratio of insulin-like growth factor-binding protein 4 to sex-hormone binding globulin, panels of urinary metabolites and amniotic fluid proteins, and maternal circulating cell-free RNA. Future integration of select biomarkers drawn from prospective validation cohorts into existing risk stratification strategies may enhance sPTB prediction, thereby identifying patients at greatest risk.}, } @article {pmid41468056, year = {2025}, author = {Karikis, I and Arda, Y and Sanyal, R and DeWane, MP and Luckhurst, CM and Kaafarani, HM and Hwabejire, JO and Velmahos, GC and Paranjape, CN}, title = {Acute Appendicitis and the Microbiome: A Review of Microbial Signatures.}, journal = {Surgical infections}, volume = {}, number = {}, pages = {}, doi = {10.1177/10962964251408687}, pmid = {41468056}, issn = {1557-8674}, abstract = {Introduction: Acute appendicitis remains one of the most common surgical emergencies, yet its pathogenesis is incompletely understood. Although mechanical luminal obstruction has traditionally been considered the initiating factor, emerging evidence suggests that the appendix hosts a unique microbial community that may influence disease onset and severity. Methods: We conducted a narrative review that summarizes current data on the role of microbiota in appendicitis, while focusing on differences between complicated and uncomplicated presentations. Results: High-throughput sequencing studies have identified key taxa associated with inflamed appendices, including Fusobacterium, Prevotella, and oral cavity genera such as Gemella and Parvimonas. On the contrary, protective commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila appear depleted. Studies suggest that there is significant variation regarding the microbial composition of complicated and uncomplicated cases. We also examine the role of the appendix as a microbial reservoir and the potential health consequences of its removal. Finally, we discuss how microbiome-based approaches may improve treatment, particularly antibiotic agent selection both in operative and non-operative management. Conclusion: Current evidence supports that appendicitis may represent a disease spectrum carrying multiple rather than a single microbial signature that dictates different pathophysiologic processes.}, } @article {pmid41467904, year = {2026}, author = {Maruyama, D and Tian, X and Doan, TNM and Liao, WI and Chaki, T and Taenaka, H and Maishan, M and Matthay, MA and Prakash, A}, title = {Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606486}, doi = {10.1080/19490976.2025.2606486}, pmid = {41467904}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Macrophages, Alveolar/metabolism/immunology ; Mice ; *Lung Injury/microbiology/metabolism/immunology ; Dietary Fiber/metabolism/administration & dosage ; Fatty Acids, Volatile/metabolism ; *Propionates/metabolism ; Mice, Inbred C57BL ; Male ; Bacteria/metabolism/classification/genetics/isolation & purification ; Lung/metabolism/immunology ; }, abstract = {Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.}, } @article {pmid41467862, year = {2025}, author = {van Straalen, KR and Gudjonsson, JE}, title = {Hidradenitis suppurativa: Why dose escalation often fails and what biology tells us about next steps.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.11.012}, pmid = {41467862}, issn = {1097-6825}, } @article {pmid41467811, year = {2025}, author = {Ha, LH and On, YY and Pohan, C and Lee, J and How, SHC and Teo, Y-Y and Seedorf, H and Gounot, J-S and Nagarajan, N}, title = {High-throughput single-cell isolation of Bifidobacterium strains from the human gut microbiome.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0303325}, doi = {10.1128/spectrum.03033-25}, pmid = {41467811}, issn = {2165-0497}, abstract = {UNLABELLED: Bifidobacterium represents a diverse genus of commensal gut bacteria with key roles in human health, from metabolizing indigestible fibers to protecting against pathogens. While metagenomic studies have highlighted significant strain diversity for Bifidobacterium species within individuals, their systematic isolation and phenotypic characterization can be hampered by the significant effort and biases inherent in traditional culturomics. Here, we explored the utility of a high-throughput single-cell dispensing system (B.SIGHT)-based workflow for accelerating the process of isolating diverse Bifidobacterium strains from fecal samples. Systematic assessment of this workflow revealed a high single-cell dispensing frequency (>88%) and the ability to preserve species diversity when a pool of Bifidobacterium strains was dispensed. Culturing-related factors including the use of an effective selection medium, such as the Bifidus Selective Medium supplemented with mupirocin, and the length of pre-dispensing incubation were found to be critical in determining isolation success. Leveraging this workflow, we obtained a total of 622 viable isolates from five Singaporean fecal samples, of which >98% were found to be from Bifidobacterium species. Whole-genome sequencing of 96 isolates identified six different Bifidobacterium species with both inter- and intra-subject strain and lineage diversity, and the majority (>66%) were novel relative to large public genomic databases. Our findings highlight the ability of this high-throughput culturomics workflow to accelerate the recovery of diverse and novel Bifidobacterium strains, enabling further interrogation of their functional characteristics and advancing our understanding of important bacterial species in the gut microbiome.

IMPORTANCE: The field of high-throughput microbial culturomics is still in its early stages. Enhancing our ability to isolate and phenotypically test bacterial strains from complex communities is crucial for advancing microbiome research and healthcare development. Given the time and cost inefficiencies of traditional culturing methods, a more efficient, high-throughput approach to obtain isolates is needed. In the present study, we assessed a single-cell dispensing platform and developed a workflow to isolate diverse Bifidobacterium strains from fecal samples. We demonstrated here the capability of this novel technology to efficiently obtain hundreds of isolates of a targeted group, covering both species and strain diversities. This generalizable and scalable method can potentially allow for the high-throughput recovery of microbes from other taxonomic groups, providing a fundamental step in improving the culturomics framework to complement metagenomic approaches and enable isolate-level functional studies of important microbes.}, } @article {pmid41467444, year = {2025}, author = {Wang, R and Hatano, T and Hattori, N and Cossu, D}, title = {Interplay of GBA1 with lysosomal dysfunction and inflammation in Parkinson's disease.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01082}, pmid = {41467444}, issn = {1673-5374}, abstract = {Mutations in the glucocerebrosidase (GBA1) gene, encoding the lysosomal enzyme glucocerebrosidase, represent the most significant genetic risk factor for Parkinson's disease. These variants define a distinct clinical subtype characterized by earlier onset, accelerated motor decline, and pronounced cognitive impairment. This review synthesizes current insights into the molecular mechanisms linking GBA1 dysfunction to lysosomal failure, α-synuclein aggregation, and neuroinflammation. Pathogenic alleles such as N370S and L444P disrupt sphingolipid metabolism, resulting in toxic accumulations of glucosylceramide and glucosylsphingosine, endoplasmic reticulum stress, and impaired clearance of misfolded proteins. This initiates a self-reinforcing cycle in which glucocerebrosidase deficiency promotes α-synuclein aggregation, which subsequently impairs glucocerebrosidase trafficking. We explore the convergence of GBA1 mutations on the lysosomal-mitochondrial-autophagy axis, where impaired autophagic flux and disrupted organelle crosstalk amplify oxidative stress and activate the NLR family pyrin domain containing 3 inflammasome. The contribution of microglia, astrocytes, and oligodendrocytes to the neuroinflammatory cascade is eamined, along with the emerging influence of the microbiome-gut-brain axis in disease progression. Finally, we evaluate emerging therapeutic strategies, including pharmacological chaperones, NLRP3 inhibitors, adeno-associated virus-based gene therapy, and microbiome modulation, highlighting both promises and translational challenges such as blood-brain barrier penetration and mutation-specific efficacy. We conclude by advocating for precision medicine approaches, supported by robust biomarker development and advanced disease models, to guide tailored interventions for this aggressive Parkinson's disease subtype.}, } @article {pmid41467389, year = {2025}, author = {Stahlke, S and Theiss, C}, title = {Sex hormones, the gut microbiome, and neurodegenerative diseases: Lifespan perspective.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00932}, pmid = {41467389}, issn = {1673-5374}, abstract = {The gut-brain axis represents a highly integrated communication network, connecting the gastrointestinal tract and the central nervous system via neural, immune, endocrine, and metabolic pathways. Steroid hormones, such as estrogens, androgens, and glucocorticoids, play a pivotal role in modulating these interactions across the lifespan. These hormones influence the composition of microbiota, intestinal permeability, and neuroimmune responses, thereby shaping brain function and behavior. Emerging evidence suggests a correlation between disruptions in the gut-brain axis and the onset and progression of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. The diseases exhibit distinct sex-specific patterns in terms of prevalence, symptomatology, and progression. These patterns are often the consequence of differences in steroid hormone levels, receptor distribution, and immune responses. Despite these differences, the role of sex as a biological variable remains underrepresented in experimental and clinical research. This review synthesizes current evidence on how steroid hormones modulate gut-brain axis interactions and how these mechanisms contribute to neurodegeneration in a sex-specific manner. We highlight recent findings on hormonal regulation of the gut microbiome and its impact on neuroinflammation and neuronal vulnerability. This overview focuses not only on Parkinson's disease, in which genetic variations in the gene for brain-derived neurotrophic factor have been observed among others as triggers for dopaminergic neurodegeneration. In addition, Alzheimer's disease and multiple sclerosis are also considered, in which the prevalence of intestinal dysbiosis and impaired intestinal barrier function have been identified as significant influencing factors. This review provides a comprehensive framework for understanding the gender-specific neurobiology of gut-brain axis by integrating perspectives from the fields of endocrinology, neuroimmunology, and microbiome research. It is argued that a targeted investigation of the interactions between hormones and gut-brain axis is essential for the development of sex-specific therapeutic strategies for neurodegenerative diseases.}, } @article {pmid41467356, year = {2025}, author = {Vadillo Gonzalez, S and Jongen, R and Thomas, T and Marzinelli, EM and Gribben, PE}, title = {Seagrass-microbe interactions: a systematic review of current research trends and mapping of the core microbiome.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1002/brv.70126}, pmid = {41467356}, issn = {1469-185X}, support = {LP200200220//Australian Research Council/ ; DP240100556//Australian Research Council/ ; }, abstract = {Seagrass-microbe interactions are crucial for seagrass performance and the coastal ecosystem services they support. However, significant variation in experimental and analytical approaches has hindered our broader understanding of seagrass-microbe interactions and the potential existence of a functional core microbiome, i.e. microbial taxa that are consistently present on hosts and likely exert a disproportionate impact on host function. Through a systematic review, we aimed first to understand current trends and knowledge gaps in seagrass-microbe research. Additionally, we conducted a systematic mapping of global 16S ribosomal RNA (rRNA) gene sequencing data to characterise core bacterial taxa in three plant microenvironments (leaves, roots and rhizosphere) across multiple species and within a highly studied seagrass species, Zostera marina. The results revealed a growing number of studies since the 2010s manipulating environmental variables and/or seagrass microbes to investigate their roles in seagrass performance and responses to stressors. Most studies have primarily focused on seagrass leaves, examined a limited number of species, and investigated only bacteria via 16S rRNA gene amplicon sequencing. A few studies attempted to characterise seagrass core microbiomes, often using highly variable approaches to define core taxa. Our systematic mapping based on global sequencing data allowed the identification of prevalent bacterial taxa belonging to the families Desulfocapsaceae and Sulfurovaceae in the seagrass rhizosphere, which may play an important role in the performance of Z. marina and other seagrass species. The results also showed that many other bacterial families were prevalent across different seagrass microenvironments, such as Rhodobacteraceae and Flavobacteriaceae, with substantial taxonomic variability and functional metabolic redundancy. We identified key challenges stemming from available data and variable methodologies and provided insights to guide future experimental work and deepen our understanding of seagrass-microbe interactions. We argue that such knowledge may improve seagrass management outcomes, especially by informing restoration strategies based on core microbial taxa.}, } @article {pmid41467315, year = {2025}, author = {Sun, Y and Li, P and Wang, X and Jiang, D and Shao, Y}, title = {Gut dysbiosis in early severe burns contributes to acute lung injury by impairing neutrophil chemotaxis.}, journal = {Journal of leukocyte biology}, volume = {118}, number = {1}, pages = {}, doi = {10.1093/jleuko/qiaf169}, pmid = {41467315}, issn = {1938-3673}, support = {82302800//National Natural Science Foundation of China/ ; 2024M751108//China Postdoctoral Science Foundation/ ; SDCX-ZG-202400032//Postdoctoral Innovation Program in Shandong Province/ ; }, mesh = {Animals ; *Dysbiosis/complications/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Acute Lung Injury/etiology/pathology/microbiology/immunology ; *Neutrophils/immunology/pathology ; Humans ; Mice ; *Burns/complications/microbiology/pathology/immunology ; *Chemotaxis, Leukocyte ; Male ; Female ; Mice, Inbred C57BL ; Butyrates/pharmacology ; Disease Models, Animal ; Neutrophil Infiltration ; Chemotaxis ; }, abstract = {Severe burns complicated by acute lung injury are critical causes of respiratory failure and multiple organ dysfunction syndrome. Neutrophils extensively infiltrate lung tissues early postburn to mediate pulmonary damage, but the underlying mechanisms remain unclear. We analyzed gut microbiota of severe burn patients via metagenomics and metabolomics, assessed neutrophil chemotaxis using a self-developed in vitro agarose model, and validated Faecalibacterium prausnitzii and butyrate's effects on restoring neutrophil chemotaxis in gut microbiota-depleted mice via oral gavage (plus in vivo validation with small animal imaging). Bronchoalveolar lavage fluid biomarkers and pulmonary function tests evaluated pulmonary injury from impaired neutrophil chemotaxis. Early postburn, F. prausnitzii and its metabolite butyrate were significantly depleted in patients, concurrent with impaired neutrophil chemotaxis-restored by butyrate supplementation. In murine burn models, F. prausnitzii or butyrate rescued neutrophil chemotaxis, reduced pulmonary neutrophil infiltration, and attenuated lung injury. Mechanistically, butyrate restored neutrophil function in a severe burn patient plasma-stimulated model by downregulating P2X1 receptor expression and suppressing myosin light chain phosphorylation. Our findings indicate postburn gut microbiota dysbiosis and metabolite alterations disrupt neutrophil chemotaxis, causing excessive pulmonary neutrophil infiltration/activation. This highlights gut microbiota-derived metabolites as potential therapeutics for mitigating neutrophil-driven lung injury early postsevere burns.}, } @article {pmid41467213, year = {2025}, author = {Wang, S and Carroll-Portillo, A}, title = {Editorial: Genetic modulation of gut microbiome: effects on neurological health and aging.}, journal = {Frontiers in genetics}, volume = {16}, number = {}, pages = {1760164}, pmid = {41467213}, issn = {1664-8021}, } @article {pmid41466840, year = {2025}, author = {Hendesi, H and Godfrey, DA and Ruble, AF and Tran, AM and Villani, DA and Landgrave, SH and Hasan, NA and Adams, DJ and Zuscik, MJ}, title = {Intermittent fasting alleviates obesity-associated impairments in bone fracture healing: Exploring the role of gut microbiome.}, journal = {Bone reports}, volume = {27}, number = {}, pages = {101876}, pmid = {41466840}, issn = {2352-1872}, abstract = {Intermittent Fasting (IF) is a dietary strategy with metabolic benefits that can reverse certain obesity-related pathologies. This study aimed to investigate whether IF can mitigate delayed bone fracture healing associated with obesity. Using cohorts of mice on high-fat or control diets, we applied either an ad libitum feeding or an alternate-day fasting regimen to animals from both diet groups. We assessed bone healing outcomes by evaluating callus mineralization and adipocyte accumulation within the callus through micro computed tomography (micro-CT), histology, and immunohistochemical analyses. Since IF is known to modulate gut microbiome composition, often associated with improvement in various metabolic and inflammatory processes, particularly in high-fat-fed mice, we also explored the microbial community changes in IF mice through 16S rRNA sequencing of cecal samples. Metabolically, IF led to reduced body weight and improved glucose tolerance in obese mice. Regarding fracture healing outcomes, reduced/delayed mineralization and adipocyte accumulation in fracture callus tissue in the high-fat-fed cohort were significantly attenuated when the high-fat-fed mice were subjected to alternate-day fasting. These benefits of IF were not observed in lean mice fed a control diet. Furthermore, IF significantly altered the gut microbiota of mice on a high-fat diet, including an increased abundance of short-chain fatty acid producing bacteria, known for their positive effect on bone density, and a reduction in various pro-inflammatory taxa. While the mechanistic role remains unknown, these findings suggest that the improved fracture healing observed in obese mice following IF may be associated with alterations in gut microbiome composition and function.}, } @article {pmid41466681, year = {2025}, author = {Gupta, PS and Padmakumar, VM and Usmani, OI}, title = {Cross-sectional analysis of gut microbiome diversity with progression of Alzheimer's disease.}, journal = {Bioinformation}, volume = {21}, number = {9}, pages = {3329-3332}, pmid = {41466681}, issn = {0973-2063}, abstract = {The relationship between gut microbiome diversity and stages of Alzheimer's disease (AD) progression is of interest. Hence, a total of 124 participants, including cognitively normal controls and patients with mild, moderate, and severe AD, were assessed for microbiome composition using 16S rRNA sequencing. Results revealed significantly reduced microbial diversity and altered bacterial profiles, notably lower levels of Bifidobacterium and Faecalibacterium and increased Proteobacteria, in advanced AD stages. Correlations were observed between cognitive declines and reduced alpha diversity. Thus, we show gut dysbiosis may play a contributory role in Alzheimer's pathology.}, } @article {pmid41466653, year = {2025}, author = {Arvindssinh, RN and Patel, TG and Karthik Raj, MRM}, title = {Cross-sectional study on ethnic variations in gut microbiome diversity and hypertension severity.}, journal = {Bioinformation}, volume = {21}, number = {9}, pages = {3043-3046}, pmid = {41466653}, issn = {0973-2063}, abstract = {Stool samples were analyzed using 16S rRNA sequencing and blood pressure measurements were categorized per AHA guidelines. Hence, 130 adults from three ethnic groups to assess differences in gut microbiome diversity and their association with hypertension severity were studied. Significant ethnic variations were observed in microbial composition, particularly in Firmicutes-to-Bacteroidetes ratios. Greater microbial diversity was associated with lower hypertension severity in certain ethnicities. Thus, we show ethnic-specific microbiome patterns may influence hypertension outcomes.}, } @article {pmid41466512, year = {2025}, author = {Merz, E and Hale, RJ and Saberski, E and Kenitz, KM and Carter, ML and Bowman, JS and Barton, AD}, title = {Temperature alters interactions and keystone taxa in the marine microbiome.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf287}, pmid = {41466512}, issn = {1751-7370}, abstract = {Marine microbes shape global biogeochemical cycles and marine food webs. Although biotic interactions underpin microbial community dynamics, most interactions between wild marine microbes are unknown. Here, we used empirical dynamic modeling to examine a six-year record of coastal microbial community composition to quantify microbial interactions and their changes through time. We found that, on average, marine microbes interact with 20% of other taxa in the community, most interactions are weak (80%), and that positive interactions are more common than negative interactions. Keystone taxa, defined as having disproportionally strong and frequent interactions, were not generally the most abundant taxa. The strength and sign of interactions, as well as the identity of the keystone taxa, varied through time and with changes in water temperature. An increase of 13°C, the dynamic range in water temperature at this location during the observational period, led to a 33% less interactive microbial community and an 11% shift towards more positive interactions. Only a few of the keystone taxa are the most interactive in the community at all times, and we found a temporal succession of keystone taxa. These results reveal that interactions in the marine microbiome are common, more facilitative than previously thought, and highly variable through time.}, } @article {pmid41466423, year = {2025}, author = {Chen, L and Tang, C and Hu, D and Yu, S and Liao, P}, title = {Brevilin a reverses colitis of inflammatory bowel disease via modulation of TNF-α signaling and microbiome dysregulation.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-025-00792-3}, pmid = {41466423}, issn = {1757-4749}, support = {2024000003-09//Middle-aged Backbone Talents in the Province/ ; }, abstract = {BACKGROUND: Brevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.

METHODS: Colitis was induced in C57BL/6 mice with dextran sulfate sodium (DSS), followed by treatment with or without Br(20 mg/kg). Fecal microbiota and metabolites were profiled by metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively. Furthermore, to delineate the essential role of the gut microbiota, we employed antibiotic-treated (microbiota-depleted) mice in our investigation of Br's mechanism of action.

RESULTS: Br significantly alleviated DSS-induced colitis and modulated the gut microbiota profile. Specifically, Br enriched beneficial bacteria such as Lactobacillus, while suppressing pathogenic bacteria including Escherichia coli and Clostridium perfringens. Metabolomic analysis revealed that Br significantly altered bacterial metabolites, including 7-Oxolithocholic Acid, Kudinoside A, Veratrine, and Soyasaponin. These metabolites were linked to key pathways such as GPCR signaling, DNA damage response, aminoacyl-tRNA biosynthesis, riboflavin metabolism, and central carbon metabolism in cancer. Transcriptomic profiling indicated that Br inhibited the TNF-α signaling pathway, and this inhibition was confirmed as TNF-α overexpression reversed its anti-inflammatory effects. Furthermore, the therapeutic effects of Br were partially recapitulated in microbiota-depleted mice through fecal microbiota transplantation from Br-treated donors.

CONCLUSION: Br's ability to regulate gut microbiota and metabolites, improve gut barrier function, and eliminate inflammation by inhibiting TNF-α highlights its potential as a novel therapeutic medicine for IBD. Future research should focus on further exploring its mechanisms and clinical applications.}, } @article {pmid41466331, year = {2025}, author = {Li, J and Zhang, X and Zhao, X and Gong, G and Li, J and Dalai, B and Mo, Z and Xu, X and Jia, X and Li, Y and Lai, J and Wang, P and Sun, L and Liu, Y and Luo, X}, title = {Characterising gut microbiome dysbiosis in diarrhoea calves from multiple farms in Inner Mongolia using 16S and metagenomics.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {259}, pmid = {41466331}, issn = {2049-2618}, support = {2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; }, mesh = {Animals ; Cattle ; *Gastrointestinal Microbiome/genetics ; *Diarrhea/microbiology/veterinary/epidemiology ; RNA, Ribosomal, 16S/genetics ; *Metagenomics/methods ; China/epidemiology ; *Dysbiosis/microbiology/veterinary ; *Cattle Diseases/microbiology/epidemiology ; Feces/microbiology ; Escherichia coli/genetics/isolation & purification/pathogenicity ; *Bacteria/classification/genetics/isolation & purification ; Farms ; }, abstract = {BACKGROUND: The pathogenesis of neonatal calf diarrhoea (NCD), a critical disease that contributes to neonatal mortality in calves, remains nebulous.

RESULTS: Inner Mongolia, a key region for cattle farming in China, was selected as a study area to provide a comprehensive overview of the epidemiology and treatment of calf diarrhoea. No significant correlation was found between the incidence of diarrhoea and sampling points or medications. The severity of diarrhoea cases was stratified into five levels based on faecal characteristics. To elucidate the pathogenesis of NCD, 16S rRNA gene and metagenomic sequencing analyses were performed across severity levels. Microbial diversity analyses revealed distinct variations in microbial communities at different severity levels. Employing binning and LEfSe methodologies, two potential bacterial pathogens were identified: Escherichia coli (bin.216), leveraging non-canonical virulence mechanisms; and Streptococcus ruminantium (bin.338), an uncharacterised diarrhoeagenic bacterium. Furthermore, the viral agent Escherichia phage VpaE1_ev108 was significantly associated with disease progression. Gene function enrichment analysis revealed a broad spectrum of antibiotic resistance genes even in farms without direct antibiotic treatment, underscoring the pervasive prevalence of drug resistance.

CONCLUSIONS: The findings of this study revealed significant gut microbial dysbiosis in calves with severe diarrhoea, through which two putative NCD-associated pathogens were identified: E. coli (bin.216) and S. ruminantium (bin.338). Marked enrichment of Bacteroides spp. and Methanobrevibacter_A sp. 900313645 was observed in healthy cohorts, suggesting their potential protective roles. Therapeutic strategies employing phage-mediated pathogen targeting combined with probiotic transplantation have demonstrated dual benefits, potentially reducing antimicrobial dependency and preserving microbial homeostasis through ecological network reconstruction. Video Abstract.}, } @article {pmid41466317, year = {2025}, author = {Subberwal, M and Giles, M and Neilson, R and Roberts, D and Caul, S and Mitchell, S and Ijaz, UZ}, title = {From farm to microbe: organic amendments and soil texture as drivers of soil Microbiome composition.}, journal = {Environmental microbiome}, volume = {20}, number = {1}, pages = {158}, pmid = {41466317}, issn = {2524-6372}, support = {BB/T010649/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Understanding how agricultural practices affect soil bacterial communities is vital to mitigating the negative impacts of intensive agriculture on soil health and preventing further deterioration of arable land. Increasing pressure on agricultural land necessitates careful management of our productive soil. This study investigates the interaction between organic amendments and soil texture in agricultural soils (n = 93) used for arable production, using a 16S rRNA-sequencing based microbial community analysis. Amendments include slurry, digestate, and farmyard manure. Additionally, soil physicochemical parameters were collected to explore the drivers of patterns of soil microbial diversity.

RESULTS: Microbial community composition was significantly influenced by organic amendments and soil texture, which both exerted distinct selective pressures. Analysis using 16S rRNA-sequencing and advanced modelling identified significant factors affecting community structure, including soil calcium levels, the crop grown one year previously, loss on ignition (LOI), and farm ID. The genus Candidatus Nitrosotalea was found to be positively associated with application of farmyard manure, while genus AD3 (phyla Chloroflexi) was found to be negatively associated with application of digestate and slurry.

CONCLUSIONS: The results highlight the importance of considering multiple, interacting factors when trying to establish how agricultural practice affects soil microbial communities. Our findings underscore the need for tailored management strategies - specific to the local environment and available resources - to promote soil health.}, } @article {pmid41466108, year = {2025}, author = {Sarafraz, F and Seo, H and Tajdozian, H and Atashi, A and Yoon, Y and Kim, S and Song, HY}, title = {Microbiome Therapeutic Lactiplantibacillus plantarum PMC105 for Systemic Carbapenem-Resistant Enterobacteriaceae Infections: Oral and Inhalation Efficacy In Vivo.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2508009}, doi = {10.4014/jmb.2508.08009}, pmid = {41466108}, issn = {1738-8872}, mesh = {Animals ; Mice ; Administration, Oral ; *Carbapenem-Resistant Enterobacteriaceae/drug effects ; Disease Models, Animal ; *Probiotics/administration & dosage/therapeutic use ; Klebsiella pneumoniae/drug effects ; *Enterobacteriaceae Infections/therapy/microbiology ; Anti-Bacterial Agents/pharmacology ; Gastrointestinal Microbiome ; Administration, Inhalation ; *Lactobacillus plantarum/physiology ; Female ; Dysbiosis ; Microbial Sensitivity Tests ; Klebsiella Infections/microbiology/therapy ; Humans ; Carbapenems/pharmacology ; }, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE), particularly Klebsiella pneumoniae, are major causes of severe systemic infections due to their resistance to most antibiotics and the high associated mortality, representing a growing global health concern. In this study, we report the in vivo efficacy of a novel probiotic strain, Lactiplantibacillus plantarum PMC105, against systemic CRE infections. In a mouse model characterized by neutropenia and antibiotic-induced gut dysbiosis, infection with carbapenem-resistant K. pneumoniae (CRKP) resulted in 60% mortality within two weeks. However, oral administration of PMC105 significantly reduced intestinal CRKP colonization, minimized body weight loss, and resulted in 100% survival. This therapeutic effect is presumed to result from enhanced gut barrier function, driven by upregulation of the tight junction protein ZO-1 in the ileum, thereby preventing bacterial translocation and subsequent systemic dissemination. In a therapeutic model of systemic infection following translocation, intranasal administration of PMC105 reduced bacterial loads in the stool, liver, kidneys, and lungs, improved clinical symptoms, and maintained body weight, thereby increasing survival rates. Comprehensive safety evaluations, including antibiotic susceptibility testing, hemolysis, bile salt deconjugation, D-lactate production, and cytotoxicity assays, confirmed the strain's safety. These findings support the potential of PMC105 as a dual-route microbiome-based therapeutic candidate for the treatment of systemic CRE infections and warrant further clinical investigation.}, } @article {pmid41466080, year = {2025}, author = {Thng, KX and Mac Aogáin, M and Chotirmall, SH}, title = {Fungal-Associated Endotypes as a Treatable Trait in Bronchiectasis.}, journal = {Pulmonary therapy}, volume = {}, number = {}, pages = {}, pmid = {41466080}, issn = {2364-1746}, support = {MOH-001636//National Medical Research Council/ ; MOH-001356//National Medical Research Council/ ; MOH-000955//National Medical Research Council/ ; AcRF Tier 1 Grant (RT1/22)//Ministry of Education - Singapore/ ; }, abstract = {Emerging evidence demonstrates the evolving role of fungi in the pathophysiology and disease progression observed in bronchiectasis. Fungal-associated traits are linked to disease severity, exacerbation frequency and airway inflammation. Structural abnormalities and impaired mucociliary clearance, characteristic of bronchiectasis, predispose to fungal colonisation, with subsequent immunopathogenic responses dependent on underlying host immunity. The diagnosis of fungal infection remains challenging in clinical settings, owing to the limitations of existing diagnostic modalities; however, the development of culture-independent molecular techniques shows promise. The use of next-generation sequencing has significantly advanced our understanding of the fungal microbiome in bronchiectasis, identifying fungi that are challenging to culture. Integrative microbiomics further elucidates the intricate and dynamic role of fungi in relation to other microbial kingdoms, and across distant organs such as the gut, revealing important relationships with bacterial pathogens including Pseudomonas aeruginosa. Airway inflammatory profiling has shown fungal-associated inflammatory endotypes which may serve as treatable traits. Environmental influences on fungi and bronchiectasis-exacerbated by air pollution and climate change-underscore the key role of the exposome in fungal-associated endotypes in bronchiectasis. This review outlines the clinical significance of fungi in bronchiectasis, the current diagnostic and treatment challenges, and emerging fungal-associated endotypes in the context of environmental influence on disease.}, } @article {pmid41466065, year = {2025}, author = {Ebrahim, NAA and Soliman, SMA and Farghaly, TA}, title = {Saliva-based molecular diagnostics in oral squamous cell carcinoma (OSCC): a non-invasive frontier in oncology.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {41466065}, issn = {1434-4726}, support = {25UQU4350477GSSR10//Umm Al-Qura University/ ; }, abstract = {PURPOSE: Saliva is increasingly recognized as a powerful, noninvasive biofluid for the diagnosis and monitoring of oral squamous cell carcinoma (OSCC), serving as a practical alternative to conventional liquid biopsy. Salivary circulatory DNA (ctDNA) detection in OSCC may exceed plasma levels. emphasizing saliva's susceptibility to local illness. Saliva collection is simple, non-invasive, and inexpensive, allowing for regular monitoring.

METHODS: Current evidence demonstrates its potential through a wide spectrum of salivary biomarkers.

RESULTS: Identified salivary biomarkers include viral nucleic acids such as human papillomavirus (HPV), host-derived molecules such as proteins and cytokines (IL-6, IL-8, VEGF), regulatory microRNAs (e.g., miR-21, miR-31, miR-184), and extracellular vesicles containing tumor-specific cargo. Moreover, oral microbiome dysbiosis has been linked to malignant transformation and progression, highlighting saliva's ability to reflect complex tumor-host interactions. Technological progress in multi-omics profiling and artificial intelligence (AI) has enhanced the interpretation of these multidimensional datasets, supporting the design of more robust and individualized biomarker panels. Concurrently, point-of-care technologies, particularly microfluidic chips and biosensor platforms, are driving the development of rapid and portable saliva-based diagnostics.  CONCLUSION: The path toward clinical implementation is constrained by several factors: the absence of FDA-approved salivary assays for OSCC, reliance on relatively small and retrospective studies, and the lack of standardized protocols for collection, processing, and analysis. Despite these challenges, salivary diagnostics are advancing as a highly promising adjunct to established modalities such as histopathology and radiologic imaging. They hold potential in early disease detection, patient stratification, therapeutic monitoring, and surveillance of recurrence. Integrative models, such as liquid TNM staging-which combine salivary and blood-based biomarkers-may ultimately redefine cancer diagnostics and follow-up. To date, no saliva-based assay has received FDA approval for oral cancer, highlighting regulatory and validation shortcomings. For translation into practice, further validation through large-scale trials, regulatory endorsement, and demonstration of cost-effectiveness remain essential. Nonetheless, saliva-based assays stand out as accessible, patient-centered tools with significant implications for the future of head and neck oncology.}, } @article {pmid41465981, year = {2025}, author = {He, Y and You, G and Qian, Y and Long, Y and Wang, B and Zhou, Y}, title = {Role of cathepsin in mediating the effect of oral flora on myocardial infarction: A multi-omics and mediation Mendelian randomization study.}, journal = {Medicine}, volume = {104}, number = {52}, pages = {e46859}, pmid = {41465981}, issn = {1536-5964}, support = {gzwkj 2021-102, gzwkj2021-111//Guizhou Provincial Health and Wellness Commission/ ; gzwkj2023-299//Guizhou Provincial Health and Wellness Commission/ ; No. 82260084//The National Natural Science Foundation of China/ ; No. 82460059//The National Natural Science Foundation of China/ ; No.82260061//The National Natural Science Foundation of China/ ; Qian Ke He Foundation ZK [2023] General 217, Qian Ke He Basic-ZK (2022) 262//Guizhou Provincial Science and Technology Agency Project/ ; Qian Ke He Foundation ZK [2022] General 268//Guizhou Provincial Science and Technology Agency Project/ ; Qian Ke He Basic-ZK (2021) 358//Guizhou Provincial Science and Technology Agency Project/ ; Gzwjrs2023-011//Guizhou High-level Innovative Talents Programme/ ; }, mesh = {Humans ; Mendelian Randomization Analysis ; *Myocardial Infarction/microbiology/genetics ; *Microbiota/physiology ; *Cathepsins/metabolism ; *Mouth/microbiology ; *Cathepsin H/genetics/metabolism ; Multiomics ; }, abstract = {The association between oral microbiome (OM) and myocardial infarction (MI) has become a noteworthy topic in recent years, yet the role played by cathepsin in this association remains unclear. The main objective of this study was to elucidate the role of cathepsin in mediating the effect of OM on MI. The mutual causality among OM, cathepsins, and MI was analyzed using two-sample Mendelian randomization (TSMR), and the mediating role of cathepsins between OM and MI was evaluated using mediation MR analysis. Furthermore, we conducted a meta-analysis to verify the causal relationship between Cathepsin H and MI. Subsequently, we employed summary-data-based MR (SMR) method to examine the potential causal genes and proteins for Cathepsin H and acute myocardial infarction. The meta analysis result indicated that each standard deviation increase in the exposure factor of Cathepsin H was associated with a reduction in the MI risk (OR = 0.9991; 95% CI = 0.9984-0.9998; P = .0089). Our study confirmed that 3 salivary flora, including Lancefieldella_unclassified_mgs_1257, Fusobacterium_unclassified_mgs_3185, Oribacterium_asaccharolyticum_mgs_3324, and one tongue dorsal flora, named Saccharimonadaceae_unclassified_mgs_1355, can regulate the development of MI via Cathepsin H. The results of the SMR analysis indicated a statistically significant negative correlation between the Cathepsin H (CTSH) gene and coronary artery disease (P-SMR < .05, P-HEIDI > .01). Conversely, a significant positive correlation was observed between the MST1 protein and MI risk (P-SMR < .05, P-HEIDI > .01). Reverse transcription polymerase chain reaction and ELISA tests on clinical samples showed a significant decrease in Cathepsin H levels - both protein and messenger ribonucleic acid - in the blood of MI patients (P < .05), while MST1 expression was notably increased (P < .05). We identified 3 salivary bacteria and one tongue dorsum bacterium that may influence MI development, with Cathepsin H playing a key mediating role. These findings strengthen the evidence linking OM to MI and clarify the role of cathepsins in this relationship. The study highlights how Cathepsin H may mediate the impact of oral flora on MI and proposes new therapeutic directions and targets for MI prevention and treatment.}, } @article {pmid41465974, year = {2025}, author = {Chen, C and Yang, Z and Guo, J and Liu, Y and Yang, X and Deng, W and Yu, H and Yang, S}, title = {Causal genetic link between gut microbiome, metabolites, and autism spectrum disorder in a European cohort.}, journal = {Medicine}, volume = {104}, number = {52}, pages = {e46526}, pmid = {41465974}, issn = {1536-5964}, mesh = {Humans ; *Autism Spectrum Disorder/genetics/microbiology/epidemiology/metabolism ; *Gastrointestinal Microbiome/genetics ; Genome-Wide Association Study ; Male ; Female ; Mendelian Randomization Analysis ; Europe/epidemiology ; Child ; Cohort Studies ; Child, Preschool ; }, abstract = {Recent studies have illuminated a significant relationship between the gut microbiota and the development and progression of autism spectrum disorder (ASD), mediated through the complex gut-brain axis, where metabolic pathways are crucial. Nevertheless, the exact causal link remains to be elucidated. This study aims to assess the potential causal relationship between the gut microbiota, metabolites, and ASD, utilizing Mendelian randomization methodology. The exposure variable of gut microbiota was ascertained using instrumental variables derived from a genome-wide association study that included a cohort of 18,340 individuals. The outcome variable comprised genome-wide association study data from 14,759 individuals diagnosed with ASD and 1,55,327 controls. The primary method of analysis was the inverse-variance weighted method. Multivariable multiple regression analysis was conducted to examine the impact of gut microbial metabolites on the established correlations. Inverse-variance weighted analyses revealed that Methanobacteria[c] (odds ratio [OR] = 1.17 [1.03-1.33]), Methanobacteriaceae[f] (OR = 1.17 [1.03-1.33]), Prevotellaceae[f] (OR = 1.29 [1.04-1.60]), Holdemania[g] (OR = 1.23 [1.03-1.45]), Lachnospiraceae[g] (OR = 1.29 [1.06-1.57]), Ruminiclostridium[g] (OR = 1.63 [1.27-2.10]), Terrisporobacter[g] (OR = 1.28 [1.00-1.63]), Methanobacteriales[o] (OR = 1.17 [1.03-1.33]), and Euryarchaeota[p] (OR = 1.16 [1.02-1.32]) serve as risk factors for ASD, while Eisenbergiella[g] (OR = 0.80 [0.68-0.94]) and Ruminococcaceae[g] (OR = 0.79 [0.63-1.00]) exhibit protective roles against ASD. Adjustments for neurotransmitter and amino acid metabolites effects diminished these associations. However, Prevotellaceae and Lachnospiraceae remained significantly associated with increased ASD risk. Reverse Mendelian randomization analyses did not establish a causal relationship between ASD and gut microbiota composition. Sensitivity tests showed no evidence of heterogeneity or pleiotropy. Alterations in metabolites induced by the gut microbiota may contribute to ASD susceptibility. Prevotellaceae and Lachnospiraceae are implicated as potential risk factors. Investigating these associations further could unveil novel therapeutic targets and provide deeper insights into ASD's etiological mechanisms.}, } @article {pmid41465904, year = {2025}, author = {Fan, Y and Chen, J and Zhuang, Y and Chang, L and Wang, W and Zhang, Y}, title = {Casual roles of gut microbiota, immune cells, and inflammatory cytokines in acute respiratory distress syndrome: A Mendelian randomization study.}, journal = {Medicine}, volume = {104}, number = {52}, pages = {e46736}, pmid = {41465904}, issn = {1536-5964}, support = {320.6750.2025-6-20//Wujieping Medical Foundation Clinical Research Special Fund/ ; }, mesh = {Humans ; Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/immunology ; *Respiratory Distress Syndrome/immunology/microbiology/genetics ; *Cytokines/immunology/blood ; Dysbiosis/immunology ; }, abstract = {Gut dysbiosis and aberrant immune activation are increasingly recognized as critical determinants of acute respiratory distress syndrome (ARDS). However, the causal contributions of specific gut taxa, immune-cell phenotypes, and their interactive pathways remain incompletely understood. In this study, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis to elucidate the individual and combined effects of the gut microbiome and immune milieu on ARDS susceptibility. Using 5 combined methodologies, the primary causal estimates were primarily derived through the Inverse-Variance Weighted approach. Heterogeneity was evaluated using Cochrane's Q test, while horizontal pleiotropy was assessed via the MR-Egger intercept, and robustness was confirmed through leave-one-out and reverse MR analyses. Following adjustments for the false discovery rate (FDR), our findings indicated that, although the overall effects of exposures on ARDS were not statistically significant (PFDR < 0.2), there were causal associations identified for 12 gut microbiota taxa, 24 immune cells, and 6 circulating inflammatory cytokines with ARDS (P < .05). Initial mediation analyses indicated that EIF4EBP1, caspase-8, IL-6, and IL-8 might partly mediate these effects, but 1000 BCa bootstrap iterations rejected all indirect pathways. These findings underscore the pivotal roles of gut microbiota and immune factors, both individually and interactively, in the pathogenesis of ARDS, offering a genetically informed basis for future treatments targeting the microbiome and immune system.}, } @article {pmid41465881, year = {2025}, author = {Kukaev, E and Krogh-Jensen, O and Starodubtseva, N and Tokareva, A and Nikitina, I and Lenyushkina, A and Frankevich, V and Sukhikh, G}, title = {Longitudinal Fecal Short-Chain Fatty Acid Trajectories in Preterm Infants with Early-Onset Neonatal Sepsis: A Pilot Study.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {41465881}, issn = {2075-1729}, support = {24-25-00068//Russian Science Foundation/ ; }, abstract = {BACKGROUND: Early-onset neonatal sepsis (EONS), defined as systemic infection occurring within the first 72 hours of life, remains a major cause of morbidity and mortality in preterm infants. Increasing evidence indicates that the gut may play an active role in systemic inflammation, yet the temporal behavior of fecal short-chain fatty acids (SCFAs) during EONS has not been characterized. SCFAs and branched-chain fatty acids (BCFAs) are key microbial metabolites involved in epithelial maturation and immune regulation and may provide a non-invasive window into early inflammatory vulnerability.

METHODS: This pilot prospective longitudinal cohort study enrolled 49 preterm infants (≤32 weeks' gestation) originally identified as at high risk for necrotizing enterocolitis (NEC) and subsequently stratified into EONS and non-sepsis groups. Serial stool samples were collected at predefined timepoints (TPs; TP1 ≈ 3 days of life [DoL], TP2 ≈ 7 DoL, TP3 ≈ 14 DoL, TP4 ≈ 21 DoL, and TP5 ≈ 28 DoL). Samples were analyzed using gas chromatography-mass spectrometry (GC-MS) to quantify a panel of 12 SCFAs, including BCFAs and medium-chain fatty acids (MCFAs). Both absolute concentrations and relative fractions were evaluated, with emphasis on ratio-based metrics (e.g., acetic/propionic acid ratio) and timepoint-specific group contrasts, complemented by partial least squares discriminant analysis (PLS-DA).

RESULTS: At the earliest sampling window (TP1), infants with EONS exhibited distinct early changes in SCFA composition, including a significantly lower median relative fraction of acetic acid (86.6% vs. 94.5% in non-sepsis), while several non-acetate components-including propionic, valeric, and branched-chain acids-were relatively enriched. Acetate-to-non-acetate ratios were markedly reduced in EONS (e.g., acetic/propionic and acetic/isobutyric ratios), indicating an early shift away from acetate dominance. PLS-DA at TP1 demonstrated partial separation between groups, with acetic-acid depletion and non-acetate enrichment among the strongest contributors to discrimination. By later TPs, these early differences narrowed to a small subset of BCFA-related ratios and largely attenuated by the end of the first month.

CONCLUSIONS: In this pilot cohort of preterm infants, EONS was associated with early, structured alterations in fecal SCFA profiles, characterized by reduced acetic-acid dominance and relative enrichment of non-acetate acids. Dynamic, ratio-based assessment proved more informative than absolute concentrations alone, revealing transient intestinal metabolic signatures accompanying systemic infection. These findings provide the first longitudinal evidence of gut metabolic involvement in EONS and lay the groundwork for larger, multi-center studies integrating SCFA trajectories with microbiome and immune profiling to refine early risk stratification for systemic infection in high-risk neonatal populations.}, } @article {pmid41465859, year = {2025}, author = {Angelova, B and Boteva, S and Traykov, I and Tsvetkov, M and Kenarova, A}, title = {Bacterial Community Composition and Structure in the Littoral of Rila Mountains Glacial Lakes.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {41465859}, issn = {2075-1729}, support = {KP-06-M71/2//The Bulgarian National Science Fund/ ; }, abstract = {High-mountain lakes are biodiversity hotspots sensitive to increasing regional and global climate warming. However, their microbial communities remain insufficiently characterized due to their remoteness and limited accessibility. This study aimed to determine how seasonal environmental parameters shape the composition, structure and diversity of littoral bacterial communities in three glacial lakes in Rila Mountains (Bulgaria). Water samples were collected during ice-free periods in 2023 and 2024, and bacterial taxonomic composition was analysed by Next-generation sequencing. A total of 1158 bacterial OTUs were identified encompassing 18 phyla and 165 families. Actinomycetota, Pseudomonadota, and Bacteroidota were dominant at the phylum level, and Sporichthyaceae, Comamonadaceae, Chitinophagaceae and Mycobacteriaceae were most abundant among the families. Community richness and diversity peaked in June, immediately after ice melting, particularly in the highest-altitude lake (Sulzata Lake), and declined during the warm season (August), when the relative abundances of Sporichthyaceae and Mycobacteriaceae (Actinomycetota) increased. Seasonal restructuring occurred across phyla and families even in a single taxon, with water temperature and organic carbon availability identified as the main environmental drivers. The findings have improved our understanding of temperature-driven bacterial responses. They have also highlighted the vulnerability of cold-adapted taxa to regional climate warming which may contribute to more effective biodiversity conservation strategies for these unique ecosystems.}, } @article {pmid41465800, year = {2025}, author = {Messina, BM and Polizzi, A and Panuzzo, C and Belmonte, A and Angjelova, A and Fuochi, V and Annunziata, M and Isola, G}, title = {Impact of Periodontal Host-Modulation Therapies on Oral-Gut Microbiome Axis in Periodontitis Patients with Hematological Diseases: A Narrative Review.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {41465800}, issn = {2075-1729}, abstract = {Host-modulating therapies and oral microbiome-targeted approaches are emerging options in periodontal care and are especially relevant for patients undergoing immunotherapy for hematologic malignancies. Immune dysregulation induced by immune checkpoint inhibitors or CAR-T cell therapy may worsen periodontal inflammation and alter the composition and functions of the oral microbiota. Beyond these, other immunomodulatory treatments commonly employed in hematologic malignancies-including monoclonal antibodies (e.g., rituximab, daratumumab), immunomodulatory drugs (e.g., lenalidomide, thalidomide), cytokine-based therapies (e.g., interferon-α), and targeted small-molecule inhibitors (e.g., BTK inhibitors, JAK inhibitors) may also influence periodontal homeostasis and oral microbial ecology by altering neutrophil function, cytokine profiles, and mucosal immune surveillance. The oral microbiota is functionally connected with the intestinal microbial ecosystem through the oral-gut axis, by periodontal pathogens may colonize the gut and modulate systemic immune responses, with potential repercussions on the efficacy and safety of immunotherapy. This narrative review examines the mechanisms and clinical applicability of host-modulating therapies, including subantimicrobial-dose doxycycline, omega-3 fatty acids, and microbiome-targeted interventions, such as oral probiotics, prebiotics and other antimicrobials in patients treated with immunotherapy.}, } @article {pmid41465793, year = {2025}, author = {Popova, N and Safonov, A}, title = {Diversity of Groundwater Microbial Communities near Sludge Repositories with Different Types and Levels of Pollution.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {41465793}, issn = {2075-1729}, support = {no//The Ministry of Science and Higher Education of the Russian Federation/ ; }, abstract = {Multicomponent pollution of groundwater with nitrates and sulfates is a common issue associated with mining and ore-processing operations. This work presents the first large-scale comparative study of groundwater microbial communities from six geographically distant sites in the Russian Federation with varying levels of nitrate and sulfate pollution. Based on high-throughput 16S rRNA sequencing data and hydrochemical analysis, a statistically significant influence of the pollution type on the structural and functional diversity of the microbiome was established. Nitrates act as a stimulating factor, increasing alpha-diversity, while sulfates have an inhibitory effect. Principal component and correlation analysis revealed spatial grouping of samples according to the predominant pollution type. Microbiome representatives common to all sites under unpolluted conditions were identified: Bacteroides, Iamia, and Paenibacillus; and under high pollution levels: Acidovorax, Pseudomonas, Sphingomonas, Acinetobacter, and Limnohabitans. Based on the obtained data, it is concluded that representatives of these genera are the most promising and universal for isolation and use in bioremediation.}, } @article {pmid41465751, year = {2025}, author = {Zhang, X and Li, Y and Zhang, F and Zhou, G}, title = {Exercise and Diet Reshape Athletes' Gut Microbiota: Countering Health Challenges in Athletes.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {41465751}, issn = {2075-1729}, support = {82304144//National Natural Science Foundation of China/ ; 32372334//National Natural Science Foundation of China/ ; }, abstract = {With the advancement of modern competitive sports, specialized training regimens and tailored dietary patterns collectively shape a distinctive gut microbiota in athletes. This unique ecosystem exhibits high microbial diversity and is enriched with beneficial bacteria-such as short-chain fatty acid-producing strains-that contribute to enhanced athletic performance, support energy homeostasis and neural coordination, and mitigate exercise-induced injuries, thereby improving competitive outcomes. This review elaborates on the characteristics of the athlete gut microbiome across different exercise modalities, examines how microbial changes may benefit or pose risks to athlete health, and provides a unique perspective for developing microbiota-driven personalized nutrition strategies aimed at optimizing athletic performance.}, } @article {pmid41465727, year = {2025}, author = {Maresca, E and Carbone, M and Gallo, G and Fusco, S and Aulitto, M}, title = {Extremophile-Derived Bioactives in Cosmeceuticals: Bridging Nutraceuticals and Skincare for Holistic Wellness.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {41465727}, issn = {2075-1729}, abstract = {The integration of extremophile-derived bioactives into cosmeceuticals and nutricosmetics offers a novel strategy to enhance skin health through both topical and systemic approaches. Extremophile microorganisms, adapted to extreme conditions, produce unique compounds such as ectoine, extremozymes, carotenoids, exopolysaccharides (EPSs), and mycosporine-like amino acids (MAAs). These molecules exhibit antioxidant, anti-inflammatory, photoprotective, and regenerative properties. This review analyzes the molecular adaptations that enable extremophiles to synthesize these compounds, and explores their cosmetic applications, including enzymatic exfoliation, UV protection, hydration, and anti-pollution effects. This paper examines their nutraceutical potential, highlighting systemic benefits such as improved skin elasticity, reduced photoaging, and modulation of the gut-skin axis via prebiotic EPSs. Industrial strategies for sustainable production, such as microbial fermentation, synthetic biology, and green extraction, are discussed. Examples of commercial ingredients like PlusXanthin™, Antarctic-G, and Desertica. Extremophile-derived ingredients combine biological efficacy with environmental sustainability, positioning them as key assets for next-generation skincare. Future directions include clinical validation, regulatory harmonization, and the development of personalized, microbiome-friendly formulations.}, } @article {pmid41465696, year = {2025}, author = {Jin, JX and Wang, Y and Zhang, GF and Ye, ZC and Liu, B and Yao, DD and Jiang, ZC and He, YF}, title = {Diversity and Functional Analysis of Gut Microbiota in the Adult of Lissorhoptrus oryzophilus (Coleoptera: Curculionidae) by Metagenome Sequencing.}, journal = {Insects}, volume = {16}, number = {12}, pages = {}, pmid = {41465696}, issn = {2075-4450}, abstract = {The gut microbiota of insects plays a fundamental role in modulating host physiology, including nutrition, development, and adaptability to environmental challenges. The rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a major invasive pest of rice worldwide, yet the composition and functional profile of its gut microbial community remain poorly characterized. Here, we employed metagenome sequencing on the Illumina NovaSeq X Plus platform to explore the gut microbial diversity and predicted functions in adults of L. oryzophilus. Our results revealed a rich microbial community, comprising 26 phyla, 42 classes, 72 orders, 111 families, and 191 genera. The bacterial microbiota was overwhelmingly dominated by the phylum Proteobacteria (85.13% of total abundance). At the genus level, Pantoea (48.86%) was the most predominant taxon, followed by Wolbachia (14.57%) and Rickettsia (11.81%). KEGG analysis suggested that the gut microbiota is primarily associated with metabolic pathways such as membrane transport, carbohydrate and amino acid metabolism, cofactor and vitamin metabolism, energy metabolism, and signal transduction. eggNOG annotation further highlighted significant gene representation in amino acid and carbohydrate transport and metabolism, while CAZy annotation revealed glycosyl transferases (GTs) and glycoside hydrolases (GHs) as the dominant carbohydrate-active enzymes. This study provides the first comprehensive insight into the gut microbiome of L. oryzophilus adults, highlighting its potential role in the ecological success of this invasive pest. Our findings lay groundwork for future research aimed at developing novel microbial-based strategies for the sustainable management of L. oryzophilus.}, } @article {pmid41465624, year = {2025}, author = {Remmal, I and El Yamlahi, Y and Bel Mokhtar, N and Galiatsatos, I and Loukovitis, D and Dionyssopoulou, E and Britel, MR and Stathopoulou, P and Maurady, A and Tsiamis, G}, title = {Analysis of the Bacterial Microbiota in Wild Populations of Prickly Pear Cochineal, Dactylopius opuntiae in Morocco.}, journal = {Insects}, volume = {16}, number = {12}, pages = {}, pmid = {41465624}, issn = {2075-4450}, support = {FAO/IAEA Contract 22662//FAO/IAEA/ ; }, abstract = {Dactylopius opuntiae (Cockerell) (Hemiptera: Dactylopiidae), the wild cochineal scale, is a major pest of prickly pear crops worldwide. This study characterized the bacterial community structure of D. opuntiae from four Moroccan regions using targeted PCR and full-length 16S rRNA MinION sequencing. We report the first detection of Wolbachia (16.6% prevalence) in D. opuntiae, with infection rates varying geographically from 0% (Rabat) to 53.3% (Ouazzane). Spiroplasma was detected at a lower prevalence (3.3%) and exclusively in males. Phylogenetic analysis showed that Wolbachia sequences likely belong to supergroup B, based on their similarity to reference sequences, while Spiroplasma sequences were placed within the poulsonii-citri complex. MinION sequencing revealed Candidatus Dactylopiibacterium as the dominant taxon (97.7%), consistent with its role as an obligate symbiont. After removing this dominant species, we uncovered a diverse bacterial community, including Flavisolibacter, Pseudomonas, Phyllobacterium, Acinetobacter, and Brevibacillus. Beta diversity analysis showed significant geographic variation (PERMANOVA p < 0.008), with distinct communities across regions. Females harbored a more specialized microbiome dominated by Flavisolibacter (except in Agadir), whereas males and nymphs showed Pseudomonas dominance. Core microbiome analysis revealed no universal genera across all groups, with females displaying a more restricted core than males and nymphs. The detection of reproductive symbionts, combined with geographic and sex-specific microbiome patterns, provides valuable insights into the potential roles of these bacteria in host adaptation and their implications for microbiome-based pest management strategies. The complementary use of targeted and untargeted sequencing methods is essential for comprehensive microbiome characterization in this economically important pest.}, } @article {pmid41465599, year = {2025}, author = {Borowik, A and Wyszkowska, J and Zaborowska, M and Kucharski, J}, title = {The Importance of Humic Acids in Shaping the Resistance of Soil Microorganisms and the Tolerance of Zea mays to Excess Cadmium in Soil.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465599}, issn = {1422-0067}, support = {30.610.006-110//University of Warmia and Mazury in Olsztyn, Faculty of Agriculture and Forestry, Department of Soil Science and Microbiology/ ; "the Regional Initiative of Excellence Program"//Minister of Science/ ; }, mesh = {*Zea mays/drug effects/growth & development/microbiology ; *Cadmium/toxicity ; *Soil Microbiology ; *Humic Substances/analysis ; *Soil Pollutants/toxicity ; *Bacteria/drug effects/genetics/classification ; RNA, Ribosomal, 16S/genetics ; Soil/chemistry ; Microbiota/drug effects ; }, abstract = {Contamination with cadmium (Cd[2+]) poses a severe threat to the soil environment due to its toxic effect on bacteria, being of key importance to soil fertility and plant health. The present study aimed to evaluate the effect of a humic preparation, Humus Active (HA), on the structure, diversity, and functional potential of soil bacteria under conditions of cadmium stress during Zea mays cultivation. A model study was conducted to analyze the response of bacteria to soil contamination with 60 mg Cd kg[-1] under conditions of soil fertilization with humic acid at doses of 2 g (HA2) and 4 g (HA4) kg[-1] of soil. Microbiological analyses were carried out with both culture and non-culture (16S rRNA gene amplicon sequencing method) methods. Bacteria function prediction was also performed using FAPROTAX software. The study results demonstrated that Cd caused a 92% reduction in Zea mays biomass and a significant decrease (by 52%) in the abundance of organotrophic bacteria. The NGS analysis showed that it also reduced the population of the Neobacillus bacteria in the soil (by 50%), simultaneously causing an over twofold increase in the population of the Nocardioides genus bacteria. The application of HA (particularly in the HA4 dose) substantially mitigated Cd phytotoxicity. In the Cd-contaminated soil, HA4 stimulated the growth of culturable actinobacteria. The soil bacteria community was predominated by chemoheterotrophic bacteria and the nitrogen cycle bacteria, driven by tolerant, Cd[2+]-resistant bacteria from the following genera: Bacillus, Nocardioides, and Arthrobacter. The study results enable concluding that even though Humus Active does not restore the original microbiome structure, it promotes the development of a new stress-resistant bacterial community exhibiting high bioremediating potential, thereby directly translating into improved plant condition. Subsequently, humic acids provide an innovative approach that not only extends knowledge about the mechanisms behind bacterial resistance but also enables developing practical methods for diminishing cadmium mobility in the soil.}, } @article {pmid41465559, year = {2025}, author = {Shen, CL and Liu, X and Cao, JJ and Neugebauer, V and Miranda, JM and Elmassry, MM and Dunn, DM and Dufour, JM}, title = {Dietary Geranylgeraniol Mitigates Pain-Associated Behaviors via Improving Mitochondrial Function and Colon Integrity and Suppressing Neuroinflammation in Male Diabetic Neuropathy Rats.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465559}, issn = {1422-0067}, support = {B1-0028, JMD//Robert A. Welch Foundation/ ; #3062-10700-002-000D//USDA-ARS/ ; R01NS038261 (VN)/GF/NIH HHS/United States ; }, mesh = {Animals ; Male ; Rats ; *Mitochondria/drug effects/metabolism ; *Colon/drug effects/metabolism/pathology ; Gastrointestinal Microbiome/drug effects ; Rats, Sprague-Dawley ; *Diabetic Neuropathies/drug therapy/metabolism ; Diabetes Mellitus, Experimental/complications ; *Diterpenes/pharmacology ; *Neuroinflammatory Diseases/drug therapy ; Behavior, Animal/drug effects ; *Pain/drug therapy ; }, abstract = {Growing evidence highlights the links between diabetic neuropathy (DNP), gut dysbiosis, mitochondrial dysfunction and neuroinflammation in colon and bone microstructure deterioration. Geranylgeraniol (GG) shows neuroprotective and osteoprotective capacity. Our study examines GG's effects on pain-associated behaviors, glucose homeostasis, gut microbiota, mitochondrial homeostasis, and bone microstructure in DNP rats. We randomly assigned 27 male Sprague Dawley rats to three groups (n = 8-10/group): a control group (regular low-fat diet), a DNP group (high-fat diet + a single dose of 35 mg/kg streptozotocin), and a GG-treated DNP group (a single dose of 35 mg/kg streptozotocin + GG at 800 mg/kg in diet) for 6 weeks. Nocifensive response was assessed via the von Frey test and an open field test, and the elevated plus maze was used to assess anxio-depressive behaviors. The mRNA expression levels of tight junction protein, mitochondrial homeostasis, and neuroinflammation were measured in the colon using qRT-PCR. We collected fecal samples for microbiota composition analysis with 16S rRNA gene sequencing and analyzed by QIIME 2. All other data were analyzed via one-way ANOVA followed by post hoc Tukey's multiple comparison. p < 0.05 was defined as statistical significance. Our study showed GG's ability to mitigate mechanical hypersensitivity and anxio-depressive behavior in rats with DNP. GG supplementation did not improve glucose homeostasis (i.e., glucose intolerance, insulin sensitivity, pancreatic β-cell dysfunction) and bone microstructure. GG increased alpha-diversity without changing microbial abundance. DNP rats exhibited elevated Clostridium sensu stricto and reduced Eubacterium coprostanoligenes, Lachnospiraceae, Oscillospiraceae, and Peptococcaceae compared with controls. GG did not reverse DNP-induced gut dysbiosis but increased colonic claudin-3 (tight junction), MFN1 (mitochondria fusion), and TFAM (mitochondria biogenesis), while reducing FIS1 (mitochondria fission), GFAP (glial activation), P62 and PINK1 (mitophagy), and TNFα (inflammation). Functionally, GG reduced pain behaviors, improved intestinal integrity and mitochondrial homeostasis, increased alpha-diversity, and suppressed neuroinflammation, but did not improve glucose homeostasis or bone microstructure in obese DNP rats.}, } @article {pmid41465485, year = {2025}, author = {Du, L and Cheng, X and Liu, B and Hao, Y and Long, Z and Hu, Q and Huo, B and Xie, T and Cheng, Q and Zhou, Y and Chen, J}, title = {A New Perspective on Nasal Microbiota Dysbiosis-Mediated Allergic Rhinitis: From the Mechanism of Immune Microenvironment Remodeling to Microbiota-Targeted Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465485}, issn = {1422-0067}, support = {2023YFC2507900//National Key Research/ ; 2022YFC2504100//National Key Research/ ; 82371124//National Nature Science Foundation of China/ ; }, mesh = {Humans ; *Dysbiosis/microbiology/immunology/therapy ; *Rhinitis, Allergic/microbiology/immunology/therapy ; *Microbiota/immunology ; Probiotics/therapeutic use ; Nasal Mucosa/microbiology/immunology ; Animals ; }, abstract = {Allergic rhinitis (AR) is a common heterogeneous chronic disease characterized by high prevalence, complex pathogenesis, and susceptibility to multiple contributing factors. Currently, its prevalence ranges from 20% to 30% in adults and reaches up to 40% in children. Extensive research has confirmed significant differences in nasal microbiota composition between AR patients and healthy individuals, most notably alterations in the abundance of four dominant phyla: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Among these, the most striking abundance alterations occur in Staphylococcus aureus and Streptococcus salivarius within the nasal mucosa of AR patients, suggesting a critical role of nasal microbiota in AR initiation and progression. In response, researchers have proposed microbiome-targeted therapeutic strategies. For example, nasal local administration of probiotics (e.g., Lactobacillus and Bifidobacterium) aims to reshape the nasal microbiota. Additionally, protective bacteria such as Corynebacterium accolens and Dolosigranulum pigrum can inhibit pathogenic bacteria, thereby correcting microbial dysbiosis and alleviating AR symptoms. This review summarizes the composition of the nasal microbiota, the latest research progress on its association with AR, and the underlying potential mechanisms. It provides novel insights and potential therapeutic strategies for the prevention and treatment of AR.}, } @article {pmid41465484, year = {2025}, author = {Kim, HB and Kim, G and Park, E and Kim, H and Yu, BS and Lee, DG and Park, CH and Jo, H and Park, H}, title = {Functional Expansion of the Skin Microbiome: A Pantothenate-Producing Rothia Strain Confers Anti-Inflammatory and Photoaging-Protective Effects.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465484}, issn = {1422-0067}, mesh = {Humans ; *Pantothenic Acid/metabolism/pharmacology/biosynthesis ; *Skin/microbiology/radiation effects/metabolism ; *Skin Aging/drug effects/radiation effects ; *Microbiota ; *Anti-Inflammatory Agents/pharmacology/metabolism ; Keratinocytes/metabolism/drug effects ; *Micrococcaceae/metabolism/genetics ; Fibroblasts/metabolism/drug effects ; Ultraviolet Rays/adverse effects ; Skin Microbiome ; }, abstract = {The functional landscape of the skin microbiome is largely defined by dominant genera such as Cutibacterium and Staphylococcus, whereas rare commensals remain poorly understood. In this study, we identified Rothia kristinae BF00107, a skin-resident strain with a complete pantothenate biosynthesis pathway, as a novel postbiotic candidate with distinct dermatological benefits. BF00107 fermentation filtrate suppressed pro-inflammatory cytokines (IL-1β and TNF-α) in keratinocytes and restored extracellular matrix homeostasis in UVB-irradiated fibroblasts by upregulating COL1A1 expression and reducing MMP-1 levels. Consistent with the observed phenotypes, transcriptomic profiling revealed a strain-specific signature characterized by downregulation and upregulation of the expression of inflammatory mediators and barrier- and ECM-associated genes, respectively. Comparative genomics and metabolite profiling confirmed BF00107 as a unique high-pantothenate producer. Supplementation with pantothenic acid reproduced the anti-inflammatory and barrier-supporting effects of the strain, confirming its role as a key effector metabolite. Furthermore, BF00107 passed standard safety assessments, including the Human Repeat Insult Patch Test (HRIPT), Ames, and irritation tests, supporting its suitability for human applications. These findings establish the pantothenate-producing R. kristinae BF00107 as the first functionally validated Rothia strain with anti-inflammatory and photoaging-protective properties. This study expands the functional scope of the skin microbiome and highlights rare commensals as valuable reservoirs for safe, strain-specific postbiotic development.}, } @article {pmid41465447, year = {2025}, author = {Duda-Madej, A and Viscardi, S and Łabaz, JP and Topola, E and Szewczyk, W and Gagat, P}, title = {Berberine in Bowel Health: Anti-Inflammatory and Gut Microbiota Modulatory Effects.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465447}, issn = {1422-0067}, mesh = {*Berberine/pharmacology/therapeutic use ; Humans ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Inflammatory Bowel Diseases/drug therapy/microbiology ; }, abstract = {Disruption of the gut-microbiome-brain axis contributes to the development of chronic inflammation, impaired intestinal barrier integrity, and progressive tissue damage, ultimately reducing quality of life and increasing risk of comorbidities, including neurodegenerative diseases. Current therapies are often limited by adverse effects and insufficient long-term efficacy, highlighting the need for more comprehensive therapeutic approaches. Berberine (BRB), a plant-derived isoquinoline alkaloid, has attracted growing attention due to its pleiotropic immunomodulatory, neuroprotective, and gut-homeostasis-modulating properties, which involve reshaping the gut microbiota and underscore its therapeutic relevance within the gut-microbiome-brain axis. The aim of this review is to synthesize current scientific evidence regarding the anti-inflammatory mechanisms of BRB in inflammatory bowel disease (IBD). We compare its activity with first-line therapies and discuss its impact on microbial composition, including the bidirectional regulation of specific bacterial taxa relevant to intestinal and systemic disorders that originate in the gut. Furthermore, we emphasize that gut bacteria convert BRB into bioactive metabolites, contributing to its enhanced intraluminal activity despite its low systemic bioavailability. By integrating molecular and microbiological evidence, this review fills a critical knowledge gap regarding the comprehensive therapeutic potential of BRB as a promising candidate for future IBD interventions. The novelty of this work lies in unifying fragmented findings into a framework that explains how BRB acts simultaneously at the levels of host immunity, microbial ecology, and neuroimmune communication-thus offering a new conceptual model for its role within the gut-microbiome-brain axis.}, } @article {pmid41465322, year = {2025}, author = {Rzeczycki, P and Pęciak, O and Plust, M and Droździk, M}, title = {Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465322}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Intestinal Mucosa/metabolism ; Multidrug Resistance-Associated Protein 2 ; *Membrane Transport Proteins/metabolism ; }, abstract = {Gut microbiota, through both its species composition and its metabolites, impacts expression and activity of intestinal drug transporters. This phenomenon directly affects absorption process of orally administered drugs and contributes to the observed inter-individual variability in pharmacotherapeutic responses. This review summarizes mechanistic evidence from in vitro and animal studies and integrates clinical observations in which alterations in gut microbiota are associated with changes in oral drug exposure, consistent with potential regulation of key intestinal drug transporters-such as P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2), MRP2/3 proteins (ABCC2/3), and selected Organic Anion-Transporting Polypeptides (OATPs, e.g., SLCO1A2, SLCO2B1)-by major bacterial metabolites including short-chain fatty acids (SCFAs), secondary bile acids, and tryptophan-derived indoles. The molecular mechanisms involved include activation of nuclear and membrane receptors (PXR, FXR, AhR, TGR5), modulation of transcriptional and stress-response pathways (Nrf2, AP-1) with simultaneous suppression of pro-inflammatory pathways (NF-κB), and post-translational modifications (e.g., direct inhibition of P-gp ATPase activity by Eggerthella lenta metabolites). The review also highlights the pharmacokinetic implications of, e.g., tacrolimus, digoxin, and metformin. In conclusion, the significance of "drug-transporter-microbiome" interactions for personalized medicine is discussed. Potential therapeutic interventions are also covered (diet, pre-/probiotics, fecal microbiota transplantation, modulation of PXR/FXR/AhR pathways). Considering the microbiota as a "second genome" enables more accurate prediction of drug exposure, reduction in toxicity, and optimization of dosing for orally administered preparations.}, } @article {pmid41465299, year = {2025}, author = {Paduraru, DN and Palcau, AC and Dinca, VG and Ciuc, DM and Constantinescu, A}, title = {The Role of Gut Microbiota in Colorectal Cancer Pathogenesis: A Comprehensive Literature Review.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465299}, issn = {1422-0067}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/pathology/etiology ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology/complications ; Animals ; Carcinogenesis ; }, abstract = {Colorectal cancer (CRC) represents a significant global health burden, ranking as the third most frequently diagnosed malignancy worldwide. Emerging evidence has established a compelling association between gut microbiota dysbiosis and CRC pathogenesis, revealing complex mechanisms through which specific bacterial communities modulate carcinogenesis. This comprehensive review synthesizes current knowledge on the mechanistic contributions of gut microbiota to CRC development, with particular emphasis on key pathogenic bacteria including Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli. We examine the molecular pathways through which these microorganisms promote tumorigenesis, including chronic inflammation induction, immune response modulation, metabolic reprogramming, and direct genotoxic effects. Furthermore, we discuss the therapeutic implications of microbiota-targeted interventions and the potential utility of microbial biomarkers for early CRC detection. Understanding the intricate host-microbiota interactions in CRC pathogenesis may facilitate the development of novel preventive strategies and therapeutic approaches for this devastating disease.}, } @article {pmid41465291, year = {2025}, author = {Chaudhuri, RK and Meyer, TA}, title = {Isosorbide Diesters: Mechanistic Insights and Therapeutic Applications in Skin and Neuroinflammatory Disorders.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465291}, issn = {1422-0067}, support = {None//Hallstar Beauty (United States)/ ; }, mesh = {Humans ; *Isosorbide/therapeutic use/pharmacology/chemistry/analogs & derivatives ; Animals ; *Neuroinflammatory Diseases/drug therapy ; *Esters/therapeutic use/chemistry ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Skin/drug effects ; *Skin Diseases/drug therapy ; }, abstract = {Isosorbide fatty acid diesters constitute a novel class of bioactive compounds with emerging therapeutic applications in inflammatory and barrier-compromised disorders. Among them, isosorbide dicaprylate (IDC) and isosorbide di-linoleate/oleate (IDL) synergistically strengthen epidermal barrier integrity, enhance stratum corneum hydration, regulate keratinocyte differentiation, suppress proinflammatory signaling, and beneficially modulate the skin microbiome. Randomized, double-blind clinical trials in both pediatric and adult populations with atopic dermatitis (AD) demonstrate that topical IDC + IDL formulations significantly reduce pruritus, corticosteroid dependence, and Staphylococcus aureus colonization while improving sleep quality, disease severity scores, and overall quality of life. Extending applications within and even beyond dermatology, isosorbide dimethyl fumarate (IDMF)-a next-generation fumarate derivative designed to mitigate sensitization risk-exhibits potent anti-inflammatory and antioxidant activities through NRF2 activation and NF-κB/IRF1 suppression. Preclinical studies in psoriasis and neuroinflammatory models, including multiple sclerosis, reveal robust modulation of oxidative stress and immune pathways with improved safety and mechanistic precision compared to conventional fumarates, although its systemic use remains exploratory and requires clinical validation. Collectively, isosorbide diesters emerge as multifunctional therapeutic agents offering barrier repair, immune modulation, and inflammation control, representing promising alternatives to corticosteroids and systemic immunosuppressants across dermatologic and systemic inflammatory disorders.}, } @article {pmid41465268, year = {2025}, author = {Goriuc, A and Luchian, I}, title = {Special Issue "Dental Health and Disease: From the Molecular and Pathological Perspectives".}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465268}, issn = {1422-0067}, mesh = {Humans ; *Oral Health ; Microbiota ; }, abstract = {Oral health extends beyond aesthetics; it represents an integral component of overall health, sustained through a delicate balance among host defense mechanisms, the oral microbiome, and environmental influences [...].}, } @article {pmid41462374, year = {2025}, author = {Zou, Q and Fu, B and Gou, Y and Zhong, G and Liu, Y}, title = {Vitamin D metabolites and the gut microbiota dietary index are associated with reduced all-cause mortality in US adults: a prospective cohort study.}, journal = {BMC nutrition}, volume = {11}, number = {1}, pages = {222}, pmid = {41462374}, issn = {2055-0928}, abstract = {BACKGROUND: Vitamin D and the gut microbiota are known to influence immune function, inflammation, and long-term health outcomes, including mortality. However, the interplay among vitamin D metabolites, microbiota-related dietary patterns, and mortality risk remains unclear.

METHODS: This prospective cohort study was conducted with data from 19,278 subjects enrolled in the National Health and Nutrition Examination Survey of 2005–2018. DI-GM, a surrogate measure derived from 24-h dietary recall data rather than direct microbiome sequencing, was used to evaluate the impacts of diet on the gut microbiota. The relationships and potential mediating effects were determined through Cox proportional hazards regression, restricted cubic splines, and mediation analysis. In addition, subgroup analyses were conducted to investigate the effect modifications based on age, diabetes status, and cancer or malignancy history. The study results were analyzed to gain a comprehensive understanding of the relationships under investigation.

RESULTS: Higher contents of vitamin D and its metabolites were related to a decreased risk of all-cause mortality (HR for 25-hydroxyvitamin D3: 0.60, 95% CI: 0.53–0.68; epi-25-hydroxyvitamin D3: 0.62, 95% CI: 0.54–0.71). DI-GM was inversely related to mortality risk (HR: 0.80, 95% CI: 0.71–0.91). In the mediation analysis, DI-GM accounted for less than 10% of the total effect.

CONCLUSIONS: The present study revealed the inverse relationships of vitamin D and DI-GM with mortality and that DI-GM partially mediated these relationships. The. results highlighted the potential effects of vitamin D and the gut microbiota in terms of improving survival outcomes, although further longitudinal studies are warranted to validate these relationships.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40795-025-01211-1.}, } @article {pmid41291108, year = {2025}, author = {Eom, JH and Cho, MY and Choi, EM and Kim, JW and Yang, SJ and Hwang, J and Hwang, I and Lee, D and Kim, YY and Kim, HS and Baek, H and Kim, SJ}, title = {Comparative genomic analysis of hydrogen peroxide and nitric oxide metabolic pathways in Limosilactobacillus fermentum.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {45320}, pmid = {41291108}, issn = {2045-2322}, support = {2024ER050700//Korea National Institute of Health research project/ ; }, abstract = {UNLABELLED: Limosilactobacillus fermentum strains influence human health through distinct metabolic pathways; however, the genetic basis of these strain-specific functions remains unclear. This study investigated phenotypic divergence between two L. fermentum strains isolated from the human oral microbiome. Despite 98.2% average nucleotide identity, comparative genomics revealed substantial strain-specific gene repertoires (485 and 542 unique genes in DM072 and DM075, respectively). Functional characterization demonstrated that DM072 synthesizes hydrogen peroxide via pyruvate oxidase (EC 1.2.3.3; K00158), conferring strong antimicrobial efficacy against the Streptococcus mutans. Conversely, DM075 lacks this oxidative pathway but exhibits six-fold elevated nitrate reductase activity during the stationary phase. Transcriptomic profiling revealed significant temporal upregulation of glutamate synthase (gltB, p < 0.05) and alkyl hydroperoxide reductase (ahpC, p < 0.05) in DM075, indicating coordinated nitrogen assimilation and oxidative stress responses. Bioinformatic analyses identified strain-specific enzymatic profiles, including differential distributions of glycosyl hydrolases and transferases, alongside disparate acid tolerance (pH 2.5 for DM075 vs. pH 3.0 for DM072). These findings demonstrate functional specialization at the strain level within closely related taxa, highlighting the potential of DM072 as an antimicrobial probiotic for dental caries prophylaxis and DM075 as a potential cardiovascular homeostasis modulator via the nitrate–nitrite–nitric oxide pathway.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-29368-6.}, } @article {pmid41467030, year = {2025}, author = {Li, F and Wang, X and Cai, Y and Lin, Y and Tang, Y and Wang, S}, title = {Gut microbiota-derived metabolites as novel therapies for inflammatory bowel diseases: Role of nuclear receptors.}, journal = {Fundamental research}, volume = {5}, number = {6}, pages = {2622-2625}, pmid = {41467030}, issn = {2667-3258}, abstract = {Inflammatory bowel diseases (IBDs) are increasingly recognized as a pressing global health concern. The gut microbiome emerges as both a potential therapeutic target and a repository for pharmacological interventions in IBDs management. This perspective aims to elucidate the pivotal findings from recent studies concerning the anti-inflammatory properties of gut microbiota-derived metabolites (GMDMs), dissect the strengths and challenges of GMDMs as treatment strategies for IBDs, and highlight the integral role of nuclear receptors in mediating the interplay between IBD pathogenesis and GMDMs. Through the integration of these perspectives, our objective is to deepen the understanding of the therapeutic promise of nuclear receptor-targeted GMDMs, thus propelling forward the exploration and formulation of new pharmacological treatments for IBDs.}, } @article {pmid41465246, year = {2025}, author = {Sokolova, EA and Smirnova, NV and Fedorets, VA and Khlistun, IV and Mishukova, OV and Tromenschleger, IN and Savenkov, OA and Saprikin, OI and Rogaev, EI and Buyanova, MD and Filippova, IM and Mayorova, TM and Glukhova, MA and Ivanovna, MM and Manakhov, AD and Voronina, EN}, title = {Microbial Consortium Application Under Temperature Stress: Effects on the Rhizosphere Microbiome and Plant Growth.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, doi = {10.3390/ijms262411814}, pmid = {41465246}, issn = {1422-0067}, support = {075-15-2025-473//Ministry of Science and Higher Education of the Russian Federation (the Federal Scientific-technical programme for genetic technologies development for 2019-2030)/ ; }, mesh = {*Rhizosphere ; Soil Microbiology ; *Microbiota ; *Microbial Consortia ; *Stress, Physiological ; *Plant Development ; Crops, Agricultural/growth & development/microbiology ; Temperature ; Bacteria/genetics ; Triticum/growth & development/microbiology ; Fagopyrum/growth & development/microbiology ; }, abstract = {The aim of the present study was to investigate the effect of a synthetic microbial consortium (SMC) containing five functionally different bacterial strains (Rahnella aquatilis, Rothia endophytica, Stenotrophomonas indicatrix, Burkholderia contaminans, Lelliotia amnigena) on the growth and development of three agricultural crops (wheat, buckwheat, and rapeseed) on two soil types (chernozem and gray forest soil) under field conditions. The experiment was conducted from June to September 2024 under extreme field conditions, with temperatures reaching 43.8 °C. This study evaluates SMC efficacy under severe abiotic stress, reflecting increasingly common climate extremes. Metagenomic data analysis showed that the introduced strains did not establish stable populations in the soil, possibly due to heat-induced bacterial mortality, though other factors including competition with indigenous microflora and lack of protective formulations may have also contributed. No statistically significant effects on plant morphometric parameters were observed. The extreme temperature and water stress conditions appear to have been the dominant limiting factors, overriding any potential benefits from microbial inoculation, as evidenced by the lack of response to mineral fertilizer application as well. Crop-specific effects were revealed: when cultivating rapeseed on chernozem, a significant increase in available phosphorus content was noted (from 278 ± 45 to 638 ± 92 mg/kg with SMC application, p < 0.001).}, } @article {pmid41465245, year = {2025}, author = {Guo, P and Qin, W and Song, W and Chen, H}, title = {Spatial Multi-Omics Analysis of the Qianqiu Goat Gut Microbiome and Metabolome.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, doi = {10.3390/ijms262411815}, pmid = {41465245}, issn = {1422-0067}, support = {WJ24CYHXM06//Wanjiang Emerging Industry Technology Development Center 2024 Industrialization Project/ ; 22576206//National Natural Science Foundation of China Natural/ ; }, mesh = {Animals ; *Goats/microbiology/metabolism ; *Gastrointestinal Microbiome/genetics ; *Metabolome ; *Metabolomics/methods ; RNA, Ribosomal, 16S/genetics ; Rumen/microbiology/metabolism ; Multiomics ; }, abstract = {This study profiled the rumen (RM), small intestine (SI), and large intestine (LI) of 24 samples collected from eight 6-month-old Qianqiu goats (body weight 28.40 ± 1.80 kg), with the samples equally divided into three groups. A combination of methods was used, including 16S rRNA sequencing, untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and weighted gene co-expression network analysis-based module detection (WGCNA) with network integration. An uncommon composition of organisms dominated the SI: the hydrogenotrophic methanogens Methanobrevibacter (SI 24.51%; RM 1.92%; LI 2.19%) and Methanosphaera (SI 0.43%; RM 0.02%; LI 0.02%), together with the acetogen Acetitomaculum (SI 1.58%; RM 0.34%; LI 0.11%), were markedly more abundant compared to the RM or LI. Correlation and pathway analyses indicated that Methanobrevibacter was positively correlated with a steroid-type lipid metabolite (r = 0.52, p < 0.05) and with bile-acid-related metabolites. Acetitomaculum was positively correlated with several metabolites: 4-Hydroxyphenyl 4-hydroxybenzoate (r = 0.79, p < 0.05), 2-Aminoethyl dihydrogen phosphate (r = 0.76, p < 0.05), 1-Myristoyl-2-stearoyl-sn-glycero-3-phosphocholine (r = 0.76, p < 0.05), and 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (r = 0.74, p < 0.05). Together, these data define a small-intestinal microbial-metabolite module in Qianqiu goats characterized by elevated abundances of specific methanogens and acetogens in the SI. Specific positive correlations were identified between these taxa and metabolites associated with lipids and bile acids.}, } @article {pmid41465235, year = {2025}, author = {Kim, H and Kim, H and Lee, Y and Park, C and Cho, B and Son, S and Kim, H and Kim, G and Park, J and Park, H}, title = {Lactobacillus delbrueckii subsp. lactis CKDB001 Ameliorates Scopolamine-Induced Cognitive Impairment Through Metabolic Modulation.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, doi = {10.3390/ijms262411804}, pmid = {41465235}, issn = {1422-0067}, support = {HU22C0150//The Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT/ ; }, mesh = {Animals ; *Cognitive Dysfunction/chemically induced/metabolism/therapy/microbiology ; Mice ; Gastrointestinal Microbiome/drug effects ; *Scopolamine/adverse effects ; Male ; *Lactobacillus delbrueckii/physiology ; Mice, Inbred ICR ; Donepezil/pharmacology ; Hippocampus/metabolism/drug effects ; *Probiotics/pharmacology ; }, abstract = {Microbiome-derived metabolites have emerged as key mediators of the gut-brain axis, influencing cognitive function and neuroprotection. This study investigated whether Lactobacillus delbrueckii subsp. lactis CKDB001 alleviates scopolamine-induced memory impairment through metabolic modulation, and how its effects compare with those of donepezil. ICR mice were administered CKDB001 or donepezil for 4-5 weeks and evaluated through behavioral, microbiome, metabolomic, and molecular analyses. CKDB001 significantly improved spatial working memory in a dose-dependent manner, with the high-dose group showing improvements comparable to those of the donepezil-treated group, while passive avoidance showed a non-significant but positive trend. Both CKDB001 and donepezil modulated gut microbial composition, leading to a partial divergence from the scopolamine-disrupted community structure, with CKDB001 inducing dose-dependent intestinal colonization. Metabolomic profiling revealed that both treatments increased tryptophan-derived indole metabolites and altered lipid and short-chain fatty acid metabolite profiles, although these effects were more pronounced in CKDB001-treated mice. At the molecular level, both CKDB001 and donepezil reduced hippocampal tau phosphorylation, downregulated glycogen synthase kinase-3 (GSK-3) signaling, enhanced intestinal tight-junction proteins, and partially normalized acetylcholinesterase activity, with CKDB001 restoring AChE levels more closely toward the normal control. Together, these findings suggest that CKDB001 mitigates cognitive deficits through coordinated modulation of microbial, metabolic, and neuronal pathways, offering a microbiome-based therapeutic approach that may provide benefits comparable to donepezil with potentially fewer limitations.}, } @article {pmid41465180, year = {2025}, author = {Raber, J and O'Niel, A and Kasschau, KD and Pederson, A and Robinson, N and Guidarelli, C and Chalmers, C and Winters-Stone, K and Sharpton, TJ}, title = {Exercise, APOE Genotype, and Testosterone Modulate Gut Microbiome-Cognition Associations in Prostate Cancer Survivors.}, journal = {Genes}, volume = {16}, number = {12}, pages = {}, doi = {10.3390/genes16121507}, pmid = {41465180}, issn = {2073-4425}, support = {CCSG CPCP-2023-002//National Institute of Health USA/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/microbiology/therapy ; *Gastrointestinal Microbiome/genetics ; *Testosterone/metabolism ; Aged ; Cancer Survivors ; Middle Aged ; *Cognition ; *Apolipoproteins E/genetics ; Genotype ; *Exercise/physiology ; Saliva ; }, abstract = {Background: Men treated with androgen deprivation therapy (ADT) for prostate cancer are at risk for cognitive decline. Patient genetics and endocrine state may shape gut microbiome features that relate to cognition. Methods: We studied a subsample of 79 prostate cancer survivors with prior ADT exposure previously enrolled in a randomized controlled exercise trial comparing three training modalities (strength training, Tai Chi training, or stretching control) who completed an additional food-frequency questionnaire and remote Montreal Cognitive Assessment (MoCA) and provided saliva and stool for APOE genotyping, salivary testosterone, and 16S rRNA sequencing. We used beta regression for MoCA (scaled 0-1), linear models for testosterone, alpha diversity regressions, PERMANOVA for beta diversity, and DESeq2 for genus-level differential abundance, with false-discovery correction. Results: Compared to post-stretching control, post-strength training testing was associated with higher MoCA scores whereas post-Tai Chi testing was not. APOE ε4 carriers exhibited a greater testosterone increase with strength training than non-carriers. Testosterone, and its interactions with exercise modality and APOE ε2 status, was related to presence/absence-based community structure; APOE ε4 interacted with exercise intervention to influence alpha diversity. At the genus level, exercise was linked to lower levels of Bacteroidota taxa (including Muribaculaceae) and higher levels of Enterobacteriaceae; APOE ε4 status was linked to higher Megamonas and lower Rikenellaceae RC9 levels; and higher salivary testosterone levels were linked to higher Prevotellaceae taxa and Succinivibrio levels. Higher MoCA scores were associated with lower abundances of several Firmicutes genera. Conclusions: Endocrine state and APOE genotype may condition the gut microbiome's response to exercise intervention in ADT-treated prostate cancer survivors, with downstream associations with cognition. These findings could inform precision survivorship strategies pairing strength training with genotype- and hormone-informed microbiome monitoring to optimize cognitive performance.}, } @article {pmid41465120, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Addiction Susceptibility: Genetic Factors, Personality Traits, and Epigenetic Interactions with the Gut Microbiome.}, journal = {Genes}, volume = {16}, number = {12}, pages = {}, doi = {10.3390/genes16121447}, pmid = {41465120}, issn = {2073-4425}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Epigenesis, Genetic ; *Substance-Related Disorders/genetics/microbiology ; *Personality/genetics ; *Genetic Predisposition to Disease ; *Behavior, Addictive/genetics/microbiology ; }, abstract = {Despite valuable insights into the individual roles of genetic factors and personality traits, their combined contribution to addiction susceptibility remains insufficiently characterized. Within this framework, the potential influence of epigenetic mechanisms, particularly those mediated by the gut microbiome, also remains underexplored. This comprehensive review aims to address these gaps in an integrative manner by examining: (i) the association of gene regulation with personality traits; (ii) the genetics of substance use disorders; (iii) the roles of genes and personality in addiction; and (iv) epigenetic influences on addiction, with a particular focus on the role of the gut microbiome. Genetic influences on personality act primarily via regulatory variants that modulate gene expression during neurodevelopment, shaping cognitive, emotional, and behavioral traits that contribute to individual differences. Substance use disorders share partially overlapping genetic foundations, with specific loci, heritability estimates, and causal pathways differing across substances, reflecting both shared vulnerability and substance-specific genetic influences on addiction susceptibility. Impulsivity, novelty-seeking, and stress responsiveness are heritable personality traits that interact to shape susceptibility to substance use disorders, with genetic factors modulating risk across different forms of addiction. Environmental factors, early-life stress, and social influences interact with the gut microbiome to shape neurobiological and behavioral pathways that modulate addiction risk. These interactions highlight the multifactorial nature of substance use disorders, in which epigenetic, microbial, and psychosocial mechanisms converge to influence susceptibility, progression, and maintenance of addictive behaviors.}, } @article {pmid41464979, year = {2025}, author = {Yang, W and Han, N and Zhang, X}, title = {Eurotium cristatum Ameliorates Glucolipid Metabolic Dysfunction of Obese Mice in Association with Regulating Intestinal Gluconeogenesis and Microbiome.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/foods14244273}, pmid = {41464979}, issn = {2304-8158}, support = {32502233//National Natural Science Foundation of China/ ; }, abstract = {Eurotium cristatum (EC), a fungus derived from Fu brick tea, exhibits anti-obesity potential, but its mechanisms regulating intestinal gluconeogenesis (IGN) remain unclear. This study aimed to elucidate whether EC alleviates obesity and glucolipid metabolic disorders by modulating the gut microbiota and activating the IGN pathway. The 8-week EC administration at low (10[4] CFU/mL), medium (10[6] CFU/mL), and high doses (10[8] CFU/mL) ameliorated high-fat-diet (HFD)-induced metabolic abnormalities, including aberrant weight gain, dyslipidemia, glucose intolerance and hepatic injury with effects showing a dose-dependent trend. EC treatment significantly activated IGN, as indicated by increased colonic levels of short-chain fatty acids (SCFAs) and succinate (key IGN substrates) and the upregulation of IGN-key enzymes (PEPCK, FBPase, and G6Pase). In addition, EC treatment significantly alleviated the HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and enriching beneficial bacteria such as Lachnospiraece_NK4A136_group, Bacteroidota and Alloprevotella. Non-targeted metabolomics analysis revealed that EC significantly altered the linoleic acid metabolism, specifically decreasing the relative levels of bile acid and chenodeoxycholic acid (p < 0.01) while increasing those of linoleic acid and ricinoleic acid (p < 0.05). EC treatment reshaped the gut microbiome, promoted the production of beneficial metabolites (e.g., SCFAs), and consequently activated the IGN pathway, ultimately ameliorating host glucose and lipid metabolic disorders. Our findings provide mechanistic insights into the anti-obesity effects of EC, suggesting its potential for further investigation as a dietary intervention for metabolic diseases.}, } @article {pmid41464971, year = {2025}, author = {Yang, Y and Guo, L and Li, Y and Ji, M and He, T and Hou, K and Li, J and Zhang, H and Shi, Z and Zhang, H}, title = {Environmental and Rhizosphere Microbiome Drivers of Metabolic Profiles in Gastrodia elata: An Integrative Analysis of Soil, Metabolomics and Anti-Inflammatory Readouts.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/foods14244265}, pmid = {41464971}, issn = {2304-8158}, abstract = {BACKGROUND: Gastrodiae Rhizoma, the dried tuber of Gastrodia elata Bl. (Orchidaceae), is a traditional Chinese medicinal (TCM) and edible plant. Its quality formation is closely associated with rhizosphere microorganisms; however, the specific underlying mechanisms remain unclear.

METHODS: Tubers and rhizosphere soils were collected from seven major production regions of G. elata. Soil physicochemical properties were analyzed, and integrative analyses combining soil microbiome and untargeted metabolome profiling were conducted. The anti-inflammatory activity of G. elata extracts was evaluated using a RAW264.7 macrophage model. Multivariate statistical approaches, including OPLS-DA and correlation network analysis, were used to decipher relationships among environmental factors, microbial communities, metabolic profiles, and bioactivities.

RESULTS: A total of 39,250 bacterial ASVs and 10,544 fungal ASVs were identified. The bacterial community, dominated by Proteobacteria and Acidobacteria, was strongly influenced by soil chemical factors, including pH and total nitrogen. The fungal community, primarily composed of Ascomycota and Basidiomycota, exhibited marked sensitivity to altitudinal gradients. Correlation analysis revealed that key secondary metabolites, including flavonoids and phenolic acids, along with their anti-inflammatory activities, were significantly associated with rhizosphere microorganisms such as Edaphobaculum, Hypocrea, and Pseudomonas.

CONCLUSIONS: Our findings outline the pathways connecting environmental factors, the microbiome, and functional metabolites in G. elata, highlighting the importance of environmental-microbial interactions in determining metabolic outcomes. This work provides new insights into the ecological and molecular mechanisms behind the quality formation of this medicinal plant.}, } @article {pmid41464936, year = {2025}, author = {Choe, H and Shin, CY and Lim, JS and Park, JS and Park, JW and Kim, WJ and Park, YI and Ree, J}, title = {Evaluation of Potential Anti-Diabetic Synbiotic Formulation of Lacticaseibacillus rhamnosus BST.L-601 Using db/db Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/foods14244230}, pmid = {41464936}, issn = {2304-8158}, support = {//Gyeonggido Business & Science Accelerator (GBSA)/ ; }, abstract = {Probiotics have been studied for their potential to treat chronic diseases. This study examined the use of Lacticaseibacillus rhamnosus BST.L-601 as an anti-diabetic symbiotic with sweet potato for fermentation. The medium supplemented with sweet potato showed increased productivity and enhanced storability. The anti-diabetic effect of fermented BST.L-601 was evaluated using the C2C12 myotube and a type 2 diabetes mellitus (T2DM)-induced db/db (Lepr[db]/Lepr[db]) mouse model. Treatment with heat-killed BST.L-601 increased glucose uptake by 125% and α-glucosidase inhibition in a dose-dependent manner without cytotoxicity for myotubes. 8 weeks of oral administration of BST.L-601 led to anti-diabetic activities in various biomarkers in the mouse model, including lowered fasting blood glucose by 88% and elevated mRNA expression of glucose metabolism-related factors IRS-1 (510%) and GLUT4 (181%) from skeletal muscle. Moreover, the improvement of induced T2DM in mice was supported by blood serum analysis. Immunohistochemistry showed increased insulin and decreased glucagon secreted from β and α cells in the pancreas islet. Microbiota analysis demonstrated elevated microbiome diversity in mice treated with BST.L-601. Furthermore, the safety and probiotic properties of the strain were confirmed. These results suggest that BST.L-601 fermented with sweet potato could be a functional symbiotic used to improve diabetes, particularly T2DM.}, } @article {pmid41464856, year = {2025}, author = {Sylwestrzak, T and Ciosek, M and Pastuszak, K and Jastrzębski, T}, title = {Fecal Short-Chain Fatty Acids in Colorectal Cancer Patients Versus Healthy Controls: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/jcm14248949}, pmid = {41464856}, issn = {2077-0383}, abstract = {Background: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. Methods: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD -0.37; 95% CI -0.63 to -0.10; p = 0.006; I[2] = 0%) and butyrate (pooled SMD -0.59; 95% CI -1.10 to -0.07; p = 0.026; I[2] = 64.4%), whereas propionate did not differ significantly (pooled SMD -0.02; 95% CI -0.85 to 0.82; p = 0.971; I[2] = 89%). Conclusions: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC.}, } @article {pmid41464714, year = {2025}, author = {Nijs, J and Ahmed, I and Vandeputte, D and R Goodin, B and Adetayo, T and Kindt, S and Vanroose, M and Elma, Ö and Johansson, E and Logghe, T and Van Akeleyen, J and Goossens, Z and Labie, C and Silva, F and Lahousse, A and Huysmans, E and Núñez-Cortés, R}, title = {In the Mouth or in the Gut? Innovation Through Implementing Oral and Gastrointestinal Health Science in Chronic Pain Management.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/jcm14248812}, pmid = {41464714}, issn = {2077-0383}, abstract = {Recent scientific advances point towards an important role for oral and gastrointestinal health in people with chronic pain. Poor oral health (e.g., periodontitis, tooth loss) is observed in subgroups of the chronic pain population, including abdominal pain, low back pain, fibromyalgia, and rheumatoid arthritis. In addition to poor oral health, studies have also revealed altered intestinal microbiota compositions in various types of chronic pain, including people with chronic low back pain, knee osteoarthritis, visceral pain, fibromyalgia, tinnitus, and migraine. While overweight/obesity contributes to the likelihood of gut dysbiosis, normal-weight individuals with chronic pain also more often present with poor gut health. Both gastrointestinal and oral health problems (e.g., periodontitis, tooth loss) are increasingly recognized across multiple chronic pain conditions, including abdominal pain, low back pain, fibromyalgia, and rheumatoid arthritis. This perspective paper provides an overview of the requirements for integrating oral and gastrointestinal health in chronic pain management. First and foremost, oral and gastrointestinal health issues need to be recognized as common chronic pain comorbidities that require tailored treatment. Next to recognition of the issue, individuals seeking care for chronic pain need to be screened routinely for these oral and gastrointestinal comorbidities. In terms of management, the following options are suggested: (1) providing oral and gastrointestinal health science education; (2) considering the possible interplay between the gut microbiome and drug treatment (including polypharmacy); (3) expanding the importance of dietary interventions; and (4) considering the potential interplay with other lifestyle factors (e.g., chronic insomnia, overweight/obesity, depression and anxiety). To inform the implementation of these suggestions, longitudinal cohort studies investigating the role of oral and gastrointestinal health in people with chronic pain, as well as studies exploring possible (modifiable) factors that affect the oral and/or gut microbiome, are needed. This includes the bidirectional interplay between the gut microbiome and drugs commonly prescribed to patients with chronic pain. Likewise, adequately powered and controlled clinical trials evaluating the effectiveness of possible treatments for oral and/or gastrointestinal comorbidities in people with chronic pain represent another research priority. Such randomized clinical trials can not only examine the possible causal link between poor oral/gut health and treatment outcomes, but also inform the development of new, innovative ways to improve care for people with chronic pain.}, } @article {pmid41464345, year = {2025}, author = {Gaia-Oltean, AI and Boitor, D and Pop, LA and Galea, G and Telecan, T and Micu, R}, title = {Non-Invasive Methods for Early Diagnosis of Endometriosis-A Comprehensive Narrative Literature Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {24}, pages = {}, doi = {10.3390/healthcare13243276}, pmid = {41464345}, issn = {2227-9032}, abstract = {Endometriosis is a common gynecological pathology, with an incidence of nearly 10% in patients of reproductive age, and is still underdiagnosed. A thorough and well-spread diagnostic study of endometriosis based on epigenetic factor dysregulation can highlight potential areas for improvement. To quantify the potential and utility of non-invasive tools in the early diagnosis of endometriosis, an overview of current knowledge on epigenetic factors, based on DNA and RNA, is presented. Among these tools, it is important to highlight the role of miRNAs (microRNAs), cfDNA (cell-free DNA), and rRNAs (ribosomal RNAs), which are small molecules involved in endometriosis and numerous other pathologies. To evaluate their potential and utility in endometriosis, a salivary miRNA diagnostic test was conducted, the cfDNA methylation patterns of fragmented DNA circulating in bodily fluids (e.g., plasma) were analyzed, and cervical and uterine microbiomes were profiled for bacterial rRNA in patients with clinical suspicion of incipient endometriosis. Specific molecular profiles associated with endometriosis were analyzed. The first profile, a 109-miRNA saliva signature, was validated as a product of miRNA biomarkers and artificial intelligence modeling. In addition, peripheral blood cfDNA methylation biomarkers were identified by investigating nine genes in a molecular signature that requires validation. A profile was also obtained from cervical swabs and uterine washes, including molecular analysis of 16S rRNA amplicon sequencing to evaluate alterations in the cervical bacterial community. This review aims to optimize the integration of a non-invasive diagnostic tool for early endometriosis diagnosis. Genetic biomarkers can be correlated with clinical factors to improve diagnostic accuracy. Of the assessed diagnostic tools, salivary miRNA tests, a peripheral blood cfDNA methylation biomarker, and a microbiome rRNA signature may be useful for early diagnosis of endometriosis, as well as, implicitly, therapeutic attitude and follow-up.}, } @article {pmid41464202, year = {2025}, author = {Holmgaard, DB and Nebrich, L and Uslu, B and Schouw, CH and Dargis, R and Pedersen, HP and Fuursted, K and Nielsen, HV and Christensen, JJ and Nielsen, XC and Poulsen, LM}, title = {Comparison of Cultures and 16S/18S Amplicon-Based Microbiome Analyses for Diagnosing Nosocomial Pneumonia in Patients Admitted to the Intensive Care Unit-An Exploratory Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {24}, pages = {}, doi = {10.3390/diagnostics15243202}, pmid = {41464202}, issn = {2075-4418}, support = {REG-48-2014//Region Zealand/ ; }, abstract = {Background: Nosocomial pneumonia (NP) is a significant cause of morbidity and mortality in intensive care unit (ICU) patients. Prior antibiotic use, polymicrobial infections, and the limitations of conventional microbiological methods often complicate an accurate diagnosis. Bronchoalveolar lavage (BAL) and tracheal suction (TS) are commonly used methods for collecting respiratory samples; however, their diagnostic accuracy can vary. Additionally, microbiome analysis using 16S/18S rRNA gene sequencing provides an alternative approach for identifying pathogens that are difficult to culture. This study aimed to compare the diagnostic value of routine culturing and microbiome analysis in identifying pathogens in ICU patients with NP. Methods: A prospective cohort study was conducted in 23 critically ill patients at Zealand University Hospital. Samples from TS and BAL were collected from patients with suspected NP. Both culturing and 16S/18S rRNA gene amplicon-based microbiome analysis were performed to identify pathogens. Findings were compared between the two types of samples and between the two analysis methods. Results: A total of 46 samples were analyzed (23 TS and 23 BAL). Culture results showed complete concordance in 60.9% of cases and partial concordance in 21.7% between results from TS and BAL. Discrepancies often involved low-virulence organisms, such as Staphylococcus epidermidis and Candida albicans. Microbiome analysis revealed a broader spectrum of microbial diversity, detecting pathogens such as Pasteurella canis and Tropheryma whipplei that were previously missed by culture methods. In 34.8% of the samples, the pathogen identified by microbiome analysis was also detected by culture. However, microbiome analysis also identified additional microorganisms in 17.4% of the cases, which were not detected by culture. When comparing microbiome results between TS and BAL, 16 out of 23 (69.5%) showed complete concordance. Conclusions: The findings were similar in TS and BAL, both for culture and 16S/18S amplicon-based microbiome analyses. Microbiome analysis using 16S/18S rRNA gene sequencing provided new insights into NP patients, identifying pathogens that were previously undetected by conventional culturing methods. Combining microbiome analysis with traditional culture techniques could enhance the diagnostic accuracy for NP. Further studies are needed to refine diagnostic thresholds and assess the clinical impact of microbiome-based diagnostics.}, } @article {pmid41463926, year = {2025}, author = {Do, ADT and Alharbi, K and Perera, R and Asnayanti, A and Alrubaye, A}, title = {Preliminary Investigation of Cecal Microbiota in Experimental Broilers Reared Under the Aerosol Transmission Lameness Induction Model.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {24}, pages = {}, doi = {10.3390/ani15243641}, pmid = {41463926}, issn = {2076-2615}, support = {PG104703//Arkansas Biosciences Institute/ ; }, abstract = {Bacterial chondronecrosis with osteomyelitis (BCO), and its associated lameness, is one of the most common and devastating issues the poultry industry constantly faces, both globally and domestically. Leveraging the currently accepted "leaky gut" model of pathogenesis, this study aims to evaluate the cecal community of broilers reared under the aerosol transmission BCO induction model. A trial involving 1320 Cobb 500 broilers was conducted using the same induction model for 56 d with the following treatments: (1) positive control (PC)-untreated birds on wire-flooring pens; (2) negative control (NC)-untreated birds on litter-flooring pens; (3) LOW-birds treated with probiotic Enterococcus faecium spray on day-of-hatch (2.0 × 10[9] CFU/bird); and (4) HIGH-birds treated with LOW spray combined with probiotic Bacillus amyloliquefaciens/Bacillus subtilis inclusion in the diet (492.1 mg/kg). Cecal contents were collected from six birds per treatment on d14, d28, d42, and d56 of the experiment; then, DNA was extracted and sent for 16 s V3-V4 amplicon sequencing. Returned sequences were assembled and taxonomically assigned, after which diversity indices were analyzed (including alpha, beta, and abundance). No significant effect was found between all treatments and positive/negative control groups in all timepoints, but timepoints were significantly different from each other in both alpha and beta diversity indices (p < 0.05). Abundance analysis also showed a high Bacillota:Bacteroidota ratio (average 18.87; p < 0.0001) with Bacillota (Firmicutes) dominating at 95.57% on average across all treatments, followed by Bacteroidota at 5.06% and Pseudomonadota at 2.59%. These findings characterize in detail the cecal microbiome in populations of broilers reared under the novel aerosol transmission induction model, offering further insights and possibilities into studies of BCO etiology and pathology.}, } @article {pmid41463923, year = {2025}, author = {Sakarnyte, L and Spinkyte, R and Merkeviciene, L and Siugzdiniene, R and Ruzauskas, M}, title = {Next-Generation Sequencing Insights into the Oral Microbiome and Antibiotic Resistance Genes in Grey Wolves (Canis lupus).}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {24}, pages = {}, doi = {10.3390/ani15243639}, pmid = {41463923}, issn = {2076-2615}, abstract = {The oral microbiome of apex predators such as grey wolves (Canis lupus) is colonised by complex microbial communities and plays a crucial role in the health of wild mammals, but remains poorly understood. In this study, a single pooled sample mixed from oral samples of 17 wolves (Canis lupus) hunted in Lithuania was investigated for the determination of a variety of oral microbiota, providing the first metagenomic insight into wolf oral microbiomes in Baltic countries. The aim of this study was to identify the zoonotic and antimicrobial resistance potential of the oral microbiota. The results revealed diverse microbiomes associated with periodontal health as well as microbiomes related to the environment. Unique microbial taxa potentially reflect the nutritional and ecological interactions of carnivores. Shotgun metagenomic sequencing yielded a total of 18,726,406 raw reads, and following quality trimming and filtering, 86.01% of these (16,106,613) were retained. Among the total reads, 45.15% (8,455,255) were identified as host-derived and were removed. The most common oral bacterial genera were Pseudomonas (50%) and Psychrobacter (22.6%). Metagenomic reads for zoonotic pathogens, including Salmonella, Mycobacterium spp., Yersinia, Coxiella burnetii, Corynebacterium pseudotuberculosis, and others, were also detected, suggesting that grey wolves are potential natural reservoirs of zoonotic infections. Genes encoding antimicrobial resistance to many classes of antibiotics were also detected. This research contributes to understanding wolf dietary habits, oral health, the carriage and possible risk of transmitting AMR, and social interactions.}, } @article {pmid41463903, year = {2025}, author = {Williams, S and Domingues, F and Manu, H and Gomez, A and Johnston, L}, title = {Effects of a Feed Sanitizer in Sow Diets on Sow and Piglet Performance.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {24}, pages = {}, doi = {10.3390/ani15243618}, pmid = {41463903}, issn = {2076-2615}, support = {Research contract//Anitox Corporation/ ; }, abstract = {This study evaluated effects of Termin-8[®], a formaldehyde, propionic acid, and terpene-based feed sanitizer, on the performance, health, and gut microbiome of sows and nursing piglets. One hundred and seven mixed-parity sows were allocated to control diets (n = 53) or diets containing 0.55% sanitizer (n = 54) from day 80 of gestation until approximately day 19 postpartum. Performance metrics, scours, and fecal microbiome composition via 16S rRNA sequencing were assessed. Feed sanitizer supplementation had no significant effects on sow body weight, backfat depth, feed intake, wean-to-estrus interval, litter size or weight at weaning, or piglet diarrhea incidence. However, stillborn pig weight was significantly reduced in the sanitized group (p = 0.010). Gut microbiome changed drastically from gestation to weaning in both groups (R[2] > 0.20, p < 0.001), but the taxa and functions that fluctuated largely differed in each group. At weaning, both groups exhibited significantly different microbiome compositions (R[2] = 0.06, p < 0.001). Feed sanitizer in sows did not influence the piglet microbiome. Supplementing formaldehyde-based feed sanitizer to sow diets did not significantly impact overall performance or health but moderately influenced sow gut microbiome composition, warranting further investigation into its potential functional implications.}, } @article {pmid41463799, year = {2025}, author = {Chen, J and Ai, G and Xiong, P and Song, W and Liu, G and Wei, Q and Chen, X and Zou, Z and Song, Q}, title = {Dietary Fagopyrum dibotrys Extract Supplementation: Impacts on Growth Performance, Immune Response, Intestinal Morphology, and Microbial Community in Broiler Chickens Infected with Escherichia coli O157.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {24}, pages = {}, doi = {10.3390/ani15243515}, pmid = {41463799}, issn = {2076-2615}, support = {JXSNKYJCRC202333//the Agricultural Scientific and Technological Innovation Project of Jiangxi Academy of Agricultural Sciences/ ; 32360847//the National Natural Science Foundation of China/ ; JXARS-12//Jiangxi Province Modern Agricultural Industry Technology System Construction Special Project/ ; }, abstract = {This study explored the efficacy of dietary Fagopyrum dibotrys extract (FDE) in mitigating Escherichia coli O157 (E. coli) infections in broilers. A total of 240 one-day-old male Shengze 901 broilers were randomly allocated to four groups (with 10 broilers per group): CON (basal diet), COLI (basal diet + E. coli challenge), FDE (basal diet + 500 mg/kg FDE), and FDEC (basal diet + 500 mg/kg FDE + E. coli challenge). The results showed that E. coli challenge reduced the average daily gain (ADG) and average daily feed intake (ADFI), increased the feed conversion ratio (FCR) and cecal E. coli load, impaired the intestinal mucosa, and induced intestinal inflammatory responses (p < 0.05). FDE supplementation improved growth performance, increased duodenal villus height and villus/crypt ratio; reduced serum interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), and endotoxin levels; and lowered cecal E. coli counts (p < 0.05). Molecularly, FDE supplementation upregulated Occludin, Claudin-1, and ZO-1 gene expressions, and downregulated jejunal TLR4 and MyD88 mRNA levels. Microbiome analysis revealed that FDE increased the relative abundance of Faecalibacterium and alleviated the E. coli-induced reduction in Clostridia_UCG-014. In conclusion, dietary supplementation with 500 mg/kg FDE could mitigate colibacillosis-related intestinal damage and inflammatory responses.}, } @article {pmid41463747, year = {2025}, author = {Priputnevich, T and Denisov, P and Zhigalova, K and Muravieva, V and Shabanova, N and Gordeev, A and Zubkov, V and Bembeeva, B and Isaeva, E and Nikolaeva, A and Sukhikh, G}, title = {The Impact of Antimicrobial Therapy on the Development of Microbiota in Infants.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/antibiotics14121245}, pmid = {41463747}, issn = {2079-6382}, support = {122020900123-4//Ministry of Health of the Russian Federation/ ; }, abstract = {Background. The establishment and diversity of the gut microbiota during early childhood are fundamental for immune regulation and metabolic processes, with factors such as prematurity, delivery method, antibiotic treatment, and breastfeeding significantly impacting microbiome development and potential health outcomes. Objectives/Methods. This comparative study examined the gut microbiota composition in children aged 6-8 and 9-12 months, born via spontaneous labor at ≥38 weeks' gestation, who either did not receive antibacterial therapy or required beta-lactam antibiotics. The composition of the colonic microbiota was analyzed in these fecal samples using a quantitative real-time PCR (qRT-PCR). Results. Significant differences in microbiota composition were observed between groups. Children treated with antibiotics exhibited a statistically significant reduction in alpha diversity indices (Shannon and Simpson), along with decreased colonization of key functionally important microorganisms, including obligate anaerobic bacteria such as Faecalibacterium prausnitzii, Clostridium leptum, Bacteroides spp., and metabolically active Bifidobacteria (B. bifidum, B. breve, B. longum). Conclusions. These microbiota alterations may adversely affect child health by diminishing microbial balance and functional potential, especially during this critical period of immune and metabolic development. The decline in anti-inflammatory, short-chain fatty acid-producing bacteria elevates the risk for allergic, atopic, dysbiotic, and metabolic conditions. Recognizing these impacts underscores the importance of strategies to supports microbiota restoration after antibiotic use, such as probiotics, prebiotics, and dietary interventions. Further research should focus on microbiota recovery dynamics to facilitate early intervention and optimize pediatric health outcomes. Overall, understanding antibiotic effects on gut microbiota can guide more judicious treatment approaches, reducing long-term health risks.}, } @article {pmid41463743, year = {2025}, author = {Almazán-Catalán, J and Carpizo-Zaragoza, P and Penalba-Iglesias, D and Sánchez, ML and González-Reguero, D and Bueno, S and Robas-Mora, M and Varela-Moreiras, G and Partearroyo, T and Jiménez-Gómez, P}, title = {Gut Resistome and Hearing Loss in Young Adults: A Preliminary Study on the Interplay Between Microbial Resistance and Auditory Health.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/antibiotics14121241}, pmid = {41463743}, issn = {2079-6382}, support = {MCP24TPC//CEU-Banco Santander/ ; }, abstract = {Background: Hearing loss (HL) affects more than 1.5 billion people worldwide and represents a major global health concern. Recent evidence suggests that alterations in gut microbial composition and antimicrobial resistance (AMR) may be linked to inflammatory and metabolic pathways that could influence auditory physiology. Objectives: This study aimed to explore the relationship between auditory function and the antimicrobial resistance in the gut microbiome of young adults. Methods: Fecal and auditory data were collected from young adults. Auditory function was assessed through pure-tone audiometry, and participants were classified according to the presence or absence of HL based on the American Speech-Language-Hearing Association (ASHA) criteria. Bacterial resistance was analyzed under aerobic and anaerobic conditions using disk diffusion and E-test methods to determine minimum inhibitory concentrations (MICs) for a panel of antibiotics. Gut microbiota composition was further characterized using quantitative polymerase chain reaction (qPCR) to quantify 15 key microbial taxa. Results: Overall, 40.9% of participants presented some degree of HL, with mild or slight HL being more frequent in women (53.3%) than in men (14.3%). Participants with HL exhibited significantly higher MICs for nalidixic acid, amoxicillin, and ciprofloxacin, as well as trends toward increased MIC variability for several other agents. Principal component analysis demonstrated distinct clustering of individuals without HL and greater dispersion among those with HL, suggesting higher interindividual variability in resistance profiles. These findings suggest potential associations between antimicrobial resistance and auditory function, possibly mediated through gut microbiome alterations. qPCR analyses demonstrated that Faecalibacterium prausnitzii abundance was significantly higher in individuals with HL and in those exhibiting greater resistance to amoxicillin. Conclusions: These findings provide preliminary evidence connecting the gut resistome with auditory function, supporting the emerging concept of a gut-ear-brain axis and underscoring the need for further research into microbiome-related mechanisms underlying HL.}, } @article {pmid41463508, year = {2025}, author = {Liu, Q and Qu, Y and Jiang, S and Guo, X and Xing, Y and Zheng, J and Dong, Z and Yu, W and Zhang, G}, title = {Corncob Returning Enhances Soil Fertility and Rhizosphere Microbiome Functions to Improve Growth and Nutrient Uptake of Eleutherococcus sessiliflorus in Cold Agroecosystems.}, journal = {Biology}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/biology14121735}, pmid = {41463508}, issn = {2079-7737}, support = {20250203140SF//the Key R&D Project of the Natural Science Foundation of Jilin Province/ ; ZKP202202//the Climbing Project of Changchun University/ ; }, abstract = {Corncob residues, an abundant but underutilized organic resource in Northeast Asia, offer substantial potential for improving soil health and plant productivity. This study investigates the effects of corncob returning on soil physicochemical properties, microbial processes, and the performance of Eleutherococcus sessiliflorus in a cold-temperate region (Jilin Province, China). The treatments included no-amendment control (CK), corncob incorporation (CI), and corncob mulching (CM). Corncob returning significantly increased soil organic carbon, moisture content, and the availability of N-P-K, while reducing soil bulk density, thus improving soil structure and nutrient availability. Both CI and CM treatments enhanced microbial biomass C, N, and P, as well as nutrient-cycling enzyme activities (β-glucosidase, urease, and alkaline phosphatase), accelerating C-N-P turnover in the rhizosphere. These improvements resulted in enhanced plant nutrient status and significant gains in biomass, with plant height and fruit number increasing by up to 44% and 136%, respectively. Multivariate analysis and PLS-SEM revealed that soil improvements strongly stimulated enzyme activity (path coefficient = 0.956), and enhances the microbial niche, thereby promoting plant traits through nutrient release (enzyme → plant path coefficient = 0.694). Microbial functional activity, rather than microbial richness, plays a more crucial role in plant growth promotion. Collectively, these findings underscore that corncob returning improves E. sessiliflorus performance through a soil biochemical activation pathway mediated by microbial metabolism and enzymatic nutrient release. This study provides strong evidence supporting corncob recycling as a cost-effective, environmentally sustainable approach for improving medicinal plant production and advancing circular agriculture in cold-region ecosystems.}, } @article {pmid41463469, year = {2025}, author = {Sá, C and Brígido, C and Fidalgo, C and Pires, A and Alves, A and Figueira, E and Cardoso, P}, title = {Influence of Plant Developmental Phase and Irrigation Level on Cultivable Microbiome of Maize Root.}, journal = {Biology}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/biology14121694}, pmid = {41463469}, issn = {2079-7737}, support = {UID/50006 + LA/P/0094/2020//FCT - Fundação para a Ciência e a Tecnologia I.P./ ; 2020.05872.BD//FCT - Fundação para a Ciência e a Tecnologia I.P./ ; 2023.06755.CEECIND//FCT - Fundação para a Ciência e a Tecnologia I.P./ ; CEEC-IND/01373/2018//FCT - Fundação para a Ciência e a Tecnologia I.P./ ; CEECIND/00093/2018//FCT - Fundação para a Ciência e a Tecnologia I.P./ ; 2022.00500.CEECIND//FCT - Fundação para a Ciência e a Tecnologia I.P./ ; }, abstract = {Plant growth-promoting bacteria can help plants survive in stressful environments. Here, we describe the isolation of root-surface and endophytic bacteria from maize roots at two different phases of the plant life cycle (vegetative and reproductive), grown under three different water regimes (100%, 50%, and 0%). Isolates were typed using BOX-PCR to identify unique genetic fingerprints, resulting in a total of 400 strains. These strains were screened for osmotic stress tolerance using 15% polyethylene glycol 6000. Isolates were also tested for bacterial plant growth-promoting traits, including the ability to produce siderophores, indole-3-acetic acid synthesis, and phosphate solubilization, both in the presence and absence of osmotic stress. The results showed that in the reproductive phase, a higher percentage of endophytic and rhizoplane bacteria were tolerant to osmotic stress. Additionally, the highest values of alginate and siderophore production by rhizoplane bacteria were also observed in the reproductive phase. These findings suggest that isolation of maize bacteria should consider the plant's developmental phase and hydric stress conditions to effectively select bacterial strains that enhance crop resilience in drought-affected areas.}, } @article {pmid41463425, year = {2025}, author = {Wang, F and Song, W and Wang, D and Huang, Z and Shan, M and Sun, S and Jin, Z and Lu, J and Ji, Y and Sun, K and Li, Z}, title = {Investigating the Dynamic Variation of Skin Microbiota and Metabolites in Bats During Hibernation.}, journal = {Biology}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/biology14121648}, pmid = {41463425}, issn = {2079-7737}, support = {YDZJ202401501ZYTS//Jilin Provincial Natural Science Foundation/ ; 32430066//National Natural Science Foundation of China/ ; 32300425//National Natural Science Foundation of China/ ; 32171525//National Natural Science Foundation of China/ ; 31961123001//National Natural Science Foundation of China/ ; 32171481//National Natural Science Foundation of China/ ; 202310193005//Innovation and Entrepreneurship Training Program for College Students in Jilin Province/ ; S202410193089//Innovation and Entrepreneurship Training Program for College Students in Jilin Province/ ; S202510193059//Innovation and Entrepreneurship Training Program for College Students in Jilin Province/ ; }, abstract = {Pseudogymnoascus destructans (Pd) invades the skin tissue of bats, leading to severe population declines. The skin microbiome plays a crucial role in protecting hosts from fungal infection and exhibits pronounced spatiotemporal dynamics in its structure and function. Meanwhile, metabolites derived from microbial communities reflect the host physiological state and participate in microbe-pathogen interactions. In this study, we investigated the spatiotemporal dynamics of skin bacterial communities and metabolites during hibernation in Rhinolophus ferrumequinum by integrating 16S rRNA sequencing with untargeted metabolomics and experimentally verified the antifungal effects of microbially derived potential metabolites against Pd. Our results revealed that the structure of the skin bacterial community varied significantly across sampling contexts, with its assembly primarily governed by stochastic processes. Bacterial diversity reached its lowest level during middle hibernation, accompanied by a simplified co-occurrence network dominated by cooperative or mutualistic interactions. Additionally, metabolomic analyses demonstrated systematic metabolic remodeling of bat skin across hibernation stages, marked by significant enrichment of multiple pathways closely involved in host antimicrobial defense. Furthermore, metabolite profiles differed across locations, and the abundance patterns of several metabolites were strongly correlated with Pd infection levels. Integrated analyses identified multiple metabolites that showed significant correlations with bacterial genera capable of synthesizing the corresponding compounds. In vitro validation confirmed that nine metabolites effectively inhibited the growth of Pd, among which melatonin exhibited the strongest antifungal activity. Collectively, this study reveals the dynamics of the skin microbiome and metabolites of R. ferrumequinum during hibernation, providing novel insights into the defensive role of skin-associated microbes and metabolites in maintaining population health and resilience against fungal pathogens.}, } @article {pmid41463367, year = {2025}, author = {Biţă, A and Scorei, IR and Soriano-Ursúa, MA and Pisoschi, CG and Biţă, CE and Dincă, L and Ştefănescu, S and Racu, MV and Pinzaru, I and Florescu, C and Hădăreanu, DR and Siloşi, CA and Neamţu, J and Gheonea, DI and Mogoşanu, GD and Zorilă, MV}, title = {Boron Bioavailability Revisited: From Plasma-Accessible Species to Microbiota-Accessible Complexes-Implications for Nutritional Essentiality.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/biom15121711}, pmid = {41463367}, issn = {2218-273X}, mesh = {Humans ; *Boron/metabolism/pharmacokinetics/blood ; *Gastrointestinal Microbiome ; Biological Availability ; Animals ; Prebiotics ; }, abstract = {Boron (B) remains one of the least understood trace elements in human nutrition. Traditionally regarded as non-essential, its biological role has been reevaluated in light of emerging microbiome research. We provide a narrative synthesis of mechanistic, preclinical, and clinical studies to assess whether the colonic actions of B meet accepted criteria for nutritional essentiality. This review revisits B bioavailability through a dual-pathway framework distinguishing plasma-accessible boron (PAB)-small, fully absorbable species with transient systemic effects-from microbiota-accessible boron complexes (MABCs)-indigestible conjugates that reach the colon intact. Evidence indicates that PAB exerts short-term metabolic modulation, whereas MABCs act as prebiotic cofactors that stabilize microbial quorum sensing (autoinducer-2-borate; AI-2B), reinforce the colonic mucus barrier through borate-diol crosslinking, and support host-microbiota symbiosis. Deficiency or low intake of MABCs leads to dysbiosis, barrier fragility, and low-grade inflammation along gut-organ axes-effects reversible by MABC-rich diets. Analytical and clinical tools are proposed to discriminate between PAB and MABC pathways, including fecal B/speciation, AI-2B assays, and mucus-penetration markers. Recognizing B's essentiality as a microbiota-dependent nutrient reframes its nutritional assessment, guiding future dietary guidelines and prebiotic design toward the microbiome-mucus interface.}, } @article {pmid41463053, year = {2025}, author = {N F Guimarães, G and Dos Santos Cardoso, F and Gamboa, L and W Barrett, D and Gonzalez-Lima, F}, title = {Abdominal Photobiomodulation and the Gut-Brain Axis: A Systematic Review of Mechanistic and Translational Evidence.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/biomedicines13123042}, pmid = {41463053}, issn = {2227-9059}, abstract = {Background/Objectives: Bidirectional communication between the gut and brain is central to neurological and psychiatric health, and abdominal photobiomodulation (PBM) has emerged as a promising non-invasive way to modulate this axis by targeting intestinal mitochondria, epithelial integrity, and the microbiota. We systematically reviewed preclinical and clinical evidence on abdominal PBM, alone or in combined protocols, reporting microbiome, metabolic, or neurobehavioral outcomes. Methods: Following PRISMA 2020 recommendations, we searched MEDLINE, Scopus, Web of Science, and ScienceDirect through May 2025 for animal and human studies applying PBM to the abdomen and reporting gut-related, metabolic, or brain-related outcomes. Results: Nine studies met the eligibility criteria (five human, four animal). Human trials, mainly in Parkinson's and Alzheimer's disease, used 630-904 nm light and reported gains in mobility, balance, cognition, and olfaction; one trial also showed microbiota modulation with a decreased Firmicutes:Bacteroidetes ratio. Animal models revealed cognitive improvement, reduced neuroinflammation, dopaminergic neuroprotection, and microbial rebalancing. Mechanistic findings converged on enhanced mitochondrial bioenergetics, redox and anti-inflammatory signaling, vagal activation, and short-chain fatty acid-mediated effects. Conclusions: Current evidence, though limited by small samples, heterogeneous dosimetry, combined treatment sites, and few sham-controlled human trials, suggests that abdominal PBM can influence the gut-brain axis through converging mitochondrial, immune, and microbial mechanisms. Adequately powered randomized trials with standardized dosimetry, validated mechanistic biomarkers, and integrative multi-omics analyses are needed to clarify causal pathways and optimize translational applications.}, } @article {pmid41463040, year = {2025}, author = {Velikic, G and Supic, G and Maric, DL and Puletic, M and Maric, MD and Barac, B and Maric, DM}, title = {Stem Cell and Exosome Therapy in Wound Healing: Traps, Paradoxes, and Tricks Transforming Paradigms.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/biomedicines13123030}, pmid = {41463040}, issn = {2227-9059}, abstract = {Cell therapies hold great promise for advancing wound healing; however, translating this promise into consistent clinical benefit has proven elusive. Numerous trials have failed to reproduce the robust outcomes suggested by preclinical studies, reflecting a landscape marked by hidden traps. These include the hostile wound microenvironment, the cytotoxicity of antimicrobial dressings, poor retention and engraftment, immune clearance, and the paradoxical risk of fibrosis and scarring. Across these challenges emerge paradoxes that redefine how traps are understood. The Scarring Paradox reveals that MSCs and EVs may either suppress or reinforce fibrosis, depending on the niche context. The Immune Double-Edged Sword captures the duality of clearance and regenerative modulation. These paradoxes illustrate that traps are not static obstacles but dynamic inflection points. Recognition of these paradoxes has inspired tricks: protective biomaterial carriers, preconditioning strategies, engineered exosomes, and combinatorial therapies with anti-fibrotic, neuromodulatory, or microbiome-targeted adjuncts. Case studies illustrate how classical traps manifest in clinical practice and how paradoxes guide innovation. Emerging adjuncts, ranging from herbal bioactives and bioelectric modulation to circadian synchronization and digital twins, point toward more unconventional but increasingly plausible frameworks for niche control. This perspective review demonstrates that the future of regenerative wound therapy depends not on avoiding traps but on reframing them through paradoxes and converting them into tricks. Stem cell and exosome therapy is thus moving beyond a linear "promise versus failure" narrative toward a systemic, context-aware, programmable approach in which paradoxes drive conceptual renewal and transformative paradigms in wound care.}, } @article {pmid41463036, year = {2025}, author = {Andriankaja, OM and Whiteheart, S and Mattos, MBA}, title = {Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/biomedicines13123023}, pmid = {41463036}, issn = {2227-9059}, abstract = {Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., "long-COVID," "post-acute sequelae of SARS-CoV-2 infection," "PASC," "post-COVID-19," "long-haul COVID") and oral/periodontal diseases (e.g., "periodontal disease," "periodontitis," "gingiva," "oral disease," "dental"), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein-Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships.}, } @article {pmid41462944, year = {2025}, author = {Radić, M and Belančić, A and Vučković, M and Fajkić, A and Rogoznica Pavlović, M and Radić, J}, title = {Eradication of Small Intestinal Bacterial Overgrowth in Systemic Sclerosis: Current Treatment and Perspectives-A Narrative Review.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/biomedicines13122932}, pmid = {41462944}, issn = {2227-9059}, abstract = {Small intestinal bacterial overgrowth (SIBO) is a major yet underrecognized driver of gastrointestinal morbidity in systemic sclerosis (SSc). Disordered motility, fibrosis, and dysbiosis promote microbial stasis, malabsorption, and malnutrition, contributing substantially to impaired quality of life and survival. Diagnostic accuracy remains limited: jejunal aspirate culture is invasive, whereas breath testing offers only moderate sensitivity and specificity. Empirical antibiotic therapy yields transient symptom relief, but recurrence is common, and evidence guiding optimal eradication strategies is sparse. Adjunctive measures, including probiotics, prokinetics, and dietary interventions, remain variably applied, with heterogeneous outcomes across studies. Novel microbiome-targeted, neuromodulatory, and antifibrotic therapies are emerging as promising mechanism-based options. Bearing this in mind, this narrative review aims to consolidate current knowledge on SIBO eradication in SSc. We first outline the pathophysiological rationale and clinical relevance of bacterial overgrowth. We then synthesize available evidence for treatment strategies, appraise barriers to durable remission, and discuss implications for multidisciplinary management. Finally, we highlight emerging approaches, including microbiome-directed therapies, novel prokinetics, and antifibrotic interventions, and define priorities for future clinical research.}, } @article {pmid41462928, year = {2025}, author = {Abdelbadiee, S and Yoon, G and Pearman, K and Kumar, A and Harvey, PR}, title = {Understanding How Mental Health Influences IBD Outcomes: A Review of Potential Culprit Biological Mechanisms.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/biomedicines13122916}, pmid = {41462928}, issn = {2227-9059}, abstract = {Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Similar to other chronic diseases, IBD is associated with negative mental health outcomes. The prevalence of anxiety and depression with IBD is increasing in western societies and there is a growing body of evidence suggesting a bidirectional relationship which remains poorly understood. This review seeks to distil current evidence on the epidemiology, biological mechanisms and microbial changes through which anxiety and depression may lead to worse IBD outcomes. The literature demonstrates that a prior diagnosis of depression is associated with an increased risk of developing IBD. Co-morbid anxiety or depression doubles the odds of adverse outcomes in IBD. Antidepressants appear to have class dependent effects on modulating disease activity in IBD with co-morbid depression. Chronic stress may drive IBD through a number of mechanisms, including inducing the hypothalamic pituitary axis, glucocorticoid resistance, increasing intestinal permeability, and releasing inflammatory cytokines. Alterations in the microbiome on either a genus or species' level has been shown to be affected by and have an impact on both mental health illness and IBD activity. Further research with high quality longitudinal follow-up data is required to clarify causal associations of anxiety/depression and IBD onset as well as measure the impact of different antidepressant classes and microbiome targeted strategies on disease progression and outcomes.}, } @article {pmid41462435, year = {2025}, author = {Zhang, H and Wang, D and Li, C and Xu, F and Cao, X and Bao, B and Zhao, M and Liu, X}, title = {Comprehensive Evaluation of the Antihyperuricemic Effect of Red Kidney Bean Anthocyanins and Molecular Screening of the Lead Candidate.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c14579}, pmid = {41462435}, issn = {1520-5118}, abstract = {This study aimed to investigate the effects of red kidney bean (Phaseolus vulgaris L.) anthocyanins (RKBA) on alleviating hyperuricemia (HUA) and screen the lead candidate. First, RKBA effectively inhibited XOD in vitro. Then, in vivo results showed that RKBA significantly reduced serum uric acid (UA) levels, protected kidney function, and alleviated inflammation and tissue damage. Mechanistically, RKBA down-regulated XOD, ADA, and 5'-NT while modulating urate transporters URAT1, GLUT9, and OAT3, thereby rebalancing UA metabolism. Additionally, it reshaped the gut microbiome (particularly enriching Ligilactobacillus and Dubosiella) and elevated short-chain fatty acids. Subsequently, the UPLC-ESI-MS/MS-based anthocyanin-targeted omics identified and quantified 42 anthocyanins. Integrating molecular docking and dynamics simulation, pelargonidin-3,5-diglucoside was selected as the lead candidate owing to its high abundance and strong affinity for XOD. Pelargonidin-3,5-diglucoside has not been reported as an antihyperuricemic nutraceutical before; hence, this study lays a foundation for future in vivo validation.}, } @article {pmid41462375, year = {2025}, author = {Zhang, Y and Zhou, K and Chen, X and Zhang, H and Han, J and Ning, K}, title = {A temporal-aware machine learning framework enables microbial community dynamics prediction with personalized precision.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {261}, pmid = {41462375}, issn = {2049-2618}, support = {Grant No. 2023YFA1800900 and 2018YFC0910502//National Key R&D Program of China/ ; Grant Nos. 32071465, 31871334, 81827901//the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Machine Learning ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; *Microbiota ; Infant ; Bacteria/classification/genetics ; }, abstract = {BACKGROUND: Accurately forecasting the dynamic behavior of microbial communities from sparse longitudinal data remains a critical challenge for microbiome-based precision medicine and ecological monitoring. Most existing models depend on data interpolation and assume population-level dynamics, which limits their ability to capture personalized microbial changes in real-world scenarios.

RESULTS: We propose MicroProphet, a personalized temporal-aware framework capable of accurately forecasting microbial abundance trajectories from incomplete longitudinal observations without requiring data imputation. Powered by a time-aware Transformer architecture, MicroProphet reconstructs subject-specific microbial trajectories using only the initial 30% of observed time points, capturing critical transitional states through an attention mechanism. We demonstrated its robust cross-ecosystem generalizability across synthetic communities, human gut microbiomes, infant gut development, and corpse decomposition. The framework consistently achieves high predictive accuracy and biological interpretability. In clinical contexts, the framework enables early detection of disease-associated microbial shifts and supports timing optimization for microbiome-targeted interventions. In forensic settings, it accurately infers decomposition timelines from early microbial signals.

CONCLUSIONS: By transforming incomplete, noisy microbiome data into actionable, individualized forecasts, MicroProphet lays the foundation for a new class of temporal-aware systems in microbial ecology and precision health.}, } @article {pmid41462337, year = {2025}, author = {Chen, S and Yuan, F and Fang, H and Gouda, M and Wu, W and Zhang, H and Ma, Z and Feng, L and Wang, M and Liu, Y}, title = {Integrating microbiome and machine learning for precision diagnosis of rice bakanae disease.}, journal = {Plant methods}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13007-025-01486-2}, pmid = {41462337}, issn = {1746-4811}, support = {U21A20219//National Natural Sciences Foundation of China/ ; 2023YFD2000103//National Key Research and Development Project/ ; 226-2024-00191//Fundamental Research Funds for the Zhejiang Provincial Universities/ ; }, abstract = {Bakanae is a fungal rice disease that is threatening global rice production, causing severe yield losses. The plant microbiome plays a significant role in plant stress resistance, but its high-dimensional characteristics have not been fully exploited. Therefore, we integrated the microbiome and machine learning (ML) to diagnose bakanae disease in this study. We found significant correlations between Gammaproteobacteria and Bacteroidia and the severity of bakanae disease. We constructed different diagnosis models based on random forests (RF), support vector machines (SVM), and convolutional neural networks (CNN) on 88 biological replicates with an independent test set. We found that the RF model demonstrated strong performance across four taxonomic levels, with an accuracy of 88.9% and an F1 score of 94.1%. Notably, a Bray-Curtis dissimilarity-based extraction method was proposed to rapidly screen practical information from the original microbial community, which can enhance the model performance to a certain extent. According to phenotypic data, the disease severity of infected samples was classified into two levels (high and low infected levels) using the K-means clustering method. In the diagnosis of infection severity based on the family level, the model's prediction accuracy reached 77.8%. Collectively, these findings highlight that the combination of microbiome with ML can advance diagnostic strategies for bakanae disease, providing new avenues for precision agriculture.}, } @article {pmid41462238, year = {2025}, author = {Serbanescu, MA and Wright, MC and Elebasy, M and Shi, P and Arnold, JW and Haines, KL and White, JR and Surana, NK and Wischmeyer, PE}, title = {Impact of fiber-containing enteral nutrition on microbial community dynamics in critically ill trauma patients: a pilot-randomized trial.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {706}, pmid = {41462238}, issn = {1741-7015}, support = {1R35GM156920-01/NH/NIH HHS/United States ; }, mesh = {Humans ; *Enteral Nutrition/methods ; *Critical Illness/therapy ; Pilot Projects ; Male ; Female ; Middle Aged ; *Gastrointestinal Microbiome/drug effects ; *Dietary Fiber/administration & dosage ; Double-Blind Method ; Prospective Studies ; *Wounds and Injuries/therapy/microbiology ; Adult ; *Dysbiosis/microbiology ; Prebiotics/administration & dosage ; Aged ; Oligosaccharides/administration & dosage ; }, abstract = {BACKGROUND: Gut microbial dysbiosis is common in the intensive care unit and certain derangements, like expansion of Enterobacteriaceae and other potential pathogens (pathobionts), are associated with increased morbidity. In other populations, dysbiosis is improved by enteral nutrition supplemented with prebiotic short-chain fructooligosaccharides (scFOS-EN). The impact of scFOS-EN on the microbiota in critical illness is unknown and difficult to predict in a dysbiotic environment. Thus, we conducted a pilot randomized control trial (RCT) in critically ill trauma patients to evaluate the effects of scFOS-EN versus a fiber-free enteral formula (NF-EN) on gut microbial dynamics.

METHODS: In this single-center, prospective, double-blind RCT, mechanically ventilated trauma ICU patients received scFOS-EN or a similar fiber-free formula (NF-EN). Microbial communities in longitudinally collected stool samples were characterized using 16S rRNA gene sequencing. We used linear mixed-effects models to assess microbial dynamics in the 10-day study period after scFOS-EN or NF-EN initiation, as well as a time-informed dimensionality reduction method to identify patient-specific temporal responses and clinical correlates and network approaches for microbe:microbe interactions.

RESULTS: A total of 57 stool samples were analyzed from 17 patients (7 NF-EN, 10 scFOS-EN). All participants had profound baseline dysbiosis and received broad-spectrum antibiotics. Compared to NF-EN, scFOS-EN was associated with an accelerated loss of Bifidobacterium (- 0.6%/day p = .026) and Firmicutes (3.5%/day, p < .001) and greater increases in several Bacteroidaceae members, with expansion of pathobiont Enterobacteriaceae (0.3%/day, p = .003) unique to scFOS-EN participants. Detrimental microbial responses to scFOS-EN, including high Enterobacteriaceae burden, were dictated by pre-existing and ongoing antibiotic exposure and associated with enhanced microbial competition.

CONCLUSIONS: In the dysbiotic gut of critically ill trauma patients, the effect of scFOS-EN is context-dependent. Prior exposure to anaerobic antibiotics appears to modify the microbial response from beneficial to detrimental. These findings challenge a universal approach to prebiotic therapy and underscore the need for personalized nutritional strategies in the ICU.

TRIAL REGISTRATION: The trial was prospectively registered at ClinicalTrials.gov (Identifier: NCT03153397; first posted May 15, 2017) prior to participant enrollment and approved by the Duke Health Institutional Review Board (IRB Pro00081414).}, } @article {pmid41462094, year = {2025}, author = {Alaeddini, Z and Nemati, I and Gholizadeh, S}, title = {Deciphering gut microbial impact in coronary artery disease through multimodal computational approaches.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {802}, pmid = {41462094}, issn = {1471-2180}, } @article {pmid41461922, year = {2025}, author = {Jin, S and Cenier, A and Wetzel, D and Arefaine, B and Moreno-Gonzalez, M and Stamouli, M and Mohamad, M and Lupatsii, M and Ríos, E and Lee, S and Zamalloa, A and Chokshi, S and Mardinoglu, A and Shoaie, S and Beraza, N and Patel, VC and Schirmer, M}, title = {Microbial collagenase activity is linked to oral-gut translocation in advanced chronic liver disease.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41461922}, issn = {2058-5276}, support = {426120468//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BBS/E/F/000PR13632//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/CCG1860/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; 268211/1134579//Foundation for Liver Research/ ; }, abstract = {Microbiome perturbations are associated with advanced chronic liver disease (ACLD), but how microorganisms contribute to disease mechanisms is unclear. Here we analysed metagenomes of paired saliva and faecal samples from an ACLD cohort of 86 individuals, plus 2 control groups of 52 healthy individuals and 14 patients with sepsis. We identified highly similar oral and gut bacterial strains, including Veillonella and Streptococcus spp., which increased in absolute abundance in the gut of patients with ACLD compared with controls. These microbial translocators uniquely share a prtC gene encoding a collagenase-like proteinase, and its faecal abundance was a robust ACLD biomarker (area under precision-recall curve = 0.91). A mouse model of hepatic fibrosis inoculated with Veillonella and Streptococcus prtC-encoding patient isolates showed exacerbation of gut barrier impairment and hepatic fibrosis. Furthermore, faecal collagenase activity was increased in patients with ACLD and experimentally confirmed for the prtC gene of translocating Veillonella parvula. These findings establish mechanistic links between oral-gut translocation and ACLD pathobiology.}, } @article {pmid41461857, year = {2025}, author = {Xie, Y and Pan, J and Li, D and Wang, Q and Sun, Y and Wang, S}, title = {MVPHI: a multi-view learning framework for predicting complex microbial interactions.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-32359-2}, pmid = {41461857}, issn = {2045-2322}, support = {No. 2022FY101100//Science & Technology Fundamental Resources Investigation Program/ ; }, abstract = {Bacteriophages (phages) are viruses that infect bacteria. As the natural regulators of microbial communities, it plays a crucial role in microbiome turnover. Predicting phage-bacteria interactions (PBIs), as well as bacteria-bacteria interactions (BBIs) is essential for advancing microbiome research. Given the high cost and risk of wet-lab techniques, computational biology and bioinformatics methods are reasonable alternatives. However, existing approaches suffer from the low predictive accuracy and poor efficiency. In this study, we proposed a multi learning-based model named MVPHI for predicting complex microbial interactions. More specifically, we first construct a heterogeneous multi-attributed microbial network (MAMN) based on pathogenic bacteria and associated phages. Next, MVPHI introduces three different view microbial characteristics for training the model, including the statistical-view, textual-view and topology-view features. Experimental results on seven benchmark datasets indicated that MVPHI achieves superior performance compared with the six variant models and eight baseline algorithms. Moreover, case study and protein docking experiments further demonstrated the robustness and generalization of our model. In conclusion, the proposed MVPHI model has potential ability to predict novel PBIs and BBIs, and can also provide valuable insights for phages screening and bacterial community research.}, } @article {pmid41461744, year = {2025}, author = {Cho, H and Nam, H and Kim, HE and Kim, JE and Park, JI and Park, J and Kim, YC and Lee, JP and Kim, DK and Joo, KW and Kim, YS and Kim, BS and Park, S and Lee, H}, title = {Gut microbiome and metabolite signatures for predicting acute kidney transplant rejection: a prospective study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44709}, pmid = {41461744}, issn = {2045-2322}, support = {2021R1I1A1A01060190//National Research Foundation grants funded by the Korean government/ ; 2018R1A3B1052328//National Research Foundation grants funded by the Korean government/ ; 2022R1A2C2011190//by National Research Foundation grants funded by the Korean government/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kidney Transplantation/adverse effects ; Female ; Male ; Prospective Studies ; Middle Aged ; *Graft Rejection/metabolism/microbiology/diagnosis/etiology ; Adult ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Dysbiosis/microbiology ; *Metabolome ; }, abstract = {Acute rejection (AR) remains a significant challenge in kidney transplantation (KT) despite advances in immunosuppressive treatment. Recognizing the critical influence of the gut microbiome on modulating host immunity, we investigated the association between gut dysbiosis and AR in KT recipients. A total of 97 patients with KT were prospectively enrolled from two centers, and their samples were collected at multiple time points, such as pre-transplant (n = 97), three months (n = 66), and twelve months (n = 37) post-transplant. Microbial profiling was performed using 16S rRNA sequencing and fecal metabolomics was done via nuclear magnetic resonance spectroscopy. Thirty-three patients developed AR after KT, exhibiting reduced bacterial richness and diversity compared with KT recipients without AR. In addition, these patients had increased Escherichia-Shigella and decreased Phascolarctobacterium abundance. Pathway analysis identified 47 enriched pathways in AR patients, notably those involved in lipopolysaccharide biosynthesis and short-chain fatty acid metabolism. Consistent results were obtained from stool metabolomics, showing reduced propionate and lactate concentrations compared with patients without AR. Finally, combining pre-KT bacterial and fecal metabolite features with clinical parameters significantly improved AR prediction accuracy. Our results suggest that integrating clinical, microbial, and metabolomic data may provide a more holistic patient care regimen across both pre- and post-transplant phases.}, } @article {pmid41461645, year = {2025}, author = {Moradi, J and Berggreen, E and Gerdts, E and Kringeland, E and Bolstad, AI and Bunæs, DF and Bertelsen, RJ}, title = {Taxonomic and functional signatures of smoking and periodontitis severity in the subgingival microbiome of older adults.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-025-00319-9}, pmid = {41461645}, issn = {2731-6068}, support = {318443//Research Council of Norway/ ; 318443//Research Council of Norway/ ; 318443//Research Council of Norway/ ; 318443//Research Council of Norway/ ; 318443//Research Council of Norway/ ; }, abstract = {Periodontitis and smoking are major contributors to oral and systemic health deterioration in aging adults. This study investigated the combined effects of smoking status and periodontitis severity on the subgingival microbiome in 1107 individuals aged 69-72 using shotgun metagenomic sequencing. Smoking was linked to reduced microbial diversity, enrichment of periodontal pathogens, and depletion of health-associated commensals, while increasing periodontitis severity was associated with broader dysbiotic shifts, including enrichment of canonical pathogens. The presence of overlapping taxa suggests shared dysbiotic pathways that may accelerate disease progression in older adults. Notably, the combination of smoking and severe periodontitis was characterized by enrichment of key pathogens, such as Tannerella forsythia, Fusobacterium nucleatum, Actinomyces israelii, and Mogibacterium timidum. Although former smokers showed fewer opportunistic pathogens than current smokers, their microbiomes remained altered compared to never smokers, suggesting persistent differences potentially related to past smoking. Functional profiling revealed largely additive effects of smoking and periodontitis, with enrichment of lipopolysaccharide biosynthesis, proteolysis, and sulfur metabolism, alongside depletion of commensal biosynthetic functions. Overall, the findings highlight the persistent and additive impacts of smoking and periodontitis on the subgingival microbiome, underscoring the importance of addressing both exposures jointly in long-term oral health strategies for older adults.}, } @article {pmid41461600, year = {2025}, author = {Chen, S and Luo, Y and Wei, G and Liu, S}, title = {Molecular Mimicry at the Gut-Immune Interface: A Mechanistic Link to Type 1 Diabetes.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.70091}, pmid = {41461600}, issn = {1365-2567}, abstract = {Type 1 diabetes (T1D) arises from T cell-mediated destruction of pancreatic β-cells. However, genetic susceptibility alone cannot account for the increasing incidence and earlier onset of T1D, suggesting a substantial contribution from environmental factors, particularly the gut microbiota. This review synthesises recent human, multiomics and experimental evidence linking gut microbiota dysbiosis and microbial metabolites to β-cell autoimmunity. We focus on two converging mechanisms: (1) metabolite-driven disruption of intestinal barrier integrity and immune regulation, and (2) molecular mimicry between microbial peptides and islet autoantigens that activate autoreactive T cells. Across human cohorts and animal models, T1D-associated dysbiosis features reduced short-chain fatty acid (SCFA)-producing bacteria (e.g., Faecalibacterium, Roseburia) and increased pro-inflammatory taxa (e.g., Bacteroides, Streptococcus spp.). SCFA deficiency compromises Treg induction and gut barrier stability, facilitating antigen translocation. Several gut-derived peptides, such as the Parabacteroides distasonis hprt4-18 peptide, share sequence homology with insulin and other islet antigens, activate insulin-reactive T cells and accelerate diabetes in NOD mice, supporting a role for molecular mimicry. Interventional approaches including FMT, probiotics and prebiotics show promise but remain heterogeneous; their efficacy is highly strain-, timing- and context-dependent and translation from animal studies to humans is still limited. Therapeutically targeting the gut-islet axis, through modulation of microbiota, microbial metabolites or cross-reactive antigens, offers potential for disease prevention or adjunctive treatment. We highlight emerging biomarkers, including MAIT-cell phenotypes, antimicrobial peptide reactivity and microbiome-derived functional signatures, and emphasise the need for stratified clinical trial designs based on age, genotype and baseline microbiota composition to address current variability. The microbiota-metabolite-molecular mimicry axis provides a coherent mechanistic framework linking gut dysbiosis to T1D pathogenesis. Advancing these insights into clinical application will require rigorous, genotype-stratified human studies and standardised, transparent methodological approaches.}, } @article {pmid41461596, year = {2025}, author = {Alqassim, AY}, title = {Confronting neglected tropical vector-borne diseases in a changing world: a review of challenges and opportunities.}, journal = {Pathogens and global health}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/20477724.2025.2609157}, pmid = {41461596}, issn = {2047-7732}, abstract = {Neglected tropical vector-borne diseases (NTVBDs) pose a significant global health challenge, disproportionately affecting low- and middle-income countries. This review begins by defining NTVBDs and their classification criteria, providing a comprehensive overview of their geographical distribution, vectors, and causative agents. Climate change, socioeconomic factors, and land-use changes are changing NTVBD transmission dynamics, with temperature increases expanding vector ranges and creating new transmission hotspots in previously unsuitable regions. The review examines both established vector control approaches and emerging technologies, including CRISPR-based gene editing, artificial intelligence, and microbiome manipulation for NTVBD control. Housing improvements have shown particular promise, with studies demonstrating significant reductions in vector presence through structural interventions. Sustainable control programs emphasize community-based and culturally appropriate interventions, with gender-responsive approaches enhancing both intervention coverage and women's economic empowerment. The review explores the integration of NTVBD control with existing health systems through formal coordination mechanisms and sustainable financing frameworks beyond traditional donor-dependent models. Recent field initiatives addressing the psychological dimensions of NTVBDs highlight the importance of comprehensive approaches that extend beyond physical symptoms. To address the complex challenges of NTVBDs in a rapidly changing world, the review concludes that a multidisciplinary approach integrating technological innovation with social and ecological considerations is essential. Future research should examine the long-term effects of climate change on NTVBD dynamics, develop broadly protective vaccines, optimize integrated control strategies, and investigate innovative funding mechanisms for resource-limited settings.}, } @article {pmid41461486, year = {2026}, author = {Kang, S and Lee, JY and Cho, KS}, title = {Bacterial and fungal metagenomes associated with atmospheric particulates in Republic of Korea: Comparison of PM2.5 and TSP larger than PM2.5.}, journal = {Journal of environmental sciences (China)}, volume = {161}, number = {}, pages = {400-410}, doi = {10.1016/j.jes.2025.08.021}, pmid = {41461486}, issn = {1001-0742}, mesh = {*Particulate Matter/analysis ; Republic of Korea ; Bacteria/genetics ; *Air Pollutants/analysis ; *Environmental Monitoring ; Particle Size ; *Fungi/genetics ; *Metagenome ; *Air Microbiology ; Microbiota ; Air Pollution/statistics & numerical data ; }, abstract = {Particulate matter (PM) significantly contributes to air pollution, potentially causing health issues, with PM-associated microorganisms implicated in some cases. While studies have explored microbial concentration and structure in PM based on particle size, comprehensive analysis of microbial functional traits and environmental influences is limited. This study evaluated microbial concentrations and diversity in PM with a diameter of 2.5 µm or lower (PM2.5) and total suspended particles (TSP) greater than PM2.5 (PM>2.5) samples relative to air temperature and other factors. DNA extracted from PM2.5 and PM>2.5 filters was sequenced to characterize bacterial and fungal community structures and functional genes. Results showed that microbial concentrations and diversity were greater in PM>2.5, with similar dominant species across PM sizes. Higher air temperatures correlated with increased microbial concentrations and diversity in PM>2.5, attributed to enhanced microbial growth. An Asian dust event from the Mongolian desert disrupted the PM microbiome. Despite consistent species dominance, gene function analysis revealed abundant drug resistance pathways in bacterial communities of both particle types, while pathotroph prevalence was higher in PM2.5 fungal communities. These findings indicate that PM2.5 microbial community analysis suffices for understanding PM ecosystems, offering valuable insights for air quality management and microbial pollution control, especially concerning potential pathogens.}, } @article {pmid41461451, year = {2026}, author = {Xiao, S and Zheng, C and Yang, J and Zhang, W and Fang, H and Wu, X and Han, L}, title = {Responses and regulatory mechanisms of soil microbiome and antibiotic resistome to carbendazim and ZnO nanoparticles.}, journal = {Pesticide biochemistry and physiology}, volume = {217}, number = {}, pages = {106891}, doi = {10.1016/j.pestbp.2025.106891}, pmid = {41461451}, issn = {1095-9939}, mesh = {*Zinc Oxide/pharmacology/toxicity ; *Soil Microbiology ; *Microbiota/drug effects ; *Benzimidazoles/pharmacology ; *Carbamates/pharmacology ; Plasmids/genetics ; *Soil Pollutants ; *Fungicides, Industrial/pharmacology ; *Nanoparticles ; Bacteria/drug effects/genetics ; *Metal Nanoparticles ; *Drug Resistance, Microbial/genetics/drug effects ; Reactive Oxygen Species/metabolism ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Exogenous pollutants may alter the profile of antibiotic resistance genes (ARGs) in soil. Substantial application of a fungicide carbendazim (CBD) and ZnO nanoparticles (nZnO) in modern agriculture has led to serious combined pollution in soil. Here, the degradation characteristics of CBD, the diversity and abundance of ARGs and their dissemination and regulatory mechanisms were investigated in response to individual and combined applications of CBD and nZnO. CBD initially degraded fast and then slowly in soil, and nZnO slightly delayed the degradation of CBD. CBD and nZnO significantly changed the soil bacterial community structure. Meanwhile, CBD and nZnO significantly increased the abundance of ARGs, especially for multidrug and beta-lactam resistance genes. The relative abundance of plasmids significantly increased in CBD and nZnO treatments, and the elevation in soil ARG abundance was associated with the increase in plasmid-borne ARG abundance, suggesting that plasmid-mediated horizontal gene transfer might contribute to the dissemination of ARGs. Moreover, the intergenus and intragenus conjugative transfer frequency of plasmid RP4 in the CBD and nZnO treatments increased by up to 9.4-fold of the control. Additionally, the cell membrane permeability and intracellular reactive oxygen species content of recipient and donor bacteria in the CBD and nZnO treatments increased by up to 1.6-fold of the control, which facilitated plasmid-mediated conjugative transfer of ARGs. It is concluded that CBD and nZnO can alter soil microbiome and improve antibiotic resistome by accelerating conjugative plasmid-mediated ARGs propagation.}, } @article {pmid41461446, year = {2026}, author = {Yuan, Y and Li, C and Yang, L and Zhao, Y and Xu, C and Tao, J}, title = {Harnessing rhizosphere bacteria for fungal disease management in Paeonia lactiflora.}, journal = {Pesticide biochemistry and physiology}, volume = {217}, number = {}, pages = {106885}, doi = {10.1016/j.pestbp.2025.106885}, pmid = {41461446}, issn = {1095-9939}, mesh = {*Rhizosphere ; *Paeonia/microbiology ; *Plant Diseases/microbiology/prevention & control ; Alternaria ; Soil Microbiology ; Bacillus subtilis/physiology ; *Bacteria/metabolism ; }, abstract = {Paeonia lactiflora Pall., a traditional Chinese ornamental flower, holds significant aesthetic and economic value but remains highly susceptible to fungal diseases. In this study, eight candidate biocontrol bacteria (SY1-SY8) were isolated and identified from the rhizosphere soil of P. lactiflora, and their antagonistic effects against four major fungal pathogens were evaluated using plate confrontation assays, fermentation broth antagonism tests, and pot experiments. Among these isolates, Bacillus subtilis SY8 exhibited the most significant inhibitory effect against all four pathogens. Treatment with SY8 significantly reduced the incidence of black spot disease caused by Alternaria alternata FSY1 and enhanced the activities of phenylalanine ammonia-lyase and polyphenol oxidase in P. lactiflora leaves. Additionally, SY8 treatment reduced the abundance of pathogenic fungi in both the phyllosphere and endophytic compartments, while increasing the diversity and evenness of the phyllosphere bacterial community, thereby promoting more complex microbial interactions. Metabolomic analysis revealed that SY8 substantially altered key metabolic pathways in P. lactiflora leaves, including carbon metabolism, amino acid biosynthesis, and the citric acid cycle. These metabolic shifts collectively enhance the antioxidant capacity, cellular repair mechanisms, and disease resistance of plants. Furthermore, metabolomic profiling of the SY8 fermentation broth identified specific bioactive metabolites associated with its antagonistic activity against FSY1. SY8 significantly enhanced the resistance of P. lactiflora to black spot disease in by increasing the activities of defense-related enzymes, modifying the rhizosphere microbial community, and regulating metabolic pathways. These findings underscore the potential of SY8 as a promising biocontrol agent for managing fungal diseases in P. lactiflora.}, } @article {pmid41461420, year = {2026}, author = {Cao, W and Yang, S and Wang, J and Chen, S and Byarlay, M and Shi, X and Li-Byarlay, H and Ma, C}, title = {Field-realistic cyfluthrin exposure alters multi-omics profiles in Bombus terrestris: Implications for wild pollinator health.}, journal = {Pesticide biochemistry and physiology}, volume = {217}, number = {}, pages = {106896}, doi = {10.1016/j.pestbp.2025.106896}, pmid = {41461420}, issn = {1095-9939}, mesh = {Animals ; Bees/drug effects/metabolism ; *Pyrethrins/toxicity ; *Nitriles/toxicity ; *Insecticides/toxicity ; Gastrointestinal Microbiome/drug effects ; Transcriptome/drug effects ; Pollination/drug effects ; Metabolome/drug effects ; Multiomics ; }, abstract = {Cyfluthrin is effective in mitigating crop damage caused by pests. However, its residues in bee colonies pose potential threats to the health and fitness of bumblebees. While previous studies have shown significant physiological effects of cyfluthrin on honeybees, its effects on bumblebees remain poorly understood. In this study, bumblebees were exposed to 30 and 120 μg/kg cyfluthrin (two field-level concentrations) for 10 days. We assessed the effects of chronic cyfluthrin exposure on bumblebee survival, sucrose solution consumption, body weight and midgut pathology. Multi-omics analyses were performed, encompassing the gut microbiome and metabolome, as well as the head transcriptome and proteome. The results demonstrated that exposure to cyfluthrin at a concentration of 120 μg/kg significantly reduced the survival probability of bumblebees. Hematoxylin-Eosin staining revealed damage to the midgut microvilli. 16S rRNA sequencing indicated a significant decrease in the relative abundance of the core gut microbiota, Bifidobacterium. Metabolomic analysis of the gut further revealed a significant reduction in multiple beneficial metabolites (crustecdysone, creatine and retinol palmitate). Head transcriptomics showed significant downregulation of genes associated with the tyrosine metabolism pathway and fatty acid β-oxidation. Furthermore, proteomic analysis of the head revealed a significant upregulation of apoptosis-related proteins, alongside a significant downregulation of proteins involved in immune responses and glycosaminoglycan biosynthesis. These findings highlight the need for cautious pesticide application in agricultural systems and emphasize the importance of considering sublethal effects on pollinators - particularly through disruptions to the gut and head.}, } @article {pmid41461407, year = {2026}, author = {Shahid, M}, title = {Molecular engineering and in-silico biotechnological innovations for microbial degradation of persistent pesticides.}, journal = {Pesticide biochemistry and physiology}, volume = {217}, number = {}, pages = {106833}, doi = {10.1016/j.pestbp.2025.106833}, pmid = {41461407}, issn = {1095-9939}, mesh = {*Pesticides/metabolism ; Biodegradation, Environmental ; *Biotechnology ; Metabolic Engineering ; Soil Microbiology ; Bacteria/metabolism/genetics ; Computer Simulation ; }, abstract = {The persistence of recalcitrant pesticides in agricultural soils poses a serious threat to environmental and public health. Conventional remediation methods often have limited efficiency and, sustainability. Whereas, microbial degradation provides an eco-friendly and attractive alternative. This review highlights advances in molecular and biotechnological tools driving microbial pesticide degradation. It also emphasizes key genes, enzymatic pathways, and resilient microbes driving recalcitrant pesticide degradation. This review discusses the integration of next-generation sequencing, multi-omics platforms, CRISPR-Cas editing, synthetic biology, and AI-driven metabolic engineering in advancing microbial pesticide degradation. It also highlights progress in rhizosphere microbiome research, bioinformatics pipelines, and field-scale validation. The transition from lab to field highlights precision bioremediations' potential for sustainable pesticide management.}, } @article {pmid41461310, year = {2025}, author = {Sun, C and Zhu, J and Sun, X and Zhang, Z and Sun, Y and Jin, Y and Wu, T}, title = {Targeting the human gut microbiome: a comparative review of probiotics, prebiotics, synbiotics, and postbiotics.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.032}, pmid = {41461310}, issn = {2090-1224}, abstract = {BACKGROUND: The human gut microbiome plays a central role in regulating host health, serving as a core hub for systemic physiological interactions. Dysregulation of the gut microbiome is implicated in a wide spectrum of local and systemic diseases. Research has evolved from establishing associations to elucidating the mechanistic roles of gut microbes and developing targeted strategies for their modulation, with a growing emphasis on their bidirectional communication with other organ systems.

AIM OF REVIEW: This review aims to synthesize current knowledge on the composition and function of the gut microbiome, its functional crosstalk with the host, and its integral role in both health and disease. A major focus is placed on critically evaluating the mechanisms, efficacy, and applications of key microbiome-directed interventions-probiotics, prebiotics, synbiotics, and postbiotics-in maintaining or restoring gut-centric ecological balance.

The gut microbiome acts as a dynamic microbial organ essential for digestion, immune maturation, and metabolic homeostasis. Dysbiosis, characterized by a loss of beneficial microbes and an overgrowth of potential pathogens, is a critical factor in the pathogenesis of gastrointestinal disorders, metabolic diseases, and other systemic conditions. The gut microbiome engages in continuous bidirectional communication with distant organs, including the oral cavity, lungs, skin, and urinary tract, via specific axes (e.g., gut-oral, gut-lung, gut-skin), thereby exerting widespread influence on host physiology. Probiotics, prebiotics, synbiotics, and postbiotics represent complementary strategies to counteract dysbiosis and reestablish gut ecological integrity, ranging from introducing live beneficial bacteria to utilizing inactivated microbial cells and their bioactive metabolites. Enhancing the translational potential of these interventions requires deeper mechanistic insights and robust clinical validation.}, } @article {pmid41461285, year = {2025}, author = {Bharathi, S and Soundara Rajan, YAPA and Prakash, S and Immanuel, G and Ramasubburayan, R}, title = {Pathobionts in the microbiome: Drivers of disease and targets for treatment.}, journal = {Microbial pathogenesis}, volume = {211}, number = {}, pages = {108268}, doi = {10.1016/j.micpath.2025.108268}, pmid = {41461285}, issn = {1096-1208}, abstract = {Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.}, } @article {pmid41461264, year = {2025}, author = {Mannon, PJ and Benson, AK and Schnable, J and Ding, W and Juritsch, AF and Rose, DJ}, title = {Food as Medicine: Enhancing Crop Breeding and Food Processing to Shift the Gut Microbiome for Prevention and Treatment of Chronic Diseases.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101298}, doi = {10.1016/j.tjnut.2025.101298}, pmid = {41461264}, issn = {1541-6100}, abstract = {Prebiotics are useful tools for shifting the gut microbiome and metabolome to confer immune, metabolic and preventive benefit for human disease. However, there are emerging concerns about methods for discovering optimal candidate compounds and their sustainable production for long-term success in targeting mechanisms of disease. In this perspective we review the current state of prebiotics moving from nutrition to function in health, highlighting the opportunities for using food as medicine in treating a model disease, inflammatory bowel disease, discussing the ways crop breeding can be used to identify and improve the functional (beyond nutritional) value of a prebiotic and the critical role that food processing plays in sustaining the integrity and scalability of the prebiotic compound while influencing consumer adoption of these agents. This information supports a trajectory for the future of "food as medicine" to be moving from population-scale dietary guidelines to personalized or precision nutrition guidelines, from "eat more fiber" to "eat this specific type of fiber that has been enhanced in and processed from this specific genotype of food crop". This could include developing "designer fibers" by crop breeding to develop panels of genotypes with different fiber structures that deliver reliable shifts in the microbiome and metabolome for most patients with the targeted disease. Finally, there needs to be a commitment to sustainability of the plant-derived product so that future generations will have access to the same benefits of the food as medicine initially developed for disease prevention and treatment.}, } @article {pmid41461105, year = {2025}, author = {Dias, MF and Freitas, APA and Collares, SF and Santos, RMS and Nogueira, YJA and Júnior, AMÁ and Martins, TC and Rocha, PMB and Romano-Silva, MA and de Miranda, DM}, title = {Gut Microbiota, Antipsychotics, and Metabolic Alterations in Children and Adolescents: Protocol for a Longitudinal Observational Study.}, journal = {JMIR research protocols}, volume = {14}, number = {}, pages = {e77374}, pmid = {41461105}, issn = {1929-0748}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Adolescent ; Child ; *Antipsychotic Agents/adverse effects/pharmacology/therapeutic use ; Longitudinal Studies ; Prospective Studies ; Male ; Female ; Metabolome/drug effects ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Over the past decade, numerous studies have emphasized the important role of gut microbiota (GM) in maintaining the body's homeostasis. Imbalances in GM have been linked to many dysfunctions, such as metabolic and neurodevelopmental disorders. GM can be influenced by many factors, among them the use of certain medications, such as second-generation antipsychotics (SGAs), and, in turn, act upon the endocrine, immune, and nervous systems. Despite the growing interest in the microbiota-gut-brain axis, significant gaps remain in our understanding of how SGAs affect GM and the host metabolic profile.

OBJECTIVE: This study aims to build on the current knowledge on the impact of SGAs on clinical parameters, microbial and metabolic profiles, and behavior of children and adolescents undergoing treatment with SGAs.

METHODS: This is a prospective longitudinal study, in which the effects of SGAs will be assessed before and 3 to 6 months after their introduction. An integrated approach will be used, encompassing clinical data (such as weight, lipid profile, and glucose levels); microbiome and metabolome analyses; emotional, behavioral, and sleep patterns (assessed through psychiatric scales); and dietary habits.

RESULTS: This project was funded in November 2023 and will start data collection in January 2026. It is expected to be completed in 2027.

CONCLUSIONS: This study is expected to provide insights into the multidimensional effects of SGAs on children and adolescents, including clinical data, GM microbial profile, metabolism, and behavior. The findings may contribute to a better understanding of treatment impacts and provide information on more personalized therapeutic strategies.}, } @article {pmid41461020, year = {2025}, author = {Palmiotti, A and Bertolini, A and Fiorotto, R}, title = {Pathophysiology of cystic fibrosis-related liver disease.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {41461020}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: Cystic fibrosis liver disease (CFLD) is a significant nonpulmonary complication of cystic fibrosis, affecting approximately 5-10% of patients. It encompasses a spectrum of hepatic abnormalities ranging from mild, transient elevations in liver enzymes to advanced CFLD (aCFLD), which is marked by clinically relevant portal hypertension due to cirrhotic or noncirrhotic liver pathology. This review focuses on aCFLD as the clinically meaningful form of the disease and summarizes recent mechanistic insights into its pathogenesis that may inform the development of targeted therapeutic strategies.

RECENT FINDINGS: CFLD pathogenesis has been traditionally linked to defective bile secretion. Emerging evidence, however, highlights additional contributors, including cholangiocyte immune dysregulation, gut dysbiosis, and intestinal barrier dysfunction, which together promote hepatic inflammation. Furthermore, recent studies underscore the role of vascular alterations independent of cirrhosis, specifically noncirrhotic portal hypertension, as the main clinical feature in aCFLD. These findings support a multifactorial, multihit model of disease in the pathogenesis of CFLD.

SUMMARY: The complex interplay of these factors suggests that effective treatment for aCFLD may require a multifaceted approach. Advances in understanding the gut-liver axis and vascular contributions provide new therapeutic targets. Future research should focus on validating these findings and evaluating the efficacy of cystic fibrosis transmembrane conductance regulator modulators and microbiome-targeted treatments in altering the course of CFLD.}, } @article {pmid41460655, year = {2025}, author = {Oso, TA and Ahmed, MM and Okesanya, OJ and Adebayo, UO and Obadeyi, KB and Othman, ZK and Lucero-Prisno, DE}, title = {Exploring the gut-brain-microbiome axis in Alzheimer's disease: Integrating metagenomics, metabolomics, and artificial intelligence for next-generation biomarker discovery.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877251407700}, doi = {10.1177/13872877251407700}, pmid = {41460655}, issn = {1875-8908}, abstract = {Alzheimer's disease (AD), a progressive neurodegenerative disorder, is increasingly understood as a multifactorial condition influenced by systemic and environmental factors beyond the central nervous system. A growing body of evidence shows that the gut-brain-microbiome axis (GBMA), a complex bidirectional communication network, is involved in neural, endocrine, immune, and metabolic pathways in AD pathogenesis. This narrative review synthesizes emerging insights into the role of gut microbiota dysbiosis in promoting neuroinflammation, amyloid-β aggregation, blood-brain barrier disruption, and cognitive decline. We explored recent advancements in metagenomics and metabolomics for profiling microbial communities and their functional metabolites linked to AD. Alterations in microbe-derived compounds, such as short-chain fatty acids and tryptophan metabolites, influence neurodevelopment, glial activation, and mitochondrial dysfunction. Multi-omics integration, enhanced by artificial intelligence (AI), enables precise biomarker discovery, patient stratification, and the development of personalized therapeutic strategies. Translational opportunities include microbiome-based diagnostics, probiotic therapy, and stratified interventions. However, clinical translation faces challenges such as methodological heterogeneity, inter-individual microbiome variation, data governance issues, and algorithmic bias. We emphasize the need for diverse reference panels, longitudinal multimodal cohorts, and shared AI-ready datasets to enhance the reproducibility and global equity of research. Strategic investment in integrative, ethically governed, and interdisciplinary approaches is essential to unlock the full therapeutic and diagnostic potential of GBMA in AD.}, } @article {pmid41460370, year = {2025}, author = {Wang, G and Li, X and Ren, P and Ai, Q and Wang, Z}, title = {Integrative Microbiome-Genetic Analysis Reveals Mechanisms of Fishmeal-Free Feed Adaptability in Large Yellow Croaker (Larimichthys crocea).}, journal = {Marine biotechnology (New York, N.Y.)}, volume = {28}, number = {1}, pages = {6}, pmid = {41460370}, issn = {1436-2236}, mesh = {Animals ; *Perciformes/microbiology/genetics/physiology ; *Gastrointestinal Microbiome/genetics ; *Animal Feed/analysis ; Diet/veterinary ; RNA, Ribosomal, 16S/genetics ; Polymorphism, Single Nucleotide ; Bacteria/classification/genetics ; Adaptation, Physiological/genetics ; }, abstract = {To address the challenge of fishmeal shortage and improve the utilization of fishmeal-free (FMF) diets in large yellow croaker (Larimichthys crocea), we conducted an integrative analysis combining host genetics and gut microbiota. A 28-day indoor feeding trial was performed with 185 fish using an FMF-based diet, during which single nucleotide polymorphism (SNP) genotyping and feed efficiency evaluations were conducted. The V3-V4 regions of the 16S rRNA gene were sequenced from both distal (DI) and proximal (PI) intestinal segments. Significant microbial contributions (microbiability) were only observed for daily feed intake (DFI) and residual feed intake (RFI). Microbiability estimates reached 0.25 (DI) and 0.17 (PI) for DFI, while RFI in DI exhibited higher microbiability (m[2] = 0.11) than heritability (h[2] = 0.08). In contrast, correlations between host genetic variation and microbial community distances were extremely weak. We further identified heritable microbial taxa, including Lactococcus, Alicyclobacillus acidoterrestris, and Bacillus, as well as microbial biomarkers such as Lactococcus, Listeria, Methylobacterium, and Alicyclobacillus acidoterrestris, which were significantly associated with FMF feed adaptation. These findings highlight the complementary roles of host genetics and gut microbiota in shaping FMF feed utilization in marine fish, and provide valuable targets for selective breeding of strains with enhanced adaptability to plant-based diets.}, } @article {pmid41460363, year = {2025}, author = {Wang, C and Li, H and Wang, T and Li, X and Liu, J and Deng, A and Jiao, X}, title = {The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {57}, pmid = {41460363}, issn = {1573-2630}, support = {2024BSQD05//the Doctoral Startup Fund of the Affiliated Hospital of Shandong Second Medical University/ ; ZR2025QC815//the Shandong Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Probiotics/therapeutic use ; Dysbiosis ; *Immunomodulation ; *Eye Diseases/therapy/microbiology/immunology ; }, abstract = {PURPOSE: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.

METHODS: PubMed and Web of Science were searched (January 2020-October 2025) using the terms "gut microbiota", "ocular diseases", and "immunomodulatory therapies". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.

RESULTS: Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.

CONCLUSIONS: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.}, } @article {pmid41459968, year = {2025}, author = {Nishimura, Y and Okumura, K and Oiki, S and Ogura, K and Hashimoto, W}, title = {Molecular evolution and diversity of isomerase-reductase clusters involved in the bacterial metabolism of glycosaminoglycans.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0081725}, doi = {10.1128/msphere.00817-25}, pmid = {41459968}, issn = {2379-5042}, abstract = {Glycosaminoglycans (GAGs), comprising uronic acids and amino sugars, are widely distributed in human tissues such as the intestine and oral cavity. Various bacteria colonize these tissues by assimilating GAGs. During GAG degradation, 4-deoxy-l-threo-5-hexosulose uronate (DHU) is produced. Pectin, an abundant plant component, is also degraded into DHU. DHU is metabolized in a stepwise manner by the isomerase KduI or its nonhomologous isofunctional enzyme DhuI, followed by the reductase KduD or DhuD, belonging to the same reductase-dehydrogenase family. Previous studies have found that the genes encoding isomerase and reductase (kduI-kduD and dhuD-dhuI, respectively) are usually organized in clusters. Therefore, it was believed that the kduI-kduD and dhuD-dhuI clusters evolved independently. However, the discovery of a hybrid kduI-dhuD cluster raised questions regarding the evolution of these clusters. This study investigated the diversity of clusters through a pan-genomic phylogenetic analysis across 3,550 bacterial strains. Among 16 possible cluster structures, 10 types were involved in DHU metabolism. Bacteroidota possessed a hybrid-type kduI-dhuD cluster, while Bacillota, but not Pseudomonadota or Bacteroidota, possessed the cluster dhuD-dhuI. Using public data sets from the human fecal microbiome and environmental habitats, we detected the prevalence of kduI-dhuD and dhuD-dhuI clusters in gut microbes. Although DHU is generated from oligomerized GAG degradation by unsaturated glucuronyl hydrolase (UGL), the UGL gene was frequently found in pathogenic strains containing kduD-kduI, dhuD-dhuI, kduI-dhuD, or dhuD-kduI, indicating that the acquisition of these clusters is advantageous for human colonization.IMPORTANCEGlycosaminoglycans (GAGs), crucial components of the extracellular matrix, play vital roles in host infection by pathogenic bacteria and host colonization by commensal bacteria. The dhuD-dhuI cluster is well conserved within certain phyla, and it appears to have a strong association with GAG metabolism. In contrast, kduI-containing clusters are more widely distributed across bacterial species. Based on the possession ratios of genes encoding the enzymes involved in the production of 4-deoxy-l-threo-5-hexosulose uronate, this study indicates that the substrates differ depending on the specific cluster type.}, } @article {pmid41459926, year = {2025}, author = {Bu, F and Zhang, K and Song, B and He, L and Lu, Z and Yuan, X and Chen, C and Jiang, F and Tao, Y and Zhang, W and Zhang, D and Chen, Y and Wang, Q}, title = {Akkermansia muciniphila alleviates experimental colitis through FXR-mediated repression of unspliced XBP1.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0158925}, doi = {10.1128/msystems.01589-25}, pmid = {41459926}, issn = {2379-5077}, abstract = {UNLABELLED: Endoplasmic reticulum (ER) stress-related mucin depletion could be involved in the pathogenesis of ulcerative colitis (UC). Akkermansia muciniphila (A. muciniphila) uses mucin as its sole energy source and shows potential in the treatment of colitis. However, the effects and underlying mechanisms of A. muciniphila on colonic epithelial ER stress in colitis are largely unknown. Colitis was induced by adding 2.5% dextran sulfate sodium (DSS) in drinking water. Mice were orally administered A. muciniphila (3*10[^]7, 3*10[^]8 cfu/day) once daily for 10 days during DSS intervention. Ultra high performance liquid chromatography q-exactive orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS)-based metabolomic analyses were performed on feces. 16S rRNA sequencing was used to quantify and characterize the gut microbiota of mice. Metabolomic analysis showed that P-hydroxyphenyl acetic acid (p-HPAA), the metabolite with the highest variable importance in projection (VIP) score that was elevated by A. muciniphila, was negatively correlated with acetic acid levels and exhibited a potential inhibitory effect on ER stress. Additionally, A. muciniphila supplementation decreases the abundance of Parasutterella, a genus implicated in bile acid homeostasis. By restoring the levels of deoxycholic (DCA) and ursodeoxycholic acid (UDCA), A. muciniphila administration normalized the bile acid pool size and composition altered by colitis. A. muciniphila supplementation protected colon shortening and histological injury in wild-type (WT) mice, but not in farnesoid X receptor-null (FXR[-/-]) mice. Mechanistically, our results demonstrate that A. muciniphila alleviates DSS-induced colitis by targeting inositol requiring enzyme 1α(IRE1α) and unspliced XBP1 (XBP1u) within the ER stress pathway, with the regulation of XBP1u being FXR-dependent. Supplementation with A. muciniphila at appropriate doses may, thus, offer a promising therapeutic strategy for Ulcerative colitis (UC).

IMPORTANCE: UC is a chronic inflammatory disease in which inflammation begins in the rectum and extends proximally throughout the colon. A.muciniphia is significantly reduced in UC patients and shows promise as a next-generation probiotic. However, the mechanisms behind its protective effects are not fully understood. Our study reveals that A. muciniphila alleviates experimental colitis by reshaping the gut microbiome and correcting imbalances in bile acid metabolism. Crucially, we identify a novel mechanism where A. muciniphila acts through the host bile acid receptor FXR to suppress a specific ER stress pathway (XBP1u) in colon cells, thereby helping to restore the intestinal barrier. These findings provide a scientific basis for using A. muciniphila as a targeted therapeutic strategy for UC.}, } @article {pmid41459925, year = {2025}, author = {Ruzickova, M and Palkovicova, J and Nesporova, K and Rysava, M and Pariza, R and Krejci, S and Literak, I and Dolejska, M}, title = {From ecology to evolution: plasmid- and colicin-mediated persistence of antibiotic-resistant Escherichia coli in gulls.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0166325}, doi = {10.1128/msystems.01663-25}, pmid = {41459925}, issn = {2379-5077}, abstract = {UNLABELLED: Antimicrobial resistance (AMR) in wildlife is an emerging concern within the One Health concept. Gulls, due to their synanthropic behavior and long-distance migration, are recognized as vectors and secondary reservoirs of resistant bacteria. These birds can facilitate the environmental spread of resistant strains across ecosystem boundaries. Understanding their role in shaping microbial communities is essential for assessing the broader ecological impact. This study investigates the persistence and competitive dynamics of cephalosporin-resistant Escherichia coli in Caspian gulls (Larus cachinnans) captured at their breeding colony at a water reservoir and subsequently monitored in captivity for three months, representing the longest in vivo experiment of its kind conducted on wild birds. We observed sustained colonization and long-term shedding of resistant E. coli throughout the entire study, marking the longest documented carriage of resistant bacteria in wild birds to date. Notably, rapid dissemination of various E. coli sequence types (STs) with CTX-M-1 was observed, with ST11138 rapidly outcompeting other strains, including the initially dominant ST11893. Genomic analyses revealed that ST11138 harboured F24:A-:B1 and IncI1/ST3/CTX-M-1 plasmids encoding colicins and corresponding immunity genes, likely conferring a competitive advantage. Our findings underscore the role of bacteriocin-mediated interactions in shaping microbial communities and highlight the importance of plasmid-encoded traits in the persistence of resistant strains in wildlife. Importantly, our findings underscore the ecological novelty of longitudinal in vivo tracking of AMR persistence in natural hosts and highlight the need to consider ecological and microbiome-level interactions when assessing the environmental dimension of AMR under the One Health concept.

IMPORTANCE: Antimicrobial resistance (AMR) in wildlife is an emerging concern within the One Health framework, with gulls recognised as important vectors and secondary reservoirs of resistant bacteria. Due to their synanthropic behavior and long-distance migration, these birds can facilitate the spread of resistant strains across ecosystems. However, the role of wildlife in resistance dynamics remains underexplored, especially in long-term, natural settings. Our study is unique in its scope and duration, representing the longest in vivo experiment of its kind conducted on wild birds. By capturing these processes in live hosts under naturalistic conditions and across an extended period, our study provides rare and ecologically grounded insights into how AMR is maintained outside clinical or laboratory settings. Our findings show sustained colonisation and long-term shedding of resistant E. coli, with strain ST11138 outcompeting others. Genomic analyses reveal plasmid-encoded traits, highlighting the ecological and evolutionary mechanisms underlying resistance maintenance in wildlife.}, } @article {pmid41459804, year = {2026}, author = {van Kalkeren, CAJ and van Deuren, T and Coenjaerds, MMJ and Galazzo, G and Barnett, DJM and Penders, J and Hartmann, B and Holst, JJ and Canfora, EE and Blaak, EE}, title = {Effects of a slowly fermentable fiber mixture against the background of a high-protein diet on insulin sensitivity and metabolic health in individuals with overweight: a randomized, placebo-controlled trial.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606473}, doi = {10.1080/19490976.2025.2606473}, pmid = {41459804}, issn = {1949-0984}, mesh = {Humans ; *Dietary Fiber/metabolism/administration & dosage ; Male ; *Overweight/metabolism/diet therapy/microbiology ; *Insulin Resistance ; Female ; Adult ; Fermentation ; Middle Aged ; Gastrointestinal Microbiome ; *Diet, High-Protein ; Fatty Acids, Volatile/metabolism ; Dietary Supplements ; Obesity/metabolism ; Solanum tuberosum/chemistry ; }, abstract = {The gut microbiota ferments dietary fibers, producing short-chain fatty acids (SCFA). Enhanced SCFA production in the distal colon has been linked to improved cardiometabolic health. However, most fibers are fermented proximally, resulting in increased protein fermentation distally, producing metabolites putatively harmful to metabolic health. This 12-week randomized, placebo-controlled trial aimed to improve metabolic health through increasing distal SCFA production while inhibiting proteolytic fermentation using a fiber supplement that increased distal SCFA production in vitro. We assessed the effects of daily potato fiber/sugar beet pectin supplementation (fiber, n = 19) versus maltodextrin (placebo, n = 21), both added to a high-protein diet (25E% protein, ±45% plant-based), on peripheral insulin sensitivity (IS) in adults with overweight/obesity. Secondary outcomes included tissue-specific IS, body composition, microbial composition and functionality, substrate metabolism, and gut permeability. Peripheral IS tended to decrease after fiber supplementation compared to placebo (p = 0.081), while whole-body IS significantly decreased (p = 0.034). Fiber mitigated the increase in insulin-mediated carbohydrate oxidation (p = 0.027) and decrease in fat oxidation (p = 0.006) that occurred in the placebo group. Additionally, fiber prevented an increase in protein oxidation (p = 0.048), while increasing colonic gut permeability (p = 0.046) and plasma interleukin-6 (p = 0.025). Body composition, microbial composition, and fecal and circulating metabolites remained unchanged. In conclusion, fibers combined with a high-protein diet reduced (peripheral) IS and decreased metabolic flexibility compared to placebo. Reduced protein oxidation after fiber may reflect diminished amino acid bioavailability. Additionally, coadministration of fiber and protein may compromise gut barrier function and inflammatory responses. More research investigating the interplay between dietary fibers and proteins is needed.}, } @article {pmid41459742, year = {2025}, author = {Kwon, Y and Choi, J and Kim, SH and Kim, PJ and Lee, SM and Cha, JK and Park, H and Kang, JW and Jo, SM and Kwak, YS and Kim, D and Kim, WJ and Lee, JH and Ryu, CM}, title = {Rice gs3 allele and low-nitrogen conditions enrich rhizosphere microbiota that mitigate methane emissions and promote beneficial crop traits.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf284}, pmid = {41459742}, issn = {1751-7370}, abstract = {Methane emissions from rice paddies represent a critical environmental concern in agriculture. Although genetic strategies for mitigating emissions have gained attention, the specific microbial and molecular mechanisms remain underexplored. Here, we investigated how the gs3 loss-of-function allele in the near-isogenic rice line Milyang360 modulates rhizosphere and endosphere microbial communities under distinct nitrogen regimes. Field experiments revealed that Milyang360 consistently reduced methane emissions compared with its parental line, Saeilmi, particularly under low-nitrogen conditions. Integrated plant transcriptomic and rhizosphere metagenomic analyses, including the reconstruction of Metagenome-Assembled Genomes, demonstrated that the gs3 allele upregulated genes related to root hair elongation or promoting microbial symbiosis. This physiological change limited substrate availability for methanogens and facilitated the colonization by beneficial microorganisms. Consequently, we observed a functional shift in the microbiome, characterized by the enrichment of methanotrophs and nitrogen-fixing bacteria. This microbial restructuring was most prominent under low-nitrogen conditions, indicating a strong genotype by environment interaction. Our findings highlight the gs3 allele's dual role in reducing methane emissions and improving nitrogen use efficiency by recruiting a beneficial microbiome. This study provides a clear mechanistic link between a plant gene and rhizosphere ecology, offering a promising genetic target for developing sustainable, low emission rice cultivars.}, } @article {pmid41459728, year = {2026}, author = {Parthasarathy, A and Li, T and Edelblum, KL}, title = {Crosstalk between the microbiota and intestinal γδ T cell compartments in health and IBD.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2604908}, doi = {10.1080/19490976.2025.2604908}, pmid = {41459728}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology ; Humans ; *Receptors, Antigen, T-Cell, gamma-delta/immunology/metabolism/genetics ; *Intestinal Mucosa/immunology/microbiology ; *Intraepithelial Lymphocytes/immunology ; Mice ; Bacteria/immunology ; Peyer's Patches/immunology/microbiology ; *T-Lymphocytes/immunology ; }, abstract = {Unconventional T cells expressing the γδ T cell receptor (TCR) are abundant within the intestine and largely function as 'first responders' to injury, infection and inflammation. To this end, murine γδ T cells are highly compartmentalized within the intestinal mucosa based on the expression of their Vγ chain and their effector function. The activation status also differs among these γδ T cell populations to ensure a timely and appropriate response within their local microenvironment. In this review, we will examine the role of γδ T cell populations in the epithelium (i.e. intraepithelial lymphocytes), the lamina propria and Peyer's patches and discuss the influence of the gut microbiota on the maintenance and effector function of each compartment. We will also highlight how γδ T cells contribute to the host response to luminal bacteria and how this reciprocal crosstalk is disrupted in the context of inflammatory bowel disease (IBD). An enhanced understanding of how γδ T cells function within distinct mucosal compartments and their regulation by commensal bacteria may lead to the development of novel microbiome-based therapies for IBD.}, } @article {pmid41459531, year = {2025}, author = {Nikolaidis, CG and Gyriki, D and Stavropoulou, E and Karlafti, E and Didangelos, T and Tsigalou, C and Thanopoulou, A}, title = {Targeting the TLR4 axis with microbiota-oriented interventions and innovations in diabetes therapy: a narrative review.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1701504}, pmid = {41459531}, issn = {1664-3224}, mesh = {Humans ; *Toll-Like Receptor 4/metabolism/immunology ; *Gastrointestinal Microbiome/immunology/drug effects ; Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 2/therapy/immunology/microbiology/metabolism ; Animals ; Signal Transduction ; NF-kappa B/metabolism ; *Diabetes Mellitus, Type 1/therapy/immunology/microbiology/metabolism ; Insulin Resistance ; }, abstract = {The gut microbiota-Toll-like receptor 4(TLR4)-nuclear factor kappa B(NF-κB) signaling is a key controller of low-grade chronic inflammation and insulin resistance in type 1 (T1DM) and type 2 diabetes mellitus (T2DM). While TLR4-mediated inflammation contributes to both T1DM and T2DM, the bulk of microbiota-targeted interventions have been studied in T2DM. The focus of the current review is on T2DM, with relevant parallels in T1DM noted where appropriate. Modulation of this pathway by dietary natural bioactive molecules, fecal microbiota transplantation (FMT), and technological innovations hold therapeutic promise for the reconstitution of metabolic and immune homeostasis. Agents like celastrol, berberine, paeoniflorin, and licorice extract exhibit anti-inflammatory and antidiabetic effects by TLR4/Myeloid differentiation primary response 88(MyD88)/NF-κB signaling inhibition. FMT enhanced β-cell function and insulin sensitivity with evidence of immune-metabolic modulation. New technologies, like ingestible biosensors and gut-on-chip platforms, allow real-time monitoring and precision modulating of the microbiota. Gastric bypass-induced microbial remodeling is linked to long-term glycemic benefit. Pharmacological, surgical, and technological manipulation of gut microbiota-immune interactions is a potential complementary strategy to diabetes. The future encompasses personalized microbiota-matching, controlled FMT regimens, and incorporation of digital therapeutics into microbiome-based precision medicine.}, } @article {pmid41459520, year = {2025}, author = {Ariizumi, H and Shimazui, M and Ogawa, C and Kaneki, M and Saito, N and Mura, E and Suzuki, R and Tsurui, T and Iriguchi, N and Ishiguro, T and Hirasawa, Y and Shimokawa, M and Ohkuma, R and Kubota, Y and Horiike, A and Wada, S and Yoshimura, K and Murakami, K and Tsunoda, T}, title = {Vinegar intake in patients undergoing immune checkpoint inhibitor therapy: food frequency questionnaire study.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1640603}, pmid = {41459520}, issn = {1664-3224}, mesh = {Humans ; Female ; Male ; *Immune Checkpoint Inhibitors/therapeutic use ; Aged ; Middle Aged ; *Acetic Acid/administration & dosage ; *Neoplasms/drug therapy/immunology ; Surveys and Questionnaires ; Gastrointestinal Microbiome ; Dietary Fiber ; Treatment Outcome ; Aged, 80 and over ; Japan ; Adult ; }, abstract = {INTRODUCTION: The gut microbiome is increasingly recognized as a key modulator of immune checkpoint inhibitor (ICI) efficacy. Dietary factors, particularly fibers, may influence the microbiome and thus affect the ICI response. Although Western studies have suggested a link between high fiber intake and better outcomes, this relationship remains unclear in Japanese populations with different dietary habits. This study investigated dietary components associated with ICI response in Japanese patients with cancer.

METHODS: In total, 32 patients with carcinomas treated with ICIs were enrolled. Nutritional customs before ICI infusion were analyzed using a food frequency questionnaire.

RESULTS: Among the 331 dietary items, only vinegar (acetic acid) intake showed an independent association with the treatment response. Higher vinegar consumption correlated with significantly lower odds of nonresponse (P = 0.017). In contrast, total and fermentable dietary fiber intake showed no significant association with ICI efficacy or survival outcomes.

CONCLUSIONS: Higher vinegar intake is associated with better ICI response in Japanese patients, whereas fiber has a limited effect. Thus, tailored dietary strategies are needed for optimal outcomes.}, } @article {pmid41459433, year = {2025}, author = {Bhojiya, AA and Saurabh, A and Jain, D}, title = {Editorial: Microbial therapeutics: harnessing the human microbiome for disease treatment and prevention.}, journal = {Frontiers in medical technology}, volume = {7}, number = {}, pages = {1751147}, doi = {10.3389/fmedt.2025.1751147}, pmid = {41459433}, issn = {2673-3129}, } @article {pmid41459350, year = {2025}, author = {Agusti, S and Alothman, A and Jin, P and Stanschewski, CS and Díaz-Rúa, R and Emwas, AH and Singh, U and Jaremko, M}, title = {Host metabolite production and microbiome dynamics: effects of long-term diatom adaptation to warming.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf103}, pmid = {41459350}, issn = {2730-6151}, abstract = {Marine diatoms contribute significantly to global oceanic primary production, constituting ~25% of earth production but are susceptible to the impacts of ocean warming. While organisms' adaptation to rising temperatures may mitigate these impacts, it could also disrupt species interactions, including those between hosts and their microbiomes. In our study, we examined thermal performance and diversity changes in the microbiome of the tropical diatom Chaetoceros tenuissimus after long-term adaptation to ambient (LA) and warming (LW) temperatures. We observed notable shifts in the metabolomic profile, with amino acids accumulating after LW adaptation and sugars accumulating after LA, while lipids content remained unchanged. After LW, the microbiota increased maximum growth rate without changing its temperature optimum. Roseovarius sp. dominated the microbiome community at both LA (49.6%) and LW strains (42.8%) proving a strong partnership. Extinctions were highest under warming occurring in the low-abundant genera, but different partners developed increasing richness, with changes induced in the core microbiome. Short-term warming, however, resulted in decreased richness. Beta diversity was associated with long-term adaptation instead of assay temperature. Our findings align with general plant species association models, suggesting that long-term evolution of mutualisms enhances diversity and strength, particularly under warming in the marine partnership studied here. Our experimental results highlight the importance of examine long-term coevolution of host- microbiome partnerships to improve our understanding of consequences of warming.}, } @article {pmid41459349, year = {2025}, author = {Nandi, S and Stephens, TG and Walsh, K and García-Camps, R and Villalpando, MF and Sellares-Blasco, RI and Zubillaga, AL and Croquer, A and Bhattacharya, D}, title = {Shifts in the microbiome and virome are associated with stony coral tissue loss disease (SCTLD).}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf226}, pmid = {41459349}, issn = {2730-6151}, abstract = {Stony coral tissue loss disease (SCTLD) is a rapidly spreading lethal coral disease, the etiology of which remains poorly understood. In this study, using deep metagenomic sequencing, we investigated microbial and viral community dynamics associated with SCTLD progression in the Caribbean stony coral Diploria labyrinthiformis. We assembled 264 metagenome-assembled genomes and correlated their abundance with disease phenotypes, which revealed significant shifts in both the prokaryotic microbiome and virome. Our results provide clear evidence of microbial destabilization in diseased corals, suggesting that microbial dysbiosis is an outcome of SCTLD progression. We identified DNA viruses in our dataset that increase in abundance in SCTLD-affected corals and are present in existing coral data from other Caribbean regions. In addition, we identified the first putative instance of asymptomatic/resistant SCTLD-affected corals. These are apparently healthy colonies that share the viral profile of diseased individuals. However, these colonies contain a different prokaryotic microbiome than do diseased corals, suggesting microbe-induced resilience (i.e. beneficial microbiome) to SCTLD. Finally, utilizing differential abundance analysis and gene inventories, we propose a mechanistic model of SCTLD progression, in which viral dynamics may contribute to microbiome collapse. These findings provide novel insights into SCTLD pathogenesis and offer consistent molecular signals of disease across diverse geographic sites, presenting new opportunities for disease monitoring and mitigation.}, } @article {pmid41459229, year = {2025}, author = {Mulec, J and Pašić, L and Oarga-Mulec, A}, title = {Metabolic traits of sediment bacteria in karst caves in the light of environmental changes.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1724116}, pmid = {41459229}, issn = {1664-302X}, abstract = {INTRODUCTION: Karst subterranean systems are vulnerable ecosystems that have not yet been studied adequately at the microbial functional level. Cave sediments deposited over different time periods host diverse microbial communities that play a critical role in nutrient cycling and pollutant degradation.

METHODS: In this study, we investigated microbial diversity and metabolic capacity in recently deposited alluvial sediments and an ancient palaeo-river deposit in a karst cave system. Using 16S rRNA gene amplicon metagenomic analysis, community-level physiological profiling (CLPP), and chemical characteristics of the environment, the influence of key environmental factors on microbial community composition and substrate degradation, concentrating particularly upon sediment age, oxygen availability, and temperature, was assessed.

RESULTS: The results showed different microbiome compositions and metabolic characteristics between sites. The old alluvial sediment exhibited low taxonomic and functional diversity, accompanied by elevated heavy-metal concentrations, suggesting that sediment age might act as a geochemical filter, limiting microbial function. In contrast, a periodically flooded site showed high metabolic versatility and taxonomic diversity, emphasizing the ecological role of hydrological pulses in maintaining functional microbial diversity. CLPP metrics linked community structure to functional potential, revealing adaptive traits in key taxa such as Polaromonas, Methylibium, and Beggiatoa.

DISCUSSION: These results demonstrated the value of integrating functional and taxonomic approaches in subsurface environments and provide insights into microbial resilience, biogeochemical processes, and the potential for applied environmental use.}, } @article {pmid41459217, year = {2025}, author = {Li, P and Wang, M and Zhang, H and Gao, X and Chen, L and Chen, H and Xu, Q and Chen, W and Liu, W and Dai, M}, title = {Integrative metagenomic and metabolomic profiling identifies gut microbial and metabolite signatures associated with lymph node metastasis in pancreatic cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1706084}, pmid = {41459217}, issn = {1664-302X}, abstract = {BACKGROUND: Lymph node metastasis (LNM) is a prognostic factor in pancreatic cancer. The association between the gut microbiota and LNM remains unexplored. This study aimed to characterize the gut microbiota and metabolomic profiles associated with LNM and to investigate their potential as predictive biomarkers.

METHODS: Fecal samples from pancreatic cancer patients undergoing surgery were analyzed using metagenomic sequencing and untargeted metabolomics. The patients were categorized into LNM and non-LNM (NLNM) groups. Differential microbiome taxa were analyzed using the DESeq2 package. Random forest predictive models were developed based on metagenomic and metabolomic data, with performance assessed using leave-one-out cross-validation (LOOCV).

RESULTS: A total of 26 patients with LNM and 29 patients without LNM were included. Principal coordinates analysis (PCoA) revealed significant differences in microbiota composition between the two groups (Anosim, p = 0.047). The absolute counts of Ruminococcus gnavus and Blautia wexlera were significantly decreased in LNM. Tryptophan-derived metabolites, indole-3-lactic acid (3-ILA) and indole-3-acrylic acid (3-IA), were downregulated in LNM. Functional pathway analysis showed downregulation of tryptophan metabolism in LNM, while cancer-related pathways were upregulated. Correlation analysis revealed a significant positive association between Ruminococcus gnavus and 3-ILA/3-IA levels. Moreover, Ruminococcus gnavus was positively correlated with CD8[+] T cells. Predictive models based on the gut microbiota and metabolites distinguished LNM from NLNM, with AUC values of 0.854 and 0.940, respectively.

CONCLUSION: The gut microbiota and metabolites exhibit significant alterations during lymph node metastasis in pancreatic cancer, especially Ruminococcus gnavus, Blautia wexlera, and tryptophan metabolites (3-ILA and 3-IA). Gut microbial and metabolite signatures may serve as potential non-invasive biomarkers for predicting LNM in pancreatic cancer. Further functional validation is required to determine whether and how the gut microbiota and metabolites may mediate lymph node metastasis.}, } @article {pmid41459215, year = {2025}, author = {Liu, P and Zhang, Y and Chen, X and Tang, L and Xu, W and Wang, G and Zhang, D and Liu, J}, title = {Effect of IFN-τ on intestinal flora and metabolomics of Escherichia coli-mediated endometritis in mice.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1687781}, pmid = {41459215}, issn = {1664-302X}, abstract = {Endometritis is a common reproductive disease in dairy cows, which can lead to low fertility or infertility and cause significant economic losses to the dairy farming industry. IFN-τ is a type I interferon that may exert significant anti-inflammatory effects in inflammatory diseases. With breakthroughs in microbial mapping sequencing and metabolomics, the role between gut flora and host metabolism and disease has been revealed from a completely new perspective. Therefore, the aim of this study was to investigate the role of IFN-τ in a mouse model of E. coli-induced endometritis by 16S rRNA sequencing and LC-MS untargeted metabolomics, the results showed that IFN-τ could affect the flora structure of the mouse intestine. The E. coli-induced endometritis in mice was found to be associated with five different metabolites and three potential metabolic pathways by LC-MS non-targeted metabolomics, which were the major players in the metabolic pathways, namely Arginine biosynthesis, Pyruvate metabolism, Arginine and proline metabolism. This may be an important metabolic pathway for IFN-τ intervention in endometritis mice. Combining the results of gut flora and metabolomics analyses suggest that changes in metabolic pathways may be influenced by gut flora. We hypothesize that IFN-τ is likely to exert its anti-inflammatory effects by regulating the levels of Oscillospira and Clostridium flora in the gut, which in turn affects the expression of five differential metabolites in uterine tissues.}, } @article {pmid41459155, year = {2025}, author = {Starodubova, A and Leonov, G and Shaposhnikova, N and Varaeva, Y and Livantsova, E and Fotin, D and Kirichenko, T and Bagheri Ekta, M and Markina, Y and Koshechkin, S and Orekhov, A and Nikityuk, D}, title = {Gut and oral microbiome profiles in patients with obesity and ischemic heart disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1695279}, pmid = {41459155}, issn = {2235-2988}, mesh = {Humans ; *Obesity/microbiology/complications ; Male ; *Myocardial Ischemia/microbiology/complications ; Female ; *Gastrointestinal Microbiome ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; *Mouth/microbiology ; *Bacteria/classification/genetics/isolation & purification ; Aged ; *Microbiota ; Adult ; DNA, Bacterial/genetics/chemistry ; DNA, Ribosomal/chemistry/genetics ; }, abstract = {BACKGROUND: Ischemic heart disease (IHD) and obesity are major contributors to global mortality. Both conditions are linked to systemic inflammation, dyslipidemia, and microbiota alterations. This study examines the relationship between the composition of the gut and oral microbiota, obesity, and IHD to gain insight into the interconnections between these factors.

METHODS: The study included 182 participants divided into four groups based on obesity and IHD status. Anthropometric and biochemical analyses were performed. Oral and gut microbiomes were analyzed using 16S rRNA sequencing.

RESULTS: Obesity and IHD were associated with distinct microbiota compositions. Obesity-IHD subjects showed elevated levels of gut Streptococcus, Intestinibacter, alongside reduced Citrobacter, Ruthenibacterium, Parabacteroides, and Flavonifractor. The oral microbiota exhibited decreased Alloprevotella, Capnocytophaga, Prevotellamassilia, and Campylobacter in Obesity-IHD. Correlation analysis highlighted associations between microbial taxa (e.g., Blautia, Oscillibacter) and clinical parameters like BMI, blood pressure, and cholesterol.

CONCLUSIONS: This study demonstrates that obesity and IHD are linked to unique microbiota alterations. Microbial dysbiosis may contribute to the pathogenesis of these conditions and should be considered as a therapeutic target in the development of personalized treatment strategies of the obesity and associated cardiovascular complications.}, } @article {pmid41459154, year = {2025}, author = {Chen, W}, title = {Editorial: Natural compounds from plant: microbiome-targeted therapeutic strategy for gastrointestinal disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1736556}, doi = {10.3389/fcimb.2025.1736556}, pmid = {41459154}, issn = {2235-2988}, } @article {pmid41459150, year = {2025}, author = {Chavez-Bueno, S and Lawrence, SM}, title = {Editorial: Advancing understanding of neonatal bacterial infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1746698}, pmid = {41459150}, issn = {2235-2988}, } @article {pmid41459147, year = {2025}, author = {Tye, KD and Liu, X and Huang, C and Li, C and Wu, C and Lin, J and Yu, Y and Lin, X}, title = {Probiotic modulation of maternal gut and milk microbiota and potential implications for infant microbial development in the perinatal period.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1715989}, pmid = {41459147}, issn = {2235-2988}, mesh = {Humans ; *Probiotics/administration & dosage ; Female ; Pregnancy ; *Gastrointestinal Microbiome/drug effects ; *Milk, Human/microbiology ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Adult ; Infant, Newborn ; Infant ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {BACKGROUND: Probiotics are live microorganisms that may enhance or restore gut microbiota. They are often recommended during pregnancy and infancy for potential benefits, but evidence is inconclusive. This study aimed to investigate probiotic supplementation's effects on maternal and infant gut and milk microbiota and its link to nutrient intake during pregnancy.

METHOD: A total of 23 pregnant women were enrolled and divided into a probiotic group (n = 11) and a non-probiotic control group (n=12). Probiotic effects were evaluated through fecal and milk microbiota analysis via 16S rRNA gene sequencing. Nutrient intake data were collected to assess differences linked to probiotics. Key microbiota diversity and richness were analyzed using linear discriminant analysis effect size (LEfSe) and weighted gene co-expression network analysis (WGCNA) to explore associations with diet and sample characteristics. Predictive microbial pathway characteristics were identified using time series analysis, random forest algorithms, and logistic regression models.

RESULTS: Nutrient intake did not significantly differ between groups, and overall microbial diversity and richness were stable. However, LEfSe revealed distinct genera in both maternal gut and milk microbiota linked to probiotic intake. WGCNA identified microbial modules correlated with specific nutrient patterns and sampling conditions. Predictive genus clusters associated with probiotics demonstrated robust classification performance, suggesting functional shifts in microbial communities with potential implications for immune programming in early life.

CONCLUSION: Probiotic supplementation during pregnancy may modulate key microbial taxa in maternal gut and milk, potentially influencing microbial recognition and immune signaling in the maternal-infant dyad. These findings highlight complex diet-microbiota-immune interactions within reproductive and lactational systems, offering insights into strategies for enhancing maternal and neonatal health resilience.}, } @article {pmid41459064, year = {2025}, author = {Anderson, M and Hrivnak, W and Prak, K and Stockert, A}, title = {Potential effects of cinnamon on cancer prevention and progression.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1717834}, pmid = {41459064}, issn = {2296-861X}, abstract = {Cinnamon has been used medicinally for centuries, but recently in vitro research has suggested it may have a role in cancer prevention and potentially treatment. The search for alternative and subjunctive therapies is essential due to the public demand and the increasing cost of healthcare. Here we review the biologically active components of cinnamon and discuss the methods of potential cinnamon activity against cancer, including: transcription factor regulation and kinase activity. Nuclear Factor kappa B (NFκB) is a stress sensitive transcription factor that regulates transcription of genes involved in tumor progression and is inhibited by cinnamon components. Another way that cinnamon inhibits tumor growth is by suppression of transcription factor activator protein 1 (AP1) which interacts with genes responsible for apoptosis, metastasis and inflammation. Hypoxia-inducible transcription factor 1 (HIF1) and vascular endothelial growth factor (VEGF) are involved in angiogenesis, especially in the tumor microenvironment. The HIF1-VEGF pathway is a target of cinnamaldehyde, a compound found in cinnamon. Nuclear factor erythroid related factor 2 (Nrf2) is also examined and has been indicated to affect cancer progression and potentially provide preventative measures; various cinnamon derivatives target Nrf2. A cinnamaldehyde derivative has been implicated in a reduction of the mitogen-activated protein kinases (MAPKs), which are a group of kinases that regulate proliferation. Additionally, cinnamon components have been tied to cancer prevention by positively affecting the gut microbiome and inhibiting inflammation. The review concludes with a discussion of the future research needed, including the need for clinical studies and potential risk associated with cinnamon intake.}, } @article {pmid41459062, year = {2025}, author = {Li, W and Gunn, A and Zheng, X and Ma, J and Sheng, N and Wang, B}, title = {Exploring human milk oligosaccharides: mechanisms linking gut function to cognitive development in human and pig physiology.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1700954}, pmid = {41459062}, issn = {2296-861X}, abstract = {Human milk oligosaccharides (HMOs) are emerging as key modulators of host physiology, with growing evidence supporting their role in shaping gut microbial communities and influencing neurocognitive outcomes. This review critically examines the impact of HMOs on gut health and behavioral responses, focusing on the complex relationship between HMOs and host physiology in both human and pigs. Given their anatomical, physiological, and microbiome similarities to humans, pigs serve as a valuable translational model for investigating the functional roles of HMOs. We summarize experimental methodologies employed in HMO research and highlight findings that demonstrate HMO-induced alterations in microbial diversity, gut integrity, and cognitive performance. Potential mechanisms of action, including gut-brain axis signaling, immune modulation, and microbial metabolite production, are explored. This review concludes by identifying current knowledge gaps and proposing future research directions aimed at elucidating HMO structure-function relationships, with implications for advancing both human nutrition and animal health.}, } @article {pmid41459056, year = {2025}, author = {Auclair-Ouellet, N and Kassem, O and Bronner, S and Oula, ML and Binda, S}, title = {Leveraging microbiome-based interventions to improve the management of neurodegenerative diseases: evidence for effects along the microbiota-gut-brain axis.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1699884}, pmid = {41459056}, issn = {2296-861X}, abstract = {The microbiota-gut-brain axis (MGBA) has recently emerged as a useful model for the understanding of the onset and progression of neurodegenerative diseases (NDDs). Microbiome-based interventions using biotic supplements (probiotics, prebiotics, synbiotics, postbiotics) can modulate the MGBA and constitute relevant solutions to help reduce the risk of neurological changes associated with NDDs and manage symptoms. This narrative review provides a summary of the functioning of the MGBA and of its interactions with disease processes involved in the onset and progression of NDDs. Microbiome-based interventions and their mechanisms of action are reviewed, and important considerations for the design of interventions are discussed. Next, preclinical and clinical studies on the potential of microbiome-based interventions in Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are reviewed. Evidence related to biomarkers of pathology (e.g., beta-amyloid or alpha-synuclein protein depositions), neuroinflammation, and metabolic activity is summarized, along with emerging evidence for the improvement of clinical symptoms and disease trajectories. Overall, preclinical studies show that microbiome-based supplements have significant positive effects on mechanisms and pathways involved in the pathophysiology of NDDs. Clinical studies show that these interventions provide important benefits both in terms of biomarkers and clinical symptoms. However, evidence is limited in some key clinical areas, such as mental wellbeing in AD and cognition in PD, and for the management of clinical symptoms in ALS and HD overall. Gaps in knowledge and open questions as well as perspectives for future research are discussed.}, } @article {pmid41458968, year = {2025}, author = {Jing, Y and Huicong, D and Xuanchi, G and Cao, L and Huanhuan, Z and Yongze, G}, title = {Fraxin modulates lipid metabolism as well as gut flora to avert NAFLD.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1657966}, pmid = {41458968}, issn = {1663-9812}, abstract = {BACKGROUND: Public healthcare systems are heavily burdened by non-alcoholic fatty liver disease (NAFLD), which is the leading "chronic liver disorder" around the globe. Fraxin, a natural compound extracted from Fraxini cortex in traditional Chinese medicine, exerts hepatoprotective effects. However, the mechanism by which fraxin alleviates NAFLD remains elusive. This research looks into fraxin's therapeutic potential in NAFLD management using an integrated experimental and pharmacological strategy.

METHODS: First, network pharmacology was used to identify core therapeutic targets of fraxin for NAFLD. Second, we built protein-protein interaction (PPI) networks, followed by "Gene Ontology (GO)" along with "Kyoto Encyclopedia of Genes and Genomes (KEGG)" pathways. Molecular docking validated the interaction of fraxin with its predicted targets. To confirm fraxin's therapeutic effect in vivo, we built a "methionine-choline-deficient" (MCD) diet-induced NAFLD mouse model. Comprehensive assessments included liver function tests, hepatic triglyceride content, inflammatory marker measurement, mRNA expression for key lipid metabolism enzymes through reverse transcription-polymerase chain reaction, fatty acid translocase/cluster of differentiation 36 (FAT/CD36) expression through Western blotting, and 16S ribosomal RNA sequencing to assess changes in metabolic dysfunction and the gut microbiota.

RESULTS: Network pharmacology identified 34 potential fraxin targets in NAFLD. GO and KEGG analyses suggested that fraxin primarily treats NAFLD by modulating lipid metabolism and atherosclerosis-related signaling pathways. In vivo, fraxin significantly lowered liver index and visceral fat accumulation, reduced serum levels of "interleukin-6 (IL-6)," "aspartate aminotransferase," "tumor necrosis factor-α (TNF-α)" and "alanine aminotransferase," and decreased hepatic TG content. Furthermore, fraxin downregulated IL-6 and TNF-α expression and lowered the gene and protein levels of FAT/CD36, controlling key targets in signaling pathways related to lipid metabolism and atherosclerosis. Additionally, fraxin altered the gut microbial composition, reducing the Firmicutes/Bacteroidota ratio while increasing the abundance of Bacteroidota, Bacteroidia, Bacteroidales, Prevotellaceae, and Alloprevotella. Therefore, fraxin attenuated gut microbiota dysbiosis in mice caused by the MCD diet.

CONCLUSION: Fraxin alleviates MCD diet-induced NAFLD by controlling lipid metabolism as well as restoring the homeostasis of gut microbiota.}, } @article {pmid41458802, year = {2025}, author = {Brasse, P and Zerdka, J and Staszkiewicz, K and Staszkiewicz, KK and Piszka, M and Kwapien, E and Bartkowski, J and Kubicka, M and Czarnecki, F}, title = {Intermittent Fasting: Efficacy, Safety, and Its Impact on Body Weight, Glucose Metabolism, and Gut Microbiota.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97773}, pmid = {41458802}, issn = {2168-8184}, abstract = {Intermittent fasting (IF) has gained significant attention as a nutritional strategy with potential health-promoting effects. It typically involves periodic restriction of calorie intake or limiting the daily eating window. Growing scientific interest has led to a wide range of clinical and observational research exploring its biological and metabolic impacts. Existing studies suggest that IF may positively influence metabolic health, weight management, and cellular processes. However, the breadth of findings varies, and questions remain regarding its long-term safety and effectiveness across diverse populations, especially individuals with chronic conditions. A comprehensive evaluation of the current evidence is therefore warranted. An analysis of 55 publications, including clinical trials, observational studies, and review articles, was conducted. These sources were examined to assess the effects of various forms of IF on metabolic health, diabetes-related outcomes, gut microbiome composition, and broader physiological functions. Across most studies, IF was associated with moderate but clinically meaningful weight loss, enhanced insulin sensitivity, reductions in blood pressure, and improvements in lipid profiles. Some evidence also pointed to beneficial changes in gut microbiota, decreased oxidative stress, and increased autophagy activity. Comparisons with traditional caloric restriction indicate similar levels of effectiveness and safety, with IF potentially offering better adherence for certain individuals. Despite these promising outcomes, the current evidence base lacks long-term studies and comprehensive evaluations in specific clinical populations, limiting conclusions about sustained benefits and generalizability. IF appears to be a promising approach for the prevention and management of obesity and metabolic disorders. Its combination of physiological benefits and relative ease of implementation makes it an appealing strategy. Nonetheless, further long-term and population-specific research is needed to fully establish its safety, durability, and applicability across diverse groups.}, } @article {pmid41458699, year = {2025}, author = {Chavhan, PKB and Sayeed, MS and Saiyad, SS and Shah, MN and Ekambaram, G and Panchal, H and B H, G and Js, S}, title = {Lactose Intolerance in Irritable Bowel Syndrome: Prevalence, Subtype Correlations, and Clinical Predictors in an Indian Cohort.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97697}, pmid = {41458699}, issn = {2168-8184}, abstract = {Irritable bowel syndrome (IBS) and lactose intolerance (LI) frequently coexist, complicating diagnosis and management due to overlapping abdominal pain, bloating, and altered bowel habits. This study aimed to quantify LI prevalence in IBS and delineate clinical predictors to inform targeted care. We conducted a single-center observational study (July 2021-December 2022) at a tertiary hospital in North India, enrolling 100 adults with Rome IV-defined IBS. Standardized hydrogen breath testing identified lactose malabsorption; demographic, dietary, and symptom data were collected, and associations were evaluated using chi-square tests and logistic regression with a prespecified α = 0.05. LI was present in 38 (38%) IBS patients in this study. The diarrhea-predominant (IBS-D) subtype showed the strongest association with LI (OR = 5.92; 95% CI 2.1-16.8; p < 0.001), whereas the constipation-predominant (IBS-C) subtype was least affected. Higher habitual lactose intake (≥26 g/day) correlated with greater symptom frequency (p < 0.001). The cohort's mean age was 36.8 ± 11.4 years, and most reported symptoms for ≥1 year, underscoring chronicity. No significant associations were observed with sex or BMI categories. These findings demonstrate that unrecognized LI contributes substantially to symptom burden in Indian IBS populations, particularly IBS-D. Incorporating structured dietary assessment and selective breath testing into diagnostic algorithms can reduce misclassification, avoid unnecessary pharmacotherapy, and enable individualized lactose restriction. The study provides population-specific evidence supporting diet-responsive, precision strategies for IBS care and highlights the value of simple, noninvasive diagnostics in resource-constrained settings. Prospective multicenter trials integrating microbiome and dietary interventions are warranted to refine subtype-specific, nutrition-based management.}, } @article {pmid41458698, year = {2025}, author = {Darwish, S and Razdolsky, N and Ditty, K and Torres, A and Mathew, S and Ali, S and Izhar, A and Ghazzawi, J and Phillips, C and Braun, A and Costin, JM}, title = {The Effects of Vaginal Virome on Women's Health: A Scoping Review.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97876}, pmid = {41458698}, issn = {2168-8184}, abstract = {While research on the vaginal microbiome (VMB) has focused mainly on its bacteriome, the role of viral communities remains largely understudied. Given the vaginal virome's potential influence on disease susceptibility and progression, understanding its exact role in different health outcomes is crucial. The objective of this scoping review was to analyze studies on the vaginal virome's influence on women's health, the virome's interactions with other microbes, assess the limitations of these studies, and highlight gaps to guide future studies and treatments in the field of gynecological health. The review was conducted using previously gathered literature on the impact of the vaginal virome among reproductive-aged women in developed countries. Articles were sourced from Ovid MEDLINE, Embase, and World of Science using the following search string: vaginal virome AND reproductive health OR infections OR pregnancy outcomes. Articles were screened using the PCC framework as follows: influence of the vaginal virome on women's health (Concept) in women aged 18 and older (Population) in developed countries (Context). Of the 352 articles originally identified, 10 studies met the inclusion criteria and were utilized in this scoping review. The vaginal virome contains a diverse array of viruses and bacteriophages that impact human papillomavirus (HPV) infection persistence and subsequent progression to cervical cancer, pregnancy outcomes, and the inflammatory response. In bacterial vaginosis, reductions in Lactobacillus-targeting bacteriophages have the potential to contribute to dysbiosis. Hormonal fluctuations throughout the menstrual cycle influence both bacterial and viral populations, potentially affecting infection susceptibility and overall vaginal health. During pregnancy, higher viral diversity is associated with preterm birth risk, and immune modulation by the virome may impact susceptibility to infections like HPV. Analysis of the included studies indicates the need for continued investigation of the manner in which the vaginal virome interacts with other aspects of the microenvironment to influence women's health. This scoping review highlights the new and emerging role of the vaginal virome in women's health, highlighting its relationship with other microbes and clinical significance. These findings underscore the importance of the vaginal virome in reproductive health, suggesting that further research is needed to better understand its role and guide effective prevention and treatment strategies.}, } @article {pmid41458627, year = {2025}, author = {Ma, J and Tao, M and Zhang, W and Zhou, L and Zhang, H and Li, F and Zhang, H and Yao, D and Lu, W and Wang, M}, title = {Tirzepatide modulates gut microbiota homeostasis to protect against diabetic kidney disease.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1715024}, pmid = {41458627}, issn = {2296-889X}, abstract = {PURPOSE: This study evaluated the effect of Tirzepatide on metabolic profiles, kidney function, and gut microbiota composition in mice with diabetic kidney disease (DKD) and clarify the relationship between gut microbiota alterations and the renoprotective effects.

METHODS: Seven-week-old diabetic db/db mice and db/m controls were randomly assigned to three groups: db/db, db/db-T, and db/m. In the db/db-T group, mice received 10 nmol/kg Tirzepatide injections for a duration of 8 weeks. Biochemical and histopathological analyses were used to assess body weight, blood glucose, lipid profile, hepatic and renal function, and renal histopathological changes in mice. An antibiotic-pretreated group (ABX-db/db-T) was established to explore the impact of gut microbiome depletion on the therapeutic effects of Tirzepatide.The composition of gut microbiota was determined through 16S rRNA gene sequencing to assess microbial differences among groups.

RESULTS: Tirzepatide notably decreased fasting blood glucose (FBG), food intake, body weight, glycated hemoglobin A1c (HbA1c), blood lipid levels, and liver function markers, while improving renal function in mice. The renoprotective effects of Tirzepatide were attenuated following gut microbiota depletion. Microbiota analysis revealed that Tirzepatide could reverse dysbiosis and reshape the gut microbial ecosystem. Tirzepatide treatment raised the proportion of beneficial genera, Clostridium_sensu_stricto_1 and Romboutsia, while reducing potentially pathogenic genera, Erysipelatoclostridium and Bacteroides. Moreover, these microbiota changes were significantly correlated with serum creatinine and urinary albumin/creatinine ratio.

CONCLUSION: Tirzepatide improves renal function and metabolic parameters in DKD mice through gut microbiome regulation. The underlying mechanism involves the modulation of gut-renal axis through the optimization of microbial composition, promoting the development of beneficial bacteria while inhibiting harmful microbes. These results establish a foundational understanding for the use of Tirzepatide in DKD and suggest that combined interventions targeting the gut microbiota may have potential clinical value.}, } @article {pmid41458603, year = {2025}, author = {Oh, B and Lamoury, G and Carroll, S and Morgia, M and Boyle, F and Pavlakis, N and Clarke, S and Guminski, A and Menzies, A and Diakos, C and Moore, K and Baron-Hay, S and Eade, T and Molloy, M and Back, M}, title = {The gut microbiome as a potential predictive biomarker for breast cancer: emerging association and geographic differences.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1666830}, pmid = {41458603}, issn = {2234-943X}, abstract = {BACKGROUND: The gut microbiome may influence breast cancer (BC) development by modulating estrogen metabolism, immune responses, and microbial metabolites. Altered microbial patterns have been reported in BC, but their value as predictive biomarkers remains uncertain.

METHODS: We reviewed 13 case-control studies that compared gut microbiome composition in women with and without BC, focusing on diversity, compositional shifts, and geographic variation.

RESULTS: Reduced microbial richness (alpha diversity, the number and balance of bacterial species) was observed in more than half of the studies, although findings were not uniform. Differences in community composition (beta diversity) were common. Across studies, BC was consistently associated with elevated Bacteroides and reduced Faecalibacterium, a genus linked to anti-inflammatory effects. Other recurrent findings included enrichment of Eggerthella and Blautia in BC, though results for several taxa were inconsistent. Geographic variation was evident: Eggerthella was enriched in U.S. cohorts, Blautia in European cohorts, and in Chinese cohorts, Prevotella was elevated while Akkermansia was reduced.

CONCLUSIONS: Despite heterogeneity, converging evidence supports reduced diversity and shifts in select taxa, particularly enrichment of Bacteroides and depletion of Faecalibacterium, as emerging features of the BC microbiome. Geographic differences underscore the influence of host and environmental factors. These findings suggest biomarker potential but highlight the need for larger, longitudinal, and standardized studies to establish causality and clinical utility.}, } @article {pmid41458324, year = {2025}, author = {Harcęko-Zielińska, E and Górska, A and Romantowski, J and Małgorzewicz, S and Gruchała-Niedoszytko, M and Wypych, TP and Gutowska-Owsiak, D and Abouali, R and Chełmińska, M and Niedoszytko, M}, title = {Changes in the Gut Microbiome is Influenced by the Level of Control and Treatment in Asthma.}, journal = {Journal of asthma and allergy}, volume = {18}, number = {}, pages = {1857-1867}, pmid = {41458324}, issn = {1178-6965}, abstract = {BACKGROUND: The influence of intestinal microorganisms on the development and course of allergic diseases has recently been the subject of intensive research, but studies describing changes in the intestinal microbiome of asthma patients in response to altering factors are still scarce.

OBJECTIVE: (1) the analysis of eating habits composition of intestinal microbiota and BMI in asthma patients compared to the control group, (2) the comparison of the results of the analyzed parameters in asthma patients and in the control group, (3) the analysis of asthma treatment results depending on the composition of intestinal microbiota.

METHODS: Clinical stool isolates were cultured and genetic material was sequenced. The study included 49 subjects with asthma and a control group of 18 healthy volunteers. Clinical data was collected through questionnaires on the most frequently reported symptoms and the FFQ questionnaire. The composition of intestinal microbiota was determined using the traditional breeding method (the serial dilution method was used) followed by 16S rRNA sequencing.

RESULTS: Patients with asthma reported the greatest severity of clinical symptoms in all the body systems examined.The most common cause of the aberrant stool test results was E. coli, with titers <10[6]. The was no difference in the dietary habits between the asthma patients and the control group. Alpha and beta diversity, was significantly lower in asthma patients compared to the control group. Asthma patients had lower abundance of Faecalibacterium vs healthy volunteers. Statistically significant depletion of Oscilospirales, Anaerovoracaceea, was demonstrated in patients with uncontrolled asthma compared to controlled and partially controlled asthma. In patients taking glucocorticoids (oral and inhaled) enriched intestinal microbiota in Anaerovoracaceae and Christensenellaceae and depleted Faecalibacterium were observed.

CONCLUSION: Patients with asthma showed less richness and diversity in the composition of their intestinal microbiota compared to the control group.}, } @article {pmid41458320, year = {2025}, author = {Ghiotto, G and Francescato, L and Biancalani, MA and Treu, L and Campanaro, S}, title = {Hydrogen excess drives metabolic reprogramming and viral dynamics in syngas-converting microbiomes.}, journal = {Environmental science and ecotechnology}, volume = {28}, number = {}, pages = {100637}, pmid = {41458320}, issn = {2666-4984}, abstract = {Microbial communities drive essential bioprocesses, including the conversion of synthesis gas into biomethane, a sustainable energy source that supports circular carbon economies. In anaerobic environments, specialized consortia of bacteria and archaea facilitate syngas methanation through syntrophic interactions, where hydrogenotrophic methanogens play a central role in reducing carbon dioxide and monoxide with hydrogen. However, imbalances in gas ratios, particularly excess hydrogen, can disrupt these interactions and impair overall efficiency. Yet, the molecular mechanisms underlying microbial responses to such imbalances remain poorly understood. Here we show that hydrogen excess triggers profound metabolic and viral remodeling in a thermophilic anaerobic microbiome, leading to reduced methane yields and ecological instability. This reprogramming involves transcriptional downregulation of methanogenesis genes in the dominant archaeon Methanothermobacter thermautotrophicus, coupled with upregulation of CRISPR-Cas and restriction-modification systems that correlate with diminished activity of an associated phage, indicating activated host defenses against viral threats. Concurrently, bacterial species such as those from Tepidanaerobacteraceae enhance carbon fixation via the Wood-Ljungdahl pathway, serving as electron sinks to mitigate redox imbalance. These adaptive responses highlight the microbiome's resilience mechanisms under stress, revealing viruses as both stressors and selective forces in syntrophic systems. Such insights advance our understanding of microbiome dynamics in bioconversion processes and guide the engineering of more stable microbial consortia for optimized syngas-to-methane conversion amid variable feedstocks.}, } @article {pmid41458082, year = {2025}, author = {Njom Nlend, AE and Nkwelle Mekone, I and , }, title = {Human Milk Oligosaccharides, Microbiome, Antiretroviral Therapy and HIV Infected Mothers: Reasons to Still Promote Breastfeeding in HIV Context of Lactating Countries, a Mini-Narrative Review.}, journal = {Sage open pediatrics}, volume = {12}, number = {}, pages = {30502225251408582}, pmid = {41458082}, issn = {3050-2225}, abstract = {Breastfeeding is the preferred feeding for newborns during the first 6 months of life and until the age of 2 years or beyond. The benefits of breastfeeding remain significant, even in cases of HIV infection. The introduction of antiretroviral therapy(ART) has greatly reduced the risk of HIV transmission from mother to child through breastfeeding. As a result, breast milk is recommended for infants born to HIV-positive mothers, regardless of the mother's HIV status. Nevertheless, breastfeeding still poses a risk of HIV transmission in the era of eliminating vertical transmission. This mini-narrative review will highlight the continued benefits of breast milk for both HIV-infected and uninfected infants, focussing on the changes in bioactive components of breast milk, such as human milk oligosaccharides, and their effects on the gut microbiota. Additionally, this review will recommend strategies to improve safe breastfeeding practices in the context of HIV when mothers are receiving ART.}, } @article {pmid41457605, year = {2025}, author = {Lin, X and Li, C and Xu, X and Jiang, J}, title = {[Synthetic microbiome design: applications and challenges from theoretical construction to environmental bioremediation].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {41}, number = {11}, pages = {4298-4320}, doi = {10.13345/j.cjb.250436}, pmid = {41457605}, issn = {1872-2075}, mesh = {*Biodegradation, Environmental ; *Microbiota/physiology ; *Synthetic Biology/methods ; *Environmental Pollutants/metabolism/isolation & purification ; }, abstract = {As artificially constructed microbial communities with specific functions, synthetic microbiomes have shown great application potential in bioremediation in recent years. Compared with single strains, synthetic microbiomes have significant advantages in mineralizing complex pollutants and simultaneously metabolizing multiple pollutants. The construction of synthetic microbiomes involves various strategies and methods, which contribute to the design of microbial communities with diverse functions and adaptability to different environments. Conventional experiment-based studies on synthetic microbiomes often struggle to systematically elucidate the complex metabolic interactions among microbial community members, which limits the design and application of synthetic microbiomes. Genome-scale metabolic model (GSMM) technology has paved new avenues for the design, construction, and functional optimization of synthetic microbiomes. This review concentrates on the advantages of synthetic microbiomes in bioremediation and the current theories and strategies involved in the design and construction of synthetic microbiomes, and highlights the application potential of GSMMs in the design of synthetic microbiomes and the bioremediation of polluted environments. This paper can provide a theoretical basis and technical support for the research on synthetic microbiomes and their application in environmental bioremediation.}, } @article {pmid41457383, year = {2025}, author = {Wu, X and Wang, D and Mao, X and Dong, B and Wang, Y}, title = {Microbiome-Driven Resistance in Cervical Cancer Therapy: From Mechanistic Dissection to Clinical Translation.}, journal = {Expert reviews in molecular medicine}, volume = {}, number = {}, pages = {1-45}, doi = {10.1017/erm.2025.10029}, pmid = {41457383}, issn = {1462-3994}, } @article {pmid41457316, year = {2025}, author = {Zhao, C and Chang, X and Fan, L and Jiang, L and Zhong, R}, title = {Innovative manure via hyper-thermophilic fermentation coupled with heat-resistant phosphate-solubilizing Bacillus inoculation promotes phosphorus transformation by assembling keystone taxa in the oat rhizosphere.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0120825}, doi = {10.1128/aem.01208-25}, pmid = {41457316}, issn = {1098-5336}, abstract = {UNLABELLED: Phosphorus forms and distribution in organic manures vary under different treatment conditions, thereby exerting distinct effects on the soil microbiome and soil phosphorus transformation process. This study examined the effects of a novel manure treated with hyper-thermophilic fermentation combined with Bacillus strain inoculation, compared with raw and composted manure, on the oat rhizosphere microbiome and phosphorus transformation across different soil types in a controlled pot experiment. Our findings demonstrate that hyper-thermophilic fermentation with Bacillus inoculation not only promotes the survival and abundance of the bacterial genus Bacillus but also selectively enriches the hyper-thermophilic bacterial genus Thermobifida in the fermented manure. Notably, the application of hyper-thermophilic fermented manure led to a significant enrichment of keystone species like Bacillus and Thermobifida across both soil types, relative to other manure applications. These genera emerged as key drivers of available phosphorus, phosphatase activity, and differential metabolites in the rhizosphere, exhibiting a synergistic effect on soil phosphorus transformation. Fermented manure exhibited superior performance relative to conventional composted manure, as it increased the phosphorus uptake rate of oats by 35.5% in black soil and 27.9% meadow soil, respectively, over a single growing season. Additionally, among all organic manures, the application of fermented manure significantly enhanced the sequestration of phosphorus from manure in the soils, with 78.0% in black soil and 56.9% in meadow soil. This consequently reduced P loss to 13.6% and 34.4% in the respective soil types.

IMPORTANCE: Phosphate-solubilizing microorganisms (PSMs) are frequently proposed as catalysts for promoting phosphorus recycling; however, their performance is often inefficient or ineffective in the context of a circular bioeconomy within agricultural systems. This study introduces innovative concepts and methodologies by integrating hyper-thermophilic fermentation with heat-resistant phosphate-solubilizing Bacillus inoculation, thereby enhancing the effective phosphorus recovery and utilization from manure waste in sustainable agricultural practices.}, } @article {pmid41457314, year = {2025}, author = {Hosmer, M and Wright, RJ and McCavour, C and Keys, K and Sterling, S and Langille, MGI and Rohde, J}, title = {Lime amendment to chronically acidified forest soils results in shifts in prokaryotic communities.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0217124}, doi = {10.1128/aem.02171-24}, pmid = {41457314}, issn = {1098-5336}, abstract = {A consequence of past acid rain events has been chronic acidification of Nova Scotian forests, leading to a loss of essential nutrients and subsequent decreases in forest productivity and biodiversity. Liming-supplementing forests with crushed limestone-can restore essential nutrients to acidified soils and increase the pH of soils and the carbon capture by forests through the promotion of tree growth. Liming treatments are often assessed through tree growth measurements, although little is known about how microorganisms respond to these changes in pH and nutrient availability. Understanding the impacts of liming on microbial communities will help determine whether liming is a good remediation strategy for Nova Scotia. A pilot study evaluating liming in acidified forests in Nova Scotia began in 2017. Microbiome analysis (prokaryotic 16S and fungal ITS2 rRNA gene amplicon sequencing) of three different horizons (depths; upper forest floor, lower forest floor, and upper B horizon) of soil in a softwood forest area showed significant differences between lime-treated and control soils for the prokaryotic but not fungal communities, particularly in the uppermost soil horizon. Several genera from the Alphaproteobacteria class were significantly higher in abundance in treated than control soils, whereas genera from the Acidobacteriia (previously Acidobacteriae) class were significantly lower in abundance in treated versus control soils. Soil chemistry analysis of the same three horizons showed a significant increase in base cations and pH of the uppermost soil horizon in control versus treatment sites.IMPORTANCEForests are increasingly being managed with an emphasis on understanding how forests function. Lime amendments are used to promote forest health and increase resilience to climate change. To date, only a handful of studies have analyzed the effects of liming on microbial communities in forest soils. Our study combines soil chemistry with prokaryotic and fungal communities of limed and control soils. Shifts in microbial composition that are coincident with liming may provide early indications of the effectiveness of liming and provide insight into the roles of microbes in forest health.}, } @article {pmid41457274, year = {2025}, author = {Catry, A and Abrouk, D and Fierling, N and Mendoza, AIS and Rey, M and Vesga, P and Heiman, CM and Garrido-Sanz, D and Bouffaud, ML and Buscot, F and Giongo, A and Smalla, K and Comte, G and Keel, C and Muller, D and Moënne-Loccoz, Y}, title = {Biogeography influences plant-microbe interactions and natural soil suppressiveness to black root rot disease of tobacco.}, journal = {Genome biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13059-025-03911-0}, pmid = {41457274}, issn = {1474-760X}, support = {BiodivERsA3 ERA-Net SuppressSOIL//Biodiversa+/ ; grant SuppressSOIL no. ANR19-EBI3-0007//Agence Nationale de la Recherche/ ; grant SuppressSOIL no. 31BD30_186540//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; grant no. 51NF40_180575//NCCR Microbiomes/ ; BU 941/30-1//Deutsche Forschungsgemeinschaft/ ; project DiControl 031A560A-F//Bundesministerium für Bildung und Forschung/ ; }, abstract = {BACKGROUND: In disease-suppressive soils, the rhizosphere microbiota protects plants from root disease(s). However, the soil microbiome follows distinct spatial patterns, and the biogeographic factors shaping plant-microbe interactions and soil suppressiveness remain poorly understood. Here, we use Swiss and Savoie soils suppressive or conducive to Thielaviopsis basicola-mediated black root rot of tobacco, to test the hypothesis that plant-microbe interactions and suppressiveness are influenced by both the geological origin and geographic positioning of soils. Soils are compared based on tobacco health, soil physicochemistry and organic matter profiles, taxonomic and functional microbial diversity, and plant physiological responses.

RESULTS: Soil physicochemistry and metabolomic profiling of soil organic matter show differences based on suppressiveness status, soil geology and geography. The taxonomic (metabarcoding of prokaryotes and fungi) and functional (metagenomics) diversity of the tobacco rhizosphere reveals that the microbiota is influenced by geography and geology which, in turn, affects suppressiveness. Additionally, shoot metabolomics shows that tobacco responses are impacted by soil geography and geology, particularly in Savoie soils regarding two nicotinic derivatives.

CONCLUSIONS: Overall, suppressiveness is influenced by both the geological origin and geographic positioning of the soils, with distinct patterns in the two regions. In Swiss soils, suppressiveness is primarily associated with major differences in rhizosphere microbiota composition and functions between suppressive and conducive soils. In contrast, in Savoie soils, suppressiveness is linked to distinct plant physiological responses (pointing to induced systemic resistance) rather than strong microbial shifts. This study highlights the importance of considering the biogeographic features shaping disease-suppressive soils and their microbiota-plant interactions.}, } @article {pmid41415463, year = {2025}, author = {Hinzke, T and Kunath, BJ and Blakeley-Ruiz, JA and Korenek, A and Vintila, S and Wilmes, P and Kleiner, M}, title = {Evaluation of statistical approaches for differential metaproteomics.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41415463}, issn = {2692-8205}, support = {P30 DK034987/DK/NIDDK NIH HHS/United States ; R35 GM138362/GM/NIGMS NIH HHS/United States ; }, abstract = {Metaproteomics characterizes and compares molecular phenotypes of organisms in communities by comprehensively analyzing their protein expression profiles using statistical methods. However, not all statistical methods are suitable for determining differentially abundant protein groups in metaproteomic analyses. Statistical challenges in metaproteomics include: data sparsity, non-normality, compositionality, and large between-sample variability. These challenges can potentially be addressed with several data processing steps, including imputation, normalization, transformation, and selection of the appropriate statistical tests. The potential combinations of different processing methods create a complex matrix of analysis options and it is currently unclear how these combinations impact the results of statistical tests on metaproteomic data. To determine what data processing methods and statistical tests are best for identifying differentially abundant proteins in metaproteomics datasets, we generated a set of thirteen metaproteomic samples with known compositions, known differences, and differing levels of complexity. These defined metaproteomes address the general challenges outlined above, using various scenarios in metaproteomic data analyses. We compared over 110 different statistical analysis combination options, including regression-based tools, general statistics inference, and machine learning techniques. Our work enables improved assessment of statistical methods for metaproteomics by establishing a framework for testing statistical approaches, including comprehensive raw mass spectrometry data and reproducible benchmarking code. We found that several combinations within the frameworks of limma, edgeR, MaAslin2, custom linear and Bayesian linear models, and random forests all offer suitable evaluation options, and highlight key recommendations for differential expression analysis in metaproteomics.}, } @article {pmid41457176, year = {2025}, author = {Paul, D and Talukdar, D and Kapuganti, RS and Gupta, V and Narendrakumar, L and Jana, P and Kumar, P and Singh, J and Kumari, S and Basak, C and Kamboj, K and Bakshi, S and Lal, S and Tanwar, S and Kumar, R and Babele, P and Bajpai, M and Kumar, Y and Mutreja, A and Mandal, S and Wadhwa, N and Banerjee, SK and Das, B}, title = {Antibiotic contamination and antimicrobial resistance dynamics in the urban sewage microbiome in India.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-68034-3}, pmid = {41457176}, issn = {2041-1723}, support = {RAD/22017/19/2022-KGD-DBT//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; GCI-13012/2/2025-GCl//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; }, abstract = {The emergence and spread of antimicrobial resistance (AMR) in clinically important bacterial pathogens has severely compromised the effectiveness of commonly used antibiotics in healthcare. Acquisition and transmission of AMR genes (ARGs) are often facilitated by sublethal concentrations of antibiotics in microbially dense environments. In this study, we use sewage samples (n = 381) collected from six Indian states between June and December 2023 to assess the concentration of eleven antibiotics, microbial diversity, and ARG richness. We find antibiotics from seven drug classes and detect over 2000 bacterial amplicon sequence variants (ASVs). Metagenomic (n = 220) and isolated genome sequences (n = 305) of aerobic and anaerobic bacterial species identify 82 ARGs associated with 80 mobile genetic elements (MGEs). These MGEs are predominantly present in multidrug-resistant (MDR) bacterial pathogens. Comparative core genome analysis of MDR bacterial isolates (n = 7166) shows strong genetic similarity between sewage-derived strains and clinical pathogens. Our results highlight sewage as a significant reservoir for ARGs, where genetic exchanges occur and facilitate the evolution and spread of AMR pathogens in both community and healthcare settings. Additionally, the dipstick-based assay developed for ARGs detection can be used for sewage surveillance in low-resource settings for better understanding of resistance prevalence.}, } @article {pmid41457081, year = {2025}, author = {Priyadarshani, HMC and Mierzejewska-Sinner, E and Kózka, B and Giebułtowicz, J and Urbaniak, M}, title = {Benomyl modulates paracetamol bioaccumulation and endophytic microbiome diversity in zucchini.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-33977-6}, pmid = {41457081}, issn = {2045-2322}, support = {2023/51/B/NZ9/00540//Narodowe Centrum Nauki/ ; }, abstract = {Paracetamol, a widely used analgesic and antipyretic, has emerged as a prevalent environmental pollutant that poses risks to various organisms, including plants. Phytoremediation, particularly the use of Cucurbitaceae family plants, offers a promising, eco-friendly approach to mitigate such pollutants. This study investigated the bioaccumulation of paracetamol in zucchini (Cucurbita pepo cv. Atena Polka) and explored the role of the fungicide benomyl in modulating paracetamol bioaccumulation. Additionally, the impacts of these compounds on zucchini health (measured by biomass, chlorophyll content, and phenolic compound concentrations) and on the diversity of the endophytic microbiome (assessed via the Biolog EcoPlate™ and identification of isolated endophytes via 16S rRNA gene sequencing) were evaluated. Four treatments were assessed over a 28-day cultivation period: control (no pharmaceutical or fungicide), paracetamol (25 mg/kg) (P), paracetamol + benomyl (P + B), and benomyl alone (B). The results revealed that paracetamol accumulated significantly more in the roots of the P variant, but notably, the P + B variant presented a 24-fold increase in paracetamol concentration in aboveground tissues compared with the P variant. The bioaccumulation factors indicated that benomyl significantly enhanced the translocation of paracetamol to aerial parts in the P + B variant. Compared with the control, all the treatments reduced plant biomass, with the lowest values observed in the P variant. The chlorophyll content, in turn, was the highest in the P + B treatment, suggesting that benomyl helped mitigate oxidative stress. The levels of phenolic compounds, particularly flavonoids and phenylpropanoids, were elevated in the P variant, indicating a stress response. Additionally, the endophytic microbial community showed diminished diversity in the P variant. In the P + B variant, in turn, the microbial diversity measured via Biolog Ecoplates and 16S rRNA gene sequencing was greater. Our findings demonstrate that benomyl significantly enhanced the accumulation of paracetamol in the aerial parts of zucchini while promoting the resilience of plants and their associated endophytic bacteria and improving their potential for the phytoremoval of pharmaceutical pollutants.}, } @article {pmid41457079, year = {2025}, author = {Moraskie, M and Li, S and Codina, JR and Roshid, MHO and Núño, K and O'Connor, G and Dikici, E and Deo, S and Beurel, E and Daunert, S}, title = {DPO production by gut commensals suggests a broader role in bacterial communication and host-microbiome interactions.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00886-5}, pmid = {41457079}, issn = {2055-5008}, abstract = {The quorum-sensing molecule 3,5-dimethylpyrazine-2-ol (DPO), known for regulating biofilm formation in Vibrio cholerae, has unknown distribution among commensal bacteria. We screened 37 bacterial strains using a validated biosensor and found widespread production. Inoculating mice with high producers elevated gut DPO levels, highlighting DPO's potential influence on gut microbiota. These findings expand DPO's ecological relevance and underscore quorum sensing as a potentially critical influence on microbiome function and host-microbe interactions.}, } @article {pmid41456898, year = {2025}, author = {Mao, C and Zhang, Q and Zhang, J and Li, X}, title = {Omics Analysis of Lignin Degradation by the Gut Microbiomes of Wood-Eating Hypomeces squamosus Fabricius.}, journal = {MicrobiologyOpen}, volume = {14}, number = {6}, pages = {e70208}, doi = {10.1002/mbo3.70208}, pmid = {41456898}, issn = {2045-8827}, support = {E5290504//"First Action Plan for Attracting Talents" of the Chinese Academy of Sciences-Category B/ ; }, mesh = {*Lignin/metabolism ; *Gastrointestinal Microbiome ; Animals ; Wood/metabolism ; Metabolic Networks and Pathways/genetics ; *Isoptera/microbiology/metabolism ; *Bacteria/classification/genetics/metabolism/isolation & purification ; }, abstract = {Microbial degradation of lignin is important to carbon cycling. The gut microbiome of wood-feeding Hypomeces squamosus Fabricius has been shown to degrade lignin efficiently. However, the specific degradation mechanisms remain incompletely understood. In this study, we investigated the mechanism of lignin degradation using omics comparative analysis, focusing on differentially expressed genes and metabolic pathways in the gut microbiome of insects fed with a lignin-rich diet. The dominant genus taxon was Pantoea (29.82%), which was predominant in insects fed with high lignin-containing Iris ensata Thunberg, whereas Wolbachia and Enterobacter were predominant in insects fed with cabbage leaves (MHS_K group). Furthermore, expression levels of carbohydrate-active enzymes from the auxiliary activities (AAs) families in the MHS_I group were 1.18 times higher than those in the MHS_K group. These mainly included lignin peroxidase and manganese peroxidase of the AA2 family, vanillyl-alcohol oxygenase of the AA4 family, and 1,4-benzoquinone reductase of the AA6 family. Expression levels of multiple genes encoding aromatic compound-degrading genes (2303 accounted for 75.76% of the total upregulated genes) were found, including about 0.03% was related to lignin degradation. Genes MHS-HN_11398_2 (protocatechuate 2,3-dioxygenase) and MHS-HN_4821_1 (muconolactone d-isomerase) were enriched in the MHS_I group. Three lignin-degrading pathways were found: ortho-cleavage and meta-cleavage of catechol, as well as ring-opening of protocatechuate. This study provides a comprehensive and theoretical evidence of the gut microbiome roles of H. squamosus Fabricius in lignin degradation.}, } @article {pmid41456824, year = {2025}, author = {Quan, H and Ouyang, J and Fu, X and Lin, D and Wu, Q and Li, D and Li, Y and Yang, F and Wu, S and Li, C and Mao, W}, title = {Elucidating the Therapeutic Mechanism of Orthosiphon aristatus in Hyperuricemic Nephropathy: An Integrated Microbiome-Metabolomics Approach.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121115}, doi = {10.1016/j.jep.2025.121115}, pmid = {41456824}, issn = {1872-7573}, abstract = {Hyperuricemic nephropathy (HN) remains challenging to treat due to the limitations, including variable efficacy and side effects, of conventional drugs. Orthosiphon aristatus (O. aristatus), used for over 2000 years in Dai medicine to treat kidney disorders by "clearing heat and promoting diuresis," shows strong potential for HN management. However, its mechanisms of action against HN remain unclear.

AIM OF THE STUDY: This study aimed to elucidate the nephroprotective effects and underlying mechanisms of O. aristatus against HN using an integrated strategy focusing on the gut-kidney axis.

METHODS: A rat model of HN was established by combined oral administration of potassium oxonate (750 mg/kg) and uric acid (300 mg/kg) daily for 7 weeks. Model rats were treated with a low- or high-dose aqueous extract of O. aristatus (3.125 or 6.25 g/kg/day), using allopurinol (5 mg/kg/day) as a positive control. Renal function was assessed by measuring serum levels of uric acid, creatinine, and urea nitrogen. Renal pathological injury and fibrosis were evaluated through histopathological examination (H&E and Masson's trichrome staining), immunohistochemistry (α-SMA, vimentin), and transmission electron microscopy. To elucidate the underlying mechanisms, an integrated multi-omics approach was employed: gut microbiota composition was profiled by metagenomic sequencing, and metabolic alterations in cecal content and kidney tissue were characterized using UPLC-MS-based metabolomics. Furthermore, the protein expression of key targets involved in intestinal barrier function (Occludin, Claudin-1) and the IDO1/AhR signaling pathway was validated by Western blot analysis.

RESULTS: O. aristatus treatment significantly ameliorated renal dysfunction and pathological injury, as demonstrated by marked reductions in serum uric acid (sUA), creatinine (Scr), and blood urea nitrogen (BUN) levels (all p < 0.001), alongside attenuated tubular injury and fibrosis. Concurrently, it restored gut microbiota diversity (e.g., increased Shannon index, p < 0.05) and composition, characterized by an enrichment of beneficial Prevotella and a reduction in Bacteroides. Integrated metabolomics analysis further linked these effects to the rectification of tryptophan metabolism, manifested by decreased renal kynurenine levels (p < 0.01) and enhanced intestinal barrier integrity (e.g., elevated Occludin and Claudin-1, p < 0.05). Collectively, our results delineate that the renoprotective effect of O. aristatus is mediated through the suppression of the renal IDO1/kynurenine/AhR pro-fibrotic signaling axis, unveiling a novel gut microbiota-metabolite-kidney interaction mechanism.

CONCLUSION: This study elucidates that the renoprotective effect of O. aristatus against HN is mediated through modulation of the gut-kidney axis, by restoring microbial ecology, reprogramming host tryptophan metabolism, and subsequently inhibiting the IDO1/kynurenine/AhR pro-fibrotic pathway.}, } @article {pmid41456636, year = {2025}, author = {Koppali, SR and Vadia, N and Varma, P and Mishra, S and Joshi, N and Bansal, P and Al-Hasnaawei, S and Chauhan, AS and Jain, H and Nathiya, D and Devi, A and Jayasingh Chellammal, HS and Gupta, P and Wal, P and Koppula, S}, title = {Neurodevelopmental origins of neurodegeneration: a lifespan perspective on brain vulnerability.}, journal = {Brain research}, volume = {}, number = {}, pages = {150134}, doi = {10.1016/j.brainres.2025.150134}, pmid = {41456636}, issn = {1872-6240}, abstract = {Neurodegenerative disorders-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-are increasingly understood to have origins in early neurodevelopmental disturbances. This review examines how genetic, epigenetic, and environmental factors impact brain development during critical periods, predisposing individuals to neurodegeneration later in life. Prenatal and early-life exposures such as maternal stress, malnutrition, infection, and environmental toxins can alter key developmental processes, leading to long-term vulnerability. Mechanistic pathways linking early-life disruptions to neurodegenerative outcomes include persistent mitochondrial dysfunction, chronic neuroinflammation, increased oxidative stress, and aberrant synaptic pruning, all of which contribute to progressive neuronal damage and dysfunction. The gut-brain axis is also discussed as a key intermediary, where early microbiota dysbiosis alters neuroimmune signaling and inflammatory responses, modulating susceptibility to age-related neurological disorders. In this context, the review highlights emerging molecular and imaging biomarkers capable of detecting subtle neurodevelopmental deviations that may precede clinical symptoms by decades. The paper emphasizes the need for early-life interventions, including maternal nutritional optimization, management of prenatal stress, and microbiome-targeted strategies, as potential tools to reduce long-term neurological risk. Furthermore, it proposes the integration of precision medicine approaches aimed at individualized risk assessment and therapeutic targeting of developmental pathways. Adopting a lifespan perspective, this review argues for a paradigm shift from reactive to preventive strategies in neurology. Understanding the developmental roots of neurodegeneration opens new avenues for research and intervention, enabling resilience and reducing disease burden through early diagnostics and tailored therapeutics across the lifespan.}, } @article {pmid41456557, year = {2025}, author = {Li, Y and Chen, Y and Du, Z and Guo, Y and Zhang, W and Xu, X and Liu, Z and Duan, H and Duan, X and Zhang, A and Zhou, A and Li, X and Makinia, J}, title = {Oriented butyrate production through a novel bacteria-yeast microbiome: batch verification, key electron donor identification, and long-term validation.}, journal = {Bioresource technology}, volume = {443}, number = {}, pages = {133892}, doi = {10.1016/j.biortech.2025.133892}, pmid = {41456557}, issn = {1873-2976}, abstract = {Recovering butyrate from organic waste enables its high-value conversion, aligning with the principles of a circular economy. Traditional butyrate fermentation emphasizes carbohydrates and protein degradation, with limited focus on chain elongation (CE). This study, for the first time, systematically evaluated the effects of different Saccharomyces cerevisiae (SC) concentrations (1, 2, 4, 6, and 8 g/L) on ethanol production (a key electron donor) and subsequent CE for butyrate synthesis, identifying 2 g/L as the optimal SC dosage. At this concentration, butyrate production reached 15.41 ± 2.84 g COD/L, which was 2.72 times higher than that of the blank. Metabolic pathway analysis revealed that yeast not only enhanced substrate degradation (>90 %) but also facilitated the in situ generation and utilization of ethanol. 16S rRNA indicated 54.10 % relative abundance of butyrate-producing bacteria (Clostridium). Long-term tests found that adding SC reversed the halt in production from prolonged distiller yeast inoculum, stabilising output at 15 g COD/L. Metagenomic analysis revealed that SC inoculation primarily enriched Clostridium luticellarii and Clostridium tyrobutyricum. In addition to raising reverse β-oxidation gene abundance, this treatment also enhanced lactate utilization genes, thereby strengthening acetyl-CoA to butyrate conversion. Through further experiments involving different electron donor ratios and long-term operation, this study highlights the critical role of yeast-bacteria synergy in enhancing butyrate synthesis, providing a theoretical foundation and technical strategy for food waste valorization in line with circular economy principles.}, } @article {pmid41456402, year = {2025}, author = {Lyte, JM}, title = {Stress neurophysiology in poultry: A functional framework for the application of microbiome science in poultry production.}, journal = {Poultry science}, volume = {105}, number = {2}, pages = {106181}, doi = {10.1016/j.psj.2025.106181}, pmid = {41456402}, issn = {1525-3171}, abstract = {Over the last two decades, scientific interest in the poultry microbiome has skyrocketed with a role ascribed for the microbiome in virtually every aspect of poultry health and production. While substantial progress has been made in revealing important correlations that can be used as a roadmap for utilization in a production setting, much remains to be understood in way of causality of the microbiome for the bird. In other words, correlation does not mean causation and there exists an overwhelming need to identify causal mechanisms if new microbiome-based modalities are to be implemented in poultry production. Therefore, this review discusses the need for function-driven hypotheses that provide an evidence-based framework when approaching poultry microbiome research. Considering that the impact of stress on both the bird and microbiome is well-appreciated across poultry species, pre-harvest stress is taken as a prototypical example of where the use of function-driven hypotheses can help bridge basic to applied microbiome-based science to benefit poultry production. Practical examples are provided and summarized herein, in which this approach can be applied ranging from areas of foodborne pathogen carriage to performance. Central to this aim is the interdisciplinary field of Microbial Endocrinology as it represents the intersection of microbiology and neurophysiology. Microbial Endocrinology has demonstrated that monoamine neurochemical systems can serve as mechanistic routes of host-microbe interaction, providing an evidence-based platform for identification of causal relationships between microbial taxa and the host. Interventions can therefore be designed to modulate these causal pathways to benefit the bird. While emphasis is given towards the nexus of gastrointestinal neurophysiology and the gut microbiome, this review also highlights the intersection of neurochemistry and the microbiome along the respiratory and reproductive tracts. The need for widespread adoption of best practices methodologies in microbiome research experimental design is integrated into function-driven hypotheses herein. It is anticipated that the cooperative use of directed hypotheses and the implementation of robust experimental design will accelerate the application of microbiome-based solutions in poultry production.}, } @article {pmid41456367, year = {2025}, author = {Peraza, P and Martinez-Boggio, G and Naya, H and Sotelo-Silveira, J and Navajas, EA}, title = {Predictive ability and mediation effects of the rumen microbiome on feed efficiency and methane traits in Hereford beef cattle.}, journal = {Animal : an international journal of animal bioscience}, volume = {20}, number = {1}, pages = {101730}, doi = {10.1016/j.animal.2025.101730}, pmid = {41456367}, issn = {1751-732X}, abstract = {The ruminant genome exerts moderate control over rumen microbial composition, which is a major determinant of feed efficiency and methane emissions. However, the integration of new omics data, whether for phenotypic prediction, selective breeding, or both, is still under discussion. This study aimed to (1) estimate the heritability and microbiability for residual feed intake (RFI), dry matter intake (DMI), BW, and methane yield (MY); (2) assess the predictive ability of models including host genome and microbiome information; and (3) evaluate the mediation effects of the rumen microbiome on feed efficiency and performance traits. The data set consisted of 537 Hereford bulls and steers with RFI, DMI, and BW records, as well as a subset of them (n = 123) with MY records. All animals were genotyped using 100 k single-nucleotide polymorphism panels, and rumen microbial abundances were determined through enzyme-restriction reduced representation sequencing (ER-RRS) analysis. Heritability estimates ranged from 0.18 for RFI to 0.36 for BW, while microbiability values were moderate (0.16-0.32), indicating that both host genetics and the microbiome significantly contribute to trait variation. We found that the use of genome and rumen microbiome information improved predictive ability for BW (r = 0.48-0.52), as assessed by Pearson's correlation between observed and predicted values, but not for RFI (r = 0.15-0.14), DMI (r = 0.72-0.73), or MY (r = 0.68-0.69). We also identified several amplicon sequence variants (ASVs) with moderate genetic control and potential mediation effects on RFI, DMI, and BW. However, given the large number of tests performed, these findings should be interpreted with caution due to the increased risk of false positives. Interestingly, our findings show better results for the use of rumen microbiome for selective breeding than for phenotypic prediction in beef cattle. Additionally, we highlighted that using genomics and rumen microbiome data within structural equation models provides new biological insights into animal performance. However, the assumption of no environmental covariance between the host and the microbiome is strict but necessary. Further exploration includes the use of instrumental auxiliary variables that allow for the inclusion of the environmental covariance between the traits of interest.}, } @article {pmid41456362, year = {2025}, author = {Islam, MT and Yang, F and Komladzei, S and Akhter, M and Sardiu, ME and Li, Y}, title = {Integrative machine learning reveals hidden and emerging co-regulatory gene networks for multi-phase glioblastoma outcome prediction.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {234}, number = {}, pages = {116197}, doi = {10.1016/j.ejca.2025.116197}, pmid = {41456362}, issn = {1879-0852}, abstract = {BACKGROUND: Glioblastoma (GBM) is a highly prevalent and aggressive type of brain tumor characterized by profound molecular complexity and poor prognosis. While conventional biomarker studies focus on highly significant genes or proteins associated with cancer outcomes, the contribution of gene-gene co-regulation to GBM progression remains unclear.

METHODS: This study employs an application of integrative machine learning approach, utilizing a high-dimensional transcriptomic profile that considers gene-gene co-regulations to identify predictive gene networks involved in GBM occurrence and 1-year survival prediction. We further integrate these network models with both empirical protein-protein interaction (PPI) data and random walk-based information flow analysis across the PPI landscape.

RESULTS: This dual-layered approach uncovers gene modules that bridge transcriptional co-regulation with functional connectivity at the protein level. This integration highlighted several hub genes, including both strong and weak (e.g. BSN, RHOC, ANXA1, CSF1R, and ITGAM), that emerged as key molecular connectors involved in critical GBM processes such as immune response and neuronal signaling. Notably, these hub genes also exhibited cross-disease associations with traits including gut microbiome composition, type 2 diabetes, coronary artery disease, and other cancers, underscoring their systemic biological relevance.

CONCLUSION: Overall, our findings through the computational approach underscore the significance of co-regulatory gene networks in GBM biology. It also demonstrates how integrating transcriptomic and protein-level interactions can refine prognostic modeling, advance biomarker discovery, and inform future therapeutic development.}, } @article {pmid41455981, year = {2025}, author = {Zhang, X and Liu, J and Li, Y and Ding, J}, title = {Long-term continuous cropping reshapes soybean rhizosphere microbiome and metabolome to alleviate allelopathic stress and enhance disease suppression.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02311-7}, pmid = {41455981}, issn = {2049-2618}, support = {ZD2023C001//Key Project of Heilongjiang Provincial Natural Science Foundation/ ; 2023ZYCX01//Department of Agriculture and Rural Affairs of Heilongjiang Province/ ; 32372048//the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Continuous cropping obstacles (CCO) pose a persistent threat to global soybean sustainability, yet paradoxically attenuate under prolonged monoculture. To explore this, we investigated the soil-plant-microbiome dynamics across 1-year, short-term continuous cropping (STCC, 7-13 years), and long-term continuous cropping (LTCC, 19-25 years) systems.

RESULTS: Our results reveal that LTCC reduces the accumulation of allelopathic autotoxin by 49.06% (P < 0.05) and enriches beneficial rhizosphere metabolites (e.g., antibiotics, monoterpenes, and glycoside compounds), driving a shift in the microbial community towards taxa with pathogen-suppressive and nutrient-cycling functions. LTCC cultivated a microbiome with enhanced genes for stress resistance and nutrient uptake. Conversely, STCC exacerbates CCO stress, with microbial dysbiosis peaking at 13 years (Simpson index down 15.4%). Notably, 25-year LTCC restores ecosystem stability and enzyme activity, restructuring microbial communities with pathogen-suppressive and nutrient-cycling functions. By reintroducing depleted taxa including Pseudomonas, Burkholderia, and Enterobacter spp., we constructed a synthetic community, SC7. SC7 boosted soil enzymes and root nodules to shield plants from stress, increasing yield by 4.83% and mimicking long-term system advantages.

CONCLUSIONS: This study demonstrates the self-repair capacity of soybean monoculture. It bridges the gap between mechanistic insights, specifically the microbiome-metabolite feedback, and actionable solutions, such as SC7 inoculation. As a result, it advances sustainable intensification strategies for global soybean production. Video Abstract.}, } @article {pmid41455937, year = {2025}, author = {Almuhayya, S and Aldehalan, F and Alzamil, L and Ibrahem, K and Alharbi, SR and Aldawood, E}, title = {Vaginal microbiome knowledge and hygiene practices among women in Saudi Arabia: a cross-sectional study.}, journal = {BMC public health}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12889-025-26075-9}, pmid = {41455937}, issn = {1471-2458}, } @article {pmid41455887, year = {2025}, author = {Tariq, H and Dutilleul, P and Geddes-McAlister, J and Geitmann, A and Smith, DL}, title = {Plant growth-promoting Bacillus strains modulate early soybean development via proteome remodeling.}, journal = {BMC plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12870-025-07972-y}, pmid = {41455887}, issn = {1471-2229}, abstract = {Plant adaptation to environmental stress involves tightly regulated cellular, molecular, and biochemical responses. Among these, microbe-assisted strategies have gained attention, particularly the role of the plant microbiome (phytomicrobiome) in promoting growth and stress resilience. Soybean (Glycine max), a major agricultural crop, actively recruits beneficial microbes through root-secreted secondary metabolites, fostering symbiotic interactions with endophytic bacteria. However, the direct and indirect impacts of root-associated endophytes on plant development remain incompletely understood. In this study, we investigated three Bacillus strains (HT1, HT2, and HT3) isolated previously from the soybean root microbiome.16 S rRNA analysis indicates that HT1 and HT2 are closely related to the Bacillus velezensis and HT3 to the Bacillus thuringiensis lineage although more detailed analyses are warranted for genus identification. These strains were selected for their demonstrated plant growth-promoting and biocontrol activities. Bacillus-HT1 and HT2 significantly enhanced soybean seed germination, while Bacillus-HT3 promoted leaf area expansion significantly compared to the control, indicating strain-specific developmental effects. To elucidate the molecular basis of these effects, we conducted shotgun proteomic profiling of soybean leaves. Enrichment analysis revealed distinct functional signatures, with Bacillus HT1 and HT2 associated with pathways linked to cellular component organization, microtubule dynamics, and organelle function, and Bacillus-HT3 inducing broader enrichment of photosynthesis, chloroplast organization, and biosynthetic processes. These findings suggest that HT1 and HT2 promote early developmental transitions, while HT3 enhances vegetative growth through large-scale metabolic reprogramming. Notably, proteins such as anthranilate synthase and proteasome subunit alpha type were differentially abundant, pointing to the potential involvement of auxin biosynthesis and ubiquitin-proteasome-mediated regulation but, the actual roles of these pathways remain to be validated. These findings provide mechanistic insights into how specific Bacillus strains modulate soybean development at the molecular level and highlight their potential for use as bio-inoculants to enhance crop productivity and resilience under stress conditions.}, } @article {pmid41455696, year = {2025}, author = {Su, L and Feng, H and Li, H and Yang, F and Yan, X and Wang, X and Li, P and Wang, K and Shu, X and Liu, Y and Shen, Q and Yan, Y and Zhang, R}, title = {General variation in the Fusarium wilt rhizosphere microbiome.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-67760-y}, pmid = {41455696}, issn = {2041-1723}, support = {32172661//National Natural Science Foundation of China (National Science Foundation of China)/ ; 42207359//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32270125//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The dominant bacteria enriched in the Fusarium wilt plants' rhizosphere are of increasing interest, as they adapt well to the diseased rhizosphere. However, general information about these bacteria is still lacking. Here, we perform a meta-analysis of Fusarium wilt plants rhizosphere and comprehensive studies to obtain information about the robust variation in the rhizosphere microbiome of Fusarium wilt plants. We demonstrate that Fusarium infection reproducibly changes the rhizosphere bacterial community composition. The rhizosphere microbiomes of Fusarium wilt plants are characterized by the enrichment of Flavobacterium, gene cassettes involved in antioxidant functions related to sulfur metabolism and the root secreted tocopherol acetate. We further isolate antagonistic Flavobacterium anhuiense from the diseased tomato rhizosphere, and reveal that the growth of F. anhuiense and the expression of genes related to carbohydrate metabolism in this strain are significantly stimulated by tocopherol acetate. Furthermore, the inhibitory effect of F. anhuiense against F. oxysporum and F. anhuiense population enhancement by tocopherol acetate are confirmed in planta. The robust variation in the rhizosphere microbiome elucidates key principles governing the general assembly mechanism of the microbiome in the Fusarium wilt plants' rhizosphere.}, } @article {pmid41455576, year = {2025}, author = {Kitagawa, H and Kajihara, T and Yahara, K and Kitamura, N and Shigemoto, N and Doi, H and Shimbara, K and Yoshimura, K and Nakashima, I and Uegami, S and Watadani, Y and Kawada-Matsuo, M and Komatsuzawa, H and Ohge, H and Sugai, M}, title = {Impact of antimicrobial prophylaxis in colorectal cancer surgery on the gut and oral microbiome and resistome: A prospective observational cohort study.}, journal = {Journal of global antimicrobial resistance}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgar.2025.12.014}, pmid = {41455576}, issn = {2213-7173}, abstract = {BACKGROUND: The use of antibiotics may facilitate the colonisation of antimicrobial-resistant organisms and genes within the host microbiome. However, studies on the effects of antibiotics on microbiomes and resistomes in clinical settings are limited.

AIM: The aim of this study was to determine the effects of antibiotic prophylaxis during colorectal cancer surgery on the oral and gut microbiomes and resistomes of patients.

METHODS: We conducted a single-centre prospective observational cohort study on patients who underwent colorectal cancer surgery with antibiotic prophylaxis. DNA was extracted from oral and stool samples 1 day prior to the procedure and on postoperative days 1, 7, and 28. Subsequently, metagenomic sequencing was performed.

FINDINGS: Among the eight patients with colorectal cancer, α-diversity in the oral and stool samples significantly decreased from baseline to each of the three post-administration time points. The abundance of anaerobic genera significantly decreased from baseline to Day 7. In the stool samples, Enterococcus, Limosilactobacillus, and Lacticaseibacillus abundances were markedly increased. Total antibiotic resistance gene (ARG) abundance significantly increased from the baseline to Day 7 in both oral and stool samples. The impact of the increase observed on Day 7 decreased but still persisted until Day 28 for diversity and total abundance of ARGs.

CONCLUSIONS: Oral and gut microbiomes and resistomes exhibited marked alterations that gradually reversed over time. Changes in the microbiome were associated with the spectrum of antibiotics used.}, } @article {pmid41455545, year = {2025}, author = {Zhang, JS and Zhang, Y and Huang, S and Chu, CH and Jakubovics, NS and Yu, OY}, title = {High-Resolution Microbial Changes in Root Caries Revealed by Type IIB Restriction-site Associated DNA for Microbiome.}, journal = {Journal of dentistry}, volume = {}, number = {}, pages = {106319}, doi = {10.1016/j.jdent.2025.106319}, pmid = {41455545}, issn = {1879-176X}, abstract = {OBJECTIVES: This study aimed to characterize the species-level microbial and functional alterations in the dental biofilms associated with root caries leveraging the high-resolution sequencing.

METHODS: Twenty-five older adults with active root caries (Patients) and 31 older adults without untreated caries (Healthy controls) were enrolled. Site-specific supragingival plaque was collected from spatially-matched carious (CC) and caries-free (CH) root surfaces from patients, and from caries-free root surfaces of healthy controls (HH). Plaque samples were analysed using Type IIB Restriction-site Associated DNA for Microbiome (2bRAD-M). Microbial diversity, species-level relative abundance, and predicted functional pathways were compared across groups using nonparametric tests.

RESULTS: No significant differences in overall microbial diversity were observed between groups. The microbial divergence between paired carious (CC) and caries-free (CH) root microbiota from patients was significantly greater than that between paired caries-free (HH) root microbiota in healthy controls. Several species showed increased abundance in CC microbiota compared to CH microbiota, with Propionibacterium acidifaciens, Prevotella multisaccharivorax, Mitsuokella sp000469545, and Parascardovia denticolens exhibiting the highest level of abundance difference. Predicted metagenomic analysis indicated that nine KEGG pathways, primarily involved in alternative carbohydrate metabolism, were positively associated with root caries status.

CONCLUSION: Within-subject comparison revealed a significant difference in microbiota between carious and caries-free root surfaces. These differences were characterized by shifts in specific species and their associated metabolic potentials, rather than by broad changes in community diversity.

CLINICAL SIGNIFICANCE: This study underscores the importance of tooth-level resolution in investigating the microbial etiology of root caries and revealed the species-level changes in carious root microbiota.}, } @article {pmid41455317, year = {2025}, author = {Caly-Simbou, E and Ramin-Mangata, S and Poussier, S and Pecrix, Y}, title = {Bacteriocins in plant pathology: current knowledge, application, challenges and perspectives.}, journal = {Biochemical and biophysical research communications}, volume = {797}, number = {}, pages = {153203}, doi = {10.1016/j.bbrc.2025.153203}, pmid = {41455317}, issn = {1090-2104}, abstract = {To address the growing emergence of multi-resistant phytopathogenic bacteria, innovative solutions are being explored in the field of plant health. Among them, bacteriocins, antimicrobial peptides or proteins secreted by bacteria, characterized by a highly specific spectrum of activity and involved in intra-specific competition, are gaining increasing interest. Bacteriocins can confer a positive selective advantage in both natural and agricultural environments, thereby contributing to microbiome modulation. Bacteriocin-producing rhizobacteria and lactic acid bacteria are already used as biocontrol agents against phytopathogenic bacteria, as well as plant growth stimulators. Bacteriocins can be produced in situ by using avirulent strains, or ex situ through industrial synthesis and applied as biopesticides. Nowadays, genetic engineering enables production of chimeric bacteriocins and their direct production in transgenic plants, avoiding the need for repeated treatments and limiting emergence of resistances. The selection of promising bacteriocins can be guided by omics-based approaches, notably metagenomics, which involve the direct extraction and sequencing of DNA from environmental samples and provides access to the genetic diversity in complex soil or plant-associated microbiomes. Combined with open-access databases and recently developed integrated tools, this approach not only facilitates the identification of known structures of bacteriocins, but also enables the prediction of potentially active peptides even those never experimentally characterized. Bacteriocin-based strategies, at the crossroads of molecular biology, microbial ecology and agronomy, hold significant potential for promoting sustainable agriculture through highly specific pathogen targeting. However, their large-scale implementation still faces several challenges, including standardization of strain screening protocols, compliance with regulatory frameworks and farmer acceptance.}, } @article {pmid41455311, year = {2025}, author = {Kolathingal-Thodika, N and Elayadeth-Meethal, M and Dunshea, FR and Eckard, R and Flavel, M and Chauhan, SS}, title = {Harnessing methane proxies to understand and mitigate enteric emissions from ruminant production systems.}, journal = {The Science of the total environment}, volume = {1012}, number = {}, pages = {181258}, doi = {10.1016/j.scitotenv.2025.181258}, pmid = {41455311}, issn = {1879-1026}, abstract = {Methane emissions from livestock, particularly ruminants, significantly contribute to global warming, necessitating the development of accurate methane monitoring systems. Direct methane measurement is technically complex, time-consuming, labour-intensive, and costly. Recent advances in methane inhibitors, such as 3-nitrooxy propanol and halogenated analogues, plant secondary compounds, including polyphenols and essential oils, to reduce methane emissions have necessitated the discovery of processes underlying rumen methane synthesis and inhibition. The identification of methane proxies, such as behavioural and input proxies (dry matter intake, neutral detergent fibre), microbial community proxies (rumen metagenome profiles), metabolic pathway proxies (fatty acids), molecular and genetic proxies (microbial genes), and downstream and non-invasive proxies (milk fatty acids and faecal lipidomes), is leading to more viable solutions. New developments in 'omic' techniques, including lipidomics, metagenomics and metatranscriptomics, have enabled the detection of proxies at the molecular level utilising rumen liquor, milk, blood, urine, and faeces. In addition to traditional methane proxies, rumen microbiota profiles, and specific genes involved in rumen methanogenesis (such as mcr and mrt, which encode methyl coenzyme reductase 1 and 2), these markers can be used to identify methane-producing pathways. Protozoa-associated methanogens (PAMs), propionate-producing bacteria, and methane-oxidising methanotrophs (Methylocystis sp.) are emerging as new proxies. Methane proxies provide scalable, affordable, and mechanistically insightful alternatives to conventional direct measuring techniques, which improve the understanding of rumen function and the biological causes of methane releases, enabling large-scale methane monitoring and will enable designing effective methane mitigation strategies in livestock production systems.}, } @article {pmid41455310, year = {2025}, author = {Changey, F and Catão, ECP and Grange, M and Tran, ML and Delannoy, S and Pons, MN and Guerold, F and Colon, JB and Poszwa, A and Merlin, C}, title = {Biodiversity-dependent invasiveness of naive river epilithic biofilms by anthropogenic antibiotic resistance at the interface between the human, animal and environmental spheres.}, journal = {The Science of the total environment}, volume = {1012}, number = {}, pages = {181237}, doi = {10.1016/j.scitotenv.2025.181237}, pmid = {41455310}, issn = {1879-1026}, abstract = {With more than 1 million deaths attributed each year, antibiotic resistance has become a major societal issue. The emergence and dissemination of antibiotic resistance in bacteria rests on two pillars, the enrichment of resistant variants upon selection and the contagion of the resistant bacteria and their resistance genes within and across the human, animal and environmental spheres. Although poorly described, this contagion process necessarily implies the persistence of invading resistant bacteria from one microbiome to another. In this study, we carefully selected a series of headwater streams located in the Vosges Mountains (North-eastern, France), with a clear pristine-like upstream part and well identified primary exposure to modest anthropic activities, to explore invasion processes while avoiding multiple pollution effect. Using high-throughput qPCR for 45 resistance genes and mobile genetic elements we showed that one third of the markers were already widespread, while another third massively invaded the river epilithic biofilm communities at primary exposure to anthropic activities, with the concomitant entry of fecal pollution. We used 16S rRNA gene metabarcoding to explore the structure of the bacterial biofilm communities along river continuums and showed that the extent of the invasion process was inversely correlated with the level of biodiversity, but positively correlated with the magnitude of propagule pressure.}, } @article {pmid41455276, year = {2025}, author = {Montecillo, JAV and Yoo, HJ and Lee, YY and Park, CM and Cho, A and Lee, H and Kim, JM and Lee, NY and Park, SH and Park, NJ and Han, HS and Chong, GO and Seo, I}, title = {Streptococcus vaginalis affects cellular dynamics of cervical cancer cells via oxidative stress-induced activation of endoplasmic reticulum unfolded protein response.}, journal = {Microbiological research}, volume = {305}, number = {}, pages = {128433}, doi = {10.1016/j.micres.2025.128433}, pmid = {41455276}, issn = {1618-0623}, abstract = {The vaginal microbiome plays an important role in the development of cervical cancer, highlighting the potential influence of specific members on disease susceptibility, progression, and suppression. In this study, we characterized a recently identified species of vaginal viridans group streptococci, Streptococcus vaginalis. By examining its prevalence, genomic features, and interactions with model cervical cancer cells, we aim to deepen the understanding of its biological significance and broader implications for vaginal health. Microbiome profiling detected S. vaginalis in 27 % of a cohort of Korean women, and the second most abundant species of Streptococcus. Pan-genome analysis and comparative genomics of S. vaginalis strains revealed their reduced pathogenic potentials. In vitro bioassays using cervical cancer cell models (HeLa, SiHa, and CaSki) demonstrated significant effects of S. vaginalis, influencing morphology, proliferation, migration, colony formation, and the induction of apoptosis. Mechanistic investigation identified the involvement of the endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). Hydrogen peroxide produced by S. vaginalis was found to induce oxidative stress, triggering the ER stress-mediated cellular stress responses in cervical cancer cells. Our study revealed the influence of S. vaginalis on the dynamics of cervical cancer cells via oxidative stress-induced activation of the ER UPR pathway. These mechanistic insights emphasize a potential avenue for therapeutic interventions aimed at modulating oxidative and ER stress responses in cervical cancer treatment strategies. Overall, our findings provide new perspectives into the biological significance of S. vaginalis, expanding our understanding of its potential role beyond simple commensalism.}, } @article {pmid41455275, year = {2025}, author = {Zhang, Y and Zhang, N and Zhang, Z and Bi, X and Feng, Z and Guo, Y and Yu, F and Zhang, B and Bi, T and Baloch, FB and Shafiq, U and Miao, J and Wang, Y and Li, B and An, Y}, title = {Microbial biofilms as drought shields: Bacillus velezensis D103 enhances maize tolerance via aquaporin regulation.}, journal = {Microbiological research}, volume = {305}, number = {}, pages = {128430}, doi = {10.1016/j.micres.2025.128430}, pmid = {41455275}, issn = {1618-0623}, abstract = {Drought stress severely constrains crop productivity, and while plant growth-promoting rhizobacteria (PGPR) are known to enhance drought tolerance by modulating host aquaporins (AQPs), the specific role of bacterial biofilm formation in this regulatory process remains poorly understood. Here, we demonstrate that biofilm formation is a pivotal mechanism through which Bacillus velezensis D103 confers drought resilience to maize. Under drought stress, maize root exudates synergistically enhanced D103 biofilm formation, which was essential for robust root colonization and mediated a drought-adaptive restructuring of the rhizosphere microbiome. Crucially, we found that an intact bacterial biofilm systemically upregulated key plant AQPs (ZmPIP2;6 and ZmTIP1;1), thereby enhancing root water transport capacity. Using virus-induced gene silencing, we further clarified the molecular mechanism underlying this biofilm-aquaporin link, revealing that ZmPIP2;6 is indispensable for D103-conferred drought tolerance. Our findings refine the current understanding of PGPR-mediated drought tolerance, highlighting that biofilms coordinate host AQP expression, rhizosphere microbiome assembly, and soil water retention to enhance drought resilience. This work provides a mechanistic basis for developing effective microbial inoculants.}, } @article {pmid41455133, year = {2025}, author = {Zhang, Y and Wu, Y and Wang, Y and Zhou, H}, title = {Group 2 innate lymphoid cells (ILC2s) in childhood allergic diseases: A review of the mechanisms and therapeutic advances.}, journal = {Cytokine}, volume = {198}, number = {}, pages = {157101}, doi = {10.1016/j.cyto.2025.157101}, pmid = {41455133}, issn = {1096-0023}, abstract = {Recent advances in pediatric immunology have clarified the pivotal role of group 2 innate lymphoid cells (ILC2s) in the pathophysiology of childhood allergic diseases. As key components of the innate immune system, ILC2s mediate the initiation and progression of these disorders. Their activation is triggered primarily by epithelial-derived cytokines, whose expression is highly elevated in children with allergies. Upon activation, ILC2s rapidly secrete type 2 cytokines, driving disease-specific pathogenesis. In allergic asthma, airway ILC2 expansion exacerbates eosinophilic inflammation, airway hyperresponsiveness, and remodeling; in allergic rhinitis, nasal mucosal ILC2 activation induces typical symptoms; and in food allergies, intestinal mucosal ILC2s cause epithelial damage and increased permeability, promoting allergic progression. These mechanistic insights have underpinned the development of innovative therapies. Clinical trials have confirmed the efficacy of treatments targeting ILC2-derived cytokines or their receptors: anti-IL-5 monoclonal antibodies (targeting the IL-5 ligand), anti-IL-13 monoclonal antibodies (targeting the IL-13 ligand), and anti-IL-4Rα monoclonal antibodies (targeting IL-4 receptor α and blocking IL-4/IL-13 signaling) are promising treatments for specific childhood allergic diseases. Emerging strategies targeting ILC2 activation pathways and modulating the microbiome to regulate ILC2 activity are under active investigation. Collectively, the past five years of research have improved the understanding of the mechanisms underlying childhood allergic diseases and established new treatment paradigms, with great potential to optimize clinical management and improve the outcomes of pediatric patients with allergies.}, } @article {pmid41455017, year = {2025}, author = {Rojas-Chacón, JA and Echeverría-Beirute, F and Madrigal, JPJ and Faggioli, V and Chacón, MS and Gatica-Arias, A}, title = {Exploring the Coffee Fruit Microbiome under Different Management Practices and its Correlation with Beverage Quality Criteria in Costa Rica.}, journal = {Current microbiology}, volume = {83}, number = {2}, pages = {101}, pmid = {41455017}, issn = {1432-0991}, support = {111-C3-994//Vicerrectoría de Investigación, Universidad de Costa Rica/ ; 2022-316296//Chan Zuckerberg Initiative/ ; }, } @article {pmid41455002, year = {2025}, author = {Karim, F and Lin, Q and Xie, H and Nargis, S and Xiao, H and Yang, S and Xiong, Y and Xie, M and Ni, Q and Yao, Y and Xu, H}, title = {Seasonal dynamics of gut microbiota in rhesus macaques (Macaca mulatta) from western Sichuan Plateau and their adaptability to high altitude climate change.}, journal = {Current microbiology}, volume = {83}, number = {2}, pages = {99}, pmid = {41455002}, issn = {1432-0991}, support = {31870355//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Macaca mulatta/microbiology ; *Gastrointestinal Microbiome ; Seasons ; Altitude ; Feces/microbiology ; *Climate Change ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; China ; }, abstract = {Seasonal fluctuations in diet and climate shape animal gut microbiota, especially those living in extreme climatic conditions. Yet their role in facilitating primate adaptation to high-altitude remains unclear. This study investigates the seasonal dynamics in gut microbiome of wild rhesus macaques (Macaca mulatta) from high altitude (over 3,000 m) in Yajiang couke. We collected 117 fecal samples across four seasons and analyzed using 16S rRNA high-throughput sequencing combined with predictive functional metagenomics. We observed clear seasonal shifts in gut microbial diversity and composition. High α-diversity in autumn and winter reflected increased dietary diversity during these periods. Firmicutes predominated in summer, while Bacteroidota increased during winter. LEfSe analysis revealed seasonal specific taxa: UCG-005, Christensenellaceae R-7, and Prevotella_9 were dominated in winter but declined in summer and spring, whereas Blautia peaked during summer and decreased toward winter. Redundancy analysis showed that temperature, humidity, and precipitation were positively associated with Blautia and Sarcina, but negatively with Monoglobus and Helicobacter, underscoring the strong influence of climatic variables on gut community structure. Functional predictions revealed seasonal differences in gut microbiota related to energy metabolism (spring), glycan biosynthesis (summer), membrane transport (autumn), and environmental adaptation (winter) indicating microbial contributions to host adaptation under fluctuating climatic conditions. These findings demonstrate that gut microbiome of high-altitude macaques is highly responsive to changes in seasonal diet and climate. By integrating microbiome dynamics with climatic drivers, our study provides new insights into host-microbe-environment interactions and advances our understanding of primate adaptation under extreme climatic conditions.}, } @article {pmid41454989, year = {2025}, author = {Ito, R and Taniguchi, Y and Kashiwamura, T and Kido, H and Kakura, K and Suzuki, N}, title = {Effects of silver nanoparticle coating on peri-implant mucosa and microbiome.}, journal = {International journal of implant dentistry}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40729-025-00664-0}, pmid = {41454989}, issn = {2198-4034}, support = {25K13332//JSPS KAKENHI/ ; 25K13357//JSPS KAKENHI/ ; }, abstract = {AIM: We conducted a study to investigate whether a silver nanoparticle (AgNP) coating on the surface of an implant superstructure could alter the microbiome of peri-implant tissues and to determine whether the AgNP coating would result in an improvement of gingival conditions and be effective in suppressing malodors.

METHOD: We conducted a single-blind, parallel group comparative study in 19 patients undergoing implant maintenance. The 9 patients in the experimental group were treated by applying an AgNP coating after ultrasonic cleaning of the implant superstructure. Ultrasonic cleaning alone was performed on the 10 patients in the control group. The efficacy of the AgNP coating was evaluated by the following procedures conducted at baseline and after 3 months: measuring the modified gingival index (mGI), analyzing odor patterns through organoleptic test and olfactometric device readings of the implant superstructure, and determining the composition of the peri-implant microbiome.Registry: the Ethics Committee for Clinical Research of Fukuoka Gakuen, TRN: 530, Registration date: 30 March 2022.

RESULTS: The mGI values in the intervention group were significantly decreased (p = 0.043) than in the control group. In the organoleptic test, no significant intergroup differences were found in the sensory scores, but the sensory comments indicated that the odor type had changed in the experimental group. Principal component analysis (PCA) of the odor patterns at baseline and after 3 months revealed a change in the axis of the first principal component in the experimental group, but no change in the control group. A comparison of the peri-implant microbiome composition between the experimental group and the control group after three months revealed that the experimental group exhibited a significantly higher relative abundance of Neisseria oralis and Ottowia species, and a significantly lower relative abundance of Veillonella parvula, Fretibacterium fastidiosum, and Tannerella forsythia than the control group.

CONCLUSION: These findings suggest that the AgNP coating of the implant superstructure changed the composition of the microbiome, and that such a change may improve gingival conditions and provide a deodorizing effect.}, } @article {pmid41454672, year = {2026}, author = {Aldriwesh, MG and Alotibi, RS and Alqurainy, N and Alrabiah, S and Arafah, AM and Alghoribi, MF and Ajina, R}, title = {The role of gut microbiome in aging-associated diseases: where do we stand now and how technology will transform the future.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2607076}, doi = {10.1080/19490976.2025.2607076}, pmid = {41454672}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Animals ; Precision Medicine ; }, abstract = {The gut microbiome has emerged as a critical regulator of human aging and healthspan, with age-related dysbiosis increasingly implicated in a broad spectrum of aging-associated diseases. This review synthesizes evidence linking gut microbial alterations to infectious diseases, antimicrobial resistance, autoimmune, neurodegenerative, psychiatric, cancer, metabolic, kidney, cardiovascular, bone, and muscular diseases, highlighting shared mechanisms such as chronic inflammation, immune dysregulation, and metabolite imbalance. We further explore how enabling technologies, including functional multi-omics, synthetic biology, artificial intelligence-driven analytics, biobanking, and autologous fecal microbiota transplantation, are revolutionizing microbiome research and the design of interventions. Ethical considerations surrounding microbiome-based therapies are also addressed. To translate these scientific insights into clinical innovations, we formulate the PRIME framework: a five-phase roadmap encompassing Profiling, Reviewing, Identifying, Mapping, and Evaluating microbiome-based interventions. By integrating microbiome science, aging biology, and emerging technologies, this review provides a comprehensive blueprint for advancing precision medicine and promoting healthy aging. Furthermore, it emphasizes the importance of building future-ready capabilities to navigate the evolving landscape of age-related diseases and microbiome-driven therapeutic innovations.}, } @article {pmid41454664, year = {2026}, author = {Fan, PC and Chua, HH and Lin, CR and Lai, TH and Chiou, LC and Lee, WT and Chen, HL and Ni, YH}, title = {Targeting the microbiome in pediatric migraine: gastrointestinal manifestations and the therapeutic role of Bifidobacterium longum.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606487}, doi = {10.1080/19490976.2025.2606487}, pmid = {41454664}, issn = {1949-0984}, mesh = {Humans ; *Migraine Disorders/microbiology/therapy ; Child ; *Gastrointestinal Microbiome/drug effects ; Male ; Female ; *Probiotics/administration & dosage/therapeutic use ; Adolescent ; Feces/microbiology/chemistry ; Animals ; *Bifidobacterium longum/physiology ; Young Adult ; Rats ; Pilot Projects ; Prospective Studies ; *Gastrointestinal Diseases/microbiology ; Calcitonin Gene-Related Peptide/blood ; }, abstract = {Migraine is a disabling neurological disorder that often begins in childhood or adolescence and is frequently accompanied by gastrointestinal (GI) symptoms. However, the microbiota signatures and gut-brain interactions underlying pediatric migraine, particularly in the presence of GI disorder, remain poorly defined. This study aimed to explore the clinical and microbial features of pediatric migraine, as well as the therapeutic potential of probiotics.We prospectively enrolled 126 pediatric migraine patients (ages 6-19) with or without GI disorder and 50 age-matched healthy controls. Fecal microbiota was profiled using 16S rRNA sequencing. Patients with migraine were stratified based on Rome IV-defined GI disorders and evaluated for headache characteristics, PedMIDAS scores (disability assessment), plasma calcitonin gene related peptide (CGRP, thought as a key biomarker of migraine), cytokines, and fecal calprotectin. Probiotic effects were tested in both young (3-4 weeks) and adult capsaicin-induced migraine rat models, and an exploratory pilot study involving 23 pediatric migraine patients.Compared to controls, migraine patients exhibited distinct gut microbiota with reduced Bifidobacterium longum. and elevated Bacteroides. GI disorders were present in 46.8% of migraine patients and were associated with significantly higher rates of abdominal pain (50% vs. 13%, p <0.001), greater migraine-related disability (PedMIDAS: 60 ± 13.2 vs. 29 ± 7.0, p = 0.042), elevated fecal calprotectin, and enrichment of Streptococcus gallolyticus. In contrast, Faecalibacterium prausnitzii, positively correlated with B. longum, was linked to milder symptoms and shorter disease duration in migraine patients without GI disorder. In animal models, B. longum attenuated trigeminal activation in both young and adult rats. An exploratory pilot study showed B. longum supplementation led to reductions in headache days, intensity, and frequency. These findings reveal distinct gut microbial signatures in pediatric migraine, and identify B. longum as a promising microbiota-targeted therapeutic strategy. Our work highlights the therapeutic potential of modifying the gut-brain axis in childhood migraine.}, } @article {pmid41454610, year = {2026}, author = {Song, R and Li, M and Tang, S and Zhang, G}, title = {Immunotherapy for virus-related hepatocellular carcinoma: recent progress and future directions.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2607229}, doi = {10.1080/07853890.2025.2607229}, pmid = {41454610}, issn = {1365-2060}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/virology/immunology ; *Liver Neoplasms/therapy/virology/immunology ; *Immunotherapy/methods/trends ; Immune Checkpoint Inhibitors/therapeutic use ; Tumor Microenvironment/immunology ; Cancer Vaccines/therapeutic use ; Antiviral Agents/therapeutic use ; Hepacivirus ; Hepatitis B, Chronic/complications ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remaining the predominant etiological factors. Chronic viral infection not only drives carcinogenesis but also reshapes the hepatic immune microenvironment, profoundly influencing the efficacy and safety of immunotherapy.

RECENT ADVANCES: Immune checkpoint inhibitors (ICIs) have revolutionized systemic therapy for advanced HCC, with agents targeting PD-1/PD-L1 demonstrating clinical benefit. Combination strategies - such as ICIs with anti-angiogenic therapies, multikinase inhibitors, or locoregional treatments - have shown synergistic efficacy and are now standard of care in certain settings. For virus-related HCC, antiviral therapy improves immune responsiveness and reduces risks such as HBV reactivation, underscoring the need for integrated management.

FUTURE PERSPECTIVES: Emerging therapeutic approaches include next-generation immune checkpoints (e.g. TIM-3, LAG-3, TIGIT), bispecific antibodies, cellular therapies (CAR-T, TCR-T, TILs), and tumor vaccines targeting viral or tumor-associated antigens. Advances in biomarker discovery, including circulating tumor DNA, immune signatures, and microbiome modulation, are expected to guide personalized treatment. Integration of multi-omics and clinical data will further refine patient selection and optimize treatment sequencing.

CONCLUSION: Immunotherapy offers new hope for patients with virus-related HCC, but challenges remain in response heterogeneity, resistance, and toxicity. Individualized strategies that combine immunotherapy with effective antiviral management and biomarker-|guided patient selection are essential. Continued translational and clinical research into virus-immune-tumor interactions will enable safer, more effective, and more durable treatment outcomes, ultimately transforming HCC into a more manageable disease.}, } @article {pmid41454222, year = {2025}, author = {Li, J and Sun, Z and Chai, S and Li, H and Wang, Y and Tian, J}, title = {AR-CDT NET: a deep deformable convolutional network for gut microbiome-based disease classification.}, journal = {BMC bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12859-025-06357-0}, pmid = {41454222}, issn = {1471-2105}, support = {No.GZY-ZJ-SY-2303//Zhejiang Province Traditional Chinese Medicine Key Laboratory Project/ ; }, abstract = {Advances in metagenomic sequencing have increasingly implicated gut microbiome dysbiosis in numerous complex diseases, yet its application for precise differential diagnosis remains a major challenge. Existing computational approaches often show limited predictive performance and insufficient robustness when applied to large-scale, imbalanced microbiome datasets, and they typically lack mechanisms to effectively capture microbial community-level or functional guild interactions. To address these limitations, we developed AR-CDT Net, a novel deep learning framework that integrates a Multi-Scale Deformable Convolution (MS-DConv) module with a Channel-wise Dynamic Tanh (CD-Tanh) activation function to achieve more accurate and robust classification of host disease states. Evaluated on a large-scale cohort comprising over 8000 samples spanning eight disease phenotypes, AR-CDT Net demonstrated highly competitive within-cohort performance, outperforming nine representative models across the majority of classification tasks. Importantly, in a stringent cross-dataset generalization test, the model was trained on the highly imbalanced primary multi-disease cohort and validated on relatively balanced independent external cohorts. It achieved a statistically significant AUC of 0.7921 on the highly heterogeneous external T2D cohort, confirming that AR-CDT captures transferable biological signals rather than dataset-specific artifacts. Furthermore, by combining dimensionality reduction with SHAP-based interpretation of our One-vs-Rest (OvR) classifiers, AR-CDT disentangles disease-specific pathogenic signatures from the shared dysbiotic background among clinically distinct yet microbially similar diseases.}, } @article {pmid41454195, year = {2025}, author = {Bao, W and Wang, T and Wang, Y and Chen, L and Qin, F and Chen, S and Miao, L and Zhou, S}, title = {Causal Inference and Prognostic Modeling in Colorectal Cancer through Integration of Computational Pathology and Mendelian Randomization.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {41454195}, issn = {1534-4681}, support = {UNPYSCT-2018053//Shandong Province Medical and Health Planning Project/ ; ZR2023MH144//Natural Science Foundation of Shandong Province/ ; 23-2-1-191-zyyd-jch//Qingdao Natural Science Foundation Project/ ; }, abstract = {BACKGROUND: While traditional pathology supports the diagnosis and staging of colorectal cancer (CRC), computational pathology provides novel prognostic insights. Mendelian randomization (MR) is effective in uncovering causal relationships in cancer research; however, studies that integrate MR with pathology to investigate gut microbiota (GM), immune cells, and CRC remain limited.

MATERIALS AND METHODS: We analyzed whole-slide images from The Cancer Genome Atlas Colon Adenocarcinoma/Rectal Adenocarcinoma (TCGA-COAD/READ) datasets using ResNet-50 and CellProfiler to extract pathological features. MR analysis and mediation analyses were then performed to identify causal links between GM, immune cells, and CRC. Causal single-nucleotide polymorphisms (SNPs) were mapped to corresponding genes (microbiome-immune genes), and the expression levels of these genes were correlated with the extracted image features. Finally, a prognostic model was constructed using machine learning algorithms.

RESULTS: We identified 55 causal relationships, 6 mediating effects, and 15 microbiome-immune genes. Among the extracted pathological features, 21 were found to be associated with these microbiome-immune genes. The prognostic model developed in this study demonstrated accurate performance in predicting CRC prognosis.

CONCLUSIONS: By integrating MR with computational pathology, we elucidated the causal relationships among GM, immune cells, and CRC, and successfully constructed a prognostic prediction model. This work provides new targets for the precision treatment of CRC.}, } @article {pmid41453954, year = {2025}, author = {Sudi, S and Suresh, SD and Kolli, T and Azamar, KM and Dickson, A and Mohammadalizadeh, Z and Porras, AM}, title = {Trimethylamine-N-oxide promotes fibrotic activation of quiescent valvular interstitial cells via endoplasmic reticulum stress.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-32038-2}, pmid = {41453954}, issn = {2045-2322}, support = {T32 AI007110/NH/NIH HHS/United States ; R35GM155229/NH/NIH HHS/United States ; }, abstract = {Calcific aortic valve disease currently lacks effective treatments beyond aortic valve replacement, largely due to an incomplete understanding of its pathogenesis. Emerging evidence suggests that the gut microbiome influences cardiovascular health through the production of metabolites derived from dietary components. Among these metabolites, trimethylamine-N-oxide (TMAO) has been identified as a potential causal factor for several cardiovascular conditions. However, its specific role in the development of aortic valve disease remains poorly understood. This study sought to investigate the impact of TMAO on valvular interstitial cells (VICs), the most abundant cell type in the aortic valve. Here, we demonstrate that TMAO activates aortic VICs towards a myofibroblastic phenotype through the induction of endoplasmic reticulum stress. Using a novel in vitro protocol to generate quiescent VICs, we found that TMAO induces the upregulation of the myofibroblastic proteins α-smooth muscle actin and transgelin in a sex-independent manner. These quiescent VICs were more sensitive to TMAO than conventionally cultured VICs. Treatment with TMAO also elevated extracellular matrix production and oxidative stress, phenotypic hallmarks of an activated profibrotic state. Finally, inhibition of the endoplasmic reticulum stress kinase prior to TMAO treatment blocked all effects of this metabolite on VIC phenotype. These findings suggest that TMAO contributes to the early stages of valve disease by promoting VIC activation and extracellular matrix production through endoplasmic reticulum stress mechanisms. Understanding the role of TMAO and other gut-derived metabolites in the pathogenesis of valve disease could inform the development of novel preventive or therapeutic strategies to modify or delay disease progression. Furthermore, these insights underscore the importance of host-microbiome interactions for cardiovascular health and highlight the potential for targeted dietary interventions to mitigate disease risk.}, } @article {pmid41453732, year = {2025}, author = {Su, J and Ma, G and Tang, X and Ma, Z and Xie, Z and Peppelenbosch, MP}, title = {Konjac mannan oligosaccharides as a sustainer of fasting-associated gut microbiome signature after discontinuation of intermittent fasting in overweight individuals: A protocol for an open-label randomized clinical trial.}, journal = {Clinical nutrition ESPEN}, volume = {}, number = {}, pages = {102888}, doi = {10.1016/j.clnesp.2025.102888}, pmid = {41453732}, issn = {2405-4577}, abstract = {BACKGROUND: Our previous studies show that the improvement in cardiometabolic traits by intermittent fasting is associated with remodeling the gut microbiome, with short-chain fatty acids (SCFA) producing bacteria being evident. These effects, however, are largely lost when intermittent fasting is discontinued. Konjac mannan oligosaccharides (KMOS) are a commercial nature-deprived prebiotic, which has been reported to increase the levels of intestinal SCFA-producing bacteria. However, the capacity of continued KMOS consumption to maintain intermittent fasting-provoked levels of SCFA-producing bacteria, remains unknown.

METHODS: This study aims to test whether a KMOS supplement positively affects fasting-provoked SCFA-producing bacteria levels during, and in particularly, after discontinuation of intermittent fasting. This prospective, randomized, controlled trial will be conducted in overweight volunteers aged 18-65. All participants will perform one month of intermittent fasting followed by one month of an ad libitum diet. Participants will be randomly assigned to receive KMOS (1.5 g/d) during fasting, both during fasting and the subsequent ad libitum period, or neither. Primary outcomes will be relative abundance of SCFA-producing bacteria in fecal samples, as determined by 16s rRNA sequencing. Secondary outcomes will be changes in body weight, blood pressure, and serum lipid levels.

CONCLUSIONS: Findings from this trial will answer the question whether KMOS can maintain fasting-associated SCFA producer level and metabolic benefits when fasting is discontinued.

CLINICAL TRIAL REGISTRATION: ChiCTR2200058139.}, } @article {pmid41453696, year = {2025}, author = {Santilli, J and Reguera-Nuñez, E and Armstrong, E and Wijesinha, Z and Levy, L and Schneeberger, PHH and Ramendra, R and Zhang, CYK and Huszti, E and Martinu, T and Coburn, B}, title = {Lung microbiome quantification and bacterial density as prognostic markers in lung transplantation.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.healun.2025.12.017}, pmid = {41453696}, issn = {1557-3117}, abstract = {BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a barrier to long-term survival following lung transplantation. Composition of the lung allograft microbiome has been explored as a prognostic marker for allograft survival, but most studies have measured bacterial relative, not absolute, abundances. Absolute quantitation of bacterial abundances improves the assessment of host-microbe interactions in diverse disease states and physiologic compartments but has not been compared to compositional indices alone for performance in identifying CLAD-associated allograft microbiomes.

METHODS: We performed a case-control study to compare the composition of the lung allograft microbiome between lung transplant recipients who developed CLAD within the first 4 years of transplant (cases) versus those who remained CLAD-free for the first 5 years post-transplant (controls). Within 12 months post-transplantation, bronchoalveolar lavage fluid was collected from 53 cases and 55 controls to compare compositional features of the microbiome and bacterial absolute abundance.

RESULTS: We identified five overlapping compositional subtypes, termed community state types, of the lung allograft microbiome that were dominated by either Prevotella species, Streptococcus and Neisseria species, Staphylococcus or Pseudomonas species, or a diverse bacterial population. Lower bacterial density was observed in the taxonomically diverse community and was lower in controls than cases. Normalizing the relative abundance of CST-defining bacteria to total bacterial density strengthened microbiome-composition/CLAD associations.

CONCLUSIONS: Absolute bacterial quantification strengthens associations between the lung microbiome and CLAD following lung transplantation and may improve our understanding of how the lung microbiome affects lung transplant outcomes.}, } @article {pmid41453658, year = {2025}, author = {Vahid, F and Loyola-Leyva, A and Tur, J and Bouzas, C and Devaux, Y and Malisoux, L and Garcia, S and De Carvalho, M and Ródenas-Munar, M and Turner, J and Lamy, E and Perez-Jimenez, M and Ravn-Haren, G and Andersen, R and Forberger, S and Nagrani, R and Onorati, MG and Bonetti, GG and Rodrigues, D and Bohn, T}, title = {Multimodal (Bio)Markers and Risk of Obesity - A Comprehensive Scoping Review.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100579}, doi = {10.1016/j.advnut.2025.100579}, pmid = {41453658}, issn = {2156-5376}, abstract = {Obesity has been associated with several chronic diseases, especially non-communicable ones and related comorbidities. Despite international efforts to decrease the prevalence of obesity, the number of persons struggling with this ailment is not decreasing. An important aspect is obesity prevention, including the early detection of the risk, i.e., whether an individual is likely to develop obesity, in order to allow for early risk stratification and countermeasure initiation. However, obesity is a complex and multi-factorial complication, and many factors appear to play a role, including age, sex, diet, physical activity (PA), psychological and emotional status, genetic make-up, epigenetics, and gut microbiota. One isolated biomarker, therefore, could not enable optimal risk stratification and prognosis for the individual; rather, a combined set or multimodal approach to tackle risk prediction is demanded. Such a multimodal interpretation would integrate biomarkers from various domains, such as more classical markers (insulin, leptin), multi-omics (e.g., genetics, epigenomics, transcriptomics, proteomics, metabolomics), behavioral attributes (dietary, PA, and sleep patterns, smoking status), psychological traits (mental health status, depression, eating disorders), and gut-microbiota (composition, diversity) into a combined interpretation, also employing more advanced interpretation tools, such as machine learning and artificial intelligence. In this scoping review, we aim to summarize the current state of the art in this area, highlighting the progress and novel approaches in combating obesity, and focusing on the feasibility and effectiveness of such biomarkers and their application within clinical trials. In addition, we outline potential future steps and recommendations for future approaches.}, } @article {pmid41453640, year = {2025}, author = {Manzanares, LD and Dehghani, Z and Herrnreiter, CJ and Ren, X and Sumagin, ME and Serdiukova, A and Naqib, A and Green, S and Wechsler, JB and Sumagin, R}, title = {Repeated DSS Exposure Elicits Distinct Immune Responses Reflecting Human Ulcerative Colitis.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101714}, doi = {10.1016/j.jcmgh.2025.101714}, pmid = {41453640}, issn = {2352-345X}, abstract = {BACKGROUND AND AIMS: Dextran sulfate sodium (DSS)-induced colitis is a widely used model to study ulcerative colitis (UC). However, the extent to which acute versus repeated DSS exposure mimics human disease remains unclear.

METHODS: Using histopathology, flow cytometry, single-cell RNA sequencing (scRNA-seq) and 16S rRNA profiling we compared disease outcomes, immune infiltrate, transcriptional programs and changes in the microbiome in mice subjected to a single (acute) versus two (repeated) DSS cycles. We further evaluated which experimental condition better represents key immune cell subtype states in human disease.

RESULTS: While disease activity indices were similar between groups, repeated DSS exposure resulted in greater colon shortening, mucosal remodeling and elevated immune infiltration, particularly by neutrophils (PMNs) in the distal colon. scRNA-seq revealed that PMNs and T cells acquired distinct transcriptional programs in repeated versus acute colitis. Cycle 1 PMNs showed inflammatory and cytotoxic signatures, whereas cycle 2 PMNs were enriched in tissue remodeling and survival pathways. CD4 and CD8 T cells in repeated colitis exhibited migratory, and pathogen-responsive phenotypes, with expanded Treg and exhausted CD8 subsets. In contrast, macrophage numbers decreased with repeated DSS, though remaining cells exhibited pro-resolution gene expression profiles. Microbiome analysis revealed normalization trends with repeated DSS exposure, including reduced pro-inflammatory and increased beneficial genera. Cross-species transcriptomic comparisons indicated cycle-specific overlap with human UC, where cycle 2 activated PMNs and alternatively activated macrophages, closer aligned with active human UC.

CONCLUSION: Collectively, our data indicate that repeated DSS cycles provide a better experimental colitis model for studying immune cells in UC and identifying distinct immune subtypes relevant to UC therapeutics.}, } @article {pmid41453335, year = {2025}, author = {Yang, X and Cao, R and Jia, C and Gao, F and Xu, Q}, title = {Gut microbiome succession and cultivation-based functional screening during intestinal regeneration in Stichopus monotuberculatus.}, journal = {Marine environmental research}, volume = {215}, number = {}, pages = {107806}, doi = {10.1016/j.marenvres.2025.107806}, pmid = {41453335}, issn = {1879-0291}, abstract = {Stress-induced evisceration impairs sea cucumber survival and growth, affecting both their ecological roles and sustainable production in marine environments. Given the critical role of gut microbiome in maintaining host health, microbiome modulation emerges as a novel strategy to improve post-evisceration recovery. This study investigated the gut microbiome during intestinal regeneration in the tropical sea cucumber Stichopus monotuberculatus by combining 16S rRNA gene sequencing with culture-dependent isolation. We (i) tracked microbial community succession, and (ii) established a collection of indigenous gut isolates with digestive enzyme activities. The results demonstrated distinct gut microbial communities across regeneration stages, reflecting the combined influence of deterministic host selection and stochastic colonization. Dominant genera Delftia and Ruegeria aligned with taxa prevalent in native coral reef environments. These genera were nearly eradicated after evisceration but rebounded to baseline levels by late regeneration, suggesting host-selected retention of taxa with potential functional importance. Cultivation efforts under varied media and oxygen conditions yielded 163 bacterial isolates (78 species, four putatively novel), substantially expanding the known cultivable diversity of the holothurian gut microbiome. Enzymatic screening identified several multienzyme-producing isolates, including Priestia megaterium, Bacillus stratosphericus and Lysinibacillus fusiformis. These isolates exhibited amylase, lipase, and cellulase activities, supporting their potential as targeted digestive probiotics. Our integrated approach deciphers gut microbiome dynamics during regeneration, providing ecological insights into host-microbe-environment interactions and microbial resources for sustainable management of sea cucumber populations.}, } @article {pmid41453095, year = {2025}, author = {Nagamine, T}, title = {The Microbiome-Brain Axis in Burning Mouth Syndrome and Its Comorbidities: An Integrated Perspective.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {34}, number = {4}, pages = {521-526}, doi = {10.15403/jgld-6398}, pmid = {41453095}, issn = {1842-1121}, mesh = {Humans ; *Burning Mouth Syndrome/microbiology/physiopathology/epidemiology/psychology/therapy ; *Gastrointestinal Microbiome ; *Brain/physiopathology/microbiology ; Dysbiosis ; *Mouth/microbiology ; Comorbidity ; Probiotics/therapeutic use ; *Microbiota ; Depression/microbiology/epidemiology ; Animals ; }, abstract = {Burning mouth syndrome (BMS) is a chronic nociplastic pain condition of unknown etiology, predominantly affecting women and highly comorbid with depression and anxiety. This narrative review proposes a comprehensive model integrating the significant role of the oral and intestinal microbiomes in BMS pathology. We explore how microbial dysbiosis compromises barrier functions, leading to systemic and neuroinflammation, and subsequently modulates key brain networks involved in pain processing and emotional regulation. Evidence suggests that dysbiosis within the oral microbiome (e.g., increased Streptococcus, Rothia, Bergeyella, Granulicatella, Neisseria) and/or the intestinal microbiome contributes to BMS pathology. This dysbiosis can compromise oral and intestinal barrier functions, leading to the systemic dissemination of bacterial components and inflammatory mediators. These factors induce neuroinflammation, which directly influences and dysregulates key brain networks such as the default mode network and salience network, crucial for pain processing and emotional regulation. The vagus nerve serves as a critical bidirectional communication pathway within this axis. Preliminary studies indicate potential therapeutic benefits of probiotics (e.g., Lactobacillus reuteri in BMS), but large-scale evidence is still emerging. The pathology of BMS, intertwined with depression and anxiety, can be significantly influenced by the oral and intestinal microbiomes. Dysbiosis contributes to chronic systemic and neuroinflammation, driving maladaptive changes in brain networks and neurotransmitter systems. While promising, the field is nascent, requiring further causal studies, detailed mechanistic insights, and robust clinical trials to establish the full therapeutic potential of microbiome-targeted interventions.}, } @article {pmid41453043, year = {2025}, author = {Yang, I and Hendler, K and Scannapieco, FA and Boykins, G and Wharton, W}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e103436}, doi = {10.1002/alz70856_103436}, pmid = {41453043}, issn = {1552-5279}, mesh = {Humans ; *Biomarkers/cerebrospinal fluid ; Female ; Male ; *Alzheimer Disease/cerebrospinal fluid ; Middle Aged ; *Microbiota ; *Periodontal Diseases/microbiology ; *Social Determinants of Health ; Aged ; Inflammation ; }, abstract = {BACKGROUND: Evidence suggest an association between periodontal disease (PerioD) and Alzheimer's disease (AD), with PerioD-associated microbial ecosystems driving oral and systemic inflammation that may activate or accelerate neuroinflammation, a hallmark of AD. Social determinants of health (SDoH) are critical factors influencing both oral health and AD risk yet are often overlooked, and rarely investigated together. This study aims to characterize and compare the oral microbiome of age- and education-matched individuals at high risk for AD by virtue of family history, with and without PerioD, and to investigate the relationships between PerioD-associated microbiome features, SDoH, systemic inflammation and brain inflammation, and AD biomarkers (in cerebrospinal fluid [CSF]).

METHOD: This two-year NINDS-funded study collects oral microbiome samples, blood, and CSF annually in a cognitively normal, racially diverse cohort (n = 165). Metagenomic sequencing will be used to investigate cross-kingdom microbial communities and their association with inflammatory and systemic markers. Surveys and interviews investigate behaviors and SDoH influencing PerioD and AD risk.

RESULT: To date, 55 participants have been recruited. Participants are 62 years of age on average, predominantly white (70%), female (63.3%), with Stage 1-2 periodontitis (85.7%). Preliminary analyses found no significant relationships between bleeding on probing, behavioral factors, SDoH variables, and Montreal Cognitive Assessment (MoCA) scores, which was expected given the small sample size. As recruitment continues, we anticipate identifying associations between oral microbiome features, inflammatory markers, AD biomarkers and cognitive outcomes. SDoH, such as access to dental care and oral hygiene behaviors, may mediate these relationships, offering insights into the interplay between periodontal disease, systemic inflammation, and AD risk.

CONCLUSION: By leveraging longitudinal data and exploring upstream sociocultural factors, this research addresses critical gaps in understanding PerioD's contribution to AD risk. Findings will provide novel insights into the interplay between the oral microbiome, systemic inflammation, brain inflammation, and AD risk.}, } @article {pmid41453016, year = {2025}, author = {Zhao, J and Xiang, D and Wang, J and Yan, G and Wang, Z and He, L and Chen, H and Wang, Z and Liu, H}, title = {Beauveria bassiana triggers the tomato 'cry for help' mechanism to assemble pest-suppressing rhizomicrobiome.}, journal = {The Plant journal : for cell and molecular biology}, volume = {124}, number = {6}, pages = {e70646}, doi = {10.1111/tpj.70646}, pmid = {41453016}, issn = {1365-313X}, support = {2023YFD1400600//National Key Research and Development Program of China/ ; XNDX2022020014//Shuangcheng cooperative agreement research grant of Yibin/ ; XZ202301ZY0014N//Key R&D Program of Tibet, China/ ; B20241NY1307//Technology Innovation and the Science and Technology Support Program of Chongqing Tobacco Company of China National Tobacco Corporation/ ; }, mesh = {*Solanum lycopersicum/microbiology/metabolism/physiology ; *Beauveria/physiology ; Animals ; Rhizosphere ; Oxylipins/metabolism ; Pseudomonas/physiology ; Hemiptera/physiology ; Cyclopentanes/metabolism ; Salicylic Acid/metabolism ; Plant Roots/microbiology ; Soil Microbiology ; Microbiota ; Plant Diseases/microbiology ; Herbivory ; Pest Control, Biological ; }, abstract = {Plants can specifically assemble beneficial rhizosphere microbiota through the 'cry for help' mechanism triggered by non-pathogenic elicitors, thereby promoting plant health. However, it remains unknown whether non-pathogenic strains can be used to induce plants to form a rhizomicrobiome capable of resisting herbivores. Here, we investigated how tomatoes enhance their defense capacity via the 'cry for help' response triggered by the entomopathogenic fungus Beauveria bassiana. Our findings show that B. bassiana induces the formation of beneficial soil legacy in tomatoes, which significantly impacts the performance of whitefly (Bemisia tabaci) on tomatoes. Amplicon sequencing revealed a specific enrichment of Pseudomonas in the soil legacy. Supplementing soils with Pseudomonas isolates reduced whitefly performance on tomatoes and increased the whitefly-induced levels of salicylic acid (SA) and jasmonic acid (JA) in the plants. Moreover, metabolomic and in vitro experiments demonstrated that the increased abundance of rhizosphere Pseudomonas, induced by enhanced root exudation of o-anisic acid, is responsible for the pest-suppressive effect of the soil legacy. This research uncovers a 'cry for help' mechanism whereby tomatoes, through interactions with a non-pathogenic strain, reshape their rhizosphere microbiome to bolster defense. It also deepens our understanding of microbiota-mediated plant defense and offers insights for biological control of herbivores.}, } @article {pmid41452759, year = {2025}, author = {Axi, L and Wang, Y and Meng, W}, title = {Research Progress on Exclusive Enteral Nutrition Combined with Biologics in the Treatment of Adult Crohn's Disease.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaf236}, pmid = {41452759}, issn = {1876-4479}, abstract = {OBJECTIVE: To critically evaluate the evidence and mechanistic basis for combining exclusive enteral nutrition (EEN) with biologics in adults with Crohn's disease (CD), addressing the gap between strong theory and limited clinical proof.

METHODS: We conducted a literature review up to May 2025, focusing on studies combining EEN with biologics (anti-TNF agents, vedolizumab, or Ustekinumab). We assessed methodological quality and bias.

RESULTS: The current literature-mainly small, retrospective cohort studies-indicates that adding EEN to biologic therapy may increase clinical and endoscopic remission rates by 30-50% compared to biologic monotherapy. This effect is believed to be attributed to enhanced mucosal healing, alterations in the microbiome, and improved pharmacokinetics. However, these findings are based on studies with significant limitations, including selection bias, varying protocols, and lack of blinding.

CONCLUSION: Combined therapy with Exclusive Enteral Nutrition (EEN) and biologics shows promise in managing complex Crohn's Disease (CD), with studies reporting improved remission rates. This clinical benefit may be attributed to a synergistic effect supported by a plausible biological basis. However, these favorable outcomes are based on low-certainty evidence from limited clinical studies. Robust randomized controlled trials are needed to establish the effectiveness, safety, and best use of this combination approach. Keywords: Crohn's disease; Exclusive enteral nutrition; Combination therapy; Biologics; Mucosal healing.}, } @article {pmid41452713, year = {2025}, author = {Gong, X and Wang, S and Xia, Q}, title = {The Emerging Triad in Cancer and Aging: Cellular Senescence, Microbiome, and Tumor Microenvironment.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.1495}, pmid = {41452713}, issn = {2152-5250}, abstract = {Aging is accompanied by a marked increase in cancer incidence and mortality, yet most studies still consider cellular senescence, the tumor microenvironment, and the microbiome as largely separate axes. Here, we propose an integrative triad framework in aging-related cancers in which cellular senescence, tumor microenvironment (conceptualized here as part of a broader tumor microecology), and the microbiome dynamically interact to shape tumor initiation, evolution, and treatment response. We summarize how senescent cells, via context-dependent senescence-associated secretory phenotypes (SASPs), remodel stromal, immune, and metabolic niches in aging hosts and how gut and intratumoral microbiota both induce and are reshaped by senescence. Focusing on colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC), together with pan-cancer transcriptomic and microbiome analyses. We highlight disease and subtype-specific patterns in which senescence signatures, immune contexture, and microbial features co-stratify prognosis and therapeutic outcomes, and integrate pan-cancer transcriptomic and microbiome analyses to illustrate shared and divergent triad configurations across tumor types. Finally, we discuss the therapeutic implications of this triad, including timing-dependent use of senolytics and senomorphics, diet and microbiome-targeted interventions, fecal microbiota transplantation (FMT), and the ecological risks of antibiotics, particularly in multimorbid older patients. We argue that triad-informed biomarkers and trial designs integrating senescence, microenvironment, and microbiome readouts will be important for mechanism-based, age-adapted cancer prevention and therapy in older adults, especially those with CRC, HCC, and PDAC.}, } @article {pmid41452539, year = {2025}, author = {Zhang, X and Li, Y and Cao, D}, title = {Update on the role of mycobiome in Gastrointestinal cancers: mechanisms and therapeutic implications.}, journal = {Medical oncology (Northwood, London, England)}, volume = {43}, number = {2}, pages = {96}, pmid = {41452539}, issn = {1559-131X}, support = {2025GXNSFHA069143 and 2025GXNSFHA069078//Joint Special project of Guangxi Natural Science Foundation/ ; GuikeAD23026078//Science and Technology Base and Talent Program in Guangxi/ ; }, mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/therapy ; *Mycobiome/physiology ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {Fungi are a vital component of the gastrointestinal microbiota and are increasingly recognized for their critical roles in the initiation, progression, and therapeutic response of digestive tract cancers. Accumulating evidence indicates that specific fungal species contribute to the pathogenesis of various gastrointestinal malignancies-including oral, esophageal, gastric, and colorectal cancers-by promoting chronic inflammation, inducing host DNA damage, and modulating immune responses. Moreover, fungal-bacterial interactions can indirectly influence tumorigenesis by disrupting microbial community homeostasis and altering the functional landscape of the gut microbiome. In this review, we systematically synthesize current evidence from human cohort studies, preclinical models, and multi-omics analyses to delineate mycobiome-cancer associations, elucidate underlying mechanisms, and evaluate emerging diagnostic and therapeutic strategies. Together, these insights position the mycobiome not merely as a bystander but as an active contributor to gastrointestinal carcinogenesis-offering novel opportunities for early detection, risk stratification, and microbiome-targeted interventions in cancer prevention and therapy.}, } @article {pmid41452451, year = {2025}, author = {Zhang, X and Li, C and Feng, X and Yuan, X}, title = {The interplay of microbiome, molecular mechanisms, and fertility -an integrated review.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41452451}, issn = {1874-9356}, support = {LBH-Z21218//Postdoctoral funding of Heilongjiang Province/ ; }, abstract = {The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility.}, } @article {pmid41452337, year = {2025}, author = {Chen, Y and Gong, X and Xiong, X and Liu, G and Wang, Z and Zhu, Y}, title = {Microbial Community Restructuring Enhances Composting Efficiency: Synergistic Roles of Thermal Cycling and Fungal Inoculants (Fomes lignosus and Penicillium glabrum) in Metabolic Adaptation.}, journal = {Microbial biotechnology}, volume = {18}, number = {12}, pages = {e70290}, pmid = {41452337}, issn = {1751-7915}, support = {2025CJE09073//the Key Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region, China/ ; 2023ZDZX-01//the Major Special Program of Gansu Academy of Sciences, China/ ; 2025RCXM056//the Key Talent Program of Gansu Province, China/ ; 24JRRA1137//the Science and Technology Program of Gansu Province, China/ ; YDZX2024033//the Science and Ttechnology Program of Shandong Province, China/ ; 2024QN-13//the Young Scientists Fund Project of Gansu Academy of Sciences/ ; 2025QYXQ-07//The Science and Technology Program of Gansu Procince, China/ ; }, mesh = {*Composting/methods ; *Penicillium/metabolism/growth & development ; *Manure/microbiology ; Cattle ; Animals ; Temperature ; Carbon/metabolism ; Humic Substances/analysis ; }, abstract = {This study demonstrates that synergistic integration of thermal cycling (28°C-58°C) and fungal inoculants (Fomes lignosus, Penicillium glabrum) enhances humification in cattle manure composting by restructuring microbial communities toward metabolic adaptation. Through a temperature-phased aerobic system, both inoculants significantly improved carbon conversion efficiency, with F. lignosus (B) and P. glabrum (G) increasing total organic matter by 4.71% and 3.42% (vs. control), humic acid content by 4.58-fold and 2.35-fold, and FDA hydrolase activity by 3.28-fold and 1.22-fold, respectively, confirming improved humification and nutrient cycling. Temperature-inoculant synergy drove functional differentiation. Respiratory profiling revealed that P. glabrum enhanced oxygen consumption by 1.3-fold during the early thermophilic phase (0-168 h at 58°C). Subsequently, temperature-induced respiration hierarchies (control > B > G) converged over time with microbial domestication. High-throughput sequencing and network analyses revealed that temperature-inoculant synergy reshaped the microbiome into simplified consortia, which comprise seven dominant bacterial phyla (e.g., Firmicutes, Actinobacteriota) and three dominant fungal phyla (e.g., Ascomycota), with marked functional differentiation characteristics. P. glabrum selectively enriched humification-related taxa, providing regulatory strategies for enhanced carbon stabilization; whereas F. lignosus favoured lignocellulose-degrading communities, optimising substrate valorisation efficiency. This strategy establishes a targeted microbial framework for optimising the resource utilisation efficiency of lignocellulosic waste within fermentation systems, thereby contributing to circular bioeconomy goals in sustainable organic waste management.}, } @article {pmid41436919, year = {2025}, author = {Nong, C and Jibril, SM and Yang, X and Huang, L and Qu, H and Yang, X and Wang, R and Wu, X and Li, C and Wang, Y}, title = {Soil sterilization accumulates higher content of antibacterial compound and recruits beneficial fungus for konjac soft rot disease management by multi-omics analyses.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {1731}, pmid = {41436919}, issn = {1471-2229}, abstract = {UNLABELLED: Konjac soft rot is a typical soil-borne disease, and while soil sterilization is known to reduce pathogen inoculum and disease incidence, the underlying mechanisms remain unclear. This study investigates how sterilization alters soil metabolite profiles and microbial communities to suppress pathogens and promote konjac health. We identified the antibacterial compound 1,4-naphthoquinone, which accumulates more abundantly in sterilized soil. Transcriptome analysis revealed that 1,4-naphthoquinone disrupts gene expressions involved in protein synthesis, thereby inhibiting the occurrence of soft rot disease. Furthermore, microbiome analysis of sterilized replanting soil showed significant changes in microbial community structures. Beneficial fungi for disease management are favored to recolonize in sterilized replanting soil. An antagonistic Aspergillus sp. NCF-16 was identified, demonstrating strong inhibitory effects on soft rot disease management. Consequently, our findings suggest that soil sterilization can foster a novel soil environment by enhancing antibacterial compounds and promoting the colonization of beneficial microorganisms for effective soil-borne disease management.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-025-07985-7.}, } @article {pmid41352665, year = {2025}, author = {Zahid Ali Khan, F}, title = {Effect of hyperosmolal lubricant on vaginal microbiome during transvaginal ultrasound.}, journal = {American journal of obstetrics and gynecology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajog.2025.12.012}, pmid = {41352665}, issn = {1097-6868}, } @article {pmid41325894, year = {2025}, author = {Staudacher, HM and So, D and Hockey, M and Mahoney, S and Shanahan, E and Loughman, A}, title = {Adherence to a Mediterranean Diet Predicts Gastrointestinal and Anxiety Symptom Response in Irritable Bowel Syndrome.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.11.025}, pmid = {41325894}, issn = {1542-7714}, abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and diet plays a key role in management of symptoms. The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has been widely adopted in clinical practice. However, emerging evidence highlights the potential of other diet interventions for IBS. We recently showed in a 6-week randomized controlled trial in 59 patients with IBS and anxiety or depression symptoms that a Mediterranean diet (MD), rich in whole-grain cereals, vegetables, legumes, fruit, fish and olive oil, was feasible and reduced gastrointestinal (GI) and psychological symptom severity compared with habitual diet controls.[1] The gut, mental, and broader health benefits of an MD are proposed to be driven by its enrichment of the microbiome.[2].}, } @article {pmid41452092, year = {2026}, author = {Kim, ES and Waltmann, A and Duncan, JA and Hood-Pishchany, I}, title = {Advances in treating bacterial vaginosis: recognizing sexual transmission and pipeline of therapies.}, journal = {Current opinion in infectious diseases}, volume = {39}, number = {1}, pages = {67-74}, pmid = {41452092}, issn = {1473-6527}, mesh = {Humans ; *Vaginosis, Bacterial/therapy/drug therapy/microbiology/transmission ; Female ; *Anti-Bacterial Agents/therapeutic use ; Vagina/microbiology ; Male ; Sexual Partners ; Microbiota ; Dysbiosis ; }, abstract = {PURPOSE OF REVIEW: Bacterial vaginosis (BV) is a common vaginal dysbiosis linked to increased risk of HIV, other sexually transmitted infections (STIs), and adverse obstetric outcomes. Standard antibiotic therapy often induces symptom remission, but recurrence rates exceed 50% within 6 months. The purpose of this review is to discuss recent clinical trials that demonstrate improved outcomes when compared to treatment according to current management guidelines and outline potential future therapies.

RECENT FINDINGS: Strong evidence supporting transmission of bacteria associated with the dysbiotic state of BV between sexual partners has accumulated over time. A recent clinical study (StepUp) demonstrated overwhelming evidence that treating male partners with combined oral and topical antibiotics significantly reduces BV recurrence in their female partners, highlighting the role of sexual transmission. Recent guideline updates reflect these advances: the American College of Obstetricians and Gynecologists now advises partner therapy for recurrent BV, signaling a shift toward partner-inclusive management strategies. In parallel, live biotherapeutic products (LBPs) and vaginal microbiota transplantation (VMT) show promise in restoring a stable, Lactobacillus crispatus-dominant microbiome. Novel approaches targeting metabolic vulnerabilities of BV-associated bacteria and L. iners, and nonantibiotic agents like metastable iron sulfides are in early development.

SUMMARY: Several advances in managing recurrent BV have shown promise in improving care of this condition. They represent a shift toward microbiome-informed, durable, and woman-controlled therapies. Strategies combining these along with continued development of promising novel approaches to treatment will be needed to optimize care of patients and reduce global BV burden.}, } @article {pmid41451983, year = {2025}, author = {Fan, Y and Ju, T and Bhardwaj, T and Korver, DR and Willing, BP}, title = {Chicken cecal microbial functional gene content and resistome differ by age and barn disinfection practice.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0373725}, doi = {10.1128/spectrum.03737-25}, pmid = {41451983}, issn = {2165-0497}, abstract = {Chemical disinfectants and water-wash methods are widely employed in sanitizing broiler chicken barns. Studies showed that disinfectants affect environmental microbial composition and antibiotic resistance genes (ARGs). However, little is known regarding how barn disinfection treatments impact the chicken gut resistome and microbial functional gene content. The current study compared the effects of disinfection and water-wash method on the gut microbiome and resistome of commercial broilers using a crossover experimental design after two production cycles at seven barns. Shotgun metagenomic sequencing performed on cecal contents collected at days 7 and 30 also allowed the evaluation of age-associated characteristics of the microbiome. The age of the chickens had the largest effects on the resistome, with younger birds having higher relative abundance of total ARGs (P < 0.05) and differences in resistance mechanism; however, functional gene content and resistome differences were also identified by barn sanitation practice. At day 7, chickens in chemically disinfected barns had decreased gene content related to amino acid synthesis compared to the water-wash group. Additionally, genes related to stringent response were enriched in chickens raised under chemically disinfected conditions (FDR-P < 0.05), suggesting the selection for stress resistance. Lower abundance of genetic pathways encoding amino acid biosynthesis associated with cecal Helicobacter pullorum was observed in the disinfection group at day 30 compared to the water-wash group, with the same pattern in short-chain fatty acid biosynthesis (FDR-P < 0.05). Overall, while the use of disinfectants in barn sanitation slightly affected the relative abundance of some ARGs in the gut, age had a dominant effect on the microbial gene function and resistome.IMPORTANCEThis is the first study to evaluate the effect of sanitation practices on microbial functional gene content and resistome of chickens in a commercial setting. It is also amongst the biggest metagenomics studies on the gut microbiome of broiler chickens. It provides new insights into the changes in resistance profiles with age that agree with other studies examining maturation of the microbiome in other species. Finally, the current study provides valuable insights for informing industry sanitation practices and future studies on broiler gut microbiome and resistome.}, } @article {pmid41451964, year = {2025}, author = {Felippe, MFP and Fink, IA and Motta, LCN and de Macêdo Neto, MP and Lopes, JV and Petry, ACG and Sorato, GB and Gonçalves, DP and Maia, GG and Koehler, LB}, title = {Drug Development.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 5}, number = {}, pages = {e107684}, doi = {10.1002/alz70859_107684}, pmid = {41451964}, issn = {1552-5279}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy ; *Drug Development ; Gastrointestinal Microbiome ; *Cognitive Dysfunction/therapy ; Clostridium Infections/therapy ; }, abstract = {BACKGROUND: The gut-brain axis plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Fecal microbiota transplantation (FMT) has emerged as a potential therapy for AD by restoring microbial balance and reducing neuroinflammation. However, clinical evidence remains limited. This study reviews its potential effects on cognition in AD and other cognitive disorders.

METHOD: PubMed, Cochrane, Scopus, and Embase databases were searched for human studies on FMT and cognition in AD. Eligible studies included clinical trials, case series, and case reports. Reviews, editorials, animal, and non-English studies were excluded. Two reviewers screened studies; four extracted data and assessed quality. Meta-analysis was not performed due to heterogeneity.

RESULT: Five studies were included, totaling 26 dementia patients, all of whom had recurrent Clostridium difficile infection (CDI). The studies included one randomized controlled trial (RCT, n = 20) and four observational studies (three case reports and one case series, n = 6). FMT was associated with cognitive improvements, particularly in patients with mild cognitive impairment or AD. The RCT demonstrated significant gains in MMSE (MD 6.0, p=0.01) and CDR-SOB (MD -3.1, p=0.048) scores at three months follow-up. One case series (n=5) reported cognitive improvements post-FMT, with MMSE increasing from 11 to 17, MoCA from 12 to 21, and CDR-SOB decreasing from 10 to 5.5. The three case reports described cases of AD exhibiting increased MMSE after FMT (15 to 29, 8 to 13, 5 to 12, respectively). They also noted improvements in mood, social interaction, and performance of daily activities. Beyond cognitive changes, FMT led to gut microbiota modulation, with increased Bacteroidaceae and reduced Enterococcaceae. These microbiome shifts correlated with reduced neuroinflammation and metabolic improvements. Adverse effects were minimal, such as transient nausea and mild abdominal discomfort, with no serious events.

CONCLUSION: Preliminary evidence suggests FMT may have cognitive benefits in AD patients and recurrent CDI. However, the limited number of studies and the presence of CDI as a common comorbidity highlight the need for larger, controlled trials to better define its role in AD management.}, } @article {pmid41451727, year = {2025}, author = {Barmadisatrio, and Hakim, ZFE and Akbar, MI and Sofyan, IAA}, title = {Gut Microbiome profile on hirschsprung diseases with hirschsprung associated enterocolitis and non-hirschsprung associated enterocolitis: A systematic review.}, journal = {The Medical journal of Malaysia}, volume = {80}, number = {Suppl 7}, pages = {85-95}, pmid = {41451727}, issn = {0300-5283}, mesh = {Humans ; *Hirschsprung Disease/microbiology/complications ; *Gastrointestinal Microbiome ; *Enterocolitis/microbiology ; }, abstract = {INTRODUCTION: Hirschsprung's disease (HSCR), commonly known as aganglionic megacolon, is a rare congenital intestinal illness. Hirschsprung-associated enterocolitis (HAEC), an HSCR complication, is the major cause of morbidity and mortality in patients. Many research has highlighted specific microbiomes that promote HAEC, although there is still controversy on microbiome management. The aim of this study is to profile the gut microbiome of paediatric patients on HSCR with or without HAEC.

MATERIALS AND METHODS: We conducted an analytical descriptive systematic review of relevant case reports from inception research articles between January 2014 to October 2024 using 3 databases following PRISMA guidelines. We extracted data of gut microbiomes in humans with HSCR with or without HAEC. Data about microbiome's effects on gut physiology were also extracted.

RESULTS: This study identified 244 citations; 17 articles were included and analyzed. Proteobacteria were the most common bacteria in HSCR patients developing HAEC and Bacteroidetes were the most common bacteria found in HSCR patients without HAEC.

CONCLUSION: Proteobacteria were associated in HSCR patient developing HAEC. Therefore, gut microbiome dysbiosis may also be the key point to prevent HAEC.}, } @article {pmid41451708, year = {2025}, author = {Chamut, S and Chamut, D and Dadras, S and Alghamdi, SB and Dye, BA}, title = {Dementia Care Research and Psychosocial Factors.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 4}, number = {}, pages = {e103578}, doi = {10.1002/alz70858_103578}, pmid = {41451708}, issn = {1552-5279}, mesh = {Humans ; *Oral Health ; *Dementia/psychology/therapy ; Aging ; }, abstract = {BACKGROUND: Poor oral health (OH), including periodontal disease and tooth loss, has been linked to systemic inflammation, neurodegeneration, and cognitive decline, underscoring the critical yet underexplored connection between oral and brain health. Alzheimer's Disease and Related Dementias (AD/ADRD) disproportionately affect aging populations, and with cases projected to triple by 2050, there is an urgent need to integrate OH into dementia care practice-and-research (DCPaR).

PERSPECTIVE: Given that there is currently no cure for AD/ADRD, the importance of prevention and early intervention is heightened, yet oral health-despite its crucial role in systemic health and cognitive function-remains largely overlooked in DCPaR. Chronic oral infections and oral microbiome dysbiosis are significant contributors to systemic inflammation, potentially accelerating AD/ADRD progression. Conversely, cognitive decline impairs individuals' ability to maintain OH, perpetuating a cycle of worsening health. The Health and Aging Brain Study-Health Disparities (HABS-HD) is the most AD/ADRD comprehensive study among diverse communities within the US. While it provides critical insights into aging and cognitive health disparities, it currently lacks direct OH measures. This limitation presents an opportunity to explore OH's impact on cognitive decline and overall quality of life. The Health Equity Scholars Program (HESP) addresses this gap by fostering a diverse, culturally competent workforce to study and treat AD/ADRD. Through the project "Exploring Neurological and Indirect Biomarkers for Potential Correlations with Oral Health: An Interdisciplinary Approach," HESP and HABS-HD are advancing efforts to integrate OH into DCPaR, crucial for developing targeted interventions and preventive care for aging populations.

CALL TO ACTION: A multidisciplinary approach is essential to address the bidirectional relationship between oral and cognitive health, promote early detection of oral diseases, and implement preventive measures. Incorporating OH into DCPaR aligns with broader health equity goals, addressing disparities in access to care and bridging existing gaps.

CONCLUSION: As the global burden of AD/ADRD continues to grow, integrating OH into DCPaR will enhance understanding of its role in AD/ADRD progression, improve outcomes for those with cognitive decline, and foster equitable, holistic geriatric healthcare systems.}, } @article {pmid41451559, year = {2025}, author = {Li, J and Ye, J and Yang, T and Hunter, DJ and Zhang, W and Doherty, M and Zhang, Y and Yang, Z and Li, H and Wang, Y and Xie, D and Wu, Z and Li, W and Wen, Z and Li, C and Zhao, K and Zeng, C and Lei, G and Wei, J}, title = {Bile acids metabolism in symptomatic hand osteoarthritis.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.70048}, pmid = {41451559}, issn = {2326-5205}, abstract = {OBJECTIVES: Although gut microbiome dysbiosis is associated with symptomatic hand OA (SHOA), the role of bile acids (BAs), key metabolites in host-microbiota interactions, in SHOA pathogenesis remains unexplored. We investigated the association between plasma BA metabolism and SHOA.

METHODS: The associations between plasma BAs and SHOA were examined in the Xiangya Osteoarthritis (XO) Study and validated in an independent cohort through logistic regression models. Gut microbiome data from a previous study conducted within the XO Study were integrated to explore associations between SHOA-related gut microbes and key BAs. As an exploratory analysis, gene-based meta-analyses evaluated associations between genes encoding key BA receptors and hand OA.

RESULTS: In the discovery cohort (n=1,359, mean age 63.1±9.0 years, 58.4% women, SHOA prevalence 5.2%, all participants being Asian), elevated levels of deoxycholic acid (DCA) species (odds ratio [OR]=1.75, 95% confidence interval [CI]:1.03-2.96) and DCA (OR=2.14, 95% CI:1.24-3.70) were positively associated with SHOA presence and severity. These associations were replicated in an independent cohort (n=142). Multi-omics analyses revealed significant correlations of DCA species, DCA, and the DCA species/total BAs ratio with SHOA-related gut microbes. DCA interacted with SHOA-related gut microbes and was associated with SHOA. Gene-based meta-analyses identified significant associations between genes encoding the Farnesoid X receptor and the pregnane X receptor and hand OA.

CONCLUSION: Dysregulated BA metabolism, particularly elevated DCA levels, is associated with SHOA. The observation that DCA interacts with SHOA-related gut microbes, together with genes encoding DCA receptors, may help guide future biologically and clinically relevant studies.}, } @article {pmid41451362, year = {2025}, author = {Wang, Y and Zeng, L}, title = {Immune modulation in inflammatory bowel disease: therapeutic promise of baicalein.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1723606}, pmid = {41451362}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD) remains a major global health burden, driven by a multifaceted pathogenesis that includes immune dysregulation, epithelial barrier disruption, oxidative stress, and gut microbiota imbalance. Addressing these interconnected processes requires multi-targeted therapeutic strategies that go beyond conventional single-pathway interventions. Baicalein, a key flavonoid derived from Scutellaria baicalensis (Huang Qin), has emerged as a promising candidate due to its broad-spectrum pharmacological properties. This review synthesizes current advances in understanding how baicalein exerts therapeutic effects against IBD through an integrated network of mechanisms. These include potent suppression of inflammatory signaling and oxidative stress, restoration of epithelial integrity via modulation of tight junction proteins and the MLCK/p-MLC2 pathway, and reprogramming of dysregulated immune circuits by rebalancing T-cell subsets and macrophage polarization. In addition, baicalein mitigates pathological cell death pathways such as ferroptosis and pyroptosis and orchestrates beneficial shifts in the gut microbiota-metabolite axis. By bridging classical anti-inflammatory mechanisms with emerging immunoregulatory and microbiome-targeted insights, this review highlights baicalein as a potential multi-dimensional therapeutic strategy for IBD and outlines future directions for its clinical translation.}, } @article {pmid41451295, year = {2025}, author = {Barker, MJ and Esquivel, MK}, title = {Food for Thought: The Role of Nutrition in Behavioral Health.}, journal = {American journal of lifestyle medicine}, volume = {}, number = {}, pages = {15598276251408332}, pmid = {41451295}, issn = {1559-8284}, abstract = {Nutrition is a core pillar of Lifestyle Medicine with growing relevance to mental and behavioral health. While traditionally emphasized for cardiometabolic disease prevention, emerging evidence demonstrates that dietary patterns directly influence mood, cognition, stress resilience, and emotional regulation. This article synthesizes current research on biological pathways linking food and mental health-including the gut-brain axis, microbiome diversity, neurotransmitter synthesis, inflammation, and dietary pattern interventions. A diverse and balanced microbiome, adequate intake of omega-3s, B vitamins, and trace minerals, and diets low in inflammatory foods support healthier brain signaling and improved emotional stability. Clinical trials show that Mediterranean and plant-forward diets reduce depressive symptoms, while micronutrient supplementation enhances attention, emotional regulation, and stress response across the lifespan. Nutrition is also a critical but underutilized component of substance use recovery and child and adolescent behavioral health. Cultural food traditions further shape well-being by reinforcing identity, belonging, and resilience. Integrating nutrition screening, counseling, and food-as-medicine interventions into behavioral health care can strengthen treatment outcomes, especially when aligned with culturally informed practices and community needs. Systems-level approaches-including policies addressing food insecurity and produce prescription programs-demonstrate meaningful improvements in mental health. Overall, nutrition represents a powerful, accessible, and culturally resonant strategy to support emotional, cognitive, and behavioral well-being.}, } @article {pmid41451293, year = {2025}, author = {Hanus, A}, title = {Culinary Medicine: Feeding the Gut for Mental Health.}, journal = {American journal of lifestyle medicine}, volume = {}, number = {}, pages = {15598276251408334}, pmid = {41451293}, issn = {1559-8284}, } @article {pmid41451263, year = {2025}, author = {Haslam, DE and Abirami, K and Starr, JR and Unnikrishnan, R and Lasky-Su, J and Gayathri, R and Gokulakrishnan, K and Manasa, VS and Rimm, EB and Anjana, RM and Krishnaswamy, K and Hu, FB and Sudha, V and Mohan, V and Bhupathiraju, SN}, title = {Effect of Replacing Added Sugars with Sucralose on Gut Microbiome Composition Among Asian Indian Adults in Two 12-week Randomized Controlled Trials.}, journal = {Current developments in nutrition}, volume = {9}, number = {12}, pages = {107600}, pmid = {41451263}, issn = {2475-2991}, abstract = {BACKGROUND: Replacing added sugars with nonnutritive sweeteners, such as sucralose, may help reduce weight gain in adults over time. Because sucralose is primarily excreted in the stool, its consumption could lead to changes in the gut microbiome.

OBJECTIVES: We aimed to explore whether replacing sucrose used in beverages with small quantities of sucralose led to gut microbiome changes among Asian Indian adults with type 2 diabetes (T2D) or overweight/obesity (BMI ≥23 kg/m[2]) without T2D.

METHODS: In 2 analogous substudies nested within two 12-wk, open-label parallel-arm randomized controlled trials, adults with T2D (n = 49) or overweight/obesity and no T2D (n = 48) were instructed to replace sucrose in their daily coffee and tea with sucralose or to continue their use of sucrose. We examined changes in gut microbiome community structure and taxonomic composition profiled using 16S rRNA sequencing in stool samples collected before and after the 12-wk interventions. The false discovery rate was controlled using the Benjamini-Hochberg method (q < 0.20).

RESULTS: Compared with the control group, the sucralose intervention decreased α diversity (Shannon index: P = 0.02; Simpson index: P = 0.03) and increased β diversity (P = 0.001) in gut microbiome communities of adults with T2D, but not among adults with overweight/obesity (all between-group P > 0.05). Among 185 genera tested in the T2D trial, compared with the control, relative abundances of 14 primarily sugar-fermenting or short-chain fatty-acid-producing Firmicutes bacteria in the Lachnospiracae family were reduced, whereas Enterococcus and Pediococcus increased during the intervention (q < 0.20). In contrast, adults with overweight/obesity and no T2D showed no similar changes.

CONCLUSIONS: Replacing daily sucrose added to coffee and tea with sucralose resulted in changes in gut microbiome community structure and taxonomic composition among Asian Indian adults with T2D, but not those with overweight/obesity and no T2D. Further studies are needed to understand potential health implications and the underlying drivers of these gut microbiome changes.Clinical Trial Register No. (India Trial Register): CTRI/2021/04/032686, CTRI/2021/04/032809.}, } @article {pmid41451009, year = {2025}, author = {Ocal, IH and Basol, O and Oguz, A and Bilge, H}, title = {Gut Microbiota-Brain Axis in Pancreatic Cystic Neoplasms: An Observational Analysis.}, journal = {Pakistan journal of medical sciences}, volume = {41}, number = {12}, pages = {3411-3421}, pmid = {41451009}, issn = {1682-024X}, abstract = {OBJECTIVE: This observational analysis aimed to explore the association between gut microbiota and brain axis in pancreatic cysts and assess the impact of this association on clinical outcomes.

METHODOLOGY: This retrospective cohort study was conducted at Dicle University Faculty of Medicine, Diyarbakır, Turkey. Forty-seven patients (serous cystadenoma n=16, mucinous neoplasm n=31) treated at a single center between 2015 to 2023 were included in the study. Microbiota analysis (16S rRNA sequencing) of stool samples, biochemical and hormonal parameters from blood samples were evaluated. Depression-anxiety scales and cognitive tests were also performed.

RESULTS: Microbiota diversity in the mucinous neoplasm group (Shannon index: 2.9±0.6) was significantly lower than in the serous cystadenoma group (3.8±0.5) (p=0.012). Firmicutes/Bacteroidetes ratio (2.89±0.5), inflammatory markers (CRP: 4.2±4.8 mg/dL) and depression scores (Beck: 18.6±6.4) were significantly higher in mucinous neoplasm patients (p<0.05). Two-year overall survival rates were 100% in the serous cystadenoma group and 80% in the mucinous neoplasm group (p=0.015).

CONCLUSION: The microbiota-brain axis has an important role in pancreatic cysts. Microbiota imbalance, increased inflammation and high depression-anxiety levels observed especially in mucinous neoplasms suggest potential targets for future therapeutic interventions in this patient group.}, } @article {pmid41450949, year = {2025}, author = {Perzon, O and Ilan, Y}, title = {Understanding gut microbial diversity using systems based on the Constrained-Disorder Principle provides a novel approach to targeting gut microbiome therapies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1713775}, pmid = {41450949}, issn = {1664-302X}, abstract = {BACKGROUND/AIMS: The diverse composition of the gut microbiome is vital for human health, influencing digestion, immune regulation, and disease resistance. While higher diversity is generally associated with resilience, reduced and excessive diversity can lead to health issues.

METHODS: This paper introduces the Constrained Disorder Principle (CDP) as a new framework for understanding microbial diversity.

RESULTS: The CDP emphasizes the significance of maintaining variability within certain boundaries to sustain ecosystem stability and promote health. It considers intra- and inter-individual variability, illustrating how microbial ecosystems adapt throughout different life stages, genetic backgrounds, and environmental exposures. Integrating CDP-based artificial intelligence systems may enable the establishment of personalized diversity thresholds, predict dysbiosis, and refine interventions such as probiotics, prebiotics, fecal microbiota transplantation, and customized dietary strategies. CDP-driven platforms enhance therapeutic precision by utilizing variability induction, feedback loops, and microbial signature analysis to optimize diversity goals and identify actionable biomarkers.

CONCLUSION: This platform can pave the way for adaptive, individualized disease prevention and treatment strategies, bridging the gap between microbial ecology and precision medicine. It provides a powerful tool for harnessing the therapeutic potential of gut microbial diversity to enhance human health.}, } @article {pmid41450947, year = {2025}, author = {Wu, B and Zhao, A and Chen, W and Zhou, Y and Zhang, W and Zhang, Y and Hou, Q and Yao, N and Zhang, S and Duan, J and Li, N and Cao, J}, title = {Microbiota-mediated modulation of radiosensitivity: mechanisms and therapeutic prospects of oral and gut microbiota, metabolites, and probiotics.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1689735}, pmid = {41450947}, issn = {1664-302X}, abstract = {Radiotherapy is a cornerstone of comprehensive cancer treatment, yet its efficacy and toxicity exhibit considerable interindividual variation. Recent evidence highlights the microbiome-the collective genomes and metabolic products of symbiotic microorganisms in a specific environment-as a key bidirectional regulator of radiosensitivity. Radiotherapy can disrupt microbial community structure, while the microbiome and its metabolites profoundly influence tumor cell radiosensitivity and normal tissue radiotolerance by modulating DNA damage repair, immune responses, metabolic reprogramming, and tumor microenvironment (TME) remodeling. This review systematically examines the mechanisms and recent advances in understanding how oral and gut microbiota, their key metabolites (e.g., short-chain fatty acids, SCFAs), and probiotics modulate radiosensitivity. By establishing a framework centered on "mechanism axis-evidence stratification-clinical translation," this paper aims to provide a theoretical foundation and identify potential targets for microbiome-based strategies to enhance radiosensitivity and protect normal tissues during radiotherapy.}, } @article {pmid41450946, year = {2025}, author = {Scott, B and Garcia-Pichel, F}, title = {Soil phototroph community resilience comes from down under.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1689042}, pmid = {41450946}, issn = {1664-302X}, abstract = {INTRODUCTION: Seed banks are widely recognized as means of recovery following disturbance across diverse ecosystems, including soil. Phototrophic microbes, while common in surface soils, have not been considered within this context.

METHODS: We subjected a variety of topsoil photosynthetically-driven communities (biocrusts) to severe disturbance by scalping off the surface layer, thereby exposing the undercrust. We collected samples from the biocrust layer, the undercrust layer, and again the recovering biocrust layer after a 4-month period. Samples were analyzed for biopigments (chlorophyll a and scytonemin) and 16S rRNA gene copies and its sequence diversity.

RESULTS: Ribosomal gene counts and pigment analyses revealed consistently rapid recovery, as much as 52% content in 4 months. Recovery could be traced to dormant cyanobacterial "seeds" in the undercrusts. Alternative pathways for recovery, including natural or interventional inoculation and lateral spread, did not constitute a comparable force.

DISCUSSION: Our findings bring soil phototrophs within the ecological framework linking seed banks to resilience following disturbance. The overlooked role of undercrusts in prior research invites a reinterpretation of past studies and may inform new restoration strategies.}, } @article {pmid41450934, year = {2025}, author = {Chen, A and Luo, Z and Zhang, J}, title = {Gut microbiota during pregnancy: a bibliometric analysis of global research trends and collaborative networks.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1708359}, pmid = {41450934}, issn = {1664-302X}, abstract = {BACKGROUND: Investigating gut microbiota during pregnancy is vital for understanding maternal-infant health, pregnancy-related disease mechanisms, and offspring development. While research in this field has grown rapidly, systematic analyses of global trends, collaborative networks, and thematic evolution remain limited. This bibliometric study maps the developmental landscape of "gut microbiota during pregnancy," identifying research priorities and future directions.

METHODS: A bibliometric analysis of pregnancy and gut microbiota studies (1991-2025) was conducted using the Web of Science Core Collection and Scopus databases. Publications were analyzed using bibliometrix, VOSviewer, and CiteSpace to evaluate publication trends, research contributions, collaboration networks, keyword co-occurrence patterns, and thematic evolution.

RESULTS: The analysis encompassed 5,432 (Web of Science Core Collection) and 5,542 (Scopus) publications, with an annual growth rate exceeding 15%. Research output has grown exponentially since 2014. The China and United States were the most productive countries, with the United States demonstrating the highest total citations and a central role in global collaborative networks. Key influential institutions included the University of Turku, University College Cork, and the Chinese Academy of Sciences. Leading authors were Collado, Maria Carmen; Tain, You-Lin; and Cryan, John F. The research was highly interdisciplinary, spanning microbiology, nutrition, immunology, and medicine. Core journals disseminating knowledge were Nutrients, Frontiers in Microbiology, and Gut Microbes. High-impact and co-cited references established the knowledge foundation, focusing on maternal microbiome remodeling, delivery mode's impact, and the gut-brain axis. Keyword analysis revealed a thematic evolution from initial descriptive studies of microbial composition to recent investigations into mechanisms linking microbiota to gestational diabetes mellitus, preeclampsia, preterm birth, and neurodevelopmental outcomes via the gut-brain axis.

CONCLUSION: This study presents an integrative bibliometric analysis of global research on gut microbiota during pregnancy, delineating its rapid evolution and current intellectual structure. The field has matured from descriptive ecology to mechanistic and translational research, with strong international collaboration and interdisciplinary integration. The identified research fronts, including the interplay between microbial dysbiosis and specific pregnancy complications, as well as the influence of the maternal gut microbiome on offspring neurodevelopment, represent promising avenues for future investigation.}, } @article {pmid41450770, year = {2025}, author = {Hoffmann, DE and Langel, FD and von Rosenvinge, EC and Palumbo, FB and Roghmann, MC and Ravel, J}, title = {Is the current regulatory framework for direct-to-consumer microbiome-based tests sufficient to protect consumers from medical, economic, and dignitary harms?.}, journal = {Journal of law and the biosciences}, volume = {12}, number = {2}, pages = {lsaf024}, doi = {10.1093/jlb/lsaf024}, pmid = {41450770}, issn = {2053-9711}, abstract = {This article offers a thorough analysis of an important public health issue-the lack of regulation of companies selling direct-to-consumer (DTC) microbiome-based tests. These companies invite curious consumers and desperate patients to submit stool and/or vaginal secretion samples to them for analysis. Purchasers receive a report about the composition of their gut and/or vaginal microbiomes with recommendations to change their diet or take certain dietary supplements. The piece is grounded in a study the authors conducted of DTC microbiome testing company websites and their practices, which are often misleading to consumers. Moreover, the tests lack analytical and clinical validity. This means they may have many "false positive" or "false negatives" and can harm consumers who rely on them as a basis for determining their health status The current regulatory framework for these tests has significant gaps. These include the lack of proficiency testing under the Clinical Laboratory Improvement Amendments (CLIA) and the lack of regulation by FDA as a medical device. Although FDA has distinguished DTC tests from other Laboratory Developed Tests and asserted that they may pose unique risks because they are ordered outside of a physician-patient relationship, they have largely ignored this group of tests, likely because they view them as low risk, general wellness tests and exempted from regulation as medical devices under the software exemptions in the 21st Century Cures Act (Cures Act). The authors conclude, however, that many of these tests are not low risk general wellness tests, nor do they meet the exemptions under the Cures Act and as a result should be more stringently regulated.}, } @article {pmid41450568, year = {2025}, author = {Carrouel, F and Miranda, DG and Arumugam, G and Usmari Moraes, M and de Paula Ramos, L}, title = {Editorial: Skin microbiome: microbiological, immunological and cellular aspects for therapies to control antimicrobial resistance and skin repair.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1736430}, pmid = {41450568}, issn = {2235-2988}, } @article {pmid41450167, year = {2026}, author = {Dovey, Z and Bort, ET and Mechanick, JI}, title = {Network and Gene Set Enrichment Analysis of Adipokine Drivers of Prostate Cancer; Unravelling the Mechanistic Link Between Excess Adiposity and Prostate Cancer Risk.}, journal = {Cancer medicine}, volume = {15}, number = {1}, pages = {e71468}, doi = {10.1002/cam4.71468}, pmid = {41450167}, issn = {2045-7634}, mesh = {Male ; Humans ; *Prostatic Neoplasms/genetics/metabolism/etiology/pathology ; *Adipokines/metabolism/genetics ; *Adiposity/genetics ; *Obesity/complications/metabolism/genetics ; *Biomarkers, Tumor/genetics/metabolism ; *Gene Regulatory Networks ; Inflammation ; Risk Factors ; }, abstract = {BACKGROUND: Adiposity-Based Chronic Disease (ABCD), a novel model housing obesity, insulin resistance, and adipokine-related inflammation, increases the risk of aggressive prostate cancer (PCa), posttreatment PCa recurrence, and PCa mortality. This paper provides a new network analysis of relevant metabolic drivers to provide insight into the ABCD-PCa relationship.

METHODS: A literature search was performed using the terms "prostate cancer" AND "obesity" AND "inflammation", with 629 references found, from which 17 reviews were chosen. Biomarkers identified from these reviews were characterized by cellular origin, signaling pathway, and oncogenic effect. The Webgestalt gene analysis toolkit was then used to generate modular-based network analyses and gene ontology (GO) categories of these biomarkers for interpretation.

RESULTS: 14 prominent biomarkers were identified influencing PCa risk through cellular proliferation, resisting cell death, metabolic reprogramming, tumor-promoting inflammation, avoiding immune destruction, angiogenesis, and activating invasion. Network analyses of biomarker interactions highlighted prominent roles of monocyte chemoattractant protein-1, interleukin-1β, and C-X-C motif chemokine ligand 1. Top GO categories for the wider ABCD-PCa network found key roles of ABCD-gut microbiome dysbiosis and exposure of periprostatic white adipose tissue to the prostate microbiome (involving bacterial and lipopolysaccharide-induced inflammation).

CONCLUSION: Top hypotheses to guide molecular targeted therapies and lifestyle biomarker panels for PCa in ABCD relate to MCP-1, IL-1β, and CXCL1 signaling, as well as gut microbiome dysbiosis and the exposure of the periprostatic adipose tissue to the prostate microbiome. Further research and possible clinical trials allowing histological examination of pre- and post-lifestyle intervention PCa tissue may provide further insights.}, } @article {pmid41449894, year = {2025}, author = {Hong, L and Zheng, Y and Yang, W and Jiang, M and Zheng, K and Chen, S and Han, H and Xia, S and Yang, Z and Li, C}, title = {Effects of probiotic supplementation on intestinal microbiota in patients with diabetes/prediabetes: a systematic review and meta-analysis of randomized controlled trials.}, journal = {The British journal of nutrition}, volume = {}, number = {}, pages = {1-34}, doi = {10.1017/S0007114525105709}, pmid = {41449894}, issn = {1475-2662}, abstract = {This study systematically evaluates the effects of probiotic interventions on gut microbiota and clinical outcomes in diabetic patients to determine the optimal target population and conditions for effective use, with an emphasis on precision treatment. A comprehensive search was performed across PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Internet (CNKI), and Wanfang databases until April 2024. Randomized controlled trials (RCTs) assessing probiotics as adjunctive therapy for diabetes were included. The control group received standard care, and the intervention group received probiotics alongside standard care. Data were managed with Endnote and Excel, and analyses were conducted using Revman 5.3 and Stata 16. Twelve RCTs involving 1,113 participants were included. Probiotics significantly increased fecal Lactobacillus (standardized mean difference (SMD) 1.42, P < 0.0001, I[2] = 95%) and Bifidobacterium levels (SMD 1.27, P < 0.0001, I[2] = 90%) and reduced fasting plasma glucose (SMD -0.35, P = 0.004). Subgroup analysis showed that shorter intervention durations (≤3 months) improved FPG, HbA1c, and Bifidobacterium levels, while younger patients (≤60 years) experienced the most significant improvements in Bifidobacterium levels. In conclusion, probiotics improve gut microbiota and clinical outcomes in diabetic patients, with intervention duration and patient age as key factors influencing treatment effectiveness.}, } @article {pmid41449683, year = {2025}, author = {M'Bra, PEH and Hamilton, LK and Aumont, A and Prévost, K and Massé, E and Fernandes, KJ}, title = {Drug Development.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 5}, number = {}, pages = {e103337}, doi = {10.1002/alz70859_103337}, pmid = {41449683}, issn = {1552-5279}, mesh = {Animals ; *Diet, Ketogenic ; *Alzheimer Disease/diet therapy/metabolism ; Mice ; Mice, Transgenic ; Disease Models, Animal ; *Triglycerides/administration & dosage ; Gastrointestinal Microbiome ; Diet, High-Fat ; Male ; }, abstract = {BACKGROUND: Lifestyle-based interventions can reduce 45% of dementia risk. Dietary supplementation with medium-chain triglycerides (MCT) is a type of ketogenic diet that shows promise against Alzheimer's disease (AD) in humans, presumably through hepatic conversion to circulating ketones. However, the physiological impacts and cellular mechanisms underlying MCT effects remain understudied, particularly in the context of AD.

OBJECTIVE: Here, we used two transgenic mouse model of AD to investigate the physiological and molecular mechanisms occurring in peripheral system upon an MCT-enriched diet versus a classic ketogenic diet.

METHOD: 3xTg-AD, 5xFAD mice and their respective control strain mice (WT) were administered at different age and duration, a standard carbohydrate-rich diet (Control diet, 70% carbohydrate, 20% fat, 10% protein), a similar Control diet that was supplemented with ketogenic medium-chain triglycerides (MCT, a ketogenic substrate), or an extreme carbohydrate-free, high fat diet (CFHF). Mice were subjected to learning/memory tests, and longitudinal monitoring of body composition, glycemia, ketonemia and fecal microbiome composition.

RESULTS: Both ketogenic interventions improved cognition in AD mice after 1 month of treatment. Interestingly, unlike CFHF diet, MCT diet did not induce a sustained ketosis suggesting different mechanisms. Only the MCT diet improved peripheral glucose tolerance, insulin response and reduced adiposity, while CFHF dietary challenge exacerbated AD mice metabolic defects. AD mice exhibited several microbial alterations preceding cognitive symptoms, notably increased levels of Bifidobacterium and decreased levels of Bacteroidetes. Ketogenic interventions restored the fecal microbiome composition by 50% inducing a strong depletion of Bifidobacterium.

CONCLUSION: Collectively, these findings reveal metabolism-improving benefits of MCT in the context of Alzheimer's disease that do not require elevated blood ketone levels and reveal potential therapeutic targets for treating AD, in the gut-brain axis.}, } @article {pmid41449665, year = {2025}, author = {Tran, M and Adam, T and Jackson, R and Cave, R and Webb, A and Kelwick, R and Crone, M and Horrocks, S and Harrison, M and Jensen, K and Freemont, P}, title = {Dementia Care Research and Psychosocial Factors.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 4}, number = {}, pages = {e103245}, doi = {10.1002/alz70858_103245}, pmid = {41449665}, issn = {1552-5279}, mesh = {Humans ; *Dementia/psychology/urine/complications ; *Urinary Tract Infections/diagnosis/urine ; Biomarkers/urine ; Female ; Extracellular Vesicles ; Male ; }, abstract = {BACKGROUND: Approximately 25% of hospital beds in the UK are occupied by people living with dementia (PLWD), with up to 20% of these admissions due to preventable acute conditions like infections. Urinary tract infections (UTIs) disproportionately affect PLWD, who often struggle to communicate their symptoms or present atypically. This delays diagnosis, increasing the risk of hospitalisation, sepsis, cognitive decline, and mortality. There is, therefore, a pressing need for improved diagnostic methods to detect UTIs early in PLWD.

METHODS: A multi-omics approach was employed to investigate urinary biomarkers for early UTI detection in PLWD. Longitudinal urine samples were collected from PLWD and analysed for inflammatory markers using OLINK inflammatory panels, focusing on cytokine profiles. Urinary extracellular vesicles (EVs), which are promising UTI biomarkers, were also characterised using nanoflow cytometry. Furthermore, we are sequencing the urinary microbiome to examine microbial dynamics over time whilst also focussing on sequencing Escherichia coli genomes isolated from urine samples, to understand their contributions to UTIs. To support future research, urine samples and bacterial isolates were stocked and stored. Alongside these efforts, we have developed a point-of-care (PoC) device that incorporates isothermal amplification for rapid UTI detection. The device uses a heating element for bacterial DNA amplification in urine and an optical detection element to measure fluorescence from DNA dyes.

RESULTS: Our biomarker studies highlight potential inflammatory mediators (figure 1) and elevated EV-associated markers for early UTI detection (figure 2). Genomic DNA was used to validate the PoC device's accuracy in predicting the presence of E. coli. Preliminary experiments observed an earlier fluorescent response from positive DNA extractions compared to negative ones. Whilst clinical sample contaminants reduced assay sensitivity and specificity, heat-treating samples beneficially increased the levels of detectable cell-free DNA thereby improving assay performance (figure 3).

CONCLUSIONS: The identification of urinary biomarkers and the development of a PoC device offer promising avenues for improving UTI diagnosis in PLWD. Reliable early detection could reduce hospital admissions, prevent severe complications and improve overall outcomes for this vulnerable population. Future work will focus on refining biomarker analyses and optimising the PoC design to enhance its diagnostic accuracy and usability.}, } @article {pmid41449435, year = {2025}, author = {Zhou, H and Lu, R and Lv, Y and Ding, Y}, title = {Alterations in gut microbiome and fecal metabolome in functional dyspepsia patients: insights into pathophysiological mechanisms.}, journal = {European journal of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40001-025-03743-5}, pmid = {41449435}, issn = {2047-783X}, abstract = {BACKGROUND: Gastrointestinal microbiota dysregulation is recognized as a key factor in the pathogenesis of functional dyspepsia (FD). Previous investigations have focused predominantly on the microbiota associated with the oral, gastric, and duodenal mucosa. However, the intestinal microbiome and fecal metabolome in FD patients remain poorly characterized. This study aims to evaluate their alterations, thereby providing novel insights into the pathophysiological mechanisms of FD.

METHODS: Fecal samples from 30 FD patients and 19 healthy controls (HCs) were subjected to 16S rRNA sequencing and metabolomics to characterize microbial-metabolic profiles, followed by Spearman correlation analysis to explore the associations between differentially abundant taxa and metabolites.

RESULTS: Compared with the HCs, the FD group presented greater microbial richness but comparable diversity, along with increased abundances of Akkermansia and Ruminococcus_gnavus_group and decreased levels of Dorea, Collinsella, and Agathobacter (p < 0.05). AUC analysis revealed Akkermansia as a potential biomarker for FD (AUC = 0.848, 95% CI: 0.708-0.988). Furthermore, the levels of the fecal metabolites phosphatidylglycerol (PG) and phosphatidylcholine (PC) were significantly reduced in the FD group (p < 0.05). KEGG enrichment analysis revealed that these metabolites were involved in glycerophospholipid metabolism. Spearman correlation analysis revealed negative associations between Ruminococcus_gnavus_group, Fusobacterium, Erysipelatoclostridium, and PG/PC (p < 0.05).

CONCLUSIONS: The FD group presented concurrent alterations in the gut microbiome and fecal metabolites. Specifically, gut microbiota-derived metabolites, such as PG and PC, may disrupt host glycerophospholipid metabolism, contributing to FD pathogenesis. Given that this is an exploratory study with a small sample size and cross-sectional design, these results require validation in larger, longitudinal cohorts and should be interpreted with caution.}, } @article {pmid41449247, year = {2025}, author = {Liu, X and Cheng, D and Wang, F}, title = {Postbiotic-mediated gut microbiome modulation enhances R-CHOP efficacy in high-risk diffuse large B-cell lymphoma: a case report.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-025-04322-0}, pmid = {41449247}, issn = {2730-6011}, abstract = {This case report describes an adult with high-risk DLBCL (IPI score 4) treated with R-CHOP combined with JK5G and JK21 postbiotics for gut microbiome modulation. The patient achieved significant tumor regression while maintaining stable hematological parameters. Microbial analysis demonstrated enrichment of beneficial genera (Veillonella, Bacteroides, Roseburia), potentially linked to postbiotic intervention. Notably, the regimen exhibited excellent tolerability without leukopenia or severe toxicities, suggesting postbiotics may enhance chemotherapy efficacy through microbiome-immune interactions while mitigating adverse effects. These findings warrant further investigation into postbiotics as adjuvant therapy for optimizing DLBCL treatment outcomes.}, } @article {pmid41449088, year = {2025}, author = {Addassi, Y and Taylor, H and McDermott, A and Roberts, M and Bennett, B and Jumbo-Lucioni, P}, title = {Drug Development.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 5}, number = {}, pages = {e102447}, doi = {10.1002/alz70859_102447}, pmid = {41449088}, issn = {1552-5279}, mesh = {Animals ; Male ; Female ; *Alzheimer Disease/drug therapy ; Disease Models, Animal ; *Probiotics/therapeutic use/pharmacology ; Humans ; Animals, Genetically Modified ; *Drug Development ; Lactobacillus plantarum ; Amyloid beta-Protein Precursor/genetics/metabolism ; Locomotion/drug effects ; Drosophila ; Drosophila melanogaster ; Memory/drug effects ; }, abstract = {BACKGROUND: Gut microbiota disruptions have been implicated in Alzheimer's disease (AD) pathogenesis. Lactobacillus probiotics have demonstrated therapeutic potential in AD by modulating the gut microbiome, while Lactobacillus postbiotics, soluble factors secreted by live bacteria, confer similar effects with advantages like longer shelf life, lower cost, and reduced infection risk. Evidence of the benefits of postbiotics in AD is limited. This study compares the effectiveness of Lactobacillus probiotics and postbiotics in mitigating behavioral deficits in a Drosophila model of AD.

METHOD: Flies overexpressing human amyloid β precursor protein and β-site APP cleaving enzyme in neurons served as AD model. Lactobacillus plantarum (Lp) was prepared at 1.0 x 10⁹ CFU/µL in MRS Lactobacilli broth, with the upper 80% of culture supernatant filtered as postbiotic fraction (Lp-PBx). Lp and Lp-PBx were diluted 1:2 in 5% sucrose and administered via capillaries in four 24-hour doses over two weeks. Food intake was recorded. Locomotion and memory were assessed at 14 days. Locomotion was evaluated using a negative geotaxis assay testing flies' ability to cross 8-cm in 10 seconds. Memory was tested through an aversive phototaxic suppression assay, where flies were trained to associate light with an aversive odor. After ten training cycles, flies were tested for dark preference. Data was stratified by sex and analyzed through a two-way ANOVA to test the main effects of genotype, treatment, and their interaction.

RESULT: Untreated AD males (0.48±0.03 vs 0.80±0.03, p<0.0001) and females (0.39±0.04 vs 0.70±0.04, p<0.0001) exhibited significant mobility impairments compared to controls. However, AD flies fed Lp or Lp-PBx showed restored mobility, climbing at speeds comparable to controls. Specifically, AD males fed Lp (0.73±0.03) or Lp-PBx (0.75±0.03) and females fed Lp (0.61±0.04) or Lp-PBx (0.59±0.04) climbed significantly faster than untreated counterparts (males: 0.48±0.03, p<0.0001; females: 0.39±0.04, p<0.05). While food intake in females was unaffected, males fed Lp ate significantly less than those given Lp-PBx (p=0.0216), regardless of genotype. Memory assays are ongoing.

CONCLUSION: In summary, our findings suggest Lp-PBx as a viable alternative to Lp for managing mobility deficits in a Drosophila model of AD. Its palatability facilitates administration, making it a practical therapeutic option.}, } @article {pmid41448985, year = {2025}, author = {Pavlíčková, Z and Jirků, K and Zimmelová, E and Hurtado, LH and Gentekaki, E and Tsaousis, AD}, title = {Blastocystis in domestic mammals and poultry: from prevalence patterns to gut physiology.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2025.12.001}, pmid = {41448985}, issn = {1471-5007}, abstract = {Blastocystis is a common intestinal protist in humans and animals, yet its ecological role and clinical significance remain debated. Companion animals and livestock are of particular interest due to their close contact with humans and potential reservoir roles. This review synthesizes current knowledge on Blastocystis occurrence and diversity in these animal groups, reframing the discussion through the lens of host digestive physiology and microbiome ecology. Rather than a taxonomic inventory, we group animals as carnivores, omnivores, or herbivores to highlight how gastrointestinal physiology and diet might shape colonization. Carnivores show low prevalence, herbivores exhibit high subtype richness, and omnivores display intermediate patterns. Growing evidence links Blastocystis to gut eubiosis, highlighting the need for broader, integrative research across hosts and environments.}, } @article {pmid41448977, year = {2025}, author = {Purcell, E and Dowling, P and O'Gorman, P and Bazou, D}, title = {Metabolic alterations in multiple myeloma and extramedullary disease- a novel niche of therapeutic targets.}, journal = {Blood reviews}, volume = {}, number = {}, pages = {101360}, doi = {10.1016/j.blre.2025.101360}, pmid = {41448977}, issn = {1532-1681}, abstract = {Metabolic reprogramming is a hallmark of cancer, actively contributing to tumour growth and therapeutic resistance. Multiple myeloma (MM) is a common haematological malignancy that exhibits distinct metabolic features, while Extramedullary Myeloma Disease (EMD) is a rare but highly aggressive manifestation of MM with increasing incidence, and an elusive metabolic landscape. Shifts in the population dietary habits have reshaped the gut microbiome, potentially altering the host metabolism and driving cancer progression, including MM and EMD. In this review, we examine the three major metabolic pathways in MM and explore emerging evidence linking gut microbiome dynamics to MM and EMD disease progression. Furthermore, we consider recent studies identifying obesity as a MM risk factor and we explore emerging metabolic targets of MM and EMD. By integrating perspectives from metabolic reprogramming, microbiome dynamics, and obesity-related risk, we aim to provide novel perspectives on MM progression from its asymptomatic precursor stage to high-risk EMD.}, } @article {pmid41448913, year = {2025}, author = {Baby, BM and Subramaniyan, Y and Rekha, PD}, title = {Concurrent bacterial infections in oral cancer: risk and mitigation strategies.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/17460913.2025.2606754}, pmid = {41448913}, issn = {1746-0921}, abstract = {The oral microbiome plays a major role in health, while its dysbiosis can contribute to oral and systemic disorders. The oral cavity hosts a complex community of commensal and pathogenic microbes, and disruptions in this balance, through bacterial infections, can contribute to cancer development and progression through chronic inflammation, inhibition of cell-death, and the release of carcinogenic substances. Microbial shifts driven by prolonged inflammation resulting from chronic oral diseases can escalate dysbiosis and promote neoplastic changes. Despite growing interest, oral microbiome-cancer-axis remains an emerging field. Current research focuses on a small number of microorganisms and associated virulence factors within the tumor-microenvironment, underscoring the need for more comprehensive, systems-level analyses. In this review, we conducted a comprehensive search of PubMed and Google Scholar (2019-2025), to identify and screen studies examining the association between bacterial infections and oral cancer. This review aims to examine and summarize the existing literature to elucidate risks and potential mitigation strategies associated with concurrent bacterial infections in oral cancer. In conclusion, more comprehensive, large-scale, and interdisciplinary studies are needed to understand the microbial influence on cancer, its impact on therapeutic responses, use of probiotics to enhance chemosensitivity and targeted-antibiotic therapy to reduce pathogenic load.}, } @article {pmid41448605, year = {2025}, author = {Goh, CE and Bohn, B and Genkinger, JM and Molinsky, R and Roy, S and Paster, BJ and Chen, CY and Johnson, S and Yuzefpolskaya, M and Colombo, PC and Rosenbaum, M and Knight, R and Desvarieux, M and Papapanou, PN and Jacobs, DR and Demmer, RT}, title = {Dietary Nitrate Intake and 16S rRNA-Inferred Nitrite-Generating Capacity of the Subgingival Microbiome May Influence Glucose Metabolism: Results From the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS).}, journal = {Journal of clinical periodontology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpe.70084}, pmid = {41448605}, issn = {1600-051X}, support = {R00 DE018739/NH/NIH HHS/United States ; R21 DE022422/NH/NIH HHS/United States ; R01 DK 102932/NH/NIH HHS/United States ; T32HL007779/NH/NIH HHS/United States ; DK-63608//Vagelos College of Physicians and Surgeons, Columbia University/ ; UL1TR001873/TR/NCATS NIH HHS/United States ; }, abstract = {AIMS: To investigate whether the association between the nitrite-generating capacity of the subgingival microbiome and early cardiometabolic risk biomarkers varies by dietary nitrate intake.

MATERIALS AND METHODS: Cross-sectional data from 668 participants (mean age 31 ± 9 years, 73% women) were analysed. Dietary nitrate intake was calculated from food frequency questionnaires. Subgingival 16S rRNA sequencing (Illumina, MiSeq) and PICRUSt2 estimated microbial genes. The Microbiome-Induced Nitric Oxide Enrichment Score (MINES) was calculated as a ratio of microbial gene abundances representing enhanced net capacity for NO generation. Adjusted multivariable linear models regressed cardiometabolic risk biomarkers (HbA1c, glucose, insulin, insulin resistance (HOMA-IR), blood pressure) on nitrate intake and MINES together with a MINES × nitrate intake interaction term.

RESULTS: Mean nitrate intake was 190 ± 171 mg/day. Significant interactions of MINES and nitrate intake were observed for insulin and HOMA-IR (p < 0.05). Among participants with a low MINES, higher nitrate intake was associated with lower HOMA-IR (1.2 [1.1-1.4] vs. 1.5 [1.3-1.6]; p = 0.002), but levels were similar in those with high MINES (p = 0.84).

CONCLUSIONS: A biomarker of higher microbial NO-generating capacity in subgingival plaque is associated with lower insulin and insulin resistance among individuals with lower dietary nitrate intake. Future trials evaluating the cardiometabolic benefits of nitrate-rich diets should incorporate measures of the entire oral microbiome.}, } @article {pmid41448591, year = {2025}, author = {Jensen, FCA and Birch, JS and Gram, A and Hansen, CHF and Nielsen, DS}, title = {Gastrointestinal Intraluminal pH of Non-Fasted Mice (Mus musculus) of Various Strains and Vendors Including Germ-Free and Streptomycin-Treated Mice.}, journal = {Journal of the American Association for Laboratory Animal Science : JAALAS}, volume = {}, number = {}, pages = {1-7}, doi = {10.30802/AALAS-JAALAS-25-093}, pmid = {41448591}, issn = {2769-6677}, abstract = {Mice are a valuable tool for preclinical research, enabling the investigation of fundamental questions about disease mechanisms, drug delivery, and pharmacokinetics. Intestinal pH influences drug delivery and pharmacokinetics of orally administered compounds. However, little is known about variations in pH along different sections of the mouse gastrointestinal tract. We therefore compared pH in 7 gastrointestinal tract sections of 48 male and female BALB/c, C57BL/6, and NMRI mice from 2 different vendors, as well as 8 streptomycin-treated and 8 germ-free BALB/c male and female mice from one vendor. The pH in the duodenum and cecum varied between strains and vendors. Relative to untreated barrier-bred mice, streptomycin-treated mice had significantly higher pH in the jejunum, and germ-free mice had significantly higher pH in the jejunum, cecum, and proximal colon, underlining the role of gut microbes in regulating pH levels throughout the gastrointestinal tract. In conclusion, we show that mouse strain, vendor, and microbial presence, but not sex, influence gastrointestinal pH in mice. Given the importance of gastrointestinal pH for pharmacokinetics, drug delivery systems, and gastrointestinal microbial behavior, these data will provide an important foundation for the choice of mouse models for research involving the gastrointestinal tract.}, } @article {pmid41448339, year = {2025}, author = {Ghosh, S and Ganguly, A and Dong, TS and Lagishetty, V and Jacobs, JP and Devaskar, SU}, title = {Intestinal Microbiome in Response to Air Pollutant Exposure in Pregestational and Gestational Murine Females and their Male and Female Offspring.}, journal = {Reproductive toxicology (Elmsford, N.Y.)}, volume = {}, number = {}, pages = {109150}, doi = {10.1016/j.reprotox.2025.109150}, pmid = {41448339}, issn = {1873-1708}, abstract = {We investigated the impact of chronic air pollutant (AP) exposure upon intestinal microbial diversity, composition, and metagenomic inferred functional pathways in murine pregestational and late gestational adult females, and male and female postnatal offspring (P21), compared to age- and sex- matched controls (CON). Intestinal microbiome analysis was undertaken with certain phenotypic characteristics in adult non-pregnant and pregnant females and the male and female offspring. In response to AP, pooled male and female offspring displayed no difference in E19 fetal and P1 postnatal body weights. At P21, females exposed in-utero to AP were heavier with increased fat and muscle mass at one month versus CON. Males were no different at P21 and 1 month revealing decreased fat mass and hyperglycemia. In pregestational/gestational females, AP did not change microbial α- or β-diversity from the respective CON. Gestational females showed AP induced changes in taxonomic composition such as reduced Bacteroides and increased Firmicutes, Verrucomicrobia, and Akkermansia, among others. In response to intra-uterine AP exposure, the offspring intestinal microbiome revealed more compelling differences in α- and β- diversity than adult females. While certain microbial changes were common in both sexes, sex-specific differences also emerged with reduced α-diversity, decreased Bacteroides and increased Akkermansia in males only. The metagenomic inferred pathways revealed perturbations in multiple pathways. We conclude that the offspring exposed in-utero to AP revealed sex-specific changes in microbial diversity, composition and function, displaying certain similarities with distinct differences from mothers. These early life changes were associated with the subsequent emergence of pre-diabetes and adiposity.}, } @article {pmid41448080, year = {2025}, author = {D'Alessandro, A and Coletta, M and Ricci, M and Petrini, A and Sagratini, G and La Terza, A}, title = {From full-scale composting of Organic Fraction of Municipal Solid Waste (OFMSW) with compostable plastic packaging to field application: Effects on wheat growth and rhizosphere microbiome structure.}, journal = {Journal of hazardous materials}, volume = {501}, number = {}, pages = {140895}, doi = {10.1016/j.jhazmat.2025.140895}, pmid = {41448080}, issn = {1873-3336}, abstract = {Global efforts toward a circular bioeconomy have promoted compostable plastics (CPs) as sustainable alternatives to petroleum-based materials. CPs can be co-composted with the Organic Fraction of Municipal Solid Waste (OFMSW) to produce compost for agricultural use, potentially reducing reliance on mineral fertilizers. Yet, their impacts on soil microbial dynamics and crop performance remain poorly characterized. In this study, we evaluated the impact of compost (BioP) derived from industrial-scale co-composting of OFMSW and 2.6 % (w/w) CP food packaging (Mater-Bi) on wheat (Triticum aestivum) performance and rhizosphere microbial communities, compared to standard OFMSW compost (Comp). A single field trial (November 2021-July 2022) tested three treatments: no fertilization (Ctrl), Comp, and BioP amendments. Wheat traits were not significantly affected by compost treatments. Compost application, however, influenced the structure and composition of rhizosphere microbial communities, promoting beneficial taxa linked to nutrient cycling and plant health. Both composts promoted carbon-linked metabolisms (e.g., fermentation, > 20 % increase), and metabolisms linked to aromatic compounds degradation (up to a + 193 %). BioP, in particular, enriched several plastic-degrading microorganisms, shaped a distinct microbial network, and harboured unique bacterial (84 genera) l and fungal (35 genera) taxa, including genera known for their role in bioplastic degradation, like Alcanivorax, Cupriavidus, Saccharomonospora, Themomonospora, Amycolatopsis, Emericellopsis, Knufia, and Rhodotorula. Within the limits of a single-season field trial, our results indicate that compostable plastic packaging can be co-composted with OFMSW without adverse short-term effects on compost quality, wheat growth, or rhizosphere microbial communities, supporting its potential as a sustainable alternative to conventional plastics.}, } @article {pmid41447958, year = {2025}, author = {Lee, Y and Liu, Q and Sun, Y and Maszczyk, P and Wang, M and Yang, Z and Lee, JS}, title = {Hypoxia and the microbiome: Significance and application for ecotoxicological studies.}, journal = {Marine pollution bulletin}, volume = {224}, number = {}, pages = {119171}, doi = {10.1016/j.marpolbul.2025.119171}, pmid = {41447958}, issn = {1879-3363}, abstract = {Hypoxia, or low oxygen availability, is a growing environmental concern that significantly impacts microbial communities. Recent studies highlight the effects of hypoxia on microbial composition and function, favoring anaerobic taxa involved in nitrogen, sulfur, and carbon cycling. These shifts influence ecotoxicological processes by modulating pollutant degradation, metal bioavailability, and greenhouse gas emissions. For instance, oxygen depletion enhances the activity of anaerobic dechlorinators but may reduce heavy metal detoxification. Advances in metagenomics and multi-omics have offered new perspectives on microbial adaptation under hypoxic stress, revealing key metabolic pathways linked to pollutant transformation. However, knowledge gaps remain in our understanding of the long-term ecological consequences of hypoxia-induced microbiome shifts. This review synthesizes recent findings on hypoxia-microbiome interactions, focusing on both environmental (e.g., sediment and water column) and host-associated (e.g., gut) microbiomes, and emphasizes their application in ecotoxicology. In addition, we discuss how hypoxia-induced microbial shifts in hypoxic environments and highlight potential applications of microbiome-based approaches for environmental risk assessment. Future research integrating experimental and modeling approaches is crucial to better predict the ecological impacts of hypoxia-driven microbial changes in contaminated environments.}, } @article {pmid41447849, year = {2025}, author = {Wang, X and Zhang, Y and Wu, J and Chen, D and Xiu, M and Chang, L and Wang, Y and Li, J and He, J and Liu, Y}, title = {Astragalus licorice prescription and its active components alleviate chemotherapy-induced intestinal mucositis by apoptosis and fatty acid β-oxidation: Integrative multi-omics approaches.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157734}, doi = {10.1016/j.phymed.2025.157734}, pmid = {41447849}, issn = {1618-095X}, abstract = {BACKGROUND: Chemotherapy-induced intestinal mucositis (CIM) is one of the most common side effects of chemotherapy agents. Astragalus licorice prescription (ALP), a traditional Chinese formula, commonly used to treat gastrointestinal disorders, has an unclear mechanism and potential active components in alleviating CIM.

PURPOSE: This study aims to comprehensively explore the mechanism and bioactive components of ALP in alleviating CIM.

METHODS: ALP's efficacy on CIM was evaluated in Drosophila melanogaster (flies) and C57BL/6 mice using phenotype assays, hematoxylin-eosin (H&E) staining, and immunohistochemistry. ALP's synergistic effect with 5-FU (5-fluorouracil) on tumors was assessed in 615 tumor-bearing mice by measuring tumor volume/weight and performing HE/immunohistochemical staining. Ki67 staining assessed tumor proliferation. Multi-omics integration (transcriptomics, lipidomics, microbiome analysis, network pharmacology) analyzed ALP's mechanism against CIM. Functional pathways were validated via RT-qPCR, biochemical kits, and immunofluorescence, as well as transgenetic flies targeted with GFP. ALP's functional components were characterized by liquid chromatography-mass spectrometry (LC-MS) and validated in CIM flies.

RESULTS: ALP significantly mitigated chemotherapy-induced systemic and intestinal damage in flies, evidenced by improved survival rate, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. Similarly, ALP alleviated intestinal mucositis symptoms and pathological damage in 5-FU-treated mice, such as reducing diarrhea levels, increasing intestinal length and villus height. Mechanistically, ALP inhibited the expressions of the JAK/STAT pathway related genes (upd3, stat92E, hop, dome, and Dronc) and proteins (UPD3, STAT92E, cleaved caspase-3), and reduced intstinal cells apoptosis. Concurrently, ALP elevated lipid metabolism levels by activating the fatty acid β-oxidation (FAO) pathway related genes expressions (Wdh, Mtp-α, Mtp-β, and Scully) and decreased intestinal free fatty acids. Integrated microbiome, lipidomic, and transcriptomic analyses revealed that ALP corrected multiple gut microbial and lipid metabolic disorders associated with the JAK/STAT apoptotic pathway and FAO lipid metabolism pathway. Furthermore, ALP combined with 5-FU enhanced the anti-tumor effect of 5-FU, as shown by reduced tumor volume and weight, and decreased the proliferation of tumor cells. Finally, four bioactive compounds in ALP, including berberine, dihydrotanshinone I, licochalcone A, and resveratrol, were identified as alleviating CIM.

CONCLUSION: ALP mitigated CIM by inhibiting the JAK/STAT pathway to reduce cellular apoptosis and activating the FAO pathway to improve lipid metabolism, thereby positioning it as a promising novel therapeutic option. Meanwhile, four bioactive compounds of ALP demonstrated protective effects against CIM.}, } @article {pmid41447757, year = {2025}, author = {Mandala, A and Undi, RB and Janssen, RC and Sugino, KY and Zhao, W and Nelson, BN and Teague, AM and Patil, NY and Zemsky Berry, K and Varshney, R and Bergman, BC and Rudolph, MC and Joshi, AD and Rajala, RVS and Jonscher, KR and Friedman, JE}, title = {Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.}, journal = {EBioMedicine}, volume = {123}, number = {}, pages = {106098}, doi = {10.1016/j.ebiom.2025.106098}, pmid = {41447757}, issn = {2352-3964}, abstract = {BACKGROUND: Disruptions in early-life gut microbiota and metabolites associated with maternal Western-style diet (WD) during critical windows of development are linked to metabolic and inflammatory diseases in offspring, including metabolic dysfunction-associated steatotic liver disease (MASLD) in later life. These disturbances can alter microbial metabolite production, such as tryptophan derivatives, which are crucial for immune and metabolic regulation. However, the specific effects of maternal supplementation with tryptophan metabolites on offspring gut microbiome maturation and MASLD risk remain unexplored.

METHODS: WD-fed mouse dams were supplemented with microbial metabolites indole (Ind) or indole-3-acetic acid (I3A) during gestation and lactation; male offspring were weaned to chow diet for 9 weeks, followed by a 4-week WD challenge. Fecal microbiota transfer (FMT) was performed from offspring to naïve recipients, followed by a 4-week WD challenge. Human LX-2 stellate cells were used to study mechanisms for indole and very long-chain (VLC) ceramide effects on TGF-β-induced fibrosis.

FINDINGS: Maternal supplementation with Ind or I3A had long-term protective effects in adult WD-challenged offspring against excess weight gain, steatosis, stellate cell activation, and fibrosis. Perinatal exposure to Ind or I3A activated offspring aryl hydrocarbon receptor (AHR) signalling in gut and liver, which trans-repressed known and new target genes, including ceramidases Asah2 and Acer3, leading to increased VLC ceramides. FMT from offspring with perinatal exposure to Ind protected recipients from WD-induced fibrogenesis and increased beneficial VLC ceramides in recipient livers. In vitro, LX-2 stellate cells cultured with Ind or VLC ceramides demonstrated an anti-fibrotic effect, which was abolished by AHR inhibition.

INTERPRETATION: Maternal indole supplementation, through sustained activation of AHR in offspring gut and liver and an increase in hepatic VLC ceramides, prevents diet-induced MASLD and fibrosis in offspring, offering a novel therapeutic pathway for prevention of paediatric MASLD.

FUNDING: See Acknowledgements.}, } @article {pmid41447511, year = {2025}, author = {Bisschops, BG}, title = {Drug Development.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 5}, number = {Suppl 5}, pages = {e099006}, doi = {10.1002/alz70859_099006}, pmid = {41447511}, issn = {1552-5279}, mesh = {Humans ; *Alzheimer Disease/drug therapy/metabolism ; *Drug Development/methods ; Gastrointestinal Microbiome ; Biofilms ; Metabolomics ; Animals ; }, abstract = {BACKGROUND: Alzheimer's Disease (AD) is influenced by an intricate interplay of genetic, metabolic, and microbial factors. Recent studies highlight the critical roles of the gut-brain axis, lipid metabolism, bile acids, and systemic inflammation in AD progression. The 3DNasal project integrates spatial intelligence, biofilm technology, and multi-omics insights to develop a scalable, precision-based therapeutic platform targeting AD's multifactorial pathology.

METHOD: Objective: To design a biofilm-based nasal spray incorporating findings from metabolomics, microbiome research, and genomics (e.g., Dilmore et al., 2024; Mohanty et al., 2024) to restore microbiome homeostasis, reduce neuroinflammation, and enhance systemic resilience against AD progression.

RESULT: Preclinical findings demonstrate improved biofilm adhesion, enhanced delivery to the olfactory bulb, and significant modulation of the gut-brain axis. Data reveal that the Mediterranean Ketogenic Diet mitigates AD risk factors through serum and CSF metabolomics (Schweickart et al., 2024). Multi-omics analyses further identify novel microbial and metabolic signatures associated with AD pathology (Dilmore et al., 2024) and systemic inflammation (Liang et al., 2024) CONCLUSION: The 3DNasal project represents a novel therapeutic paradigm by integrating spatial intelligence, multi-omics, and bioengineering. This precision-based approach targets localized and systemic drivers of AD, paving the way for scalable and adaptive interventions. Future research will focus on clinical validation, adaptive personalization, and exploration of lifestyle-microbiome interactions to optimize therapeutic outcomes.}, } @article {pmid41447442, year = {2025}, author = {Mishra, SP and Jain, S and Yadav, D and Buddendorff, L and Hoover, JP and Shukla, R and Kumar, V and Holland, P and Masternak, MM and Labyak, C and Williams, C and Golden, A and Agronin, M and , and Yadav, H}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {Suppl 2}, pages = {e104153}, doi = {10.1002/alz70856_104153}, pmid = {41447442}, issn = {1552-5279}, mesh = {Humans ; Biomarkers/blood ; Male ; Female ; *Interleukin-6/blood ; Aged ; *Cognitive Dysfunction/blood/microbiology ; *Gastrointestinal Microbiome ; Inflammation/blood ; Cohort Studies ; Feces/microbiology ; Aged, 80 and over ; }, abstract = {BACKGROUND: The increasing prevalence of cognitive decline and dementia poses a significant public health challenge for older adults, and effective preventive and therapeutic strategies remain elusive. This is largely due to an incomplete understanding of the precise etiology and contributing factors underlying these conditions. Increased systemic inflammation is suspected to elevate the risk of dementia and cognitive decline, yet the causes of chronic inflammation remain poorly understood. Emerging evidence suggests that gut microbiome abnormalities are linked to increased inflammation and a higher risk of dementia. However, it remains unclear whether the rate of cognitive impairment differs with higher systemic inflammation and whether unique microbiome signatures are associated with inflamed cognitive decline and dementia.

METHOD: Using 165 samples from the Microbiome in Aging Gut and Brain (MiaGB) consortium cohort, systemic inflammatory marker interleukin-6 (IL-6) was measured in human plasma via ELISA. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) questionnaire, and fecal microbiomes were analyzed through shotgun metagenomic sequencing. Subjects were grouped based on IL-6 levels (high and low) and cognitive status (normal cognition and cognitive impairment), and their corresponding microbiome signatures were analyzed.

RESULT: Interestingly, individuals with high IL-6 levels (IL-6[High]) exhibited over twice the prevalence of mild cognitive impairment (MCI) compared to those with low IL-6 levels (IL-6[Low]) (n = 41 IL-6[High] vs. 18 IL-6[Low]). Older adults with low IL-6 and MCI displayed higher abundances of Bacteroides, Prevotella, Alistipes, Fusicatenibacter, and Parabacteroides, but lower levels of Lachnospira, Akkermansia, and Subdoligranulum compared to sex- and age-matched cognitively healthy controls with low IL-6. Conversely, those with high IL-6 and MCI exhibited higher abundances of Blautia, Prevotella, and Fusicatenibacter and lower abundances of Lachnospira, Akkermansia, and Subdoligranulum compared to IL-6[High] controls with normal cognition.

CONCLUSION: These findings reveal that butyrate-producing genera such as Lachnospira, Akkermansia, and Subdoligranulum are significantly reduced, while potentially pathogenic Fusicatenibacter and commensal Prevotella are elevated in individuals with MCI and high IL-6 levels. These distinct microbial profiles may serve as biomarkers for the early detection of cognitive decline in older adults, highlighting potential targets for therapeutic strategies to preserve brain health during aging.}, } @article {pmid41447357, year = {2025}, author = {Worachotsueptrakun, K}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {Suppl 2}, pages = {e100663}, doi = {10.1002/alz70856_100663}, pmid = {41447357}, issn = {1552-5279}, mesh = {Humans ; *Biomarkers/blood ; *Gastrointestinal Microbiome/physiology ; Female ; Male ; *Alzheimer Disease/blood ; Aged ; tau Proteins/blood ; Amyloid beta-Peptides/blood ; }, abstract = {BACKGROUND: The imbalance of microbial composition in the gut of elderly individuals can contribute to the development of Alzheimer's disease due to the bidirectional communication between the brain and the gut. Certain groups of gut bacteria can produce metabolites that are toxic to neurons, leading to inflammation and neuronal death in the central nervous system through various pathways. Diet plays a crucial role in influencing the composition of gut bacteria. Consuming prebiotic foods or dietary fibers from vegetables, fruits, and whole grains can stimulate the growth of bacteria that produce short-chain fatty acids or probiotic microorganisms.

METHOD: Patients who met the inclusion criteria were recruited for this study. Clinical conditions were assessed, and blood samples were collected to analyze the accumulation of abnormal beta-amyloid (as the ratio between 42/40), p-Tau 181, brain damage markers (neurofilament light chain [NFL] and glial fibrillary acidic protein [GFAP]), and APOE. Additionally, gut microbiome analysis was performed using amplicon-based metagenomic methods. The data analysis was conducted in correlation with clinical symptoms.

RESULT: To confirm the results from the discovery sample, participants were recruited for the study. Gut microbiome compositional analysis was performed on fresh stool samples collected from both the study group (n = 40) and age- and sex-matched control participants (n = 40). Microbiome features correlated with plasma phosphorylated tau 181 (p-tau181) and plasma neurofilament light chain (NFL), but not with APOE ε3 or neurodegeneration biomarkers, suggesting that changes in the gut microbial community occur early in the disease process. Specific taxa and microbial pathways associated with preclinical Alzheimer's disease were identified.

CONCLUSION: These beneficial bacteria can produce anti-inflammatory metabolites and reduce the entry of neurotoxic metabolites into the system. Therefore, understanding the relationship between gut bacteria, prebiotics, and Alzheimer's disease could provide a preventative approach to reduce the risk of Alzheimer's disease caused by microbial imbalance in the elderly.}, } @article {pmid41447216, year = {2025}, author = {Bedzhanyan, AL and Kovalskaya, YV and Petrenko, KN and Frolova, YV}, title = {[Role of gut microbiota in aging processes].}, journal = {Khirurgiia}, volume = {}, number = {11. Vyp. 2}, pages = {67-73}, doi = {10.17116/hirurgia202511267}, pmid = {41447216}, issn = {0023-1207}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology/immunology ; *Dysbiosis/microbiology/physiopathology/complications ; Sarcopenia/microbiology ; }, abstract = {This review examines the fundamental role of intestinal microbiota in modulating aging processes. According to current data, age-related microbiome changes are not a consequence, but an active mechanism of aging, determining individual developmental trajectory along the path of «successful» or pathological aging. Primary focus is on analysis of cause-and-effect relationship between dysbiosis and systemic aging. Age-related disruption of microbiota (decreased diversity, reduced amount of Bifidobacterium and Akkermansia muciniphila, butyrate deficiency) leads to disruption of intestinal barrier, lipopolysaccharide translocation, and chronic systemic inflammation through TLR4/NF-κB pathway activation. This cascade of pathological processes causes immune senescence and underlies major geriatric syndromes and age-associated diseases. This review provides a detailed analysis of dysbiosis influences on various body systems: neurodegenerative diseases via the gut-brain axis, sarcopenia via suppressed muscle protein synthesis, type 2 diabetes via impairment of insulin resistance, cardiovascular disease via TMAO production, and osteoporosis via impaired bone metabolism. Particular attention is paid to unique microbiota profile in centenarians, where combination of dysbiosis and preservation of specific symbionts (Christensenellaceae, Akkermansia muciniphila) is thought to promote healthy longevity. The article concludes by substantiating potential for therapeutic modification of microbiota as a strategy for correcting the manifestations of aging.}, } @article {pmid41447103, year = {2025}, author = {Shukla, R and Kumar, V and Yadav, D and Holland, P and Masternak, MM and Labyak, CA and Dangiolo, MB and Agronin, ME and , and Yadav, H and Jain, S}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e101631}, doi = {10.1002/alz70856_101631}, pmid = {41447103}, issn = {1552-5279}, mesh = {Humans ; Biomarkers ; Male ; Female ; Aged ; *Cognitive Dysfunction/microbiology ; Alzheimer Disease/microbiology ; *Microbiota ; *Dementia/microbiology ; Cohort Studies ; Metagenomics ; Aged, 80 and over ; Gastrointestinal Microbiome ; *Mouth/microbiology ; }, abstract = {BACKGROUND: Over recent decades, growing evidence has highlighted the pivotal role of the microbiome in Alzheimer's disease (AD) and dementia. Studies suggests the disruptions in the gut microbiome may contribute to cognitive impairment, but the association between the oral microbiome and cognitive impairment remains unclear. This study aims to characterize the oral microbiome and investigate its role in cognitive decline among elderly participants of MiaGB cohort.

METHOD: Whole-genome metagenomics sequencing was performed on 368 samples (Controls: 236, MCI: 107, and Dementia: 25) collected from the MiaGB (Microbiome in Aging Gut and Brain) consortium, a multi-site, clinical research study. The data was processed and analyzed using KneadData, MetaPhlAn, and HUMAnNnn tools.

RESULT: Taxonomic analysis revealed an increasing abundance of the genus Porphyromonas, and species Neisseria subflava, Neisseria sicca, and Streptococcus australis from controls to MCI to dementia participants. Random forest (RF) and LEfSe analysis identified significant increase in abundance of species N. subflava, Veillonella parvula, N. sicca, and Neisseria flavescens in MCI and dementia participants compared to controls. Additionally, Lautropia mirabilis, Eubacterium sulci, and Gemella sanguinis species were enriched in MCI compared to Controls and Dementia participants. Genera Porphyromonas are associated with cognitive impairment in other studies. Also, S. australis and V. parvula and Gemella sanguinis has been linked to neurodegenerative diseases and infective endocarditis. Distinct microbial profiles specific to each group could serve as biomarkers to identify the risk of cognitive impairment.

CONCLUSION: This study revealed a strong link between oral microbiome alterations and cognitive impairment. Further analysis will provide a more comprehensive understanding about the role of these microbes in cognitively impaired participants. These findings offer new insights into early biomarkers for cognitive impairment and the development of potential therapeutic approaches for the prevention and intervention of Alzheimer's disease (AD).}, } @article {pmid41446797, year = {2025}, author = {Yang, Z and Zhou, M and Luo, F and Feng, S and Tan, Y and Wang, Q and Cheng, Z and Tan, R and Li, R}, title = {Cryptotanshinone targets tumor-immune-microbiome axis to suppress colorectal cancer.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1667500}, pmid = {41446797}, issn = {1663-9812}, abstract = {BACKGROUND: Colorectal cancer (CRC) progression involves complex interactions between tumor cells, immune evasion, and metabolic reprogramming. Cryptotanshinone (CTS), a bioactive diterpenoid from Salvia miltiorrhiza, has demonstrated anticancer potential, but its integrated effects on CRC remain unclear.

METHODS: We employed both in vitro and in vivo models to evaluate the therapeutic effects and mechanism of CTS. Using MC38 cells and mouse-derived CRC organoids, we assessed its impact on proliferation and apoptosis through CCK-8, clonogenic, and Annexin V/PI assays. For vivo evaluation, a murine AOM/DSS-induced CRC model was established and administered CTS via intraperitoneal injection for 8 weeks. Comprehensive analyses included histopathology, immune profiling by flow cytometry, 16S rRNA sequencing of gut microbiota, and LC-MS-based metabolomics.

RESULTS: CTS exerted potent anti-CRC effects, suppressing tumor cell proliferation and inducing apoptosis in vitro. In AOM/DSS-induced mice, CTS significantly inhibited tumor growth, ameliorated colon shortening and pathological damage, and reduced inflammation. Mechanistically, CTS alleviated T cell exhaustion, reversed metabolic dysregulation, and restored gut microbiota community structure.

CONCLUSION: CTS effectively suppresses CRC progression. Its efficacy is associated with the coordinated modulation of the tumor-immune-microbiome axis, involving direct cytotoxicity, reduced PD-1+ T cell levels, and restructuring of the gut microbial community. These results highlight CTS as a promising multi-faceted therapeutic candidate and provide a preclinical rationale for its further development.}, } @article {pmid41446733, year = {2025}, author = {Dai, CS and Qi, TT and Shang, HL and Xie, RH and Liu, H and Liu, ZM and Cui, YM and Zhang, YH}, title = {Intratumoral microbiota-derived S1P sensitizes the combination therapy of capecitabine and PD-1 inhibitors.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114202}, pmid = {41446733}, issn = {2589-0042}, abstract = {Clinical responses of colorectal cancer (CRC) treatments vary considerably due to the heterogeneity of tumor microenvironment (TME), where intratumoral microbiota may reshape the unique inflammation imprints. However, its complex mechanistic underpinnings remain incompletely elucidated. Herein, we sought to delineate the critical role of intratumoral microbiota in potentiating combination therapeutics against CRC. By comparing germ-free (GF) and specific pathogen-free (SPF) mouse models of 33 potential CRC treatments, we screened out capecitabine-MIH4 (anti-PD-1 antibody) combination regimen significantly augmented by intratumoral microbiota in tumor regression. The enrichment of enterotoxigenic Bacteroides fragilis induced by Capecitabine-MIH4 was concomitant with elevated microbial sphingosine-1-phosphate, which further up-regulated tumoral PD-L1 expression by enhancing histone deacetylation at the CD274 locus. This activation ultimately led to effector memory CD8 [+] T cell expansion and exhausted T cell subset reduction within TME. To conclude, these findings highlight microbial sphingolipids as potential predictive biomarkers for strategies of targeting intratumoral microbiota in CRC management.}, } @article {pmid41446669, year = {2025}, author = {Liu, J and Yuan, Q and Zhang, K and Sheng, X and Zhu, Z and Sui, N and Wang, H}, title = {Rotation of soybean and Corydalis yanhusuo enhances yield and active compounds of C. yanhusuo via soil nutrient optimisation and rhizosphere microbiome engineering.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1692138}, pmid = {41446669}, issn = {1664-462X}, abstract = {Corydalis yanhusuo W.T. Wang, a herb in the Papaveraceae family used for pain treatment, faces challenges with continuous cropping. Crop rotation with soybean can mitigate soil issues and facilitate the development of subsequent crops. This study evaluated how varying durations of soybean-C. yanhusuo rotation affect yield and active component of C. yanhusuo, soil nutrients, and microbial communities. Rotation with soybean progressively improved yield and active component of C. yanhusuo. Concurrently, soil organic matter, total/hydrolysable nitrogen, and soil enzyme activities improved over time. Microbial OTUs increased in the bulk soil, rhizosphere soil, and roots, along with significant improvements in α-diversity. Over time, the Proteobacteria and pathogenic genera decreased, while Firmicutes and other beneficial genera increased. Network complexity and functions related to nitrate denitrification, cellulolysis, and xylanolysis improved with increased rotation duration. Significant positive correlations were detected between Bacillus, Mortierella, Trichoderma, and yield, medicinal components in C. yanhusuo, and soil nutrients. Structural equation modelling revealed that crop rotation affects C. yanhusuo yield by influencing the microbial community, which in turn alters soil nutrients. The soybean-C. yanhusuo rotation system enhances C. yanhusuo yield and active component content by improving soil nutrients and microbial diversity, providing valuable insights for sustainable medicinal plant cultivation.}, } @article {pmid41446667, year = {2025}, author = {Zhang, Y and Ahmed, W and Dai, Z and Meng, H and Li, H and Moussa, IM and Ma, Y and Zhang, J and Ji, G}, title = {Cultivar-specific responses of the citrus endophytic microbiome to Xanthomonas citri subsp. citri infection reveals Lysobacter as a key biocontrol taxon.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1700610}, pmid = {41446667}, issn = {1664-462X}, abstract = {INTRODUCTION: Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a major threat to citrus production worldwide, resulting in significant losses in yield and fruit quality. This study investigates the differential responses of endophytic microbial communities to Xcc infection in citrus cultivars with distinct resistance levels, specifically comparing the highly susceptible Citrus reticulata cv. 'Orah' and the more resistant Fortunella crassifolia cv. 'Cuimi'. Through high-throughput amplicon sequencing, we characterized the bacterial and fungal communities in both cultivars before and after Xcc inoculation.

RESULTS: The results revealed distinct shifts in microbial diversity, with bacterial community diversity largely maintained in resistant cultivars but significantly reduced in susceptible ones following Xcc infection. Conversely, fungal community richness decreased in both cultivars post-inoculation, with notable cultivar-specific changes in the relative abundance of key genera. Notably, Lysobacter emerged as the only bacterial genus that significantly increased in abundance in the resistant cultivar under pathogen pressure, highlighting its potential as a key biocontrol agent. Further, we identified several fungal genera, including Penicillium and Aspergillus, which proliferated in susceptible plants under pathogen pressure. The study also isolated and identified a Lysobacter antibioticus GJ-6 strain with potent antagonistic activity against Xcc, offering insights into its potential role in enhancing disease resistance.

CONCLUSIONS: This work provides a comprehensive understanding of how endophytic microbiomes differ between resistant and susceptible citrus cultivars, suggesting new avenues for developing sustainable biocontrol strategies to manage citrus canker. These findings underscore the potential of endophytes in mitigating plant diseases and advancing the application of microbiome-based interventions in agriculture.}, } @article {pmid41446647, year = {2025}, author = {Cui, X and Qi, J and Yi, C and Liu, J and Yuan, XL and Deng, W and Xu, H}, title = {The microbiome exists in the neuroretina and choroid in normal conditions and responds rapidly to retinal injury.}, journal = {Frontiers in ophthalmology}, volume = {5}, number = {}, pages = {1719090}, pmid = {41446647}, issn = {2674-0826}, abstract = {PURPOSE: To investigate the microbial profiles in the retina and RPE/choroid, and how they respond to retinal injury.

METHODS: Adult C57BL/6J mice were subjected to retinal laser burns using a photocoagulator. One and 24h later, the retina and RPE/choroid were collected under strict sterile conditions and processed for 16S rRNA paired-end sequencing (2×250). The data were analyzed using R software, GraphPad Prism, OmicShare, and Wekemo Bioincloud.

RESULTS: Microbiota were detected in the retina and RPE/choroid under normal physiological conditions. The alpha diversity was higher in the retina than in the RPE/choroid. All retinal microbiotas at the phylum level and 12 out of 14 at the genus level were shared with those of RPE/choroid. The top phyla were Firmicutes, Proteobacteria, and Actinobacteria. Retinal laser injury reduced the alpha diversity but did not affect beta diversity. In the RPE/choroid, the abundance of Actinomyces and Roseburia decreased, and the abundance of Lactobacillus increased significantly after laser injury. The abundance of Sphingomonas in the retina decreased, and the abundance of Faecalibacterium and Bifidobacterium increased (P<0.05) after laser injury in the retina. Faecalibacterium and Bifidobacterium are positively linked to Th17/IL-17 signaling and RIG-I-like receptor signaling pathways, as well as antigen processing and presentation.

CONCLUSIONS: The neuroretina and RPE/choroid have diverse microbiomes under normal conditions. Their richness and evenness are relatively stable in the retina compared to those in the RPE/choroid. Retinal laser injury enriches Faecalibacterium and Bifidobacterium in ocular tissues, and these microbiotas may participate in retinal wound healing through modulating inflammation.}, } @article {pmid41446590, year = {2025}, author = {Zhao, Y and Wang, F and Wang, Y and Tan, J and Niu, H and Guo, G and Fang, L and Jiang, L}, title = {Heat stress compromises nutritional quality and flavor of bovine raw milk: Evidence from multi-omics analyses.}, journal = {Food chemistry: X}, volume = {32}, number = {}, pages = {103361}, pmid = {41446590}, issn = {2590-1575}, abstract = {Heat stress is a growing concern for dairy production under global climate change. This study employed integrated multi-omics approaches to investigate how heat stress affects the antioxidant capacity, microbiota, metabolite profiles, lipid composition, and flavor compounds in raw milk. Results revealed that heat stress reduced antioxidant levels and altered the milk microbiome, favoring potentially spoilage-associated bacteria. Metabolomic analysis indicated disrupted energy, amino acid, and lipid metabolism, with reductions in beneficial unsaturated fatty acids, conjugated linoleic acid, and polar lipids such as phosphatidylcholine and sphingomyelin. Notably, several off-flavor volatiles, including hexanal, ketones, and sulfur compounds, increased in heat-stressed milk, while sweet esters declined. These compositional and sensory changes may compromise milk quality, nutritional value, and consumer acceptability. This study provides a comprehensive biochemical basis for understanding how heat stress affects milk quality, offering important references for quality assessment and risk monitoring in dairy production under warming climates.}, } @article {pmid41446577, year = {2025}, author = {Zu, J and Zhang, W and Du, L and Zhao, H and Xu, M and Chen, R and Zhang, Y and Chen, S and Xu, C and Dong, L and Zhu, J and Xiao, L and Liu, C}, title = {Sex-dependent alterations of salivary microbiome in Parkinson's disease: associations with motor and non-motor clinical phenotypes.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1726620}, pmid = {41446577}, issn = {2296-889X}, abstract = {BACKGROUND: Parkinson's disease (PD) shows considerable heterogeneity in motor and non motor features. The contribution of the salivary microbiome and its modification by sex remains unclear.

METHODS: In a single center cross sectional case control study, we profiled unstimulated saliva from 24 patients with Parkinson's disease and 25 age and sex matched controls using 16S rRNA sequencing. Alpha and beta diversity were evaluated, group associated taxa were identified by indicator analysis, and community structure was related to clinical measures including Unified Parkinson's Disease Rating Scale part III in off and on medication states, the Non Motor Symptoms Scale, and the Hamilton Depression Rating Scale.

RESULTS: Alpha diversity was broadly preserved, whereas richness was higher in men with Parkinson's disease than in women with PD. Beta diversity showed modest but significant separation across disease by sex groups at multiple taxonomic levels with PERMANOVA R [2] about 0.13 and significant P values. Women with PD displayed higher Prevotella and Veillonella with lower Akkermansia, and men with PD showed a TM7 skewed profile typified by Candidatus Saccharimonas and reduced Haemophilus. The coupling between community structure and clinical burden was strongest for motor severity and was more evident in the on medication state.

CONCLUSION: The salivary microbiome in Parkinson's disease exhibits sex specific alterations that track clinical burden, supporting sex aware development of salivary biomarkers and microbiota focused strategies. Validation in larger longitudinal cohorts with multi omics and standardized oral and medication metadata is warranted.}, } @article {pmid41446456, year = {2025}, author = {Gupta, M and Patanvadia, D and Bhavsar, RA and Rajak, VS}, title = {Evaluation of Antibiotic Resistance Genes in Commensal Gut Flora Among Healthy Individuals: A Hidden Reservoir for Resistance Transmission.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97542}, pmid = {41446456}, issn = {2168-8184}, abstract = {Background Antimicrobial resistance (AMR) poses a major global health challenge, undermining the effectiveness of existing antibiotics and complicating the management of infectious diseases. The human gut microbiome serves as an important reservoir of antibiotic resistance genes (ARGs), which can be transferred among bacterial populations, including those inhabiting healthy individuals. Understanding the diversity and distribution of these ARGs at the community level is essential to identifying the hidden reservoirs of resistance within apparently healthy populations. However, data on the prevalence and determinants of ARGs in the general population of India remain limited. Methods A community-based cross-sectional study was conducted among 150 healthy adults (aged 18-60 years) in a tertiary care center of Central India from January to September 2025. Stool samples were analyzed using culture and multiplex quantitative PCR for nine major ARGs (blaTEM, blaCTX-M, blaNDM, tetM, ermB, sul1, qnrS, vanA, and mcr-1) and mobile genetic elements (MGEs). Associations between ARG carriage and demographic and exposure factors were assessed using the chi-square, Kruskal-Wallis, and regression analyses. Results The most common ARGs were tetM (42.7%), blaTEM (38.7%), and sul1 (34%) genes. ARG richness was significantly associated with recent antibiotic use (χ[2] = 17.3, p < 0.001) and MGE detection (χ[2] = 12.5, p < 0.001). Probiotic use was independently protective against blaTEM carriage (adjusted odds ratio = 0.19, 95% CI = 0.05-0.69, p = 0.011), whereas MGE detection showed a positive trend (p = 0.060). Linear regression (R[2] = 0.283) indicated that younger age (p = 0.014) and "Other" sex (p < 0.001) were associated with a higher total ARG load. Conclusion Healthy individuals harbor diverse and transmissible ARGs in their gut microbiota. Antibiotic exposure and MGEs increase ARG diversity, whereas probiotics may reduce blaTEM carriage. These findings highlight the need for One Health surveillance and prudent antimicrobial stewardship to limit the spread of AMR at the community level.}, } @article {pmid41446346, year = {2025}, author = {Rusu, LM and Moldovan, M and Labunet, A and Objelean, A and Muntean, A and Sava, S}, title = {Natural Strategies for Dental Hard-Tissue Remineralization: A Scoping Review of Galla Chinensis and Its Dual Anticaries Action.}, journal = {Clinical, cosmetic and investigational dentistry}, volume = {17}, number = {}, pages = {609-622}, pmid = {41446346}, issn = {1179-1357}, abstract = {Dental caries remains a global public health challenge, traditionally managed through fluoride-based strategies that enhance enamel remineralization and inhibit demineralization. However, concerns regarding fluoride resistance, fluorosis, and the growing demand for minimally invasive alternatives have stimulated interest in bioactive, plant-derived compounds. Galla chinensis extract (GCE), rich in polyphenols and tannins, has emerged as a promising candidate with dual effects on hard tissue repair and microbial control. This scoping review aimed to assess the evidence on Galla chinensis extract (GCE) as a non-fluoride agent for enhancing enamel and dental hard tissue remineralization and preventing dental caries. A structured search of available literature was conducted, focusing on experimental, in vitro, in vivo, and clinical studies evaluating GCE's biological properties, mechanisms of action, and translational potential in dentistry. Our findings indicate that GCE consistently promotes mineral deposition and enhances enamel surface microhardness, effectively inhibiting demineralization processes. In addition, GCE exhibits strong antimicrobial activity against cariogenic biofilms, particularly Streptococcus mutans, highlighting its potential to reduce caries risk by modulating the oral microbiome. Preliminary clinical studies show favorable outcomes, although the available evidence is limited in scale and duration. Collectively, these results demonstrate a dual action of GCE: supporting enamel repair while concurrently suppressing cariogenic activity. This suggests that GCE may serve as a promising adjunct or alternative to conventional fluoride-based strategies within minimally invasive dentistry. However, further well-designed clinical trials are necessary to confirm its efficacy, safety, and long-term benefits in caries management.}, } @article {pmid41446282, year = {2025}, author = {Zhu, L and Gao, H and Li, Q and Wang, Y and Li, J and Li, X and Huang, Z and Wang, C and Nie, J}, title = {Shaoyao Gancao decoction alleviates functional constipation by inhibiting Escherichia-Shigella expansion, modulating gut microbiota, and suppressing dysbiosis-induced endocannabinoid production: evidence from a self-controlled pilot study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1705271}, pmid = {41446282}, issn = {2235-2988}, mesh = {Humans ; Pilot Projects ; *Gastrointestinal Microbiome/drug effects ; *Constipation/drug therapy/microbiology ; Female ; Male ; *Drugs, Chinese Herbal/therapeutic use/administration & dosage/pharmacology ; *Dysbiosis/drug therapy/microbiology ; Middle Aged ; Feces/microbiology/chemistry ; Adult ; *Endocannabinoids/metabolism/biosynthesis ; Treatment Outcome ; Fatty Acids, Volatile/analysis/metabolism ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/drug effects ; }, abstract = {INTRODUCTION: Shaoyao Gancao Decoction (SGD), a classical traditional Chinese medicine formula, has been clinically reported to improve symptoms of functional constipation (FC), although its underlying mechanisms remain unclear. This study aimed to explore the clinical efficacy and gut microbiota modulation of SGD in patients with FC.

METHODS: A self-controlled pilot study was conducted in 20 patients diagnosed with FC according to the Rome III (IV) criteria. Participants received a 3-5 day oral intervention with SGD. Clinical outcomes, including stool frequency, consistency, and ease of defecation, were evaluated using self-reported questionnaires. Fecal samples collected before and after treatment were analyzed for microbial composition (16S rRNA sequencing) and short-chain fatty acids (SCFAs).

RESULTS: Ninety percent of participants reported symptomatic improvement, with 70% achieving increased stool frequency (> 3 times/week). SGD treatment markedly shifted the fecal microbiota from a dysbiotic state dominated by Proteobacteria, Enterobacteriaceae, and Escherichia-Shigella to a community enriched in Firmicutes, Veillonella, Roseburia, and Ruminococcus. These microbial changes were accompanied by significant increases in fecal SCFAs and improvements in stool consistency and frequency. Functional prediction analysis revealed that SGD suppressed unsaturated fatty acid and arachidonic acid metabolism, thereby attenuating retrograde endocannabinoid signaling associated with intestinal hypomotility. Feature taxa enriched in responders-such as Ruminococcus sp. N15.MGS-57 and Bacteroides coprophilus-were linked to enhanced estrogen activity and secondary bile acid metabolism.

DISCUSSION: These findings suggest that SGD alleviates FC by restoring microbial balance, enhancing SCFA production, and suppressing dysbiosis-induced endocannabinoid signaling. As a pilot study, the results are preliminary but provide mechanistic insights that warrant validation in larger, randomized controlled trials.}, } @article {pmid41446280, year = {2025}, author = {Zhang, X and An, Y and Liu, Y and Li, G and Qiu, X and Lu, Y and Lin, G}, title = {Comparison of currently common neoadjuvant therapy strategies for rectal cancer: a three-arm retrospective study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1545195}, pmid = {41446280}, issn = {2235-2988}, mesh = {Humans ; *Rectal Neoplasms/therapy/pathology ; *Neoadjuvant Therapy/methods ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Gastrointestinal Microbiome ; Treatment Outcome ; *Adenocarcinoma/therapy ; Adult ; Magnetic Resonance Imaging ; Immunotherapy/methods ; Feces/microbiology ; }, abstract = {BACKGROUND: The evolving neoadjuvant therapy regime is revolutionizing the management of local advanced rectal cancer (LARC). Total neoadjuvant therapy (TNT) and neoadjuvant immunotherapy are currently the most prominent strategies. However, existing studies predominantly evaluate these approaches in isolation, leaving their comparative efficacy unresolved.

METHODS: A three-arm retrospective study was conducted including a total of 160 consecutive patients pathologically diagnosed as adenocarcinoma with pMMR or non-MSI-H and receiving neoadjuvant therapy followed by radical resection in Peking Union Medical College Hospital (PUMCH). Based on the neoadjuvant therapy regimen, patients were divided into three groups: the nCRT group (n=81), the TNT group (n=42), and the PD-1 group (n=37). The clinical data including baseline characteristics, treatment information, and MRI accuracy on rectal cancer restaging were analyzed. Considering the possible impact of gut microbiome on antitumor immunity, we also analyzed differences in gut microbiome between baseline stool samples from pCR and non-pCR patients in the PD-1 group.

RESULTS: No significant differences were found in baseline characteristics among the three groups. The rates of pathologic complete response (pCR, corresponding to pTRG 0) were 25.9% (21/81) in the nCRT group, 40.5% (17/42) in the TNT group, and 45.9% (17/37) in the PD-1 group (p=0.048). The accuracy of MRI for restaging rectal cancer T stage was not ideal, particularly in the TNT and PD-1 groups. Additionally, the α and β diversity of gut microbiome between baseline stool samples from pCR and non-pCR patients in the PD-1 group were similar.

CONCLUSIONS: Both TNT and PD-1 combination therapy demonstrated higher tumor regression and pCR rates compared with nCRT, suggesting enhanced local tumor control. However, improvements in rectal MRI accuracy and gut microbiome research are needed to enhance precision in diagnostics and therapy.}, } @article {pmid41446276, year = {2025}, author = {Chen, S and Jiang, Y and Lv, D and Zheng, Y and Zhang, R and Dai, H and Wang, Z and Li, S and Qi, R and Xu, H and Yu, Y and Xu, C and Lu, X and Xu, Y and Jin, S and Wu, X}, title = {Identification of subtypes and construction of a predictive model for novel subtypes in severe community-acquired pneumonia based on clinical metagenomics: a multicenter, retrospective cohort study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1676502}, pmid = {41446276}, issn = {2235-2988}, mesh = {Humans ; Retrospective Studies ; *Community-Acquired Infections/microbiology/mortality/classification/diagnosis ; Male ; Female ; Middle Aged ; *Metagenomics/methods ; Aged ; China/epidemiology ; *Pneumonia/microbiology/classification/mortality ; Adult ; Microbiota/genetics ; Prognosis ; ROC Curve ; Bronchoalveolar Lavage Fluid/microbiology ; Intensive Care Units ; High-Throughput Nucleotide Sequencing ; Nomograms ; Community-Acquired Pneumonia ; }, abstract = {OBJECTIVE: It is well recognized that high heterogeneity represents a key driver of the elevated mortality in severe community-acquired pneumonia (sCAP). Precise subtype classification is therefore critical for both treatment strategy formulation and prognostic evaluation in this patient population. This study aimed to develop a predictive model for novel clinical subtypes of sCAP, leveraging microbiome profiles identified via metagenomic next-generation sequencing (mNGS).

METHODS: This retrospective multicenter cohort study enrolled adult patients with sCAP who underwent clinical mNGS testing of bronchoalveolar lavage fluid in intensive care units (ICUs) across 17 medical centers in China. Based on mNGS-identified microbiome characteristics, unsupervised machine learning (UML) was employed for clustering analysis of sCAP patients. LASSO regression and random forest (RF) algorithms were applied to screen and identify predictors of novel sCAP subtypes. A predictive model for the new clinical subtypes was constructed according to the screening results, with a nomogram generated. The discriminative ability, calibration, and clinical utility of the model were evaluated using ROC curves, calibration curves, and decision curve analysis, respectively.

RESULTS: A total of 1,051 sCAP patients were included in the final analysis. The 28-day all-cause mortality rate was 45% (473/1,051). UML clustering identified two distinct sCAP subtypes: the 28-day mortality rate was 42.19% (343/813) in subtype 1 and 54.62% (130/238) in subtype 2. Incorporating clinical and microbial features, a predictive model for the novel sCAP subtypes was developed using the following predictors: immunosuppression (OR = 37,411.46, P < 0.001), connective tissue disease (CTD) (OR = 12,144.60, P = 0.004), hematological malignancy (HM) (OR = 107,768.13, P < 0.001), chronic kidney disease (CKD) (OR = 49.71, P < 0.001), cytomegalovirus (CMV) (OR = 0.00, P < 0.001), Epstein-Barr virus (EBV) (OR = 131.97, P < 0.001), Pneumocystis (OR = 47,949.56, P < 0.001), and Klebsiella (OR = 0.02, P = 0.003). The model demonstrated excellent discriminative ability with an area under the ROC curve (AUC) of 0.992. Calibration curves showed good agreement between predicted and observed outcomes. Decision curve analysis confirmed high clinical utility for predicting novel sCAP subtypes.

CONCLUSION: This study identified novel clinical subtypes of sCAP based on mNGS-derived microbiome characteristics. This approach exhibits superior performance in identifying high-risk sCAP patients, facilitating precise subtyping.}, } @article {pmid41446208, year = {2025}, author = {Gómez-Garzón, C and Chen, Q and O'Brien, VP and Salama, NR}, title = {Metaplasia Enables Stomach Colonization by Fusobacterium animalis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.16.694801}, pmid = {41446208}, issn = {2692-8205}, abstract = {Infection with Helicobacter pylori is the major risk factor for gastric cancer worldwide; yet the exact mechanisms behind this link remain unclear. H. pylori -associated tissue changes often disrupt the gastric microbiome, enabling secondary gastric colonization by oral bacteria. Among these secondary colonizers, Fusobacterium species have documented associations with several gastrointestinal cancers. We found that both F. animalis and F. nucleatum invade cultured human gastric adenocarcinoma cells, but F. animalis exhibited higher adherence and invasion, and hypoxic conditions promoted higher bacterial survival. Both adherence and invasion were inhibited by exogenous GalNAc, a glycan commonly observed in membrane glycoproteins of adenocarcinoma cells, and a target of the fusobacterial adhesin Fap2. Using a mouse model of gastric metaplasia, we found that F. animalis colonized gastric tissue only after metaplasia onset, growing in multispecies biofilms in the mucus layer, while F. nucleatum colonized neither healthy nor metaplastic gastric tissue. Metaplasia led to upregulation of Gal-GalNAc in the stomach, and reduced gastric acidity allowed higher F. animalis loads in this model. By contrast, inflammation and the presence of H. pylori did not significantly influence stomach colonization by F. animalis . Overall, our data support a model in which H. pylori -induced metaplasia makes the stomach susceptible to secondary infection by another cancer-associated microbe, F. animalis .}, } @article {pmid41446111, year = {2025}, author = {Wang, T and Binion, B and Alves, JMP and Ridlon, JM}, title = {Characterization of an NADPH-dependent 17α-hydroxysteroid dehydrogenase encoded by the desF gene from the gut bacterium Clostridium scindens VPI 12708.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.17.694922}, pmid = {41446111}, issn = {2692-8205}, abstract = {Epitestosterone (epiT) is the isomer of the androgen testosterone. Historically, the role of epiT has remained unclear. Recently, it has been reported that epiT promotes AR-dependent prostate cancer cell proliferation. The gut bacterium Clostridium scindens VPI 12708 converts androstenedione (AD) to epiT. The bacterial enzymatic pathways involved in epiT formation have been reported, where the desF gene that encodes 17α-hydroxysteroid dehydrogenase converts AD to epiT using NADPH as a cofactor. In this study, we quantitatively characterized DesF kinetic parameters and substrate specificity. The results revealed that the optimal pH for the reductive reaction is 7.0, and for the oxidative reaction it is 7.5 and 8.0. The kinetic analysis showed that for the reductive reaction, the K M was 8.67 ± 2.04 µM and the V max was 1.95 ± 0.11 µM min [-1] ; for the oxidative direction, the K M was 27.17 ± 3.56 µM and the V max was 2.18 ± 0.08 µM min [-1] . Moreover, the substrate specificity analysis revealed that 11-keto-AD is the most favourable substrate for DesF, and the 17-keto group of 11-keto-AD can be converted to the 17α-hydroxy group. These results are a significant advance in understanding epiT formation by the gut microbiome.}, } @article {pmid41446096, year = {2025}, author = {Pauer, H and Nasiri, S and Magalhães, NS and Nguyen, VT and Ferreira, NV and Silva Ferreira, LD and Bradshaw, AB and Kirby, KE and Sabapathy, T and Udensi, CG and Feofanova, V and Moreira, DA and Parente, TE and Wilde, J and Pride, DT and Allen-Vercoe, E and Antunes, LCM}, title = {Enterocloster citroniae and related gut microbiome species modulate Vibrio cholerae biofilm formation through the production of bioactive small molecules.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.15.694346}, pmid = {41446096}, issn = {2692-8205}, abstract = {UNLABELLED: Cholera is a diarrheal disease that affects millions of people globally. Although the causative agent, Vibrio cholerae , has been extensively studied in isolation, investigation of its interactions with the gut microbiota started relatively recently. We and others previously showed that microbiota-derived metabolites significantly influence V. cholerae behavior. By investigating how an organic extract of human feces affects V. cholerae gene expression, we showed that gut metabolites strongly suppress swimming motility, a trait important for host colonization. Interestingly, extracts of pure cultures of a gut commensal, Enterocloster citroniae , recapitulated this inhibition. Here, we present a comprehensive examination of the effect of small molecules produced by E. citroniae and related species on V. cholerae behavior. We show that E. citroniae small molecules inhibit motility by various V. cholerae strains, and that several phylogenetically related species produce this activity, although the magnitude of the effect varies between strains. Using biofilm formation assays in static and flow conditions, we show that V. cholerae strongly induces biofilm formation in response to E. citroniae metabolites. Transcriptome and reporter analyses showed that several genes involved in synthesis of an extracellular polysaccharide are induced by E. citroniae metabolites. Lastly, we show that V. cholerae interactions with host cells are also modulated by this commensal. These findings advance our understanding of microbiome-pathogen interactions and how commensal bacteria influence V. cholerae virulence through the production of small molecules. In the future, this knowledge may be used to design novel microbiome-based therapeutic approaches to combat cholera and other infections.

IMPORTANCE: The human gut is home to a dense and rich community of microbes termed microbiota. This community has critical functions for host health, including protection against enteric pathogens. Despite this important role, we have only recently scratched the surface of the interactions that occur between members of the microbiota and pathogenic invaders. Cholerae is a disease that still causes significant morbidity and mortality worldwide. Studying how the causative agent, Vibrio cholerae , interacts with the microbiota will have implications not only for our understanding of this important microbial community, but may also lead to the development of new therapeutic strategies against cholera and potentially other infectious diseases.}, } @article {pmid41446056, year = {2025}, author = {Wang, T and Ahmad, S and Rosa, RSL and Binion, B and Fernandez-Materan, FV and Igbalaye, JO and Chung, D and Bushra, A and Perez, V and Biedak, MA and Tang, E and Barnick, B and Olukoya, D and Mbuvi, P and Dutta, D and Erdman, JW and Gaskins, HR and Yang, G and Irudayaraj, J and Bernardi, RC and Ridlon, JM}, title = {The urinary pathobiont Actinobaculum massiliense generates androgens via the dirAB pathway.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.18.695155}, pmid = {41446056}, issn = {2692-8205}, abstract = {While overlooked during the Human Microbiome Project, characterizing the urinary microbiota in health and disease is a new frontier in microbiome science. Recent studies have associated differential abundance of bacterial taxa including Propionimicrobium lymphophilum and Actinobaculum / Actinotignum spp. with prostate cancer. In this study, we collected urine from subjects prior to prostate biopsy and applied a novel H uman S terolbiome D iscovery H igh-throughput (HSDH) assay to identify culturable urinary bacteria with the ability to generate androgens. Application of the HSDH assay to urine samples led to the isolation of eight P. lymphophilum strains positive for cortisol side-chain cleavage (steroid-17,20-desmolase), 17β-HSDH activity, or both. In addition, we isolated three strains of Actinobaculum massiliense that encode D HEA isomerase reductase (dir) genes. The dirA gene encodes a novel 3β/17β-hydroxysteroid dehydrogenase/Δ [4,5] -isomerase and the dirB gene encodes a novel 17β-hydroxysteroid dehydrogenase isoform. Structural prediction and molecular dynamics reveal probable catalytic mechanisms based on the shared catalytic triad but distinct binding pocket geometries of the DirA and DirB that describe their respective reactions. Phylogenetic analysis of DirA and DirB revealed homologs in urinary tract commensals as well as bacteria associated with steroid degradation found in aquatic and terrestrial environments. Taken together, the development of the HSDH assay and the identification of the dir pathway genes is a significant advance in microbial endocrinology, laying the methodological foundation and providing the molecular basis for understanding the role of urinary tract bacteria in host endocrine physiology.}, } @article {pmid41445956, year = {2025}, author = {Yang, H and Wang, A and Yang, J and Luo, R and Yang, Y}, title = {Alterations in gut microbiota composition in neurodevelopmental disorders: a systematic review and meta-analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1650212}, pmid = {41445956}, issn = {1664-302X}, abstract = {BACKGROUND: Neurodevelopmental disorders (NDDs) have been linked to changes in the gut microbiome, but the exact nature of these alterations is not fully understood. This research seeks to explore the variations in both the diversity and composition of the gut microbiota in individuals diagnosed with NDDs.

METHODS: We conducted a systematic literature search up to April 2025. Meta-analyses using STATA 16.0 evaluated alpha diversity, beta diversity, and relative abundance between individuals with NDDs and healthy controls.

RESULTS: No significant alpha diversity differences were found between NDD and control groups. Beta diversity analysis revealed distinct microbial communities across autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and tic disorder (TD) subgroups. At the family level, NDDs showed increased Peptostreptococcaceae (SMD = 0.47; 95% CI: 0.05 to 0.90). Genus-level analysis demonstrated reduced Escherichia/Shigella (SMD = -0.39; 95% CI: -0.59 to -0.19) and Roseburia (SMD = -0.39; 95% CI: -0.78 to 0), alongside elevated Eubacterium (SMD = 0.33; 95% CI: 0.20-0.47) in NDDs.

CONCLUSION: This study highlights the complex changes in gut microbiota in NDDs, particularly significant differences at the beta diversity, family, and genus levels. However, the results are constrained by research heterogeneity and small sample sizes. To better elucidate these associations, larger, more standardized studies are required.

https://www.crd.york.ac.uk/prospero/, CRD42024585913.}, } @article {pmid41445807, year = {2025}, author = {Wang, XW and Wang, T and Liu, YY}, title = {Artificial Intelligence for Microbiology and Microbiome Research.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {41445807}, issn = {2331-8422}, abstract = {Advancements in artificial intelligence (AI) have transformed many scientific fields, with microbiology and microbiome research now experiencing significant breakthroughs through machine learning applications. This review provides a comprehensive overview of AI-driven approaches tailored for microbiology and microbiome studies, emphasizing both technical advancements and biological insights. We begin with an introduction to foundational AI techniques, including primary machine learning paradigms and various deep learning architectures, and offer guidance on choosing between traditional machine learning and sophisticated deep learning methods based on specific research goals. The primary section on application scenarios spans diverse research areas, from taxonomic profiling, functional annotation \& prediction, microbe-X interactions, microbial ecology, metabolic modeling, precision nutrition, clinical microbiology, to prevention \& therapeutics. Finally, we discuss challenges in this field and highlight some recent breakthroughs. Together, this review underscores AI's transformative role in microbiology and microbiome research, paving the way for innovative methodologies and applications that enhance our understanding of microbial life and its impact on our planet and our health.}, } @article {pmid41445404, year = {2025}, author = {Pagowong, N and Suparan, K and Kunasol, C and Piriyakunthorn, C and Sripusanapan, A and Suntornlekha, N and Leemasawat, K and Suwannasom, P and Chattipakorn, N and Chattipakorn, SC}, title = {Clinical Manifestations.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 3}, number = {}, pages = {e100074}, doi = {10.1002/alz70857_100074}, pmid = {41445404}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Middle Aged ; Aged ; *Acute Coronary Syndrome/microbiology/complications ; *Cognitive Dysfunction/microbiology ; Feces/microbiology ; Mental Status and Dementia Tests/statistics & numerical data ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Previous studies have shown that gut dysbiosis correlates with cognitive impairments in both animal models and clinical settings. Additionally, alterations in gut microbiota have been linked to acute coronary syndrome (ACS). However, the relationship between gut microbiota changes and cognitive outcomes in recent ACS patients remains poorly understood. The present study aims to investigate these changes in gut microbiota and cognitive function in recent ACS patients, comparing them to individuals with high cardiovascular (CV) risks.

METHOD: The present study enrolled 50 hemodynamically stable ACS patients who experienced myocardial infarction within the past 24 hours, along with 42 patients with high CV risks who served as a control group. This study received approval from the Ethics Committee of the Faculty of Medicine, Chiang Mai University. The Montreal Cognitive Assessment (MoCA) was used to evaluate neurocognitive function. Fecal samples were collected for gut microbiome analysis via 16S rRNA next-generation sequencing.

RESULTS: Baseline characteristics between stable ACS patients and the control group were significant differences in genders, smoking status, alcohol consumption and some underlying conditions including hypertension and dyslipidemia. Recent ACS patients exhibited a significant decline in MoCA scores (Figure 1A), with lower scores across all subdomains than the control group (Figure 1B). Additionally, recent ACS patients showed gut dysbiosis, evidenced by an increased diversity in the gut microbiota (Figure 1C) and significant differences in microbial composition (Figure 1D) relative to the control group. Notably, recent ACS patients showed mark increases in the Firmicutes/Bacteroidota and Enterobacteriaceae/Proteobacteria ratios, suggesting further gut dysbiosis (Figures 1E and 1F). A negative correlation was observed between certain differential taxa-such as Peptostreptococcales-Tissierellales and Peptostreptococcus-and MoCA scores in recent ACS patients (Figure 1G).

CONCLUSION: Our findings suggest an association between alterations in gut microbiota and cognitive impairments in recent ACS patients. Specifically, the presence of Peptostreptococcales-Tissierellales and Peptostreptococcus may serve as potential biomarkers for cognitive impairmentsin this population.}, } @article {pmid41445292, year = {2025}, author = {Govindarajan, M and Aware, C and Ivanich, K and Pathak, I and Zhu, Y and Balchandani, P and Davis, D and Ericsson, A and Ma, L and Lin, AL}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e105884}, doi = {10.1002/alz70855_105884}, pmid = {41445292}, issn = {1552-5279}, mesh = {Animals ; Mice ; *Alzheimer Disease/microbiology ; *Nitric Oxide Synthase Type II/genetics ; Humans ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Cognitive Dysfunction/microbiology ; Mice, Knockout ; *Dysbiosis ; Male ; Aged ; Fecal Microbiota Transplantation ; Female ; Cerebrovascular Circulation ; Mice, Transgenic ; Middle Aged ; Aged, 80 and over ; }, abstract = {BACKGROUND: Inducible Nitric Oxide Synthase (iNOS) is implicated in exacerbating Alzheimer's Disease (AD) mechanisms. The relationship between imbalanced gut microbiota composition (dysbiosis) and AD pathology is well characterized. Many gut bacteria, including E. Coli induce iNOS production, potentially contributing to AD development. To investigate the antagonistic role of iNOS, we created a novel iNOS knockout (iNOS-KO) mouse model using the 3xTg-AD mouse model background and performed fecal microbiome transplantation (FMT) to iNOS-KO/3xTg-AD mice from mild cognitive impairment (MCI) patients and age-matched healthy controls (HC). We aim to determine, whether iNOS-KO can protect cerebral blood flow (CBF), an early marker of AD progression, despite dysbiosis induced by FMT from MCI donors.

METHOD: Stool samples from MCI patients (n =  3) and HC (n =  3) (aged 55-80) were used for FMT in 4-month-old iNOS-KO/3xTg-AD mice (FMT-MCI, n = 4 and FMT-HC, n = 6) for three consecutive days after a 7-day antibiotic treatment. Mice without FMT (CTL, n = 8) served as naive controls. Four weeks post-FMT, mouse fecal samples and corresponding donor samples were analyzed using 16S rRNA metagenomic sequencing. Global CBF was measured in a subset of mice (n = 4/group) using 7T MRI with Continuous Arterial Spin Labelling (CASL) - Echo Planar Imaging (EPI) sequence.

RESULT: Beta diversity analysis revealed that the significant microbial diversity observed in MCI and HC donors was imprinted in their respective FMT-MCI and FMT-HC recipient mice, indicating a strong donor-derived microbial signature (Figure 1). FMT-MCI mice showed increased levels of pathobiont Gram-positive bacteria (Clostridium bolteae, Sellimonas intestinalis) when compared to FMT-HC mice indicating higher dysbiosis. Despite FMT induced dysbiosis, CBF levels (Figure 2) across the three groups were comparable to each other, attributable to the effect of the iNOS knockout.

CONCLUSION: We observe that MCI patients had higher gut dysbiosis than HC. However, despite increased dysbiosis, iNOS-KO may preserve CBF and mitigate AD-like symptoms, highlighting its potential neuroprotective role in the 3xTg-AD model. Future studies should investigate the impact of iNOS-KO on mitigating AD pathology, such as amyloid-β and tau accumulation, or preserving cognitive functions. Our preliminary data shows that iNOS could be a potential target to ameliorate AD risk.}, } @article {pmid41445049, year = {2025}, author = {Loew, EB}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e107794}, doi = {10.1002/alz70855_107794}, pmid = {41445049}, issn = {1552-5279}, mesh = {Humans ; *Alzheimer Disease/immunology/metabolism ; Aged ; Male ; Female ; *Gastrointestinal Microbiome ; Feces/microbiology/chemistry ; *Cognitive Dysfunction/immunology/metabolism ; Metabolomics ; Aged, 80 and over ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. However, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. In addition to the amyloid plaques, tau tangles, and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD. It is currently unknown what underlies dysfunction in the peripheral immune system or whether changes in peripheral immune cells are associated with cognitive decline.

METHOD: We have performed unbiased stool metabolomics combined with machine leaning to identify bacterial metabolites associated with AD versus propensity matched healthy controls. In our ongoing work, we are longitudinally characterizing resting peripheral immune cell populations by flow cytometry and gut microbiome composition by metagenomic sequencing.

RESULT: We have identified an increase in the metabolites methionine sulfone, homocysteine, and cysteine in the stool of older adults with AD compared to controls and found machine learning models supported bacterial methionine production as a key AD associated variable. Among the population of AD patients experiencing cognitive decline, determined by increasing ADAS-Cog score >6 points over one year (n = 10 declining vs n = 8 stable cognition), we have identified increases in the bacterial genes responsible for methionine production at the point of cognitive decline compared to previous timepoints and between patients with decline versus stable cognition. In accordance with the role of methionine in promoting immune cell proliferation and differentiation, we have compared the composition of peripheral immune cells among adults with declining versus stable cognition and identified increased CD4[+] effector memory T cells at the point of cognitive decline.

CONCLUSION: This longitudinal clinical study identifies changes in stool metabolites and resting peripheral T cell populations in AD patients and among AD patients with cognitive decline. We propose that gut bacterial produced methionine acts to promote peripheral immune differentiation and dysfunction, leading to cognitive decline in AD.}, } @article {pmid41444876, year = {2025}, author = {Xie, J and Liu, S and Wong, X}, title = {The role of microbiome-modulating supplements in managing metabolic syndrome risk factors among overweight and obese youth: a GRADE-assessed meta-analysis.}, journal = {BMC pediatrics}, volume = {25}, number = {1}, pages = {991}, pmid = {41444876}, issn = {1471-2431}, mesh = {Humans ; *Metabolic Syndrome/prevention & control/etiology ; *Probiotics/therapeutic use/administration & dosage ; *Pediatric Obesity/therapy/complications/microbiology ; *Prebiotics/administration & dosage ; Child ; *Gastrointestinal Microbiome ; Adolescent ; *Synbiotics/administration & dosage ; *Overweight/therapy ; *Dietary Supplements ; Risk Factors ; Body Mass Index ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Gut microbiota modulation has been proposed as a potential intervention for managing obesity. This meta-analysis aimed to evaluate the effects of prebiotic/probiotic/synbiotic supplementation on metabolic syndrome risk factors in obese pediatrics.

METHODS: A comprehensive search was conducted in databases up to January 2025. Randomized controlled trials (RCTs) evaluating prebiotics/probiotics/synbiotics in children and adolescents with overweight/obesity were included. The outcomes were body weight (BW), body mass index (BMI), BMI-z score, fasting blood sugar (FBS), homeostatic model assessment for insulin resistance (HOMA-IR), insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C). Data were pooled using a random-effects model.

RESULTS: Prebiotic supplementation was associated with significant reductions in weight (SMD = - 0.81; 95% CI: - 1.44 to - 0.19) and BMI (SMD = - 0.76; 95% CI: - 1.38 to - 0.14), whereas BMI z-scores remained unchanged (p > 0.05). Probiotics and synbiotics did not significantly affect weight, BMI, or BMI z-scores (p > 0.05). Glycemic and lipid profile parameters were not significantly altered by any biotic supplementation (p > 0.05). Subgroup analyses by intervention type, duration, sample size, or baseline BMI did not reveal consistent effects (p > 0.05).

CONCLUSION: Biotic supplementation has not been shown to consistently improve metabolic syndrome risk factors in overweight and obese children, except for a modest beneficial effect of prebiotics on weight and BMI (with very-low certainly of evidence); however, alternative probiotic organisms or formulations not tested to date may have different effects.}, } @article {pmid41444837, year = {2025}, author = {Lu, P and Wang, Z}, title = {Lipid metabolism in colorectal cancer: dual roles and statin therapy.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-025-04349-3}, pmid = {41444837}, issn = {2730-6011}, abstract = {Colorectal cancer (CRC) remains a prevalent global malignancy with increasing incidence. This review systematically explores the intricate and often paradoxical dual roles of lipid metabolism components-triglycerides, cholesterol, HDL-C, and LDL-C-in CRC development and progression. A key focus is on the therapeutic potential of statins, cornerstone lipid-lowering agents. We summarize evidence that statins may confer protection through multifaceted mechanisms: inhibiting HMG-CoA reductase, modulating inflammation and immune responses, and reprogramming the gut microbiome. However, we critically synthesize the significant controversy surrounding their efficacy, attributing discrepant findings to factors such as statin lipophilicity, treatment duration, and tumor anatomical subsite. Ultimately, this review highlights the complex interplay between lipids and CRC and underscores the need for stratified, personalized approaches in future research and potential therapeutic applications.}, } @article {pmid41444762, year = {2025}, author = {Chancharoenthana, W and Kamolratanakul, S and Pinitchun, C and Vorapreechapanich, A and Wannigama, DL and Somboonna, N and Cheibchalard, T and Settachaimongkon, S and Schultz, MJ and Leelahavanichkul, A}, title = {Modulation of sepsis by Lacticaseibacillus rhamnosus and the potential role of short-chain fatty acid levels in feces and blood.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-33032-4}, pmid = {41444762}, issn = {2045-2322}, abstract = {The efficacy of probiotics for sepsis attenuation might be associated with the alteration of short-chain fatty acids (SCFAs). We investigated the impact of probiotics with the different production of SCFAs in vitro, including Lacticaseibacillus rhamnosus strains fa1 and fg2 in mice with cecal ligation and puncture. Administration of either fa1 or fg2 probiotics, but not the heat-killed probiotics, prior to surgery effectively reduced sepsis severity. Metabolome analysis revealed elevated levels of acetate and 3-hydroxybutyrate in blood, whereas butyrate and propionate levels were diminished in the feces of sepsis mice compared to sham controls. Both probiotics similarly attenuated sepsis-induced gut dysbiosis, as indicated by the normalized Firmicutes and reduced Proteobacteria (fecal microbiome analysis), with the similar levels of fecal SCFAs. In parallel, the administration of butyrate, but not acetate, partly attenuated sepsis severity (gut permeability and serum TNF-α). Conditioned media from both probiotic strains or butyrate demonstrated a protective effect against enterocyte injury following activation by Klebsiella pneumoniae lysate, irrespective of their SCFAs production. To support the possible use of SCFAs in sepsis, the lower serum SCFAs in patients with sepsis compared to healthy controls was demonstrated. In conclusion, both fa1 and fg2 attenuated sepsis severity, partly through the increased levels of SCFAs. These findings endorse the potential of probiotics in preventing sepsis and the use of SCFAs for sepsis disease monitoring.}, } @article {pmid41444706, year = {2025}, author = {Viñado, IG and Correa, F and Trevisi, P and Bee, G and Ollagnier, C}, title = {Dynamic picture of the pig gut's microbiota under normal and pathological conditions.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {129}, pmid = {41444706}, issn = {2524-4671}, support = {955374//HORIZON EUROPE European Research Council/ ; }, abstract = {BACKGROUND: Recent advancements in sequencing technologies and associated bioinformatic tools have eased the analyses of the factors influencing variability in host-associated microbial communities in the gastrointestinal tract (GIT). Although extensive research has focused on fecal microbiota, the small intestine represents a critical, yet less explored, site for understanding the interplay between microbiota, diet, and host health. Study 1 employed CapSa, a non-invasive sampling capsule, to collect microbiota at five distinct administration time points. The aim was to use amplicon sequencing to investigate changes in the small intestine microbiome composition throughout the grower-finisher pig lifespan. Study 2 examined the long-term impact of enterotoxigenic Escherichia coli (ETEC) F4 infections, which cause post-weaning diarrhea (PWD), on small intestine microbiota dynamics. The study provides insights into the long-term responses of microbiota after a short pathological challenge.

RESULTS: In both studies, microbiota analysis of the small intestinal content revealed that Firmicutes predominated across all samples, and at weaning, Lactobacillaceae and Lactobacillus were the most abundant. In Study 1, following CapSa administration, Clostridium sensu stricto 1 and Terrisporobacter increased with age/body weight and at slaughter, Streptococcaceae dominated. Significant differences in microbial composition were observed based on sample type and diet, indicating dynamic shifts throughout the pigs' lives under normal conditions. In Study 2, the abundance of Lactobacillaceae was consistently lower in ETEC-infected pigs. At slaughter, only minimal differences in microbial composition emerged based on the early post-weaning infection status in specific small intestine segments, indicating dynamic infection-induced shifts in the gut microbiota composition. The CapSa sampling method was successful, with a retrieval rate higher than 70% in both studies.

CONCLUSIONS: This study monitored porcine intestinal microbiota dynamics using an ingestible capsule. In healthy pigs, microbial composition changes occurred from post-weaning to slaughter. In contrast, ETEC infection only minimally altered communities, though small differences at slaughter suggest lasting impacts.}, } @article {pmid41444705, year = {2025}, author = {Oladele, P and Dong, W and Richert, BT and Johnson, TA}, title = {Route of fecal microbiota transplantation delivery determined the dynamics and predictability of donor microbe colonization.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {130}, pmid = {41444705}, issn = {2524-4671}, support = {ICASASHTWG0000000082//Foundation for Food and Agriculture Research,United States/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) and the colonization of delivered donor microbes has been reported to improve the negative effects (decrease in body weight, diarrhea, and gut barrier disruption) associated with weaning in pigs. However, delivery of FMT in pigs is still invasive and predicting the colonization or rejection of donor microbes remains challenging. Therefore, this study developed a non-invasive in-feed delivery of FMT and evaluated the effect of FMT mode of delivery on growth performance, gut physiology, microbiota dynamics, and predictability of colonization or rejection of donor microbes in recipient pigs. Forty weaned piglets (10 per group) were administered FMT through one of three routes; oral, rectal, or amended in-feed. The control group was orally administered sterile saline to simulate handling stress.

RESULTS: Pigs in the FMT groups had higher average daily weight gain (ADG) from day 0–2 post-weaning. An increase in community diversity and a shift in the recipient community towards the donor in all FMT groups was observed on day 5. The oral group had the highest colonization (15.12%) and the lowest rejection (19.34%) rates, while colonization was 13.82% and 11.78% in rectal and in-feed group respectively. On day 4, colon crypt depth was increased in all FMT groups but an increase in villus length was only observed in the in-feed group. Colonization and rejection of donor microbes in the recipient animals could be predicted in all routes of administration, but the efficacy of prediction was influenced by the route of delivery. In-feed FMT had the lowest colonization prediction which may have been influenced by the need for voluntary consumption of fecal materials in the in-feed group. The ten most abundant genera (Prevotella, Alloprevotella, Phascolarctobacterium, Lactobacillus, Cloacibacillus, Bacteroides, Lachnoclostridium, Escherichia-Shigella, unclassified Lachnospiraceae sequences, and archaea Methanobrevibacter) in the recipient prior to FMT (background community) was the most important feature in predicting colonization for all routes of fecal microbiota transplant.

CONCLUSION: FMT administered as a lyophilized feed additive shows promise in altering microbiome community structure. While colonization and rejection of donor microbes within the recipient community are predictable, the efficacy of these predictions varies with the route of transplant. This suggests that different prediction models are necessary for each delivery mode of FMT in pigs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00495-9.}, } @article {pmid41444701, year = {2025}, author = {Touchon, JC and Hughey, MC}, title = {Effects of naturalistic housing conditions on amphibian growth and microbiome in captivity.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {128}, pmid = {41444701}, issn = {2524-4671}, abstract = {BACKGROUND: Animals in captivity are inherently separated from their natural environments, which both exposes them to new heterospecific organisms as well as reduces contact with naturally occurring predators, prey or microbiota. The microbes that live on and in animals are increasingly recognized as having important impacts on animal health, development and behavior. We raised post-metamorphic treefrogs in 1) naturalistic containers in groups, 2) regularly sterilized containers in groups, or 3) regularly sterilized containers but solitary. Froglets were raised for over eight months; in addition to monitoring growth and development, we collected fecal samples on three occasions, gut samples on two occasions, and skin swab samples once. We compared the diversity of microbial communities across sample types and over time.

RESULTS: Froglets raised in group housing, either naturalistic or regularly cleaned, had the fastest growth and sexual differentiation, but naturalistic housing also improved survival. Alpha diversity of bacteria on the skin or in the gut did not vary with rearing conditions, whereas diversity in the gut increased over time. Alpha diversity of feces did vary with rearing treatment and changed over time. Bacterial community composition (beta diversity) varied most strongly with sample type, but also with rearing conditions and over time. In addition, bacterial communities of feces were highly correlated with those of guts, indicating that feces can serve as an accurate and non-invasive biomarker of the gut microbiome. Lastly, transferring frogs from regularly sterilized environments to naturalistic vivaria improved bacterial community diversity.

CONCLUSIONS: Our study suggests that naturalistic housing improves the overall health and development of captive amphibians and that these improvements may occur by facilitating a more stable and diverse microbiome.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00491-z.}, } @article {pmid41444596, year = {2025}, author = {Tang, R and Shi, M and Ji, X and Zhang, Y and Fan, L and Huang, F and Li, X}, title = {Integrative oral and gut microbiome profiling highlights microbial correlates of complications in type 1 diabetes: a cross-sectional analysis.}, journal = {Cardiovascular diabetology}, volume = {24}, number = {1}, pages = {461}, pmid = {41444596}, issn = {1475-2840}, support = {2024XQLH049//Graduate Innovation Project of Central South University/ ; grant 2023ZD0508200 and 2023ZD0508205//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; grant 82470871//National Natural Science Foundation of China/ ; grant R2023001//Hunan Provincial Health High-Level Talent Scientific Research Project/ ; LYF2022039//Sinocare Diabetes Foundation/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 1/diagnosis/microbiology/blood/complications ; Male ; Female ; Adult ; Dysbiosis ; *Bacteria/genetics/metabolism/classification/isolation & purification ; *Mouth/microbiology ; Case-Control Studies ; Middle Aged ; *Diabetic Angiopathies/microbiology/diagnosis ; Young Adult ; Risk Factors ; Feces/microbiology ; Biomarkers/blood ; Host-Pathogen Interactions ; Risk Assessment ; Metagenomics ; Blood Glucose/metabolism ; }, abstract = {BACKGROUND/OBJECTIVE: Chronic vascular complications are the primary threat in long-standing type 1 diabetes (T1D) patients. We examined the associations between oral-gut microbiome dysbiosis and these complications, offering novel insights into therapeutic strategies and underlying mechanisms.

METHODS: This cross-sectional study enrolled 75 T1D participants (disease duration ≥ 10 years) and 43 healthy controls who underwent comprehensive clinical assessment, including blood glucose, lipid profile, and complication-related examinations. Fecal and oral rinse samples were collected for shotgun metagenomic sequencing. T1D participants were stratified by the presence of microvascular (retinopathy, nephropathy, or neuropathy) or macrovascular complications separately. Microbial differences across groups were assessed.

RESULTS: Significant differences in oral and gut microbiota compositions were observed between T1D participants with and without complications (both microvascular and macrovascular). A core set of 26 gut and 8 oral microbial species was specifically associated with vascular complications. Butyrate-producing gut bacteria (Blautia wexlerae, Anaerobutyricum hallii, Roseburia inulinivorans, A. soehngenii) and specific oral Neisseria species were enriched in T1D without complications individuals, suggesting protective effects against complications. Mediation analysis indicated associations consistent with partial mediation between certain microbial species and the relationships of glycemic control or insulin resistance (HbA1c, glucose risk index, estimated glucose disposal rate) with complication risk. Moreover, potential oral-gut microbiome interconnections were implicated in complication development. Finally, classification models integrating both oral and gut microbial features significantly outperformed models based on either site alone in distinguishing T1D patients with complications.

CONCLUSIONS: Distinct oral and gut microbiome features are associated with chronic vascular complications in T1D. These findings highlight the potential of microbiome-targeted strategies for understanding and preventing T1D-related complications.}, } @article {pmid41444526, year = {2025}, author = {Hao, J and Liu, H and Guo, T and Zhang, Q and Wang, X and An, L and Xu, S}, title = {Seasonal dietary shifts drive gut microbiome plasticity and metabolic adaptation in wild yaks on the Qinghai-Xizang Plateau.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {799}, pmid = {41444526}, issn = {1471-2180}, mesh = {Animals ; *Seasons ; *Gastrointestinal Microbiome/physiology ; Cattle/microbiology ; *Diet ; *Bacteria/classification/genetics/metabolism/isolation & purification ; *Adaptation, Physiological ; China ; Fatty Acids, Volatile/metabolism/analysis ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The gut microbiota in different diets helps hosts to obtain sufficient nutrients from food, which is important for wild yaks in the Qinghai-Xizang Plateau to adapt to different seasons. The relationship between the host diet and the gut microbiota in different seasons is important for exploring the adaptation of these wild yaks to their environments. This study used wild yaks as a model organism. Using high-throughput sequencing and liquid chromatography-mass spectrometry, we investigated their seasonal diet, gut microbiota composition and function, and short-chain fatty acid profiles. The inter-season differences in them were compared, and relationships among these differences were explored. Wild yaks in summer had a diet higher in Polygonaceae and lower in Rosaceae compared to their diets in autumn and winter. The broadest dietary niche width (8.8449) was detected in autumn, and the lowest diet niche overlap (0.3751) was found between summer and winter. Co-occurrence network analyses revealed that microbial interactions were more complex in autumn, likely due to transitional dietary adjustments, whereas summer and winter exhibited simpler but more robust interactions. The abundance of Firmicute increased in winter, suggesting enhanced energy extraction from low-quality forage. Specific taxa, such as Alistipes_A in autumn and Romboutsia in winter, were linked to key metabolic pathways, including carbohydrate degradation and short-chain fatty acid production. The study highlights the critical role of gut microbiota plasticity in facilitating wild yaks' adaptation to the extreme and variable conditions and provides the basis for explaining the harsh environment adaptation of wild herbivores in the Qinghai-Xizang Plateau.}, } @article {pmid41444426, year = {2025}, author = {Sirvent, P and Langhi, C and Vallier, M and Oliveira, AR and Croyal, M and Otero, YF and Chavanelle, V and Michaux, A and Bargetto, M and Le Joubioux, F and Maugard, T and Cazaubiel, M and Bouchard-Mercier, A and Sapone, V and Pereira, B and Dutheil, F and Peltier, SL and Bard, JM}, title = {Effect of a polyphenol-rich extract on LDL cholesterol in mild to moderate hypercholesterolemia: a randomized, double-blind, placebo-controlled trial.}, journal = {European journal of clinical nutrition}, volume = {}, number = {}, pages = {}, pmid = {41444426}, issn = {1476-5640}, abstract = {BACKGROUND/OBJECTIVE: Hypercholesterolemia is a well-known risk factor for cardiovascular disease. This clinical trial evaluated the effects of TOTUM-070, a polyphenol-rich blend of plant extracts, on lipid metabolism in individuals with moderate hypercholesterolemia.

SUBJECTS/METHODS: This was a 6-month, multicenter, randomized, double-blind, placebo-controlled trial. Individuals not receiving lipid-lowering treatment and with fasting low-density lipoprotein cholesterol (LDL-C) between 1.3 and 1.9 g/L received TOTUM-070 (5 g/day) or placebo. The primary outcome was the change in fasting LDL-C. Secondary endpoints included safety, changes in the lipid profile, anthropometric measurements, and gut microbiome composition.

RESULTS: A total of 120 subjects (mean age:53.1 ± 10.3 years; BMI: 25.9 ± 3.7 kg.m[2]; 69.2% women; baseline LDL-C: 1.44 ± 0.23 g/L) were included and randomized. TOTUM-070 was well tolerated. After 6 months, fasting LDL-C was reduced in the TOTUM-070 group compared with the placebo group (Mean estimate: 1.31 ± 0.03 [1.25 ; 1.37] vs 1.41 ± 0.03 [1.35 ; 1.47], p = 0.0041). Compared with placebo, TOTUM-070 also reduced total cholesterol (p < 0.01), non-high-density lipoprotein cholesterol (non-HDL-C) (p < 0.001), triglycerides (p < 0.05), apolipoprotein (apo)B100 (p < 0.01), the apoB100/apoA1 ratio (p < 0.01), oxidized LDL (p < 0.05), and body weight (-1.4 kg; p < 0.001). Furthermore, a decrease in the abundance of Dorea in fecal samples was observed in the TOTUM-070 group.

CONCLUSIONS: This clinical trial showed that supplementation with TOTUM-070 significantly lowers LDL-C and improves other lipid parameters in subjects with moderate hypercholesterolemia. As a polyphenol-rich plant-based blend, TOTUM-070 represents a promising non-pharmacological strategy that could complement lifestyle modifications for the management of early-stage hypercholesterolemia.}, } @article {pmid41444353, year = {2025}, author = {Shahbazi, R and Yasavoli-Sharahi, H and Hebbo, MJ and Alsadi, N and Ibrahim, N and Matar, C}, title = {Lentinula edodes cultured extract intake alleviates long-term immune deregulation induced by early-life gut microbiota dysbiosis.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-33160-x}, pmid = {41444353}, issn = {2045-2322}, abstract = {The establishment of gut microbiota during early life is crucial for immune system development and its disturbance within this critical period exerts enduring adverse effects on health. Perinatal antibiotic exposure perturbs early-life microbiota and leads to long-term immune dysregulation. However, the underlying mechanisms remain inadequately explored. We investigated the persistent consequences of perinatal exposure to low-dose penicillin on gut immunity and the potential protective role of a prebiotic compound, Lentinula edodes cultured extract referred to as AHCC, against antibiotic-induced dysbiosis and immune dysregulation. Pregnant mice were subjected to penicillin and AHCC treatment from the third week of gestation until weaning of pups. Subsequently, the offspring were evaluated for gut microbiota at weaning as well as immune function, and microRNA (miRNA) changes at eight weeks of age. Microbiome analysis revealed substantial alterations in gut microbiota composition, characterized by an increase in Proteobacteria and a decrease in Firmicutes following antibiotic exposure. Lactobacillus, and some short-chain fatty acid (SCFA)-producing species were diminished by the antibiotic. AHCC intake prevented antibiotic effects on Proteobacteria in dams and offspring and some SCFA-producing bacteria in male offspring. In adult offspring, AHCC exhibited immunomodulatory activity by decreasing pro-inflammatory cytokines, including IL-2, IL-6, IL-15, and IL-21. In addition, antibiotic-induced increase in NF-κB was mitigated by AHCC. Early-life antibiotic exposure altered gut miRNA expression, increasing pro-inflammatory miR-221 and decreasing anti-inflammatory miR-145 in males while AHCC intake prevented antibiotic-mediated dysregulation of miRNA-145. These results highlight the potential of prebiotic intake as a promising strategy to prevent and mitigate persistent health issues arising from early-life dysbiosis.}, } @article {pmid41444281, year = {2025}, author = {Domínguez-Sánchez, CA and Gendron, D and Álvarez-Martínez, RC and Acevedo-Whitehouse, K}, title = {Respiratory bacteriome and its predicted functional profiles in blue whales (Balaenoptera musculus).}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44434}, pmid = {41444281}, issn = {2045-2322}, support = {558253//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; Grants in Aid of Research//Society for Marine Mammalogy/ ; SIP20160496 and 2017014//Instituto Politécnico Nacional/ ; Grant for Nature Conservation 2017//Rufford Foundation/ ; }, mesh = {Animals ; *Balaenoptera/microbiology ; *Microbiota ; *Bacteria/genetics/classification/isolation & purification ; High-Throughput Nucleotide Sequencing ; *Respiratory System/microbiology ; RNA, Ribosomal, 16S/genetics ; Phylogeny ; }, abstract = {The respiratory microbiome plays a critical role in the health of organisms and studying it in natural populations can reveal interactions between hosts and their environment, as well as help predict responses to environmental stressors. We characterized the core respiratory bacteriome and functional profiles of Eastern North Pacific blue whales (Balaenoptera musculus) sampled in the Gulf of California using next-generation sequencing. Our compositional analysis identified 15 dominant bacterial phyla in the respiratory tract, with Proteobacteria (34.44%), Firmicutes (26.98%), Bacteroidota (20.26%), Fusobacteriota (7.61%), and Actinobacteria (5.55%) as the most abundant. Nineteen ASVs, representing 12 bacterial genera (primarily Corynebacterium, Oceanivirga, Tenacibaculum, and Psychrobacter), were shared by over 60% of whales, with a relative abundance greater than 0.02%. These bacteria, proposed to be the core respiratory bacteriome of blue whales, contributed to functional pathways associated with metabolism, environmental information processing, and cellular processes. Notably, two whales with high relative abundance of Mycoplasma spp. and of Streptococcus spp., exhibited overrepresented pathways related to nucleotide metabolism and translation, suggesting a suboptimal immune status or dysbiosis. To our knowledge, this is the first functional profiling of the bacteriome in any cetacean. Future studies are needed to explore how the blue whale respiratory bacteriome may vary over time, seasonally or across geographical locations. This study establishes a baseline for future research on the plasticity of the bacteriome, its associations with other microbiome components, the impact of environmental changes on its diversity, and its relevance for health. Our novel approach underscores the ecological and physiological importance of the bacteriome and its potential for long-term monitoring of a sentinel marine species in a rapidly changing ocean.}, } @article {pmid41443984, year = {2025}, author = {Tursi, A and Brandimarte, G and Di Mario, F and Ma, W and Kupcinskas, J and Regula, J and Maconi, G and Malfertheiner, P and Barbara, G and Stollman, N and Papagrigoriadis, S and Golda, T and Amato, A and Bafutto, M and Bassotti, G and Binda, GA and Biondo, S and Crafa, P and Dumitrascu, D and Elisei, W and Flor, N and Gwee, KA and Humes, DJ and Kessoku, T and Kruis, W and Lahat, A and Lanas, A and Nakajima, A and Picchio, M and Spiller, RC and Adamopoulos, A and Scarpignato, C}, title = {Revised version global guidelines on diverticular disease of the colon: the Fiesole Consensus report.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336902}, pmid = {41443984}, issn = {1468-3288}, abstract = {INTRODUCTION: Colonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential.

METHODS: This International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management.

RESULTS: Key statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count.

CONCLUSIONS: These Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.}, } @article {pmid41443494, year = {2025}, author = {Lashus, DC and Gomez, A and Hummel, T and Jacobs, LF and Majid, A and Raju, RM and Smith, CJ and Williams, J and Bratman, GN}, title = {Associations of forest vs. urban environmental exposure with well-being and nasal microbiome composition: An exploratory pilot study.}, journal = {Environmental research}, volume = {}, number = {}, pages = {123582}, doi = {10.1016/j.envres.2025.123582}, pmid = {41443494}, issn = {1096-0953}, abstract = {The benefits of nature exposure for human well-being are well-recognized, yet much remains to be understood about the underlying causal mechanisms. This exploratory, hypothesis-generating pilot study used a natural experimental design with University of Washington students (Seattle, WA, USA; 2024) to investigate links between the nasal microbiome and well-being over an 8-week forest vs. urban environment exposure. After an academic year (September-May) during which all participants (N = 13) were full-time students in Seattle, one group relocated to remote forest sites in western Washington (n = 5; forest condition), while another group remained in urban Seattle (n = 8; urban condition). Self-reported affect, rumination, and mental well-being were assessed pre- and post-exposure using validated surveys, and nasal swabs were collected pre- and post-exposure for nasal microbiome profiling via 16S rRNA gene sequencing. Compared to the urban group, the forest group exhibited significantly greater increases in positive affect and decreases in negative affect and rumination. While no between-group differences in overall nasal bacterial community composition were detected pre-exposure, significant differences emerged post-exposure. Moreover, the forest group exhibited greater post-exposure taxonomic richness at a marginally statistically significant level and significant enrichment of taxa previously associated with well-being (e.g., Bifidobacterium, Akkermansia), changes not observed in the urban group. Increases in taxonomic richness and the relative abundance of these key taxa were significantly associated with affective improvements. These preliminary results suggest that nasal microbiome-mediated pathways linking nature exposure with well-being merit further investigation.}, } @article {pmid41443467, year = {2025}, author = {Prabhakaran, V and Poovizhi, V and Verma, VK and Therayil, A and Bhatia, J and Arya, DS}, title = {The Novel Triad of Atherosclerosis, ACE2, and Dysbiosis: A literature Review.}, journal = {Life sciences}, volume = {386}, number = {}, pages = {124168}, doi = {10.1016/j.lfs.2025.124168}, pmid = {41443467}, issn = {1879-0631}, abstract = {Atherosclerosis, a chronic inflammatory disease and the leading cause of myocardial infarction and stroke, is marked by lipid accumulation, arterial stiffening, and plaque formation initiated by endothelial dysfunction. Despite its well-understood pathogenesis, therapeutic outcomes remain variable, highlighting the need for a more comprehensive understanding of its underlying mechanisms. ACE2, a crucial component of the renin-angiotensin system (RAS), converts pro-inflammatory Angiotensin II (Ang II) into anti-inflammatory and vasodilatory Angiotensin (1-7). ACE2 also supports gut health, facilitating essential amino acid transportation and maintaining intestinal immunity. Inflammation and oxidative stress in atherosclerosis can downregulate ACE2 expression and activity, impairing its protective functions. Dysbiosis may contribute to atherosclerosis because of a compromised intestinal barrier and translocation of pro-inflammatory bacterial components into circulation, triggering systemic inflammation. It also alters lipid metabolism, promoting the production of trimethylamine N-oxide (TMAO), linked to increased cardiovascular risk, and a reduction in protective short-chain fatty acids (SCFAs). This proposed triad reveals critical feedback loops in Atherosclerosis-induced inflammation, ACE2 function, as well as gut dysbiosis that exacerbate atherosclerosis. Conversely, optimal ACE2 function can support a healthy gut microbiome, offering protection against atherosclerosis. Understanding this triad provides a more holistic understanding of atherosclerosis and explains the observed heterogeneity in disease progression. Traditional monotherapies often fail to capture this complexity. This triad elucidates integrative therapeutic approaches for ACE2 dysregulation and gut dysbiosis, aiming to treat atherosclerosis more effectively.}, } @article {pmid41443297, year = {2025}, author = {Aoun, J and Kabrah, A and Ahuja, M and Leblanc, B and Zhang, C and Li, L and Wang, Y and Muallem, S}, title = {Role of innate oral immunity and the salivary fluid in inflammatory bowel disease.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101713}, doi = {10.1016/j.jcmgh.2025.101713}, pmid = {41443297}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: Oral and gut health are tightly connected through their microbiome and immunity, including in disease states. The oral adaptive immunity contributes to the severity of inflammatory bowel disease (IBD). However, the role of oral innate immunity, and more specifically the saliva in gut microbiome and IBD, is poorly understood.

METHODS: We used two mouse models with reduced saliva, NOD and Aqp5[-/-] mice, and recovery of salivation in the NOD mice by treatment with a CFTR corrector to examine the role of salivation in oral and gut microbiome, IBD, and survival.

RESULTS: Analysis of the oral microbiome at various conditions revealed that the saliva has a minimal role in shaping the oral microbiome. However, salivation affected the composition of the gut microbiome. Moreover, the lack of saliva significantly delayed development of DSS-induced colitis, but resulted in a later, age-dependent, rapidly developed weight loss and death. The dual roles of the saliva were caused by two immunomodulatory peptides secreted by salivary glands. Fractionation and mass spectroscopy analysis identified trefoil factor 2 (TFF2) as a protective component and the cytokine macrophage migration inhibitory factor (MIF) as the damaging component of the saliva. The effects of the salivary fluid, TFF2, and MIF were primarily due to control of the gut barrier, rather than the gut microbiome. Scavenging salivary TFF2 and MIF with antibodies resulted in exacerbating and protection, respectively, of IBD.

CONCLUSIONS: The oral innate immunity has a major role in shaping the gut microbiome through secretion of MIF and TFF2. Control of MIF and TFF2 can benefit the treatment of colitis.}, } @article {pmid41443199, year = {2025}, author = {Lucas, TN and Biehain, U and Gautam, A and Gemeinhardt, K and Lass, T and Konzalla, S and Ley, RE and Angenent, LT and Huson, DH}, title = {MMonitor for real-time monitoring of microbial communities using long reads.}, journal = {Cell reports methods}, volume = {}, number = {}, pages = {101266}, doi = {10.1016/j.crmeth.2025.101266}, pmid = {41443199}, issn = {2667-2375}, abstract = {Real-time monitoring of microbial communities offers valuable insights into microbial dynamics across diverse environments. However, many existing metagenome analysis tools require advanced computational expertise and are not designed for monitoring. We present MMonitor, an open-source software platform for real-time analysis and visualization of metagenomic Oxford Nanopore Technologies (ONT) sequencing data. MMonitor includes two components: a desktop application for running bioinformatics pipelines through a graphical user interface (GUI) or command-line interface (CLI) and a web-based dashboard for interactive result inspection. The dashboard provides taxonomic composition over time, quality scores, diversity indices, and taxonomy-metadata correlations. Integrated pipelines enable automated de novo assembly and reconstruction of metagenome-assembled genomes (MAGs). To validate MMonitor, we tracked human gut microbial populations in three bioreactors using 16S rRNA gene sequencing and applied it to whole-genome sequencing (WGS) data to generate high-quality annotated MAGs. We compare MMonitor with other real-time metagenomic tools, outlining their strengths and limitations.}, } @article {pmid41443137, year = {2025}, author = {Chai, D and Wang, Q and Yong, Q and Chen, C and Liao, Y and Pan, R and He, Y and Sun, K and Liu, B and Liu, R and Li, Z}, title = {Multidimensional development of gut-on-a-chip technology: from fabrication processes, models, gut microbiome to gut-organ axis.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {271}, number = {}, pages = {117322}, doi = {10.1016/j.jpba.2025.117322}, pmid = {41443137}, issn = {1873-264X}, abstract = {Gut-on-a-chip (GoC) platforms integrate microfluidics and 3D culture to replicate the intestinal microenvironment, offering physiologically relevant alternatives to traditional models. Coupled with multi-organ chips (e.g., gut-brain/gut-liver axes), they unveil microbiome-regulated systemic crosstalk via metabolite signaling-a key yet unresolved mechanism. This review highlights multidimensional advances in organ-on-chip (OoC) technologies for intestinal research, covering fabrication methods (e.g., soft lithography, bioprinting) and their applications in physiological, patient-derived, or indirectly acquired GoC models. We also emphasize breakthroughs in biomimetic intestinal-microbiome symbiosis and spatiotemporal multi-organ integration (e.g., gut-X axis), enabling emulation of complex inter-organ signaling. Yet, critical challenges persist: reproducibility is limited by fabrication variability and cell heterogeneity; standardization lacks universal benchmarks for physiological relevance; and long-term culture stability (e.g. 7-10 days) is constrained by epithelial senescence and microbial imbalance. These gaps highlight needs for standardized protocols, quality control metrics, and strategies to sustain functional homeostasis. By bridging gaps between traditional models and human biology, GoC technologies establish transformative tools for mechanistic studies and therapeutic discovery in gastroenterology and beyond.}, } @article {pmid41443129, year = {2025}, author = {Sukarni, S and Kunimitsu, M and Ogai, K and Liana, DF and Mahyarudin, M and Aminuddin, M and Mukai, K and Haryanto, H and Jais, S and Oe, M}, title = {Relationship between microbiota and healing status in diabetes-related foot ulcers treated with Trigona honey.}, journal = {Journal of tissue viability}, volume = {35}, number = {1}, pages = {100981}, doi = {10.1016/j.jtv.2025.100981}, pmid = {41443129}, issn = {0965-206X}, abstract = {AIMS: Diabetes-related foot ulcers (DFUs) are a major complication of diabetes, and treatment with honey, which has antimicrobial properties, has been utilized in patients. However, the effects have been shown to vary, with the causes of these differences remaining unclear. Recently, microbiota has been reported to be associated with wound healing. Therefore, we hypothesized that differences in microbiota might explain the variations observed in response to honey. The present study aimed to investigate the relationship between the microbiota and the healing status in DFUs treated with Trigona honey.

METHODS: A cohort study involving 12 DFUs categorized into healing and deteriorating groups was conducted. Wound and peri-wound microbiota observed at baseline and at 1 week later (after starting honey application) were investigated and then compared in the healing status.

RESULTS: Enterococcus was higher in the deteriorating group at baseline in the wound (p = 0.02), while Corynebacterium was higher in the healing group at 1 week later in the peri-wound skin (p = 0.02). Changes in the relative abundance of Prevotella and Brevundimonas in the peri-wound skin significantly differed based on the healing status.

CONCLUSION: The findings suggest that the honey's effects might differ based on the composition of the wound microbiota, and they highlight the bacterial interactions with the changes in the wound and peri-wound skin environment induced by the honey. These results also imply that honey therapy on its own may not be enough for treating DFUs. This study is limited by the small sample size and short follow-up period; further research will need to explore combined treatment strategies and long-term microbiota dynamics to improve DFU management.}, } @article {pmid41443021, year = {2025}, author = {Salamatullah, HK and AboAljadiel, L and Halabi, MH and Alqurashi, S and Aljohani, R and Aljafari, D and Alkhiri, A and Almaghrabi, AA and Makkawi, S}, title = {The association between antimicrobial exposure and subsequent multiple sclerosis risk: A systematic review and meta-analysis.}, journal = {Multiple sclerosis and related disorders}, volume = {107}, number = {}, pages = {106936}, doi = {10.1016/j.msard.2025.106936}, pmid = {41443021}, issn = {2211-0356}, abstract = {BACKGROUND: Multiple Sclerosis (MS) is a complex autoimmune inflammatory disease of the central nervous system with an incompletely understood etiology. Emerging evidence suggests a critical link between gut microbiome disruption and MS pathogenesis, with antibiotics potentially playing a significant role in microbiome alterations. We conducted a systematic review and meta-analysis to explore the relationship between antimicrobial exposure and the risk of developing MS.

METHODS: A comprehensive systematic review was conducted across four electronic databases, searching for studies until March 29, 2025. The meta-analysis included comparative studies examining antibiotic usage frequency prior to MS onset/diagnosis in MS patients versus control group. Adjusted odds ratios (OR) were pooled using the generic inverse variance method with corresponding 95% confidence intervals (CIs).

RESULTS: The analysis encompassed nine reports involving 109,784 participants (23,960 MS patients and 85,824 controls). A statistically significant association was observed between antibiotic exposure and MS odds (OR=1.18; 95% CI [1.03-1.36]; p = 0.02). Data source-based analysis showed that studies with high-quality registry data maintained the association (OR=1.36; 95% CI [1.17-1.58]; p < 0.0001). Time-trend analysis showed significant association when the exposure occurred ≥4 years prior MS onset/diagnosis (OR=1.26; 95% CI [1.19-1.33]). Stratified analysis revealed significant associations for multiple antimicrobial classes, including tetracyclines, macrolides, quinolones, nitrofurantoin, aminoglycosides, metronidazole, sulfonamides, and antimycotics.

CONCLUSION: This meta-analysis reveals a significant association between antimicrobial exposures, particularly those based on high-quality data and occurring at least four years prior to MS onset/diagnosis, and increased MS incidence. Longitudinal, prospective studies are required to conclusively determine whether antibiotic exposure is a true risk factor for MS.}, } @article {pmid41442921, year = {2025}, author = {Guo, H and Li, W and Peng, J and Fan, Y and Yang, S and Mao, H and Wang, Y and Lu, Z}, title = {Bacillus affects Taihe Silky Fowls growth performance, cecal microbiota, and metabolite during growing period.}, journal = {Poultry science}, volume = {105}, number = {2}, pages = {106251}, doi = {10.1016/j.psj.2025.106251}, pmid = {41442921}, issn = {1525-3171}, abstract = {Bacillus, a well-recognized probiotic genus, regulates intestinal microbiota to maintain gut homeostasis and enhance host immunity. Taihe Silky Fowl (Taihe SF)-a high-quality Chinese indigenous chicken breed-has poor disease resistance, limiting its commercial farming efficiency. This study evaluated the effects of four strains (Bacillus subtilis, Bacillus coagulans, Bacillus licheniformis, Clostridium butyricum) on growth performance, antioxidant capacity, intestinal barrier integrity, and cecal microbiota of 3-13-week-old Taihe SF, to identify the optimal strain for this stage. 1,200 3-week-old Taihe SF, with close body weights (45.2 ± 2.1 g, P > 0.05) and health status were randomly divided into 5 groups (6 replicates/group, 40 birds/replicate). Four experimental groups received diets supplemented with B. subtilis, B. coagulans, B. licheniformis, or C. butyricum (10[10] CFU/g, 1000 mg/kg). It was observed that four experimental groups remarkedly decreased (P < 0.05) the feed conversion ratio in Taihe SF from 3 to 13 weeks. The catalase, total antioxidant capacity, and total superoxide dismutase levels in serum experienced a significant rise (P < 0.05) in the BS and CB groups, compared with the CON group, while the content of malondialdehyde significantly decreased (P < 0.05). Compared with CON group, all four experimental groups significantly increased the villus length and reduced the crypt depth in the jejunum (P < 0.05). The level of diamine oxidase in the jejunum saw a notable decline (P < 0.05), and there was an increase in the relative mRNA expression of Occludin, Claudin-1, Claudin-2, and zonula occludens1 within the jejunum. Furthermore, the BS group exhibited a significant enhancement in the relative abundance of Firmicutes in the cecum, accompanied by a marked reduction in the relative abundances of Bacteroidota and Proteobacteria. B. subtilis also led to an elevation of indole-3-propionic acid concentrations in the intestines of Taihe SF. Based on these findings, B. subtilis is deemed the most advantageous among the tested strains for Taihe SF during the 3-13 week growth period.}, } @article {pmid41442918, year = {2025}, author = {Li, R and Quan, T and Chen, Y and Gao, T}, title = {Butyrate improves dextran sulfate sodium-induced imbalance of intestinal stem cell homeostasis in broilers.}, journal = {Poultry science}, volume = {105}, number = {2}, pages = {106307}, doi = {10.1016/j.psj.2025.106307}, pmid = {41442918}, issn = {1525-3171}, abstract = {BACKGROUOND: Intestinal homeostasis is maintained through the ongoing self-renewal and differentiation of intestinal stem cells (ISCs). Butyrate, a microbial metabolite, connects the gut microbiome with the epithelium. This research delves deeper into how butyrate influences ISC to enhance the intestinal mucosal barrier in broilers.

RESULTS: Our research results show that dextran sulfate sodium (DSS)-treated broilers exhibit damaged intestinal villi structure (including reduced villus length and increased crypt depth) and impaired intestinal mucosal barrier, including decreased numbers of goblet cells, mast cells and paneth cells, and MUC2 protein and tight junction protein expression. Importantly, DSS treatment not only reduces the number of ISCs but also hinders their differentiation and proliferation abilities. However, butyrate intervention can effectively improve intestinal mucosal barrier function by restoring the homeostasis of intestinal stem cells.

CONCLUSION: The findings imply that butyrate might promote ISC self-renewal and differentiation, improving the structure and function of the intestinal lining by triggering the Wnt/β-catenin and Notch signaling pathways. The study provides clinical value by highlighting the key role of immunometabolism in intestinal diseases and potential therapeutic targets, and it has broad application prospects in livestock and poultry farming for improving growth performance by enhancing gut health.}, } @article {pmid41442770, year = {2025}, author = {Liu, C and Zhang, L}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e103718}, doi = {10.1002/alz70856_103718}, pmid = {41442770}, issn = {1552-5279}, mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome/genetics ; *Apolipoprotein E4/genetics ; Aged ; *Biomarkers ; *Alzheimer Disease/genetics/microbiology ; Feces/microbiology ; Middle Aged ; }, abstract = {BACKGROUND: The gut-brain axis hypothesis proposes a bidirectional communication network between the gut microbiome and the central nervous system, shaping neuroinflammatory processes linked to Alzheimer's disease (AD). Although the APOE4 allele is the strongest genetic risk factor for AD-raising the likelihood of disease by two- to three-fold with even one copy-its association with the gut microbiome remains underexplored. This gap limits our full understanding of the pathways contributing to AD.

METHOD: We investigated the relationship between APOE4 status and gut microbiome composition in 114 healthy participants (average age: 77, 57% women). Stool samples underwent shotgun metagenomic sequencing. Rigorous quality control steps removed low-quality reads and human DNA contaminants. We performed taxonomic profiling and applied rarefaction to normalize sequencing depth. Alpha diversity (richness and evenness) and beta diversity (unweighted UniFrac-based principal coordinates analysis) were assessed. We then used permutational multivariate analysis of variance, adjusting for demographic and clinical variables, to identify group differences. Differential taxonomic analysis pinpointed bacterial taxa enriched in APOE4 carriers versus non-carriers.

RESULT: Alpha diversity metrics did not differ significantly between APOE4 carriers and non-carriers at the species level (p = 0.070). However, beta diversity analysis showed significant differences in overall community composition after adjusted by the covariates (p = 0.003), and APOE4 carrier status remained significant in PERMANOVA (p = 0.039). Furthermore, subgroup analysis of APOE4 genotypes (2/4, 3/4, 4/4) also revealed significant compositional differences (p = 0.030). Differential taxonomic analysis identified 21 species enriched in APOE4 carriers and 20 species enriched in non-carriers. Among non-carriers, Alistipes finegoldii (p = 0.035) and Odoribacter splanchnicus (p = 0.024) were more abundant. These species are involved in metabolic pathways related to short-chain fatty acid production, which can have anti-inflammatory effects. Their presence suggests a protective gut microbiome-mediated mechanism in individuals without the APOE4 allele.

CONCLUSION: Our findings suggest that APOE4 carriers have distinct gut microbiome patterns that may heighten the risk of neuroinflammation through the gut-brain axis, potentially contributing to AD onset or progression. These results highlight the interplay between genetic risk factors and gut microbial communities. They also underscore the potential for microbiome-targeted interventions to reduce AD risk in genetically susceptible individuals.}, } @article {pmid41442682, year = {2025}, author = {Monzón, ÁRR and Ramos, JFO and Narvaez, YC and Rosales, MH}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e097688}, doi = {10.1002/alz70856_097688}, pmid = {41442682}, issn = {1552-5279}, mesh = {Humans ; *Biomarkers/metabolism ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; *Alzheimer Disease/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Metabolomics ; Middle Aged ; Adult ; Aged ; Young Adult ; }, abstract = {BACKGROUND: T2DM and AD are major public health concerns characterized by metabolic and cognitive impairments, respectively, with growing evidence suggesting that gut microbiota alterations contribute to their pathogenesis. Metagenomic and metabolomic analyses provide valuable insights into the microbiota's role in glucose regulation, inflammation, and dementia risk, offering potential for early diagnosis and targeted interventions. Understanding the interplay between gut microbiota and metabolic pathways could lead to novel therapeutic strategies to improve patient outcomes.

METHOD: A descriptive study with a quantitative approach, cross-sectional observational comparative, of relational scope will be conducted. The study population will be segmented into four groups and two subgroups: Control (CTRL) (n = 30), Type 2 Diabetes Mellitus (T2DM) (n = 30), Alzheimer's Disease (AD) without T2DM (n = 30), and AD with T2DM (n = 30). Subgroups include Control (Young adults) (n = 30) and T2DM (Young adults) (n = 30). All groups will undergo characterization, which includes blood chemistry, and clinical, mental, nutritional, and anthropometric evaluations. We obtained urine and stool samples for DNA extraction and library preparation. We used Magnetic Resonance Mass Spectrometry (MRMS) for metabolomic analysis, which uses eluents to detect metabolites. We will apply MetaHit bioinformatics tools to assess sample diversity and perform metabolomic analysis in RStudio.

RESULT: The study revealed distinct patterns of intestinal dysbiosis and metabolic changes in patients with T2DM and AD, categorized by age. A comprehensive taxonomic and functional representation of the gut microbiome highlighted condition-specific differences. Significant correlations were found between microbiological, metabolomic, and clinical biomarkers, particularly those related to cognitive decline. Key metabolic pathways and molecular processes underlying dysbiosis were identified. Fecal metabolite analysis uncovered distinctive compounds such as (+/-)-Ethylketocyclazocine, (-)-Quebrachamine, and (-)-jasmonoyl-L-isoleucine, while urinary metabolites like (Phenylthio) acetic acid and 2,3-Diketo-L-gulonate showed disease-associated variations. These findings support the development of personalized interventions to mitigate cognitive decline through microbiota and metabolomic profile modifications.

CONCLUSION: The study identifies distinct gut microbiota and metabolic patterns linked to cognitive decline in T2DM and AD, offering insights into disease mechanisms and supporting the development of personalized therapeutic strategies to improve patient outcomes.}, } @article {pmid41442661, year = {2025}, author = {Ivanich, K and Yackzan, A and Chang, YH and Aware, C and Govindarajan, M and Kramer, S and Yanckello, LM and Ericsson, A and Lin, AL}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e104646}, doi = {10.1002/alz70855_104646}, pmid = {41442661}, issn = {1552-5279}, mesh = {Animals ; *Gastrointestinal Microbiome ; Female ; Mice, Transgenic ; Male ; Apolipoprotein E4/genetics ; *Brain/metabolism ; Mice ; *Diet, Ketogenic ; *Alzheimer Disease/genetics/metabolism ; Apolipoprotein E3/genetics ; Metabolomics ; Disease Models, Animal ; }, abstract = {BACKGROUND: The apolipoprotein ε4 (APOE4) polymorphism is the primary genetic risk factor for Alzheimer's disease (AD). APOE4 carriers exhibit early deficits in brain metabolism and gut microbiome diversity, both elevating AD risk. This study investigated whether a ketogenic diet (KD) can restore brain metabolism and gut microbiome diversity in young, asymptomatic APOE4-positive mice, while also assessing sex-based differences, given the higher AD risk in females. Comparisons were also made with APOE3 mice, which carries a neutral AD risk, to determine genotype differences. Additionally, a correlative analysis explored relationships between microbes and brain metabolites, identifying potential therapeutic and screening targets for AD risk mitigation.

METHOD: Female and male APOE3 (n =  44) and APOE4 (n =  39) transgenic mice were randomly assigned to a control diet (5.1% fat) or a KD (75.1% fat). Mice ate ad libitum for 16 weeks, starting at 12 weeks of age. Brain tissue was collected for untargeted metabolomics (UPLC-MS/MS via Metabolon Inc.), and fecal samples were collected for 16s rRNA shotgun metagenomic sequencing (CosmosID). Gut microbiome species richness and evenness were measured using Shannon index (α-diversity). Bray-Curtis dissimilarity (β-diversity) measured intra-subject dissimilarity for pre- and post-diet gut microbiome composition, and Spearman's correlation heatmaps linked metabolites and microbes to correlations within amino acid, energy, and lipid metabolic pathways.

RESULT: The KD restored brain metabolism in APOE4 females by recovering levels of metabolites associated with mitochondrial function (Figure 1A) and glutamate metabolism (Figure 1B), while exerting variable effects on these metabolites in APOE3 mice and APOE4 males. The KD increased species' richness and evenness in APOE4 females (Figure 2A) and balanced microbiome composition in APOE4 mice, as indicated by limited changes pre- and post-dietary intervention (Figure 2B). Correlation analyses revealed that Bacteroides intestinalis, Clostridium sp. ASF502, Lachnospiraceae bacterium A4, Lactobacillus johnsonii, Lactobacillus reuteri had significant associations with metabolites involved in amino acids and energy (Figure 3A) and lipid (Figure 3B) pathways.

CONCLUSION: The KD effectively restored brain metabolism and gut microbiome diversity in APOE4 female mice. These effects were absent in APOE3 mice and APOE4 males. Correlations between microbes and metabolites provide potential targets for AD interventions and risk assessment.}, } @article {pmid41442536, year = {2025}, author = {Kazen, AB and Umfleet, LG and Aboulalazm, FA and Cohen, AD and Terhune, S and Mason, L and Obarski, S and Franczak, M and Kindel, T and Wang, Y and Kirby, J}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e097652}, doi = {10.1002/alz70856_097652}, pmid = {41442536}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; Aged ; Biomarkers ; Magnetic Resonance Imaging ; Neuropsychological Tests/statistics & numerical data ; Feces/microbiology ; *Dysbiosis/microbiology ; *Cerebrovascular Circulation/physiology ; Middle Aged ; Cognition ; }, abstract = {BACKGROUND: Gut dysbiosis and cerebrovascular disease have both been implicated in Alzheimer's disease (AD) progression and pathophysiology. However, the interplay between them is unclear. The goal of this study was to identify relationships between gut microbiota (GMB), cerebrovascular functioning, and cognition in patients diagnosed with amnestic mild cognitive impairment (aMCI) compared to cognitively unimpaired older adult controls.

METHODS: Participants (N = 14 aMCI and 10 controls) provided fecal samples for 16S and shotgun metagenomics GMB sequencing, underwent an MRI, and completed neuropsychological tests. For MRI, cerebral vascular reactivity (CVR), cerebral blood flow (CBF) and arterial transit time (ATT) were assessed. Spearman rho correlational analysis was used to evaluate relationships between discriminatory microbial taxa, cerebrovascular metrics, and cognition.

RESULTS: Sequencing revealed differentially abundant bacterial and viral taxa distinguishing aMCI from controls. Spearman correlations revealed that bacteria known to induce inflammation were negatively associated with cognition and cerebrovascular function, whereas bacteria associated with a healthy gut microbiome had positive associations with cognitive and cerebrovascular function. For example, Alistipes indistinctus, which depletes intestinal urate levels was enriched in aMCI and had significant negative correlations with Trail Making Test-B (TMT-B; rs=-.587) and category fluency (CF) scores (rs=-.422), CVR (rs=-.437), and CBF (rs=-.546). Bilophila wadsworthia was negatively associated (trend-level) with CVR and CBF, and significantly correlated with TMT-B (rs = -.499) and category fluency (rs = -.503). The bile acid modifying bacterium, Turicibacter sp., had a significant positive correlation with CBF (rs=.423). Finally, we found that several bacteriophages had significant correlations with cognitive and cerebrovascular measures, such as a B. wadsworthia phage that was enriched in aMCI and had significant negative correlations with TMT-B (rs=-.491), delayed recall (rs=-.589), and CVR (rs=-.474). Further, this phage contained an acyl-coA synthetase capable of influencing central metabolism.

CONCLUSIONS: Consistent with previous research, we found that persons with aMCI have an altered gut microbiome relative to controls. Further, we demonstrate through metagenomics sequencing that both bacterial and viral taxa are associated with cognitive and neurovascular functioning in aMCI. Knowledge about the relationships between the microbiota, cognition, and cerebrovascular function paves the way for future studies cross-sectional and longitudinal studies.}, } @article {pmid41441924, year = {2025}, author = {Dias, V and Vaigankar, D and Gaonkar, SK and Thakur, NL}, title = {Mudflat halophilic microbiome: research progress in biotechnology and eco-environmental sustainability.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {1}, pages = {3}, pmid = {41441924}, issn = {1573-0972}, } @article {pmid41441899, year = {2025}, author = {Lee, JT and Ngoi, S and Deng, B and Hill, M and He, K and Yang, Y and Liu, B}, title = {Commensal bacteria antigen-mediated immune response enhances anti-tumor immunity.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {75}, number = {1}, pages = {28}, pmid = {41441899}, issn = {1432-0851}, support = {AI125859//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Melanoma, Experimental/immunology/therapy/pathology ; Tumor Microenvironment/immunology ; *Antigens, Bacterial/immunology ; *Lung Neoplasms/immunology/secondary ; Cell Line, Tumor ; Immunotherapy/methods ; Female ; Gastrointestinal Microbiome/immunology ; Th17 Cells/immunology ; Humans ; }, abstract = {Immunotherapy has transformed cancer treatments, but the majority of cancer patients would inevitably develop resistance to immunotherapy. Th17 cells play complex but crucial roles in anti-cancer immune response, although their therapeutic potential remains underutilized. Segmented filamentous bacteria (SFB) function as prototypical commensal bacteria that can induce intestinal Th17 cells and impact host immune response. In this study, we investigated how SFB antigen-mediated immune responses modify the tumor microenvironment and enhance anti-tumor efficacy through a coordinated gut-lung immunological axis. We engineered B16F1 melanoma cells to express either the SFB3340 epitope (B16-3340, an I-A[b]-restricted epitope derived from SFBNYU_003340 and recognized by 7B8 TCR) or a control vector (B16-MEM) to evaluate SFB antigen effects on tumor immunogenicity. We found that expression of the SFB epitope in cancer cells decreased the number of lung tumor nodules, and SFB colonization further reduced tumor growth in a lung metastasis model. In addition, Th1, Th17, and CD8[+] Tc1 cells were all increased in the lungs of the B16-3340 tumor-bearing mice compared with B16-MEM control tumor-bearing mice without triggering a compensatory expansion of immunosuppressive Tregs. Interestingly, SFB triggers systemic metabolic changes and an increase metabolites from aromatic amino acid degradation pathways, providing biochemical evidence for a functional gut-lung conduit, which integrates innate microbial detection with adaptive tumor-specific immunity. Our research provides evidence to further investigate and develop novel cancer immunotherapies that utilize microbial antigens and microbiome modifications to improve patient outcomes.}, } @article {pmid41441714, year = {2025}, author = {Seong, H and Yoon, JG and Nham, E and Choi, YJ and Noh, JY and Cheong, HJ and Kim, WJ and Lim, S and Song, JY}, title = {Vaccine Platform-Dependent Differential Impact on Microbiome Diversity: Potential Advantages of Protein Subunit Vaccines.}, journal = {Vaccines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/vaccines13121248}, pmid = {41441714}, issn = {2076-393X}, support = {Q2208691//Joon Young Song/ ; Q2208671//Sooyeon Lim/ ; Q2208341//Hye Seong/ ; }, abstract = {Background: The COVID-19 pandemic accelerated the development of diverse vaccine platforms, including mRNA, adenoviral vector, and protein subunit vaccines. Given the growing evidence that the gut microbiome modulates vaccine-induced immunity, this study compared the effects of a protein subunit vaccine (NVX-CoV2373), an mRNA vaccine (BNT162b2), and an adenoviral vector vaccine (ChAdOx1) on gut microbiome diversity following booster vaccination. Methods: We conducted a prospective cohort study involving 35 healthy adults who received an NVX-CoV2373 booster. Stool and blood samples were collected before vaccination and three weeks afterward. Gut microbiome profiles were analyzed using 16S rRNA gene sequencing, and the results were compared with our previous cohorts who received BNT162b2 or ChAdOx1 vaccines. Results: The NVX-CoV2373 booster was associated with a significant increase in the Shannon diversity index (p = 0.027), indicating enhanced alpha diversity. This finding contrasts with the decrease or absence of significant short-term change observed following repeated administrations of adenoviral vector and mRNA vaccines, respectively. Notably, NVX-CoV2373 vaccination was accompanied by an increased relative abundance of beneficial taxa such as Bacteroides fragilis and a decrease in Prevotella bivia. In comparison, repeated ChAdOx1 doses resulted in a sustained reduction in alpha diversity, whereas BNT162b2 showed a transient post-booster rise followed by a long-term decline in species richness. Conclusions: In the booster setting, the protein subunit vaccine NVX-CoV2373 exerted a distinct and favorable effect on gut microbiome diversity, increasing alpha diversity in contrast to the patterns observed with mRNA and adenoviral vector booster vaccines.}, } @article {pmid41441257, year = {2025}, author = {Sutton, SC and Hills, RD}, title = {Role of Nanoplastics in Decreasing the Intestinal Microbiome Ratio: A Review of the Scope of Polystyrene.}, journal = {Toxics}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/toxics13121036}, pmid = {41441257}, issn = {2305-6304}, abstract = {Micro- and nanoplastics (MNPs) are increasingly recognized as emerging intestinal toxicants. This scoping review maps and integrates evidence from 56 studies (47 primary and 11 review articles, 2000-mid-2025) on how nanoplastics, particularly ≤100 nm polystyrene, disrupt gut homeostasis. The evidence consistently supports a three-stage mechanistic cascade: 1. Oxidative-stress initiation-Nanoplastics generate reactive oxygen species (ROS) and suppress antioxidant defenses, producing redox imbalance in intestinal tissue and commensal bacteria. 2. Barrier dysfunction-Resulting oxidative injury reduces tight-junction proteins, depletes mucus-secreting goblet cells, and activates inflammatory signaling (NF-κB, TLR4). 3. Microbiome reconfiguration-The altered intestinal microenvironment favors Gram-negative expansion and depletion of Gram-positive commensals, observed as decreases in the Firmicutes/Bacteroidetes (F/B) and Gram+/Gram- ratios. High-dose nanoplastic exposures reproducibly induced these effects in mice and zebrafish, whereas environmentally realistic, low-dose PET fragments produced minimal dysbiosis. Functionally important taxa-short-chain-fatty-acid producers (Faecalibacterium, Roseburia) and mucin degraders (Akkermansia muciniphila)-were consistently reduced, linking microbial shifts to epithelial injury and inflammatory tone. Together, these findings define an oxidative-barrier-microbiome axis as the dominant pathway of nanoplastic-induced intestinal disruption. Future work should emphasize environmentally relevant exposures, multi-omics functional endpoints, and mechanistic models that integrate oxidative stress, epithelial pathology, and microbiome ecology to guide realistic human-health risk assessment.}, } @article {pmid41441238, year = {2025}, author = {Qin, J and Jiang, S and Zhang, Z and Wang, J and Li, Y and Li, Y and Zhang, H and Li, C and Ma, H and Wang, J}, title = {Involvement of the Gut-Lung Axis in LMW-PAHs-Induced Pulmonary Inflammation.}, journal = {Toxics}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/toxics13121017}, pmid = {41441238}, issn = {2305-6304}, support = {81828011//National Natural Science Foundation of China/ ; 72064002//National Natural Science Foundation of China/ ; 25JRRA1273//Gansu Joint Reasearch Fund/ ; lzuyxcx-2022-122//Medical Innovation and Deveopment Project of Lanzhou University/ ; lzujbky-2024-14//Fundamental Research Funds for the Central Universities/ ; lzujbky-2024-it21//Fundamental Research Funds for the Central Universities/ ; }, abstract = {Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants recognized for their toxicological significance. Increasing evidence suggests that chronic exposure to low-molecular-weight PAHs (LMW-PAHs) contributes to heightened disease vulnerability and immune dysregulation, particularly among rural female populations. Recent studies have further linked a significant association between PAH exposure and gut microbiome (GM) modifications. Considering the common embryonic origin of the intestinal and respiratory systems, cross-organ communication under conditions of PAH exposure warrants deeper exploration. Although current gut-lung axis research largely emphasizes microbial metabolites such as short-chain fatty acids and bile acids, the contribution of arachidonic acid (AA) metabolites in LMW-PAH-induced pulmonary inflammation via this axis remains poorly defined. To address this knowledge gap, we developed an animal model employing integrated 16S rRNA sequencing and metabolomics approaches to systematically examine phenanthrene (Phe) and fluorene (Flu) induced GM compositional shifts and associated metabolic reprogramming. Through comprehensive profiling, we identified candidate microorganisms and metabolites potentially involved in dysbiosis-mediated pulmonary inflammation, thereby elucidating the mechanistic basis of Phe and Flu-associated health risks.}, } @article {pmid41441197, year = {2025}, author = {Logan, AC and Berryessa, CM and Greeson, JM and Mishra, P and Prescott, SL}, title = {The Metabolic Mind: Revisiting Glucose Metabolism and Justice Involvement in Neurolaw.}, journal = {NeuroSci}, volume = {6}, number = {4}, pages = {}, doi = {10.3390/neurosci6040120}, pmid = {41441197}, issn = {2673-4087}, abstract = {Neuropsychiatric interest in the relationship between glucose metabolism and criminal behavior dates back nearly a century. In particular, hypoglycemia was thought to play a causative role in some criminal acts, especially non-planned incidents involving impulsivity and in-the-moment risk-taking or aggression. While interest in carbohydrate metabolism in forensic populations faded in the 1990s, recent years have witnessed a renewed interest in metabolic dysfunction, mental health, and cognition. This area of research has grown increasingly robust, bolstered by mechanistic discoveries, epidemiological work, and intervention trials. Advances in microbiome (legalome) sciences, aided by omics technologies, have allowed researchers to match objective markers (i.e., from genomics, epigenomics, transcriptomics, and metabolomics) with facets of cognition and behavior, including aggression. These advances, especially the concentrated integration of microbiome and omics, have permitted novel approaches to the subject of glucose metabolism, and cast new light on older studies related to justice involvement. With current technologies and contemporary knowledge, there are numerous opportunities for revisiting the subject of glucose metabolism in the context of neurolaw. Here in this viewpoint article, we reflect on the historical research and emergent findings, providing ideation for future directions.}, } @article {pmid41441091, year = {2025}, author = {Hu, J and Bao, G and Hu, W and Wu, J and Du, J and Zhou, H and Zhao, Y and Xing, N and Liu, W and Fu, Z}, title = {Molecular Trojan Effect of Microplastic Diethyl Phthalate Drives Multiscale Stress Vortex through Interfacial Engineering in Cold Agroecosystems during Freeze-Thaw Cycles.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.5c16751}, pmid = {41441091}, issn = {1936-086X}, abstract = {Global climate change exacerbates the synergistic effects of freeze-thaw (FT) cycles and emerging pollutants in cold-region ecosystems. To elucidate their multidimensional stress mechanisms, this study integrated a "seed-to-seed" full-life-cycle soil cultivation experiment (120 days), physio-ecological assays, molecular dynamics (MD) simulations, and multiomics technologies to systematically analyze the cascading damage mechanisms in rye induced by the combined stress of FT, microplastics (MPs), and diethyl phthalate (DEP). Long-term experiments demonstrated that MPs + DEP copollution led to approximately 27.5% reduction in spike length, over 36% decrease in 1000-grain weight, and an 18-23 d delay in flowering time; these indicators worsened further with the superposition of FT, indicating significant inhibition of reproductive growth. At the physiological mechanism level, DEP competitively inhibited ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity, impeding carbon assimilation; MPs induced thylakoid membrane lipid peroxidation, disrupting the electron transport chain; and FT exacerbated chloroplast ultrastructural damage, collectively causing a 41.1% decrease in the photosynthetic rate (Pn), a 65.8% reduction in stomatal conductance (Gs), and a 140% increase in the malondialdehyde (MDA) content. MD simulations revealed that FT enhanced the binding stability of nonspecific lipid-transfer protein (nsLTP) with DEP, promoting the upward translocation of pollutants, with the highest DEP residue in grains reaching 0.306 ± 0.038 mg/kg, posing a potential food safety risk. Metabolomic analysis indicated that MPs activated genes promoting cell wall fibrosis defense, whereas DEP inhibited lipoxygenase, leading to lipid accumulation, with Mg[2+] loss and S accumulation exacerbating the oxidative damage cascade. The endophytic microbiome facilitated cooperative pollutant degradation via the Pseudomonas acidovorax module, achieving partial ecological compensation. This study reveals a "stress compensation-metabolic imbalance-oxidative damage" vicious cycle mechanism, which advances our understanding of composite pollution risks in high-latitude farmland and the synergistic effects of climate change and pollutants.}, } @article {pmid41441029, year = {2025}, author = {Carbonell-Garzón, E and Ibanco-Cañete, R and Sanchez-Jerez, P and Egea, FCM}, title = {Osmolytes vs. Anabolic Reserves: Contrasting Gonadal Metabolomes in Two Sympatric Mediterranean Sea Urchins.}, journal = {Metabolites}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/metabo15120787}, pmid = {41441029}, issn = {2218-1989}, support = {GASTERRA 2024//CONVOCATORIA DEL PROGRAMA PROPIO DEL CENTRO DE GASTRONOMÍA DEL MEDITERRÁNEO (Gasterra 2023-24) UA_DENIA PARA EL FOMENTO DE LA I+D+i EN El ÁMBITO DE LA GASTRONOMÍA (GASTERRA 2024)/ ; }, abstract = {Background an Objectives: The Mediterranean sea urchins Paracentrotus lividus and Arbacia lixula co-occur on shallow rocky reefs but display contrasting ecological and physiological traits. We compared their gonadal metabolomes to identify species-specific metabolic strategies. Methods: High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy to intact gonadal tissues, combining multivariate chemometric modelling with targeted integration, boxplot-based univariate analysis and pathway analysis. Results:A. lixula showed an osmolyte- and redox-oriented phenotype with elevated betaine, taurine, sarcosine, trimethylamine (TMA), trimethylamine N-oxide (TMAO), carnitine, creatine, malonate, methylmalonate, uridine and xanthine. In contrast, P. lividus exhibited an amino-acid-enriched anabolic profile dominated by lysine, glycine and glutamine, together with higher levels of formaldehyde, methanol and 3-carboxypropyl-trimethylammonium. Pathway analysis indicated that A. lixula metabolites mapped onto glycine/serine-threonine metabolism and the folate-linked one-carbon pool, whereas P. lividus metabolites were enriched in glyoxylate/dicarboxylate, nitrogen and amino-acid pathways. These contrasting osmolyte-C1 versus nitrogen-amino-acid strategies are compatible with species-specific host-microbiota metabolic interactions inferred from published microbiome data. Conclusions: Overall, our results support a framework in which A. lixula adopts a resilience-oriented osmolyte strategy and P. lividus an efficiency-oriented anabolic strategy, highlighting HR-MAS NMR metabolomics as a powerful approach to investigate adaptive biochemical diversity in marine invertebrates.}, } @article {pmid41441026, year = {2025}, author = {Godsey, TJ and Eden, T and Emerson, SR}, title = {Ultra-Processed Foods and Metabolic Dysfunction: A Narrative Review of Dietary Processing, Behavioral Drivers and Chronic Disease Risk.}, journal = {Metabolites}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/metabo15120784}, pmid = {41441026}, issn = {2218-1989}, abstract = {Background/Objectives: Ultra-processed foods (UPFs) have become a dominant component of the modern diet, paralleling the rise in obesity and chronic disease prevalence worldwide. This narrative review aims to synthesize evidence on how dietary processing and UPF consumption interacts with dietary quality, energy balance, and biological pathways to influence metabolic health. Methods: We performed a targeted literature search of peer-reviewed articles and authoritative reports examining UPF definition (via the NOVA classification), global consumption patterns, behavioral drivers of overconsumption, nutrient composition, and mechanistic links to metabolic dysfunction. Emphasis was placed on recent human and animal research relating UPFs to obesity, cardiometabolic outcomes, inflammation and gut microbiome alterations. Results: High UPF intake is consistently associated with reduced diet quality (higher saturated fat, sugar, sodium; lower fiber and micronutrients), increased energy density, faster eating rates and activation of reward pathways. These factors facilitate excessive energy intake and adiposity, promoting metabolic dysregulation, chronic low-grade inflammation, hormonal disturbances and gut microbiome shifts. While cross-sectional and cohort evidence is extensive, causal intervention trials and mechanistic human work remain limited. Conclusions: The accumulated evidence suggests that UPFs may influence chronic disease risk through their unbalanced nutrient profiles and through additional effects introduced by industrial processing. To translate these insights into public health strategies, future work should prioritize real-world intervention studies to reduce UPF consumption and examine resulting effects on energy balance, inflammation and gut health.}, } @article {pmid41441004, year = {2025}, author = {Alabi, JO and Kholif, AE and Ike, KA and Okedoyin, DO and Adelusi, OO and Wuaku, M and Anotaenwere, CC and Enikuomehin, JM and Oderinwale, OA and Adebayo, JO and Gentry-Apple, AR and Anele, UY}, title = {Rumen Fluid Metabolomics and Microbiome Profiling of Dairy Cows Fed Combinations of Prebiotics, Essential Oil Blend, and Onion Peel Using the RUSITEC System.}, journal = {Metabolites}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/metabo15120762}, pmid = {41441004}, issn = {2218-1989}, support = {NC.X338-5-21-120-1//United States Department of Agriculture/ ; }, abstract = {BACKGROUND AND OBJECTIVES: Dairy products provide vital energy, high-quality protein, and micronutrients for over six billion people worldwide, with dairy cows contributing nearly 81% of global milk production. Sustainable strategies to enhance productivity are therefore critical. Feed additives such as essential oil blends (EOB), onion peel (OPE), and prebiotics including mannan oligosaccharides (MOS) and galacto-oligosaccharides (GOS) have been proposed to improve rumen fermentation, modulate microbial ecology, and mitigate greenhouse gas emissions. This study evaluated the combined effects of EOB, OPE, MOS, and GOS on rumen metabolism using the rumen simulation technique (RUSITEC).

MATERIALS AND METHODS: Rumen inoculum from three cannulated Holstein Friesian cows was incubated across 16 vessels (four treatments × four replicates) for nine days. Treatments included a control (CON; TMR only), GEO (TMR + GOS + EOB + OPE), MEO (TMR + MOS + EOB + OPE), and OLEO (TMR + a 1:1 mixture of GOS and MOS + EOB + OPE). Additives were included at 3 µL/g TMR for EOB and 30 mg/g TMR (3% w/w) for OPE, GOS, MOS, or OLG. Rumen effluents were collected for untargeted metabolomic profiling by liquid chromatography-mass spectrometry, identifying 661 metabolites.

RESULTS: Partial least squares-discriminant analysis revealed clear separation between CON and additive groups, confirming distinct metabolic shifts. GEO primarily enhanced tryptophan, tyrosine, and purine metabolism; MEO stimulated phosphonate and pyrimidine pathways and bile acid biosynthesis; OLEO promoted phosphonate, nicotinamide, and taurine metabolism. Microbial analysis showed enrichment of taxa such as Lachnospira, Succinivibrionaceae, Macellibacteroides, Lysinibacillus, and Christensenellaceae, indicating complementary effects on fermentation and microbial stability.

CONCLUSIONS: These results demonstrate that dietary supplementation with GEO, MEO, or OLEO modulates rumen metabolism and microbial ecology without impairing fermentation, supporting improved nutrient utilization, antioxidant defenses, and metabolic resilience in dairy cows, with potential benefits for productivity and sustainability.}, } @article {pmid41440958, year = {2025}, author = {Rahmani, AR and Madani, SA and Aminov, E and Gogokhia, L and Bench, T and Kalogeropoulos, A}, title = {Heart Failure and Cognitive Impairment Through the Lens of the Gut Microbiome: A Narrative Review.}, journal = {Journal of personalized medicine}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/jpm15120595}, pmid = {41440958}, issn = {2075-4426}, abstract = {Heart failure (HF) affects over 55 million individuals globally, with prevalence projected to exceed 11 million in the United States by 2050 and is increasingly recognized as a systemic disorder extending beyond hemodynamic dysfunction to encompass profound alterations in neural and gut physiology. Cognitive impairment affects nearly half of HF patients and represents a major determinant of morbidity, self-care capacity, and mortality. Recent advances suggest that the gut microbiome serves as a pivotal intermediary in the heart-brain crosstalk, influencing neurocognitive outcomes through inflammatory, metabolic, and neurohumoral pathways. Dysbiosis in HF disrupts intestinal barrier integrity, facilitating translocation of endotoxins and microbial metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids, which in turn modulate neuroinflammation, cerebral perfusion, and neuronal signaling. The gut-heart-brain axis provides an integrative framework linking HF and cognitive impairment pathophysiology through dysbiosis-driven systemic inflammation and metabolite dysregulation. Gut-derived biomarkers and microbiome-targeted interventions represent promising strategies for detection of early alterations and precision treatment, highlighting the urge for prospective, multi-omics studies to establish causality and therapeutic efficacy. This review synthesizes current evidence connecting gut microbiome dysbiosis and metabolite alterations to both HF and cognitive impairment pathophysiology and proposes translational strategies for integrating microbiome-targeted therapies in HF patients with cognitive dysfunction.}, } @article {pmid41440831, year = {2025}, author = {Kuehn, JF and Zhang, Q and Heston, MB and Kang, JW and Harding, S and Davenport-Sis, NJ and Kerby, RL and Schiffmann, EC and Wheeler, JL and Clements, E and Shankar, S and Mickol, A and Zemberi, J and Chow, H and Zhang, E and Harpt, J and Mushtaque, A and Yoo, M and Cook, A and Carlsson, CM and Johnson, SC and Asthana, S and Zetterberg, H and Blennow, K and Ulland, TK and Bendlin, BB and Rey, FE}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 2}, number = {}, pages = {e098071}, doi = {10.1002/alz70856_098071}, pmid = {41440831}, issn = {1552-5279}, mesh = {Humans ; *Biomarkers/cerebrospinal fluid ; Male ; *Alzheimer Disease/metabolism/diagnosis ; Female ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Feces/chemistry/microbiology ; Aged ; Middle Aged ; Cohort Studies ; Metagenome ; }, abstract = {BACKGROUND: Short-chain fatty acids (SCFA), including acetate, propionate, and butyrate, are abundant gut bacterial metabolites produced via the fermentation of dietary fibers and resistant starch. Several lines of evidence, particularly in preclinical mouse models, suggest a protective role of SCFA against Alzheimer's Disease (AD) pathology. In one study, supplementation of mice with tributyrin, a butyrate prodrug, significantly attenuated AD pathology. However, the relationships between SCFA, the bacterial taxa that produce them, and AD biomarkers require further elucidation in humans.

METHOD: We assessed gut metagenomes and SCFA levels in fecal samples from 213 cognitively unimpaired Microbiome Alzheimer's Risk Study (MARS) participants (Table 1). The cohort was co-enrolled in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention, which track preclinical disease progression in middle-aged and older adults at risk for AD. We sequenced DNA extracted from 213 fecal samples (one sample per participant, 30 million reads per sample), created metagenome-assembled genomes (MAGs), and annotated their functions. We measured levels of the major SCFA in fecal samples using headspace gas chromatography. We performed multiple linear regressions between levels of cerebrospinal fluid (CSF) AD biomarkers and each SCFA or MAG, controlling for age, sex, body mass index, and APOE genotype.

RESULT: We found an inverse association between amyloid positive status (CSF Aꞵ42/Aꞵ40 <0.046) and MAGs encoding propionate or butyrate production pathways. Fecal acetate, propionate, and butyrate levels were reduced in females and in participants with amyloid-positive status. Mediation analysis detected a trend indicating that butyrate may mediate the inverse relationship between MAGs with butyrate production pathways and amyloid positive status.

CONCLUSION: Relative abundances of MAGs encoding enzymes for propionate and butyrate production were reduced in amyloid-positive participants in a cognitively unimpaired human cohort enriched for AD risk. These results, combined with the extensive literature in preclinical AD mouse models, suggest that SCFA may play a causal role in AD progression.}, } @article {pmid41440729, year = {2025}, author = {Hirji, I and John, D and Jith, J and Khoshnaw, H and Ganeshananthan, M}, title = {Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults.}, journal = {Geriatrics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, doi = {10.3390/geriatrics10060158}, pmid = {41440729}, issn = {2308-3417}, abstract = {BACKGROUND: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness.

CASE PRESENTATIONS: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk.

DISCUSSIONS: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings.

CONCLUSIONS: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults.}, } @article {pmid41440663, year = {2025}, author = {Gong, W and Chen, M and Lai, Y and Yang, D and Soares, MA and Gond, SK and Li, H}, title = {Deciphering the Role of Reshaped Fungal Microbiome in Cadmium Accumulation in Rice Grains.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/jof11120837}, pmid = {41440663}, issn = {2309-608X}, support = {202403AP140035//Yunnan International Joint Laboratory of Research and Development of Crop Safety Produc-tion on Heavy Metal Pollution Areas/ ; 202501AS070148//Yunnan Fundamental Research Projects/ ; 42267059//Natural Science Foundation of China/ ; KUST-AN2023006Y//Medical Joint Special Project of Kunming University of Science and Technology-The First People's Hospital of Anning/ ; }, abstract = {Rice cadmium (Cd) contamination is a serious threat to global food security and human health. Plant-associated microbiomes are known to affect Cd accumulation in plants. However, the response of the rice microbiome to Cd contamination and its role in modulating grain Cd accumulation remain poorly understood. In the present study, the responses of the rhizospheric fungi (RF) community and seed endophytic fungi (SEF) community to the soil physiochemical properties of rice from moderately (MC) and severely (SC1 and SC2) Cd-contaminated paddies were investigated. Moreover, the effects of soil physiochemical properties, RF community and SEF community on grain Cd accumulation were analyzed through correlation analysis. The results showed that the Cd concentration in rice grains from SC2 exceeded the food safety standard of China and was higher than that of SC1 and MC. The Cd concentration in rice grains was positively correlated with the soil-available Cd concentration, while being negatively correlated with the available nutrient elements and pH value of soil. In addition, it was found that the diversity of RF increased with the soil-available Cd concentration, while the diversity and richness of SEF decreased with the soil-available Cd concentration. Moreover, the RF community was influenced by soil physiochemical properties. The Spearman correlation analysis showed that the soil-available Cd was positively correlated with RF Sebacina, Clonostachys, Acremonium, Talaromyces and Fusarium, and most of them were related to grain Cd concentration, while unclassified SEF Pleosporales and Xylariales were associated with grain Cd concentration. These results suggested that Cd stress triggered a niche-specific response of the rice fungal microbiome. The fungi related to soil Cd availability and rice grain Cd accumulation may have a great potential application in food safety production in Cd-contaminated soil.}, } @article {pmid41440534, year = {2025}, author = {Orjichukwu, CK and Orjichukwu, RO and Akpunonu, PK and Ugwu, PC and Nnabuife, SG}, title = {Microbiome and Heart Failure: A Comprehensive Review of Gut Health and Microbiota-Derived Metabolites in Heart Failure Progression.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, doi = {10.3390/medsci13040302}, pmid = {41440534}, issn = {2076-3271}, mesh = {Humans ; *Heart Failure/microbiology/metabolism/physiopathology ; *Gastrointestinal Microbiome/physiology ; Disease Progression ; Dysbiosis/microbiology ; Probiotics ; Methylamines/metabolism ; Animals ; }, abstract = {A multifaceted clinical disease, heart failure (HF) is typified by decreased cardiac function and systemic symptoms caused by anatomical or functional abnormalities in the heart. Although traditional studies have concentrated on hemodynamic and neurohormonal processes, new data highlight the vital role that the gut microbiota and its byproducts play in the pathogenesis of HF. An imbalance in the microbial structure known as gut dysbiosis is common in HF patients and is linked to increased gut permeability, systemic inflammation, and changed bioactive metabolite synthesis. Prominent metabolites generated by the microbiota, including phenylacetylglutamine, short-chain fatty acids (SCFAs), secondary bile acids, and trimethylamine N-oxide (TMAO), have a major impact on endothelial function, cardiac remodeling, and inflammation. Together with gut-derived lipopolysaccharides, these metabolites interact with host systems to exacerbate the course of HF. Further impacting HF outcomes are comorbidities such as diabetes, obesity, and chronic renal disease, which intensify gut dysbiosis. The importance of metabolites originating from the microbiota in the progression of HF is highlighted in this review, which summarizes recent findings regarding the gut-heart axis. Additionally, it investigates how dietary changes, probiotics, prebiotics, and multi-omics techniques can all be used to improve the management of HF. This thorough analysis emphasizes the necessity of integrative therapy approaches and longitudinal research to better address the complex link between HF and the gut microbiota.}, } @article {pmid41440484, year = {2025}, author = {Ramos-Nino, ME}, title = {Operationalizing Chronic Inflammation: An Endotype-to-Care Framework for Precision and Equity.}, journal = {Clinics and practice}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/clinpract15120233}, pmid = {41440484}, issn = {2039-7275}, abstract = {Background/Objectives: Chronic inflammation arises from self-reinforcing immune-metabolic circuits encompassing pattern-recognition signaling, inflammasome activation, cytokine networks, immunometabolic reprogramming, barrier-microbiome disruption, cellular senescence, and neuro-immune-endocrine crosstalk. This review synthesizes these mechanistic axes across diseases and introduces an operational endotype-to-care framework designed to translate mechanistic insights into precision-based, scalable, and equitable interventions. Methods: A narrative, mechanism-focused review was performed, integrating recent literature on immune-metabolic circuits, including pattern-recognition receptors, inflammasome pathways, cytokine modules, metabolic reprogramming, barrier-microbiome dynamics, senescence, and neuro-immune-endocrine signaling. Validated, low-cost screening biomarkers (hs-CRP, NLR, fibrinogen) were mapped to phenotype-guided endotyping panels and corresponding therapeutic modules, with explicit monitoring targets. Results: We present a stepwise, pragmatic pathway progressing from broad inflammatory screening to phenotype-specific endotyping (e.g., IL-6/TNF for metaflammation; ISG/IFN for autoimmunity; IL-23/17 for neutrophilic disease; IL-1β/NLRP3 or urate for crystal-driven inflammation; permeability markers for barrier-dysbiosis). Each module is paired with targeted interventions and prespecified treat-to-target outcomes: for example, achieving a reduction in hs-CRP (e.g., ~40%) within 8-12 weeks is used here as a pragmatic operational benchmark rather than a validated clinical threshold. Where feasible, cytokine and multi-omic panels further refine classification and prognostication. A tiered implementation model (essential, expanded, comprehensive) ensures adaptability and equity across clinical resource levels. Conclusions: Distinct from prior narrative reviews, this framework defines numeric triage thresholds, minimal endotype panels, and objective monitoring criteria that make chronic inflammation management operationalizable in real-world settings. It embeds principles of precision, equity, and stewardship, supporting iterative, evidence-driven implementation across diverse healthcare environments.}, } @article {pmid41440381, year = {2025}, author = {Otálora-Otálora, BA and Payán-Gómez, C and López-Rivera, JJ and Patiño-Unibio, LF and Arboleda-Mojica, SL and Aristizábal-Guzmán, C and Isaza-Ruget, MA and Álvarez-Moreno, CA}, title = {The Exosome-Mediated Epigenome: Non-Coding RNA and mRNA-Coding Networks in Microbiome-Cellular Communication, Inflammation, and Tumorigenesis Along the Oral-Gut-Lung Axis.}, journal = {Epigenomes}, volume = {9}, number = {4}, pages = {}, doi = {10.3390/epigenomes9040052}, pmid = {41440381}, issn = {2075-4655}, abstract = {Background/Objectives: The oral-gut-lung axis represents a dynamic system where exosomes carrying mRNAs and non-coding RNAs might help to regulate microbiota and human cell crosstalk to establish transcriptional regulatory networks controlling cellular biological processes and signaling pathways. Methods: We conducted a comprehensive transcriptomic analysis to characterize the molecular cargo of extracellular exosomes in the context of gut and lung cancer. Results: By analyzing gut and lung exosomes cargo with our previous transcriptomic studies from tumoral and inflammatory tissues, we found that exosomes can transport key RNAs that codify specific receptors that facilitate pathogenic interaction with microorganisms and RNAs that are part of interacting gene and transcriptional regulatory networks that control the function of differentially expresses genes, all involved in biological processes like cell cycle, plasticity and growth regulation, invasion, metastasis, microenvironmental remodeling, epigenetic, and microbial and immunological modulation, during the unlocking of phenotypic plasticity for the acquisition of the hallmarks of cancer in the oral-gut-lung axis. Conclusions: Exosomal RNA regulation of transcriptional networks represents a pivotal axis in the interplay between inflammation and cancer, offering opportunities for innovative diagnostic and therapeutic approaches.}, } @article {pmid41440353, year = {2025}, author = {Chauca-Bajaña, L and Ordoñez Balladares, A and Lorenzo-Pouso, AI and Caicedo-Quiroz, R and Erazo Vaca, RX and Dau Villafuerte, RF and Avila-Granizo, YV and Salazar Minda, CH and Salavarria Vélez, MA and Velásquez Ron, B}, title = {Periodontitis and Oral Pathogens in Colorectal Cancer: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.}, journal = {Dentistry journal}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/dj13120595}, pmid = {41440353}, issn = {2304-6767}, abstract = {Background: Periodontitis and oral dysbiosis have been linked to systemic inflammation and carcinogenesis. Among oral pathogens, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) are biologically plausible contributors to colorectal cancer (CRC) via inflammatory and immunomodulatory pathways. However, the magnitude and consistency of these associations remain uncertain. Objective: To evaluate whether periodontitis and key oral pathogens are associated with CRC risk and prognosis through a systematic review, meta-analysis, and trial sequential analysis (TSA). Methods: We searched PubMed, Scopus, and Web of Science from inception to December 2024 following PRISMA 2020. Eligible observational studies assessed periodontitis exposure or detection of oral bacteria in relation to CRC incidence or survival. Effect estimates (RRs/HRs) were log-transformed and pooled using random-effects models; heterogeneity was quantified with I[2]. TSA was conducted to appraise information size and the stability of the primary association. Risk of bias was evaluated with ROBINS-I/QUIPS as appropriate. PROSPERO: CRD420251168522. Results: Five studies evaluating periodontitis/oral-pathogen exposure and CRC incidence yielded a 70% higher risk (HR = 1.70; 95% CI: 1.33-2.19; I[2] = 0%). Detection of Fn was associated with approximately threefold higher risk of CRC (RR = 3.20; 95% CI: 1.76-5.82; p < 0.001). Pg presence was linked to worse overall survival (HR ≈ 2.4; p < 0.01). TSA suggested that the accrued evidence for the primary incidence association is likely sufficient to reduce random errors; nevertheless, interpretability is constrained by the small number of observational studies and between-study differences in exposure and outcome ascertainment. Conclusions: Current evidence indicates that periodontitis and oral pathogens-particularly Fn and Pg-are significantly associated with CRC development and progression. These findings support the clinical relevance of the oral-gut axis and underscore oral health as a potentially modifiable factor in cancer prevention. Further large, well-designed prospective cohorts and mechanistic studies are warranted to strengthen causal inference.}, } @article {pmid41440348, year = {2025}, author = {Sonets, IV and Galeeva, IS and Krivonos, DV and Pavlenko, AV and Vvedenskiy, AV and Ahmetzyanova, AA and Mikaelyan, KA and Ilina, EN and Yanushevich, OO and Revazova, ZE and Vibornaya, EI and Runova, GS and Aliamovskii, VV and Bobr, IS and Tsargasova, MO and Kalinnikova, EI and Govorun, VM}, title = {In-Depth Multi-Approach Analysis of WGS Metagenomics Data Reveals Signatures Potentially Explaining Features in Periodontitis Stage Severity.}, journal = {Dentistry journal}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/dj13120590}, pmid = {41440348}, issn = {2304-6767}, abstract = {Background: Periodontitis is a chronic inflammatory disease mostly associated with Porphyromonas gingivalis infection and characterized by progressive destruction of the supporting structures of the tooth, including the gingiva, periodontal ligament and alveolar bone. However, the impact of other members of the periodontal microbiome on stage of the severity of the periodontitis remains largely uncharacterized. Methods: This exploratory study employs whole-genome shotgun (WGS) metagenomics to characterize the periodontal microbiome in patients suffering from mild and severe periodontitis, aiming to identify microbial signatures linked to disease severity via analysis of taxonomic composition, predicted metabolic pathways and metagenome-assembled genomes (MAGs). After initial selection, 28 adult patients with a computer tomography (CT)-confirmed diagnosis of mild and severe stage of periodontitis from 2 clinics were included in the research project. Results: Taxonomic analysis confirms the presence of various commensal and pathogenic bacteria detectable at the species level, especially belonging to so-called "red, orange and green periodontal complexes"-P. gingivalis, T. forsythia, C. rectus, and Capnocytophaga spp. that may contribute to disease heterogeneity. The conducted investigation suggests that non-microbial factors such as cardiovascular diseases and antibiotic usage in the last 6 months prior to the hospital admission could explain variance of disease progression and impact on severity. Analysis of microbial functional composition revealed metabolic traits showing positive correlations with severe stage of periodontitis. Robust network analysis suggested interactions between pathogenic bacteria of the red complex and other members of the periodontal microbiome. Conclusions: These findings underscore the multifactorial nature of periodontitis pathogenesis, highlighting the need for integrated approaches combining microbial, host, and environmental data to unravel drivers of disease progression. The study provides a foundation for future large-scale investigations into personalized diagnostic or therapeutic strategies.}, } @article {pmid41440336, year = {2025}, author = {Burlea, ȘL and Buzea, CG and Nedeff, F and Mirilă, D and Nedeff, V and Agop, M and Ochiuz, L and Armencia, AO}, title = {Deep Learning Analysis of CBCT Images for Periodontal Disease: Phenotype-Level Concordance with Independent Transcriptomic and Microbiome Datasets.}, journal = {Dentistry journal}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/dj13120578}, pmid = {41440336}, issn = {2304-6767}, abstract = {BACKGROUND: Periodontitis is a common inflammatory disease characterized by progressive loss of alveolar bone. Cone-beam computed tomography (CBCT) can visualize 3D periodontal bone defects, but its interpretation is time-consuming and examiner-dependent. Deep learning may support standardized CBCT assessment if performance and biological relevance are adequately characterized.

METHODS: We used the publicly available MMDental dataset (403 CBCT volumes from 403 patients) to train a 3D ResNet-18 classifier for binary discrimination between periodontitis and healthy status based on volumetric CBCT scans. Volumes were split by subject into training (n = 282), validation (n = 60), and test (n = 61) sets. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and calibration metrics with 95% bootstrap confidence intervals. Grad-CAM saliency maps were used to visualize the anatomical regions driving predictions. To explore phenotype-level biological concordance, we analyzed an independent gingival transcriptomic cohort (GSE10334, n ≈ 220 arrays after quality control) and an independent oral microbiome cohort based on 16S rRNA amplicon sequencing, using unsupervised clustering, differential expression/abundance testing, and pathway-level summaries.

RESULTS: On the held-out CBCT test set, the model achieved an AUROC of 0.729 (95% CI: 0.599-0.850) and an AUPRC of 0.551 (95% CI: 0.404-0.727). At a high-sensitivity operating point (sensitivity 0.95), specificity was 0.48, yielding an overall accuracy of 0.62. Grad-CAM maps consistently highlighted the alveolar crest and furcation regions in periodontitis cases, in line with expected patterns of bone loss. In the transcriptomic cohort, inferred periodontitis samples showed up-regulation of inflammatory and osteoclast-differentiation pathways and down-regulation of extracellular-matrix and mitochondrial programs. In the microbiome cohort, disease-associated samples displayed a dysbiotic shift with enrichment of classic periodontal pathogens and depletion of health-associated commensals. These omics patterns are consistent with an inflammatory-osteolytic phenotype that conceptually aligns with the CBCT-defined disease class.

CONCLUSIONS: This study presents a proof-of-concept 3D deep learning model for CBCT-based periodontal disease classification that achieves moderate discriminative performance and anatomically plausible saliency patterns. Independent transcriptomic and microbiome analyses support phenotype-level biological concordance with the imaging-defined disease class, but do not constitute subject-level multimodal validation. Given the modest specificity, single-center imaging source, and inferred labels in the omics cohorts, our findings should be interpreted as exploratory and hypothesis-generating. Larger, multi-center CBCT datasets and prospectively collected paired imaging-omics cohorts are needed before clinical implementation can be considered.}, } @article {pmid41440201, year = {2025}, author = {Ye, G and Zhang, H and Feng, Q and Xiao, J and Wang, J and Liu, J}, title = {Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.}, journal = {Current oncology (Toronto, Ont.)}, volume = {32}, number = {12}, pages = {}, doi = {10.3390/curroncol32120673}, pmid = {41440201}, issn = {1718-7729}, support = {2021ZQNZD009//Major Scientiffc Research Program for Young and Middle-aged Health Professionals of Fujian Province, China/ ; 2023Y9416//Fujian Science and Technology Innovation Joint Fund Project/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism ; *Liver Neoplasms/therapy/microbiology/immunology/metabolism ; *Bacteria/metabolism ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites-such as bile acids, short-chain fatty acids, and polyamines-remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e.g., FXR, TLR, and mTOR). We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites-including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants-to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite-immunometabolism-hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment.}, } @article {pmid41439783, year = {2025}, author = {de Lima, AMDL and Bastiani, M and Borelli, WV and Senger, JE and Werle, BM and Zanella, L and Netson, LV and Detogni, A and Bruscato, NM and Schumacher-Schuh, AF and Senger, J and Moriguchi, EH and Perquim, L and de Souza, IC and Barth, RA and Ebert, ELK and Guerra, RR and Barboza, JVC and Gaio, EJ and Martins, AF and da Rocha, JBT and Souza, DO and Zimmer, ER}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e106628}, doi = {10.1002/alz70855_106628}, pmid = {41439783}, issn = {1552-5279}, mesh = {Humans ; Male ; Aged ; Female ; *Alzheimer Disease/microbiology ; *Cognitive Dysfunction/microbiology ; *Gastrointestinal Microbiome ; *Saliva/microbiology ; Feces/microbiology ; Brazil ; RNA, Ribosomal, 16S/genetics ; Aged, 80 and over ; Pilot Projects ; }, abstract = {BACKGROUND: Longevity is influenced by a combination of genetic factors, lifestyle choices, and environmental conditions. These factors can alter microbiota composition, potentially influencing susceptibility to Alzheimer's disease (AD) and cognitive decline. We hypothesize that the microbiome in elderly individuals may be associated with different clinical stages of AD. This study aims to investigate the relationship between oral and gut microbiota composition in a Brazilian long-lived population and cognitive impairment within the AD continuum.

METHOD: We conducted a pilot characterization of the oral and gut microbiota of 12 elderly individuals (>65 years) recruited by the Moriguchi Institute in Veranópolis, a longevity hotspot in southern Brazil. Participants underwent clinical-cognitive assessment, including the Clinical Dementia Rating (CDR), and were classified as cognitively unimpaired (CU), mild cognitive impairment (MCI), or Alzheimer's disease (AD). Saliva and fecal samples were sequenced using Illumina MiSeq™, targeting the V3-V4 regions of the 16S rRNA gene, and processed in R using DADA2. Amplicon sequence variants (ASVs) were inferred, and taxonomic assignments were performed with SILVA. Abundance data were used for alpha and beta diversity, and relative abundance analyses.

RESULT: Alpha diversity was similar across groups, except for reduced salivary richness in MCI (Chao1, p = 0.002; Figure 1). Rarefaction curves indicated higher richness in the feces compared to saliva. PCoA analysis showed distinct group separations in feces, with MCI and AD being more similar, while saliva samples were more uniform. Relative abundance demonstrated alterations in phylum Bacillota, Bacteroidota, and Pseudomonadota in MCI and AD compared to the CU group (Figure 2). Changes were particularly evident in fecal families Lachnospiraceae, Bacteroidaceae, and Ruminococcaceae, and genus such as Bacteroides, Blautia, and Faecalibacterium. Notably, Streptococcus was almost exclusively elevated in fecal samples of the AD group. Saliva samples were more homogeneous across groups, though changes were observed in families Prevotellaceae and Streptococcaceae, and genus Prevotella, Streptococcus, Haemophilus, and Neisseria in MCI and AD compared to CU.

CONCLUSION: Fecal microbiota exhibited clinical-stage-specific changes, while salivary microbiota displayed more stability, underscoring microbial adaptations to the distinct. These findings highlight microbiome changes along the AD continuum, emphasizing the potential microbiome's role in healthy aging and resilience against neurodegeneration.}, } @article {pmid41439715, year = {2025}, author = {Bae, M and Dong, X and Avila-Pacheco, J and Nguyen, QD and Inyama, F and Hill-Maini, V and Clish, CB and Balskus, EP}, title = {Distinct classes of gut bacterial molybdenum-dependent enzymes produce urolithins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {52}, pages = {e2501312122}, doi = {10.1073/pnas.2501312122}, pmid = {41439715}, issn = {1091-6490}, support = {CHE-20380529//NSF (NSF)/ ; N/A//Biocodex Microbiota Foundation (BMF)/ ; N/A//HHMI (HHMI)/ ; N/A//Kwanjeong Educational Foundation (KEF)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Coumarins/metabolism ; *Molybdenum/metabolism ; Inflammatory Bowel Diseases/microbiology/metabolism ; *Bacteria/enzymology/metabolism/genetics ; *Bacterial Proteins/metabolism/genetics ; Xanthine Oxidase/metabolism/genetics ; }, abstract = {Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain largely unidentified. Here, we use differential gene expression analysis, anaerobic protein production, and enzyme assays to identify members of two distinct molybdenum enzyme families (the DMSO reductase family and the xanthine oxidase family) capable of regioselective dehydroxylation and urolithin generation. These two enzyme families have distinct substrate requirements, suggesting they employ different catalytic mechanisms for phenol dehydroxylation. Multiomics analysis of a human cohort uncovers decreased levels of urolithin A and genes encoding urolithin A-producing enzymes in patients with inflammatory bowel disease (IBD), implying reduced health effects of EA consumption in this setting. Together, this study elucidates the molecular basis of urolithin production, expands the known enzymatic repertoire of the human gut microbiome, and suggests a potential link between gut bacterial urolithin production and reduced host inflammation.}, } @article {pmid41439692, year = {2025}, author = {González-García, S and Bustos-Hamdan, A and Hamdan-Partida, A and Bustos-Martínez, J}, title = {Staphylococcus aureus colonization in the pharynx and nasal cavity: why are some people more susceptible?.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/17460913.2025.2605944}, pmid = {41439692}, issn = {1746-0921}, abstract = {Staphylococcus aureus is one of the most important pathogenic bacteria in humans. The nose and pharynx constitute two fundamental ecological niches for this bacterium, supporting the asymptomatic carrier state and acting as sources of infection in susceptible organisms. Colonization dynamics depend on the balance between the bacteria's virulence factors, the host's immune response, and the environment. Colonization is favored by attenuated immune responses, with evidence of partial tolerance and low protective antibody titers. Colonization also appears to depend on the microbiome of the colonized site. Genetic, metabolic, lifestyle, and age factors of the host may also contribute to colonization. Global prevalence rates vary widely depending on the geographic, social, and economic context. Recently, emerging strategies such as the use of phages, microbiome modulation, nanoparticles, gene editing technologies, and vaccines have been developed as promising alternatives to prevent colonization and infection by this bacterium. This review summarizes the current evidence on the factors that allow nasal and pharyngeal colonization of S. aureus, as well as therapeutic perspectives to prevent colonization by this bacterium.}, } @article {pmid41439635, year = {2025}, author = {Sioutas, GS and Reavey-Cantwell, J and Rivet, DJ}, title = {The gut-brain axis: a nationwide propensity score-matched analysis of gastrointestinal syndromes preceding ischemic stroke.}, journal = {Brain injury}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/02699052.2025.2604022}, pmid = {41439635}, issn = {1362-301X}, abstract = {BACKGROUND: It has been hypothesized that the gut microbiome affects ischemic stroke occurrence. However, the relationship between stroke and gastrointestinal (GI) disorders is not well understood. We aimed to determine whether GI syndromes are associated with an increased risk of ischemic stroke.

METHODS: We conducted case-control and cohort studies using the TriNetX US Collaborative Network database (2018-2022). In the case-control study, patients with ischemic stroke were compared to propensity-score-matched controls with at least 3 years of prior data. The cohort study assessed the risk of stroke in patients with specific GI syndromes over 5 years compared to matched controls.

RESULTS: For the case-control study, 551,738 patients with ischemic stroke were matched with 19,419,979 negative controls, resulting in 548,179 pairs after matching. Compared to matched negative controls, all GI syndromes, appendectomy, and GI medications were significantly associated with ischemic stroke (all p < 0.001). In the cohort study, all GI syndromes were significantly associated with ischemic stroke (all risk ratio (RR) > 1, p < 0.001), but appendectomy was not [RR 1.28, 95% Confidence Interval (CI): 0.89-1.82].

CONCLUSION: Several GI disorders were associated with an increased risk of future ischemic stroke, providing more evidence on the gut-brain axis. Further research is warranted to confirm these findings and investigate underlying mechanisms.}, } @article {pmid41439619, year = {2026}, author = {Haykal, D}, title = {Translating Geroscience Into Clinical Longevity Dermatology: From Mechanisms of Aging to Skin-Centered Interventions.}, journal = {Journal of cosmetic dermatology}, volume = {25}, number = {1}, pages = {e70616}, doi = {10.1111/jocd.70616}, pmid = {41439619}, issn = {1473-2165}, mesh = {Humans ; *Longevity/physiology ; *Skin Aging/physiology ; Artificial Intelligence ; *Dermatology/methods/trends ; *Geroscience/methods ; Biomarkers/metabolism ; Skin/microbiology ; Translational Research, Biomedical ; *Aging/physiology ; Microbiota ; }, abstract = {BACKGROUND: Longevity medicine is an emerging clinical framework aimed at extending healthspan by targeting the biological mechanisms of aging rather than treating disease in isolation. Geroscience, which investigates the molecular and cellular pathways linking aging to chronic pathology, provides the scientific foundation for this approach. Dermatology is uniquely positioned within this paradigm, as the skin represents both a visible marker of biological aging and an accessible source of biomarkers.

OBJECTIVE: To explore how principles of geroscience can be translated into clinical dermatology and cosmetic practice, with a focus on skin-centered biomarkers, artificial intelligence (AI), and preventive longevity-oriented interventions.

METHODS: This piece integrates current evidence from geroscience, dermatologic aging research, microbiome science, and AI-driven analytics to examine emerging models of longevity-focused dermatologic care. Conceptual frameworks, clinical readiness of interventions, and ethical considerations are critically discussed.

RESULTS: Advances in biological aging biomarkers, including epigenetic clocks, inflammatory signatures, mitochondrial and metabolic markers, and skin microbiome profiling, offer promising tools for assessing cutaneous and systemic aging. AI-enabled platforms facilitate the integration of multidimensional data, enabling refined biological age assessment and potential prediction of treatment responses. However, most longevity-oriented diagnostics and interventions remain in early or experimental stages, requiring rigorous validation before routine clinical adoption.

CONCLUSION: Dermatology can serve as a translational bridge between geroscience and clinical longevity medicine by integrating validated skin biomarkers, aesthetic procedures, and preventive strategies within an evidence-based framework. Careful attention to scientific limitations, ethical considerations, and health equity is essential to ensure responsible implementation. Dermatologists would play a key role in shaping clinically sound, prevention-focused longevity care centered on long-term skin health and resilience.}, } @article {pmid41439545, year = {2025}, author = {Ding, J and Yu, C and Gao, J and Luo, W and Yang, Y and Li, H and Wu, QL}, title = {Stratification-driven divergence between taxonomic and functional diversity in a deep lake microbiome.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiaf129}, pmid = {41439545}, issn = {1574-6941}, abstract = {Thermal stratification drivers of microbial community organization and functional potential in deep lakes, yet comparative analyses of epilimnetic and hypolimnetic microbiome dynamics remain limited. In this study, we combined 16S rRNA gene sequencing with functional microarray (GeoChip 5.0) to investigate stratification-induced shifts in microbial community composition and functional structure in Lake Fuxian, a deep monomictic plateau lake in Yunnan Province, Southwest China. Our analyses revealed a partial decoupling between taxonomic and functional diversity across water layers: the oxygen-depleted hypolimnion harbored higher bacterial taxonomic richness and distinct taxa (Nitrospirae, Parcubacteria, Thaumarchaeota), whereas the epilimnion exhibited greater functional gene richness with lower beta diversity, indicating enhanced metabolic flexibility. Molecular ecological network analysis uncovered contrasting interaction patterns, with hypolimnetic communities exhibiting greater complexity and modularity. Notably, the Chloroflexi-associated amyA gene emerged as a module hub in hypolimnetic functional molecular ecological networks while distinct connector taxa characterized both epilimnetic and hypolimnetic species molecular ecological networks. Multivariate analyses identified dissolved oxygen and nutrient availability as key environmental drivers of vertical microbial stratification. These findings elucidate microbial adaptation to stratified conditions and underscore the distinct roles of epilimnetic and hypolimnetic communities in biogeochemical cycling in deep lakes experiencing climate-mediated thermal regime shifts.}, } @article {pmid41439395, year = {2025}, author = {Chakkarai, S and Tabar, MS and Jian, X and Satizabal, CL and Casale, FP and Gutiérrez, JB and Habes, M and Blangero, J and Seshadri, S and Sargurupremraj, M}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e103860}, doi = {10.1002/alz70855_103860}, pmid = {41439395}, issn = {1552-5279}, mesh = {Humans ; Male ; *Gene-Environment Interaction ; Female ; Quantitative Trait Loci ; Magnetic Resonance Imaging ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Aged ; *Brain/pathology/diagnostic imaging ; Risk Factors ; Genome-Wide Association Study ; Hippocampus/pathology/diagnostic imaging ; }, abstract = {BACKGROUND: Epidemiological studies highlight the relation between environmental exposures and the risk of Alzheimer's disease (AD) and related disorders (ADRD). However, due to the prolonged preclinical phase of ADRD, the underlying molecular mechanisms disrupted by environmental factors and their impact on brain structure remain poorly understood. Additionally, investigating gene-environment interactions has been challenging, primarily due to difficulties in accurately defining environmental variables and the substantial inter-study heterogeneity.

METHOD: Since gene-environment interaction effects influence phenotypic variability across genotypes, we leveraged deviations in phenotypic variance to identify variance quantitative trait loci (vQTLs) with heightened environmental sensitivity. Utilizing UK Biobank data (N = 45,275) with comprehensive genomic, brain imaging, and risk factor profiles, we mapped vQTLs for key MRI markers: hippocampal volume (HV) for atrophy, white matter hyperintensity (WMH) for vascular injury, and diffusion MRI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) for microstructural changes. Sentinel vQTLs were further examined using linear mixed models to pinpoint environmental exposures, such as air pollution, physical activity, and lifestyle factors, that mediate these associations.

RESULT: The genome-wide vQTL analysis identified five novel, genome-wide significant loci associated with WMH burden (2q12.3, 3q27.3-q28, 5p13.2, 10p11.22, and 17p11.2) along with four suggestive loci for HV and FA. Notably, associations at 2q12.3 (ST6GAL2), 10p11.22 (ZEB1), and 17p11.2 (EPN2) with WMH burden were significantly mediated by sedentary behavior and lifestyle factors (smoking, alcohol consumption). Functional insights suggest that ZEB1 regulates gut microbiome species involved in inflammatory bowel diseases, while ST6GAL2 has been implicated as an inflammatory biomarker associated with alcohol consumption. Additionally, differential gene expression analysis revealed significant downregulation of these risk loci in the spleen, with further enrichment observed in kidney cell-type specific signatures.

CONCLUSION: Our study identifies novel genome-wide loci that interact with environmental factors and are associated with preclinical MRI markers of AD. These findings underscore the impact of modifiable lifestyle factors on genetic risk, offering potential avenues for preventive and therapeutic strategies. Ongoing efforts aim to replicate these findings in well-characterized cohorts, including the Framingham Heart Study and the San Antonio Family Heart Study of predominantly Mexican-Americans.}, } @article {pmid41439274, year = {2026}, author = {Li, Y and Xu, C and Park, H and Omstead, AN and Anees, M and Sherry, C and Khan, AF and Grayhack, E and Weksler, B and Wagner, P and Bartlett, DL and Meltzer, SJ and Zaidi, AH and Goel, A}, title = {A machine-learning informed circulating microbial DNA signature for early diagnosis of esophageal adenocarcinoma.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2604334}, doi = {10.1080/19490976.2025.2604334}, pmid = {41439274}, issn = {1949-0984}, mesh = {Humans ; *Esophageal Neoplasms/diagnosis/microbiology/blood ; *Adenocarcinoma/diagnosis/microbiology/blood ; *Machine Learning ; *Early Detection of Cancer/methods ; Barrett Esophagus/diagnosis/microbiology ; Male ; Female ; Middle Aged ; Aged ; Gastroesophageal Reflux/diagnosis/microbiology ; Bacteria/genetics/classification/isolation & purification ; *DNA, Bacterial/blood/genetics ; Liquid Biopsy/methods ; *Cell-Free Nucleic Acids/blood/genetics ; Metagenomics ; Biomarkers, Tumor/blood ; }, abstract = {Esophageal adenocarcinoma (EAC) has seen a dramatic rise in incidence in developed countries over the past three decades. Early detection of its precursors-gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and high-grade dysplasia (HGD) is critical for cancer prevention. This study presents the development and validation of a novel liquid biopsy assay based on circulating microbial DNA (cmDNA) for the early detection of EAC and HGD. Using metagenomic sequencing, we identified significant differences in microbial diversity and composition between EAC and HGD patients, as well as between BE and GERD patients. A total of 46 microbial candidates in tissue and 419 in serum were upregulated in EAC & HGD, with 11 consistently elevated in both sample types. Following qRT-PCR validation and LASSO regression, a 6-marker cmDNA panel was selected. This signature was incorporated into a diagnostic model trained with the XGBoost algorithm, achieving an AUC of 0.93 in the training cohort (52 HGD & EAC cases vs. 54 BE & GERD controls). Importantly, the model demonstrated robust performance in an independent testing cohort (23 HGD & EAC cases vs. 22 BE & GERD controls), yielding AUCs of 0.91 for EAC and 0.88 for HGD. These findings highlight the diagnostic potential of cmDNA-based profiling and support its utility as a minimally invasive, accurate, and generalizable tool for early detection of esophageal adenocarcinoma.}, } @article {pmid41439255, year = {2025}, author = {Dodani, D and Talhouk, A}, title = {Multi-cohort ensemble learning framework for vaginal microbiome-based endometrial cancer detection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1641413}, pmid = {41439255}, issn = {2235-2988}, mesh = {Humans ; Female ; *Endometrial Neoplasms/diagnosis/microbiology ; *Vagina/microbiology ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Machine Learning ; Cohort Studies ; Early Detection of Cancer/methods ; ROC Curve ; Bacteria/classification/genetics/isolation & purification ; Middle Aged ; Sensitivity and Specificity ; Ensemble Learning ; }, abstract = {INTRODUCTION: Endometrial cancer is the most common gynecological malignancy in high-income countries and lacks an established strategy for early detection. Prior studies suggest that the vaginal microbiome may hold diagnostic potential, but inconsistent findings have limited clinical translation.

METHODS: We conducted a systematic review to collect and analyze vaginal 16S rRNA sequencing data from five independent cohorts (n = 265). These studies included women with histologically confirmed endometrial cancer and controls with benign gynecologic conditions. We used these datasets to identify microbial signatures associated with endometrial cancer and to develop a predictive machine learning model.

RESULTS: Microbial diversity was significantly higher in endometrial cancer samples, and host characteristics influenced community composition. Peptoniphilus was reproducibly enriched in cancer samples across cohorts. An ensemble classifier accurately identified endometrial cancer in a held-out test set, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI: 0.71-0.93), sensitivity of 1.0 (95% CI: 0.74-1.0), and a negative predictive value of 1.0 (95% CI: 0.59-1.0).

DISCUSSION: These findings support the potential of vaginal microbiome profiling as a minimally invasive approach for early detection of endometrial cancer.}, } @article {pmid41439252, year = {2025}, author = {Tu, Y and Zhou, Z and Lu, Y and Wei, B and Ge, Y and Ding, G and Dong, X and Sheng, J and Zhang, Y and Jin, L and Huang, H}, title = {The composition of lower genital tract microbiota correlates with in vitro fertilization and frozen embryo transfer outcomes in women with polycystic ovarian syndrome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1617187}, pmid = {41439252}, issn = {2235-2988}, mesh = {Humans ; Female ; *Polycystic Ovary Syndrome/microbiology ; *Fertilization in Vitro ; *Embryo Transfer ; Adult ; *Microbiota/genetics ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Pregnancy ; Lactobacillus/isolation & purification/genetics ; *Genitalia, Female/microbiology ; }, abstract = {Adverse reproductive outcomes remain a significant concern for women of reproductive age with polycystic ovary syndrome (PCOS), yet the role of the lower genital tract (LGT) microenvironment has been largely overlooked. This study aimed to investigate the association between the LGT microbiome and the outcomes of in vitro fertilization and frozen embryo transfer (IVF-FET) in women with PCOS. A total of 191 reproductive-aged women undergoing assisted reproductive technology (ART) treatment between December 2018 and October 2021 were recruited. The LGT microbiota was profiled using 16S rRNA sequencing and analyzed in relation to ART outcomes and clinical parameters. Furthermore, cervical transcriptome sequencing was performed in a subset of PCOS patients to investigate whether LGT microbiota alterations were associated with functional changes in mucosal epithelial cells. The results demonstrate significant dysbiosis of the LGT microbiome in patients with PCOS, characterized by a reduction in Lactobacillus abundance. Among 72 PCOS patients undergoing IVF-FET, those with a relative Lactobacillus abundance of ≥50% (n = 57) exhibited significantly improved reproductive outcomes compared to those with Lactobacillus abundance <50% (n = 15). Elevated testosterone levels were identified as the most significant factor associated with a reduced abundance of Lactobacillus in PCOS patients. Transcriptomic analysis further revealed that the LGT microbiota was associated with maintaining mucosal epithelial barrier integrity and immune homeostasis in PCOS. In conclusion, the findings highlight that dysbiosis of the LGT microbiota may significantly influence reproductive outcomes in PCOS patients, emphasizing the importance of targeting the LGT microenvironment to improve ART success rates.}, } @article {pmid41439238, year = {2026}, author = {Kumar, A and Solanki, MK and Kumar, M and Kaushik, A and Arya, A and Saikia, M and Gaur, VK and Singh, RP and Singh, SK and Singh, VK and Dufossé, L}, title = {The microbial strategies for the management of chemical pesticides: A comprehensive review.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100519}, pmid = {41439238}, issn = {2666-5174}, abstract = {Chemical pesticides considered as one of the emerging environmental contaminants that severally affect the human health and soil and water ecosystem. Despite their well-documented adverse effects on fruit quality, soil structure, the emergence of pesticide-resistant pests, and human well-being, chemical pesticides are still widely used for crop protection, particularly in developing countries. Although to manage the chemical pesticides, various traditional approaches have been employed, however the higher cost, and the generation of toxic residues have shifted research attention toward eco-friendly and sustainable bioremediation strategies. Microorganisms including the bacteria, fungi, and algae play a crucial role in pesticide degradation by transforming toxic compounds into less toxic forms. However, to optimize microbial bioremediation, a comprehensive understanding of microbial metabolism and physiology is essential. In this context, omics technologies such as genomics, metagenomics, transcriptomics, proteomics, and metabolomics, offer powerful tools for elucidating the molecular mechanisms involved in pesticide degradation. These approaches facilitate the identification of microorganism, key genes, enzymes, and metabolic pathways responsible for the breakdown of pesticide compounds and their by-products. Furthermore, advanced technology like the gene editing can enhance the efficacy of pesticides biodegradation by knocking out undesirable genes or introducing beneficial ones in the microorganisms. The Artificial intelligence also plays a significant role in analysing big data, understanding microbial communities' structure, identifying nature of pesticides and selecting or predicting the microbial species with enhanced pesticides degrading efficacy.}, } @article {pmid41439235, year = {2026}, author = {Zou, B and Huo, Q and Zhou, X and Lv, Y and Li, G and Fu, G and Shen, H and Shu, S}, title = {Characteristics and longitudinal stability of Gut Microbiota in healthy individuals across different age groups.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100512}, pmid = {41439235}, issn = {2666-5174}, abstract = {Fecal microbiota transplantation (FMT) efficacy relies on donor microbiome composition and temporal stability, yet the influence of donor age remains inadequately investigated. This longitudinal analysis addressed this gap by examining 81 healthy individuals (3-30 years), stratified into four age groups, who provided monthly fecal samples over 12 months (n = 972 samples). Gut microbiota composition (16S rDNA sequencing) and temporal stability were assessed using Bray-Curtis dissimilarity, intraclass correlation coefficient (ICC), and genus-level co-occurrence network analysis. Results demonstrated a strong age-dependency in microbiota stability. The teenage cohort (13-17 years) exhibited the highest stability, characterized by minimal fluctuations in α- and β-diversity and significantly stronger network centrality. Furthermore, specific genera, notably Faecalibacterium and Bifidobacterium, displayed exceptionally high ICC values (>0.90), identifying them as core taxa associated with temporal consistency. These findings underscore the critical role of donor age in microbial stability and highlight teenagers as possessing optimal microbiota characteristics for FMT. They strongly support the development of an ICC-based screening framework to enhance donor selection protocols.}, } @article {pmid41439197, year = {2025}, author = {Liang, J and Qiu, Y and Fu, T and Li, J and Yang, J and Tong, Y}, title = {The Gut-Kidney Axis in Uric Acid Nephropathy: Microbiota, Metabolic Crosstalk, and Translational Prospects.}, journal = {Journal of multidisciplinary healthcare}, volume = {18}, number = {}, pages = {8111-8132}, pmid = {41439197}, issn = {1178-2390}, abstract = {Uric acid nephropathy (UAN) represents a critical and multifactorial renal disorder closely linked to hyperuricemia, inflammation, and gut microbiota dysregulation. Recent advances have revealed the pivotal role of the gut-kidney axis in modulating urate metabolism, immune activation, and oxidative stress. This review synthesizes emerging preclinical and clinical evidence to construct an integrative framework for understanding UAN, highlighting both crystal-dependent and crystal-independent mechanisms that drive tubular injury and fibrosis. Accumulating data underscore the reciprocal crosstalk between renal dysfunction and gut dysbiosis, mediated by microbial metabolites such as short-chain fatty acids (SCFAs), indoxyl sulfate, and p-cresol sulfate. We further evaluate therapeutic interventions targeting the gut-kidney axis-including probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and engineered microbial therapies-which have shown promise in restoring microbial balance and improving urate handling. By integrating multi-omics profiling with systems biology, this review proposes a precision-medicine roadmap that leverages microbiome signatures and metabolic phenotyping for risk stratification and personalized intervention. Moreover, we emphasize the need for supportive regulatory frameworks and interdisciplinary collaboration to enable the clinical translation of microbiota-based strategies. Collectively, this work provides a strengthened conceptual foundation for microbiome-informed prevention and treatment of uric acid-related kidney disease.}, } @article {pmid41439190, year = {2025}, author = {Tronel, A and Roger-Margueritat, M and Plazy, C and Biennier, S and Craspay, A and Mohanty, I and Portier, SC and Laiola, M and Roeselers, G and Mathieu, N and Hupe, M and Dorrestein, PC and Alcaraz, JP and Martin, D and Cinquin, P and Silvent, AS and Giai, J and Proust, M and Soranzo, T and Buelow, E and Le Gouellec, A}, title = {Exploring the human small intestinal luminal microbiome via a newly developed ingestible sampling device.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf224}, pmid = {41439190}, issn = {2730-6151}, abstract = {Because accessing the small intestine is technically challenging, studies of the small intestinal microbiome are predominantly conducted in patients rather than in healthy individuals. Invasive clinical procedures, such as endoscopy or surgery, usually performed for therapeutic purposes, are typically required for sample collection. Although stomas offer a less invasive means for repeated sampling, their use remains restricted to patient populations. As a result, the small intestinal microbiome of healthy individuals remains largely understudied. This study evaluated a novel ingestible medical device for collecting luminal samples from the small intestine. A monocentric interventional trial (NCT05477069) was conducted on 15 healthy subjects. Metagenomics, metabolomics, and culturomics were used to assess the effectiveness of the medical device in characterizing the healthy small intestinal microbiome and identifying potential biomarkers. The small intestinal microbiota differed significantly from the fecal microbiota, displaying high inter-individual variability, lower species richness and reduced alpha diversity. A combined untargeted and semi-targeted LC-MS/MS metabolomics approach identified a distinct small intestinal metabolic footprint, with bile acids and amino acids being the most abundant metabolite classes. Host- and host/microbe-derived bile acids were particularly abundant in small intestinal samples. Using a fast culturomics approach on two small intestinal samples, we achieved species-level characterization and identified 90 bacterial species, including five potentially novel ones. This study demonstrates the efficacy of our novel sampling device in enabling comprehensive small intestinal microbiome analysis through an integrative, multi-omics approach. This approach allows distinct microbiome signatures to be identified between small intestinal and fecal samples.}, } @article {pmid41439181, year = {2025}, author = {Yang, M and He, T and Moukarzel, R and Li, M and Li, M and Zhang, Z and He, Y and Liu, Y and Yu, L and Zhu, S and Du, F}, title = {Phyllosphere microbiome responses to nano-berberine and chemical fungicides in powdery mildew infected strawberry.}, journal = {Frontiers in plant science}, volume = {16}, number = {}, pages = {1712123}, pmid = {41439181}, issn = {1664-462X}, abstract = {Strawberry powdery mildew, caused by the obligate biotroph Podosphaera aphanis, is a major threat to commercial strawberry production, reducing both yield parameters and fruit quality. While chemical fungicides remain a standard control method, their non-target effects on phyllosphere microbial communities have raised important ecological and environmental concerns. Nano-pesticides are increasingly applied in plant disease management, however, their influence on the composition and functional potential of phyllosphere microbial communities remains poorly understood. The nano-berberine formulation (BBR-M) used in this study was provided by a collaborative group, with synthesis and physicochemical characteristics consistent with those previously reported for this material. In this study, we compared the field-level effects of a nano-berberine formulation (BBR-M) and conventional chemical fungicides (e.g., bupirimate) on the strawberry phyllosphere microbiota using high-throughput sequencing, bioinformatics analysis, and microbial isolation techniques. The results showed that nano-fungicide application significantly reduced the disease index of powdery mildew and markedly decreased its incidence in field-grown strawberries, ultimately lowering leaf disease incidence to 5.06% with a control efficacy of 96.81%. Furthermore, nano-fungicides and conventional chemical fungicides treatments were associated with distinct impacts on the phyllosphere microenvironment of strawberry. Application of BBR-M was associated with a more structured and potentially stable microbial community, characterized by increased fungal diversity and higher modularity in co-occurrence networks. In contrast, bupirimate treatment increased microbial complexity but coincided with reduced network stability. A strain of Bacillus siamensis-a genus identified as a core taxon within the BBR-M phyllosphere network-was subsequently isolated from nano-berberine-treated leaves and exhibited strong antagonistic activity against Colletotrichum nymphaeae. Field assays showed that this strain effectively suppressed strawberry powdery mildew with 98.18% control efficacy. Collectively, these findings provide important insights into the ecological safety and functional implications of novel pesticide technologies, underscoring the potential of nano-fungicides and native biocontrol agents for sustainable strawberry disease management.}, } @article {pmid41438919, year = {2025}, author = {Eissenberg, JC}, title = {Autism Spectrum Disorder: Nature vs. Nurture.}, journal = {Missouri medicine}, volume = {122}, number = {6}, pages = {501-507}, pmid = {41438919}, issn = {0026-6620}, mesh = {Humans ; *Autism Spectrum Disorder/genetics/etiology/epidemiology ; Genetic Predisposition to Disease ; Environmental Exposure/adverse effects ; }, abstract = {Autism Spectrum Disorder (ASD) is associated with a variety of inherited disorders, but most diagnoses have no identifiable genetic etiology. There has been a significant increase in the incidence of ASD diagnoses in the past three decades. The now-discredited vaccine theory of ASD causation has driven concerns over environmental exposures that may or may not lead to ASD. Here, I discuss the evidence for an underlying genetic basis for ASD, the evidence that environmental inputs could play a significant role ASD and potential treatments for associated symptoms.}, } @article {pmid41438742, year = {2025}, author = {Chen, PJ and Devkota, S and Shiao, S and Hendifar, A and Yang, JD}, title = {Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1568962}, pmid = {41438742}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; Precision Medicine/methods ; Biomarkers, Tumor ; Animals ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut-liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.}, } @article {pmid41438680, year = {2025}, author = {Li, Z and Zhang, J and Zhang, Y and Chen, H and Bao, Y}, title = {Skin Microbiome in Health and Disease: Mechanisms and Emerging Therapeutic Strategies.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {18}, number = {}, pages = {3443-3455}, pmid = {41438680}, issn = {1178-7015}, abstract = {The skin microbiome plays a vital role in maintaining skin homeostasis by regulating immune responses, preserving barrier integrity, and inhibiting pathogen colonization. This review systematically explores the mechanisms underlying its dysregulation in conditions such as acne, atopic dermatitis, psoriasis, and impaired wound healing, with a focus on key factors including microbial over colonization, diminished diversity, and host immune dysregulation. The influence of microbial metabolites, such as short-chain fatty acids and porphyrins, is also examined. We further evaluate emerging microbial-targeted therapeutic strategies, including live biotherapeutic products, skin microbiota transplantation, epigenetic and metabolic interventions, and precision antimicrobial polymers. These approaches aim to restore microbial balance rather than achieve broad-spectrum sterilization, representing a significant shift in the treatment paradigm for cutaneous diseases. In contrast to previous reviews, this article places special emphasis on the mechanisms of multi-organ interactions within the gut-skin axis and discusses the potential of integrating multi-omics technologies and artificial intelligence to advance the clinical translation of personalized microbial therapies, thereby providing a forward-looking perspective on the field.}, } @article {pmid41438381, year = {2025}, author = {Chen, X and Zhang, Y and Zhang, G and Wang, D and Dou, L and Wang, Y and Huang, Z and Liu, X}, title = {Spatial microbiome-metabolic crosstalk drives CD8[+] T-cell exhaustion through the butyrate-HDAC axis in colorectal cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1704491}, pmid = {41438381}, issn = {1664-302X}, abstract = {BACKGROUND: The spatial organization of intratumoral microbiota and its metabolic impact on immunotherapy response in colorectal cancer (CRC) is unclear, limiting targeted interventions.

METHODS: We integrated single-cell RNA-seq, spatial transcriptomics, and microbial multi-omics from a discovery cohort of 23 treatment-naïve CRC patients. Findings were validated in an independent validation cohort from The Cancer Genome Atlas (TCGA-CRC, n = 159).

RESULTS: Spatial depletion of Streptococcus and Acetivibrio in tumor niches disrupts butyrate-histone deacetylase (HDAC) signaling, leading to programmed cell death 1 (PDCD1) hyperacetylation and CD8[+] T-cell exhaustion. The Colorectal Cancer Microbiome Score (CMS) may serve as a predictive biomarker for immunotherapy response and HDAC inhibitor-based combination therapy. We developed the CMS, a spatial biomarker that stratifies patients by microbial-metabolic dysfunction, predicting immunotherapy resistance (e.g., higher tumor immune dysfunction and exclusion (TIDE) scores; p < 0.01) and guiding combinatorial HDAC inhibition for CMS-defined subgroups. In silico fecal microbiota transplantation (FMT) validated CMS as an actionable target for microbiota modulation. Butyrate supplementation in vitro restored HDAC activity and reduced PD-1 expression on CD8[+] T cells, validating the proposed mechanism.

CONCLUSION: Our study unveils a spatially defined, microbiome-driven metabolic niche that epigenetically programs CD8[+] T-cell exhaustion via the butyrate-HDAC axis, revealing a targetable mechanism to overcome immunotherapy resistance in CRC.}, } @article {pmid41438378, year = {2025}, author = {Yang, W and Liu, H and Xu, R and Peng, Y and Xu, T and Yang, Y and Li, Y and Xiang, H}, title = {Integrated genomics, metagenomics and metatranscriptomics to reveal the biocontrol mechanism of Bacillus velezensis JY10 against tobacco target spot disease.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1707097}, pmid = {41438378}, issn = {1664-302X}, abstract = {Tobacco target spot (TTS) disease, a prevalent fungal disease caused by Rhizoctonia solani, severely reduces tobacco yield and quality, imposing substantial economic losses on the tobacco industry. In this study, we employed a biological control approach against TTS using a Bacillus velezensis JY10 isolated from healthy tobacco stems. We further elucidated the mechanism of JY10 in controlling TTS through genomics, metagenomics and metatranscriptomics. The results showed that JY10 exhibited robust inhibitory effects against R. solani, with an inhibition rate exceeding 95%, and achieved a TTS control efficacy of 68.63% in pot experiments. Whole-genome sequencing demonstrated that the JY10 genome spans 3,929,772 bp, contains 4,026 protein-coding genes, and has a GC content of 46.5%. AntiSMASH analysis predicted 12 secondary metabolite biosynthetic gene clusters, encoding antimicrobial compounds such as surfactin, fengycin, difficidin, bacillaene, bacillibactin, macrolactin H, and bacilysin. Metagenomic profiling showed that JY10 treatment had no significant influence on tobacco phyllosphere and rhizosphere microbiome structure, however, it significantly increased the relative abundance of beneficial microbes, including Bacillus, Pseudonocardia, and Pseudomonas. Metatranscriptomic analysis revealed that JY10 might enhance tobacco TTS resistance by modulating oxidative phosphorylation pathway and upregulating several antibiotics biosynthesis. Taken together, JY10 may employ a dual control strategy against TTS, involving the direct production of antifungal compounds, as well as indirectly increasing the abundance of beneficial microbes and modulating their oxidative phosphorylation and antibiotic synthesis pathways in the phyllosphere and rhizosphere of tobacco. These findings provide a theoretical foundation for understanding biocontrol mechanisms of JY10 and introduce a promising bacterial resource for the development of sustainable TTS management strategies.}, } @article {pmid41438377, year = {2025}, author = {Shang, X and He, Z and Chen, W and Jin, X}, title = {Soil bacterial community diversity, composition, and species specificity across different geographical landscapes in the Mu Us Sandy Land.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1714794}, pmid = {41438377}, issn = {1664-302X}, abstract = {The Mu Us Sandy Land represents a typical region for ecological restoration in China, characterized by the development of diverse landscapes including desert, meadow patches, arbor forests, and mixed arbor-shrub forests. This study aimed to investigate the diversity, composition, and differential taxa of soil bacterial communities across these distinct geographical landscapes, thereby elucidating the driving mechanisms of vegetation restoration on the sandy land soil microbiome. Soil samples were collected from four typical landscapes in the Mu Us Sandy Land: desert (B), meadow patch (D), arbor forest (T), and mixed arbor-shrub forest (C). High-throughput sequencing of the 16S rRNA gene was performed using the Illumina NextSeq 2000 platform. Our results revealed distinct patterns of bacterial community composition: Actinobacteria dominated the desert (37.42%), while Proteobacteria were more abundant in meadow patches and mixed arbor-shrub forests, and Bacillota were significantly enriched in arbor forests (20.32%). Beta diversity analysis combined with the ANOSIM test (R = 0.7168, P = 0.001) revealed significant divergence in bacterial community structure among the different landscapes. LEfSe analysis further identified specific biomarkers for each landscape, such as Rubrobacter and Streptomyces in the desert, and taxa associated with Acidobacteria and Proteobacteria in the mixed arbor-shrub forests. The research demonstrates that the different geographical landscapes in the Mu Us Sandy Land shape distinct soil bacterial communities. The mixed arbor-shrub forest exhibited a more complex community structure compared to the pure arbor forest, indicating its potential as a more sustainable and resilient ecological restoration model. These findings provide a baseline understanding of microbial community shifts associated with vegetation restoration, which may inform future studies integrating soil physicochemical drivers.}, } @article {pmid41438373, year = {2025}, author = {Burgio, M and Pellegrini, F and Frattina, L and Carbonari, A and Bramante, G and Andriulo, OM and Camero, M and Lanave, G and Parisi, A and Martella, V and Rizzo, A and Cicirelli, V}, title = {Oral microbiota in cesarean-delivered puppies.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1711728}, pmid = {41438373}, issn = {2297-1769}, abstract = {INTRODUCTION: The microbiota plays a fundamental role in host health, and alterations in its composition have been associated with numerous pathological conditions. The neonatal period is a critical window for establishing a stable microbiota that shapes long-term health. The aim of this study was to characterize the oral microbiota of cesarean-delivered puppies at birth and 15 days postpartum, using 16S rRNA gene sequencing. This microbiota was compared with the maternal oral and colostrum microbiota.

METHODS: The study included 15 puppies delivered by cesarean section from four French Bulldogs. Oral swabs were collected from puppies at birth (T0) and day 15 (T15), and from dams together with colostrum before anesthesia. DNA was extracted and the full-length 16S rRNA gene amplified with universal primers. Libraries were prepared, purified, and sequenced on a MinION Mk1C for 24 h. FastQ files were analyzed with EPI2ME (Fastq 16S), and taxonomic assignment was performed using the NCBI_16S database via BLAST.

RESULTS: Microbial DNA was detected in neonatal samples at birth, indicating that colonization had already begun. Diversity analyses showed significant differences between the puppies' oral microbiota at T0 and T15 (p = 0.006), as well as between neonates at T0 and their mothers (p = 0.018). By contrast, no significant differences in alpha diversity were observed between puppies at T15 and their mothers, suggesting convergence toward an adult-like microbial profile. Colostrum did not show significant differences compared with the puppies' oral microbiota at both time points, suggesting it may act as a possible, though not exclusive, source of microbial transfer.

CONCLUSION: The oral microbiota of cesarean-delivered puppies undergoes rapid compositional changes within the first 15 days of life, marked by increased alpha diversity and a shift toward a microbial profile resembling that of the mother. Initial colonization likely derives from non-oral maternal or environmental sources, with convergence by day 15 due to maternal contact. Maternal colostrum did not significantly influence oral diversity, though it may act as a vector of microbial transfer. These findings underscore the dynamic nature of early-life colonization and contribute to our understanding of host-microbiota interactions in a One Health context.}, } @article {pmid41438339, year = {2026}, author = {Van Espen, L and Brol, MJ and Close, L and Schierwagen, R and Gu, W and Keller, MI and Balogh, B and Fullam, A and De Coninck, L and Nakamura, T and Kuhn, M and Bork, P and Laleman, W and Bajaj, JS and Papp, M and Schnabl, B and Trebicka, J and Matthijnssens, J and , }, title = {L actococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {1}, pages = {101622}, pmid = {41438339}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: As portal hypertension progresses in cirrhosis, bacterial translocation across a compromised gut barrier leads to endotoxemia, systemic inflammation and immune dysfunction. Gut phages play a key role in these processes by influencing bacteria-host interactions. This study explores the role of the human gut virome in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF).

METHODS: The fecal virome was longitudinally assessed by metagenomic sequencing in two independent cohorts: 93 patients (292 samples) with acute decompensation or ACLF from the PREDICT study, and 94 patients (94 samples) with decompensated cirrhosis undergoing TIPS (transjugular intrahepatic portosystemic shunt) surgery collected in a tertiary care setting. Besides descriptive analysis, phages were grouped according to their predicted bacterial host and lifestyle, and associated with clinical parameters.

RESULTS: Phage alpha-diversity was higher in patients with ACLF and correlated with ACLF severity. In the absence of ACLF, the phageome was dominated by virulent phages, but in ACLF, temperate phages became more prevalent. Genus-level analysis showed that phageomes were highly patient-specific. Lactococcus A phages were the only phage-host group predicting ACLF development (odds ratio [OR] = 14; Fisher test p = 0.0129). Enterococcus B phages (OR = 14.7; p = 0.0015; adj. p = 0.037) and their bacterial hosts (OR = 2.8; p = 0.020) were significantly more prevalent in cases of proven systemic bacterial infection. The presence of both phage families was linked to increased 90-day mortality rates.

CONCLUSION: ACLF is characterized by increased fecal virome diversity and a shift from virulent toward temperate phages at disease onset. Our study links Lactococcus A phages to ACLF development, and Enterococcus B phages to bacterial infection, while both are associated with increased 90-day mortality.

CLINICAL TRIAL NUMBER: NCT03056612.

IMPACT AND IMPLICATIONS: The human gut virome is a poorly investigated part of the human gut microbiome, especially in the context of decompensated cirrhosis and acute-on-chronic liver failure. This study identified two phage groups (Lactococcus A phages and Enterococcus B phages) with particular prognostic value. In the future, virome analysis of fecal samples could be useful for patient stratification in clinical practice.}, } @article {pmid41438083, year = {2025}, author = {Spiess, K}, title = {Sensing the good vibes: Audience vocal engagement with the oral microbiota.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114071}, pmid = {41438083}, issn = {2589-0042}, abstract = {This immersive performance explores speech as a biological environment for oral microbiota, merging art and science to promote ecological awareness. Using scientific data, recursive echo, and tactile feedback, it encourages visitors to engage directly with microbial processes through vocalizations and vibrations, blurring boundaries between human and non-human elements. Here an art-science collaboration turns laboratory research into a public, sensory experience that supports reflection on our shared biological environments, fostering sensory, evocative, and scientific engagement with microbiome ecology.}, } @article {pmid41438065, year = {2025}, author = {Xia, W and Gao, C and Cui, X and Li, H and Wang, X and Wang, F and Zhu, L and Li, D}, title = {Evidence for the effects on the wildlife gut microbiome by grazing: The potential gut microbiota transmission between Yunnan snub-nosed monkeys (Rhinopithecus bieti) and sympatric livestock.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114147}, pmid = {41438065}, issn = {2589-0042}, abstract = {Grazing can impact wildlife by resource competition, habitat degradation, and pathogen transmission. The Yunnan snub-nosed monkeys (Rhinopithecus bieti) are endemic and endangered primates, facing the negative effects of grazing. In the study, we conducted 16S rRNA sequencing to investigate the gut microbiota of Yunnan snub-nosed monkeys and sympatric livestock. Our results revealed that cattle exhibited relatively higher microbial similarity with monkeys compared to pigs. The SourceTracker analysis further indicated a potential cattle-origin gut microbiome in monkeys (mean ± standard deviation (SD): 11.24% ± 0.43%), while no pig-derived microbiome was detected. We speculated that shared environment and partial dietary similarities may drive the microbial similarity and transmission. Furthermore, our findings suggested potential microbial transmission between the gut microbiome of livestock and the environment, revealing probable environmental influence caused by grazing. Overall, our study showed the impacts of grazing on the wildlife microbiome and the environment and provided insights for conservation management.}, } @article {pmid41438044, year = {2025}, author = {Dennis, N and Vazquez-Prada, M and Freeman, LM and Xue, F and White, LJ and Karamalegos, AA and Sullivan, WG and Kudzminkaite, B and Brown, I and Hiscock, JR and Ezcurra, M}, title = {A microbial community that alters mitochondrial morphology and age-related motor function in C. elegans.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114128}, pmid = {41438044}, issn = {2589-0042}, abstract = {Across diverse taxa, the composition of the microbiota is associated with host fitness. A mechanistic understanding of how microbial communities influence host physiology could lead to microbiota-based interventions for lifelong health. Here, we have developed a host-microbiota model system consisting of the model organism C. elegans combined with a defined natural microbiota (DefNatMta) consisting of 11 bacterial strains isolated from wild C. elegans to study natural host-microbiota interactions in the laboratory. We show that DefNatMta persists in the C. elegans gut, forming a stable and distinct gut microbiota. Utilizing this host-microbiota system, we find that DefNatMta affects age-related motility and protects against age-related decline in motor function. DefNatMta acts by altering metabolism and mitochondrial network dynamics in muscle and requires dynamin-related protein 1 (DRP-1), a regulator of mitochondrial fission to protect against age-related motility decline. Our findings are consistent with microbe-mitochondria communication affecting age-related muscle function.}, } @article {pmid41438041, year = {2025}, author = {Zhou, J and Li, Y and Zhu, T and Yang, K and Zhang, C and Zhang, R and Zhang, X and Zhou, D and Ding, X and Qiao, Y and Han, C and Zhu, Z}, title = {Single-cell analysis of testicular bacterial microbiome changes during aging and effect on reproductive capacity in mice.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114174}, pmid = {41438041}, issn = {2589-0042}, abstract = {The testis supports spermatogenesis through a tightly regulated microenvironment, and the bacterial microbiome (BM) may influence host cells through immune and metabolic pathways, thereby impacting reproductive capacity. Here, we applied invasion-adhesion-directed expression sequencing (INVADE-seq), a single-cell RNA sequencing approach that simultaneously captures host and bacterial transcripts, to examine how bacterial signals shape testicular cell states. We detected a sparse but widespread bacterial presence across multiple cell types, with somatic and early germ cells outside the blood-testis barrier (BTB) showing relatively higher bacterial abundance. Bacterial load increased with age, coinciding with transcriptional signatures of reduced BTB function. At the cellular level, bacterial-positive Leydig cells exhibited activation of steroidogenic genes, whereas macrophages upregulated pathways related to autophagy and immune modulation. These findings not only deepen our understanding of testicular microbiome biology but also hold promise for the discovery of novel diagnostic biomarkers and therapeutic targets for BM-related and age-associated male subfertility.}, } @article {pmid41438035, year = {2025}, author = {Thon, T and Kopelentova, E and Srutkova, D and Coufal, S and Kreisinger, J and Rob, F and Reiss, Z and Kverka, M and Capkova, S and Cadova, J and Bulantova, L and Bystry, V and Sediva, A and Tlaskalova-Hogenova, H and Jiraskova Zakostelska, Z and Polouckova, A}, title = {Skin and gut microbiota composition and immune regulatory response differentiate IgE and non-IgE cow's milk allergy patients with atopic dermatitis.}, journal = {iScience}, volume = {28}, number = {12}, pages = {113943}, pmid = {41438035}, issn = {2589-0042}, abstract = {Precise identification of food allergy and atopic dermatitis (AD) endotypes in infants is needed to target treatments effectively. Therefore, we investigated markers associated with changes in the microbiota and immune responses within the gut-skin axis of immunoglobulin E (IgE) and non-IgE-mediated cow's milk allergy (CMA) patients with AD. We report that the skin microbiota of patients with IgE CMA differs significantly from healthy controls (HCs) and from patients with non-IgE CMA, despite similar AD severity. Regarding the immune response to bacteria, we found a significant increase in soluble CD14 in patients with non-IgE CMA compared to patients with IgE CMA. Patients with a non-IgE CMA have more regulatory T cells in their blood that migrate into the intestine than patients with IgE CMA. These findings provide insights into the complex interplay between the damaged epithelial barrier, microbiome, and immune responses in CMA patients with AD.}, } @article {pmid41438002, year = {2025}, author = {Guantai, LM and Bavinton, CE and Shazzad, JB and Mahajan, S and Thompson, S and Pereira, FC}, title = {Taxonomic and mechanistic insights into gut microbiota bioaccumulation of entacapone using bioorthogonal drug labelling.}, journal = {Microbiome research reports}, volume = {4}, number = {4}, pages = {41}, pmid = {41438002}, issn = {2771-5965}, abstract = {Aim: The gut microbiota plays a key role in shaping individual responses to drugs, but current tools have limited potential to probe drug-microbe interactions within the complex, individualised gut environment. This study employed bioorthogonal labelling to track and identify gut microbial taxa and molecular mechanisms involved in the bioaccumulation of entacapone, a Parkinson's disease drug. Methods: We synthesised alkyne-tagged derivatives of entacapone and evaluated their suitability as molecular probes in ex vivo incubations with faecal communities or different Escherichia coli (E. coli) strains. Following incubation, tagged drugs were conjugated to a fluorescently labelled azide via click chemistry. Labelled cells were visualised, quantified, sorted via fluorescence-activated cell sorting (FACS), and identified via 16S ribosomal RNA (rRNA) gene amplicon sequencing. Results: Entacapone alkyne derivatives retained the biological activity and effects of the original drug on the microbiota, significantly reducing microbial loads and shifting community composition across the three donors tested. Conjugation of alkyne-entacapone with a labelled azide revealed that between 80% to 96% of all microbial cells in a donor's faecal sample accumulate entacapone. Nearly all taxa detected in incubations were recovered in labelled FACS fractions, confirming widespread uptake of the drug. Finally, we demonstrate that different E. coli strains exhibit varying levels of entacapone accumulation and identify a siderophore transporter that plays a role in this process. Conclusion: Our findings reveal that entacapone is widely bioaccumulated by the gut microbiota across three donors and identify a key molecular mediator of this accumulation. This study expands the toolkit for investigating drug-microbiome interactions and holds significant potential to advance our understanding of drug-microbiome dynamics and therapeutic outcomes.}, } @article {pmid41437936, year = {2025}, author = {Guan, C and Li, X and Zeng, X and Du, Z and Zhou, Z and Zhao, J and Song, L and Yu, L}, title = {Unraveling the alterations and biomarkers in the tumor microenvironment in lung adenocarcinoma metastases and their indications for therapeutic response and prognosis.}, journal = {Therapeutic advances in medical oncology}, volume = {17}, number = {}, pages = {17588359251403904}, pmid = {41437936}, issn = {1758-8340}, abstract = {Lymph nodes, brain, bone, and liver are recognized as the four most common metastatic sites for lung adenocarcinoma (LUAD). Metastasis to these locations exhibits some common features, such as immune suppression, and distinct tumor microenvironment (TME) heterogeneity involving differentiation of immune cells, impacting treatment efficacy and prognosis. Lymph node metastases are characterized by immune suppression with exhausted CD8+ T cells, expanded regulated T cell (Tregs), M2-polarized macrophages, and high programmed death ligand-1 (PD-L1) expression. Brain metastases display an "immune desert" phenotype due to blood-brain barrier constraints, reduced T-cell infiltration, and microglia-mediated immunosuppression. Bone metastases involve osteoclast activation, RANKL/OPG pathway dysregulation, and metabolic reprogramming, while liver metastases show Kupffer cell-driven PD-L1/ programmed death 1(PD-1) axis suppression and elevated Treg infiltration. Key biomarkers across all types of metastases include PD-L1, cytokine profiles, immune cell ratios, and metabolic markers. Therapeutic strategies focus on combination therapies such as immune checkpoint inhibitors (ICIs) with metabolic modulators, localized drug delivery, and biomarker-guided approaches. Challenges in this field encompass spatial heterogeneity, dynamic TME evolution, and clinical translation barriers. Future research directions highlight spatial transcriptomics, microbiome interactions, and organoid models to optimize personalized immunotherapy. This article aims to provide a comprehensive review of regarding TME alterations across these four main metastatic locations of LUAD. It will also discuss relevant TME biomarkers and their clinical significance on therapeutic response and prognosis. We expect this article to serve as a source of evidence and inspiration for the future development of treatment strategies based on LUAD TME.}, } @article {pmid41437842, year = {2026}, author = {Siewert, LK and Berve, K and Pössnecker, E and Dyckow, J and Zulji, A and Baumann, R and Munoz-Blazquez, A and Krishnamoorthy, G and Schreiner, D and Sagan, S and Nelson, C and Sabatino, JJ and Nagashima, K and Diard, M and J Macpherson, A and Ganal-Vonarburg, SC and Fischbach, MA and Zamvil, SS and Schirmer, L and Baranzini, SE and Pröbstel, AK}, title = {Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2601430}, doi = {10.1080/19490976.2025.2601430}, pmid = {41437842}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Mice ; *Encephalomyelitis, Autoimmune, Experimental/immunology/microbiology ; Mice, Inbred C57BL ; T-Lymphocytes/immunology ; B-Lymphocytes/immunology ; Disease Models, Animal ; *Neuroinflammatory Diseases/immunology/microbiology ; Multiple Sclerosis/immunology/microbiology ; Autoimmunity ; Bacteria/genetics/immunology ; Female ; Antigens/immunology ; }, abstract = {Microbiome-based therapies are promising new treatment avenues. While global alterations in microbiota composition have been shown in multiple sclerosis, whether and how gut microbiota influence autoimmune responses in an antigen-specific manner is unclear. Here, we genetically engineered gut bacteria to express a brain antigen and dissect their pathogenic potential in a murine model of autoimmune neuroinflammation. Colonization with bacteria expressing myelin - but not ovalbumin-peptide exacerbates an encephalitogenic immune response in the gut by activating antigen-specific T cells as well as B cells leading to accelerated neuroinflammatory disease. These results demonstrate how antigen-specific microbial modulation can influence autoimmunity, providing insight for development of therapeutic strategies targeting specific bacterial taxa for treatment of MS and other autoimmune diseases.}, } @article {pmid41437750, year = {2025}, author = {Marano, G and Bardi, F and De Chiara, E and Lisci, FM and Brisi, C and Caroppo, E and Sani, G and Gasbarrini, A and Pola, R and Gaetani, E and Mazza, M}, title = {Neuroimmune Crossroads: Pathophysiological Links Between Bipolar Disorder and Inflammatory Bowel Disease.}, journal = {Actas espanolas de psiquiatria}, volume = {53}, number = {6}, pages = {1432-1447}, doi = {10.62641/aep.v53i6.2001}, pmid = {41437750}, issn = {1578-2735}, mesh = {Humans ; *Bipolar Disorder/physiopathology/immunology/epidemiology/complications ; *Inflammatory Bowel Diseases/physiopathology/immunology/complications/epidemiology ; *Neuroimmunomodulation/physiology ; }, abstract = {BACKGROUND: Bipolar disorder (BD) and inflammatory bowel disease (IBD) frequently co-occur, posing unique treatment challenges and implicating shared inflammatory mechanisms. Although each condition has been extensively studied in isolation, the clinical and pathophysiological interplay between BD and IBD remains poorly characterized.

METHODS: We conducted a narrative review of peer-reviewed literature from January 2000 through May 2025, retrieved from PubMed, Web of Science, and PsycINFO. Search terms included "bipolar disorder", "inflammatory bowel disease", "comorbidity", and related inflammatory markers. Titles/abstracts were screened by two reviewers, and eligible studies reporting clinical, epidemiological, or mechanistic data on BD-IBD overlap were included.

RESULTS: Prevalence estimates suggest that BD affects approximately 3-7% of IBD patients, compared with 1-2% in the general population. Comorbid BD-IBD is associated with increased hospitalization rates, more severe gastrointestinal and psychiatric symptoms, and reduced quality of life. Treatment interactions are complex: mood stabilizers and antipsychotics may exacerbate gastrointestinal inflammation, while corticosteroids and biologics can destabilize mood. Mechanistic studies highlight dysregulated cytokine profiles (e.g., elevated Interleukin-6, Tumor Necrosis Factor-alpha I), gut-microbiome alterations, and genetic pleiotropy as convergent pathways.

CONCLUSIONS: The intersection of BD and IBD underscores a bidirectional gut-brain neuroimmune axis, with systemic inflammation as a central mediator. Recognizing and managing this comorbidity requires integrated multidisciplinary care. Future research should focus on longitudinal studies and targeted anti-inflammatory interventions to improve outcomes in this high-risk population.}, } @article {pmid41437718, year = {2025}, author = {Wee, CL}, title = {You are what you eat, and more.}, journal = {Essays in biochemistry}, volume = {69}, number = {6}, pages = {}, doi = {10.1042/EBC20254001}, pmid = {41437718}, issn = {1744-1358}, } @article {pmid41437389, year = {2025}, author = {Morales, MFG and Hogue, SR and Pitcher, S and Jeong, D and Radosavljevic, I and Stefanou, A and Felder, SI and Burns, JR and Dowd, SE and Vogtmann, E and Sinha, R and Wang, L and Wang, X and Permuth, JB and Sears, CL and Andersen, SW and Greathouse, KL and Kresovich, JK and Friedman, MS and Siegel, EM and Byrd, DA}, title = {Survival implications of the age-associated tumor and normal adjacent tissue microbiome among colorectal cancer patients.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {109}, pmid = {41437389}, issn = {1757-4749}, support = {IRG-21-145-25//American Cancer Society and Tampa Merit Society/ ; }, abstract = {BACKGROUND: CRC incidence is rising among individuals younger than 50 years of age, with significant gaps in our understanding of the composition of the tissue microbiome across the age spectrum. The microbiome of tumors and normal adjacent tissue among colorectal cancer (CRC) patients may provide critical insights into the tumor microenvironment and CRC prognosis.

METHODS: We characterized the tumor and normal adjacent tissue microbiome of early-onset (EoCRC, n = 46) and frequency-matched later-onset (LoCRC, N = 101) CRC patients who underwent surgery at Moffitt Cancer Center. We extracted DNA from archival tissue from 147 patients and sequenced the 16 S rRNA gene. We estimated the relative abundance of a priori and exploratory bacteria and alpha and beta diversity. We used multivariable linear regression models to estimate the association of age with the tumor and normal adjacent tissue microbiome. Then, we estimated associations of primarily age-associated microbiome metrics with overall survival using multivariable Cox proportional hazard models.

RESULTS: In normal adjacent tissue, for every 10-year increase in age, there was a 1-SD higher relative abundance of a priori-selected Porphyromonas (Beta = 0.14, P = 0.03), Peptostreptococcus (Beta = 0.14, P = 0.03), and Prevotella (Beta = 0.13, P = 0.04). Fusobacterium and Bacillus were more abundant among EoCRC cases than LoCRC cases. In turn, Prevotella was associated with a 47% higher risk of mortality per 1-SD increase (95% CI = 1.19, 1.81; P < 0.001). Fusobacterium was not associated with mortality, but Bacillus was inversely associated with mortality.

CONCLUSION: We found that age at diagnosis was associated with the relative abundance of several bacteria, including oral-origin genera that were previously CRC-associated, in CRC normal adjacent tissue. In turn, some of these bacteria were associated with survival, suggesting potential age-related mechanisms underlying associations of the microbiome with survival.

Emerging evidence has highlighted the important role of the microbiome in colorectal cancer (CRC). Since the 1990s, there has been an increase in cases of early-onset colorectal cancer. However, there is still a limited understanding of the risk factors contributing to this rise. Investigating the associations between the microbiome of tumors and normal adjacent tissue in relation to aging offers a unique perspective on potential modifiable factors. Notably, our study has shown that age-related changes in the abundance of bacteria originating from the oral cavity, such as Porphyromonas, Peptostreptococcus, and Prevotella, are linked to CRC prognosis. These findings suggest that changes in the tissue microbiome with age may serve as prognostic markers for CRC and could help inform future prevention strategies that consider dietary and oral health interventions.}, } @article {pmid41437386, year = {2025}, author = {Aminu, S and Ascandari, A and Mokhtar, MM and Allali, AE and Benhida, R and Daoud, R}, title = {Genome-resolved surveillance and predictive ecological risk modeling of urban microbiomes.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02315-3}, pmid = {41437386}, issn = {2049-2618}, abstract = {BACKGROUND: Human-built environment microbiomes mediate pathogen persistence and antimicrobial resistance (AMR) circulation, yet their ecological organization and resilience remain poorly quantified. Hospitals, sewage systems, ambulances, and public transport form interconnected microbial networks where contamination potential and compositional stability define biosurveillance risk. Understanding these dynamics requires genome-resolved frameworks capable of linking community composition to ecological behavior.

METHODS: We analyzed 767 publicly available Illumina metagenomes from four urban environments using the GRUMB workflow. Quality-filtered reads were assembled into 10,834 metagenome-assembled genomes (MAGs) and dereplicated into 1542 species-level representatives. Functional annotation with CARD and VFDB identified ARG- and VF-carrying species, producing a genome-resolved abundance matrix used for ecological and predictive modeling. Alpha and beta diversity, indicator taxa, and prevalence were assessed in R, while machine learning (Random Forest, scikit-learn) achieved a nested cross-validation balanced accuracy of 0.97 ± 0.01. Synthetic donor-recipient simulations (α = 0-1) implemented in Python modeled compositional blending, entropy-based uncertainty, and Minimal Detectable Contamination (MDC) thresholds.

RESULTS: Microbial communities exhibited strong environment-specific structure (PERMANOVA R[2] = 0.12, p < 0.001). Hospital sewage contained the highest richness and compositional heterogeneity, whereas ambulances and hospital environments showed low-diversity, surface-filtered microbiomes. Machine learning identified consistent ecological predictors (Pseudomonas_E fragi, Sphingomonas sp000797515, Acinetobacter variabilis, Roseomonas mucosa) that delineated environmental identity. Synthetic blending revealed a directional source-sink hierarchy with hospital sewage acting as the primary donor (MDC = 0.2-0.3), while hospital environments displayed the greatest compositional resilience (MDC ≥ 0.8). Entropy-based uncertainty analysis identified tipping zones (α = 0.3-0.5), and dominance mapping highlighted hospital environments as stabilizing ecological nodes. WHO-priority pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli) occupied central positions in the network, bridging environmental and clinical compartments.

CONCLUSIONS: This genome-resolved and simulation-driven framework reveals a directional microbial continuum across urban infrastructures governed by dominance, resilience, and clinical connectivity. Hospital sewage functions as a microbial donor, while hospital environments act as ecological stabilizers anchoring built-environment microbiomes. These findings advance biosurveillance from descriptive profiling to predictive ecological modeling, offering quantitative metrics for risk-informed infrastructure design. Video Abstract.}, } @article {pmid41437366, year = {2025}, author = {Park, Y and Yang, J and Son, H and Park, MJ and Moon, SJ and Kim, KJ and Kwok, SK}, title = {Distinct gut microbiome profiles in Korean systemic lupus erythematosus patients.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-025-07438-7}, pmid = {41437366}, issn = {1479-5876}, abstract = {BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with systemic inflammation and multi-organ involvement. Emerging evidence suggests that gut microbiota dysbiosis may contribute to its immunopathogenesis.

OBJECTIVE: This study aimed to characterize gut microbial composition and diversity in Korean SLE patients and evaluate associations with clinical features.

METHODS: Fecal samples from 157 SLE patients and 50 healthy controls (HC) were analyzed using 16S rRNA gene sequencing. Alpha and beta diversity metrics were assessed, and taxonomic differences were analyzed. Subgroup comparisons were conducted based on lupus nephritis (LN) status and disease activity. Functional predictions were inferred using PICRUSt2.

RESULTS: SLE patients exhibited significantly reduced microbial richness (Chao1, ACE, Fisher indices), while evenness (Shannon, Simpson) was preserved. Beta diversity analysis revealed distinct clustering between SLE and HC groups. SLE was characterized by enrichment of Bacteroides, Streptococcus, and Veillonella, and depletion of Collinsella, Ruminococcus, and Bifidobacterium. LEfSe identified several discriminatory taxa. However, no significant microbial differences were observed between LN-positive and LN-negative groups or between high and low disease activity groups. Functional prediction revealed minimal differences in microbial pathways between groups.

CONCLUSION: These findings highlight distinct gut microbial alterations in Korean SLE patients and support the potential utility of microbiome profiles as diagnostic biomarkers or therapeutics.}, } @article {pmid41437272, year = {2025}, author = {Zhu, W and Li, F and Lin, D and Cai, L and Dai, C and Liu, H and Lin, Y}, title = {The airway mycobiome in chronic respiratory diseases: current advances and future frontiers.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1411}, pmid = {41437272}, issn = {1479-5876}, } @article {pmid41437205, year = {2026}, author = {Dinesh, D and Morgan, XC and Kim, H and Scott, TM and Garelnabi, M and Lee, JS and Mangano, KM and Nguyen, LH and Huttenhower, C and Tucker, KL and Palacios, N}, title = {Gut Microbial Variations Associated With Proton Pump Inhibitor Use in the Boston Puerto Rican Health Study.}, journal = {Pharmacology research & perspectives}, volume = {14}, number = {1}, pages = {e70205}, doi = {10.1002/prp2.70205}, pmid = {41437205}, issn = {2052-1707}, support = {RF1AG075922/AG/NIA NIH HHS/United States ; P01 AG023394/NH/NIH HHS/United States ; P50 HL105185/NH/NIH HHS/United States ; R01 AG055948/NH/NIH HHS/United States ; R01 NS09772/NH/NIH HHS/United States ; //University of Massachusetts/ ; }, mesh = {Humans ; *Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Female ; Male ; Aged ; Middle Aged ; Prospective Studies ; Boston ; Cross-Sectional Studies ; Puerto Rico/ethnology ; Hispanic or Latino ; Feces/microbiology ; White ; }, abstract = {Proton pump inhibitors (PPI), used to treat gastrointestinal disorders, are associated with alterations in the gut microbiome. However, this is understudied in Puerto Ricans who have unique lifestyle characteristics. Puerto Ricans, including participants of the Boston-Puerto Rican Health Study (BPRHS), report high PPI use. Therefore, we examined gut microbial variations associated with PPI use in the BPRHS. BPRHS is a prospective cohort. 309 BPRHS participants self-reported PPI use and self-collected, metagenomically profiled, stool samples. PPI use was classified as any use in the past 30 days. Cross-sectional associations between gut microbial taxa, functional pathways, and PPI use were examined using omnibus analyses, multivariate linear modeling in MaAsLin2, and random forest classifier in feature-wise analyses. We further compared our results with the non-Hispanic Health Professionals Follow-Up Study (HPFS) to validate key findings and examine ethnicity-related differences. Among 309 participants (mean age 68.8 years; female 74.6%), 112 (36%) self-reported PPI use. After adjusting for relevant covariates, we observed an enrichment of Streptococcus parasanguinis (β = 3.16, FDR p = 0.01), S. anginosus (β = 2.89, FDR p < 0.01), S. salivarius (β = 2.56, FDR p = 0.01), S. gordonii (β = 1.98, FDR p = 0.15), and Rothia mucilaginosa (β = 1.54, FDR p = 0.06), among PPI users compared to non-users. Streptococci, Lactobacilli, and Enterococci predominantly contributed to the functional pathways associated with PPI use. The observed enrichment of oral-typical taxa, such as Streptococci, among PPI users in the BPRHS suggests the potential of PPIs to alter gut microbial composition. More studies are needed to understand the impact of PPI use on the gut microbiome in different ethnicities. Trial Registration: Parent study (BPRHS) NCT01231958.}, } @article {pmid41437183, year = {2025}, author = {Cai, X and Sun, T and Feng, M and Chen, G and Zhou, J and Zhuang, H and Wang, D and Chen, Y and Cheng, Z and Xu, Z and Zheng, X and Zhang, X and Yuan, Y}, title = {Taurocholic Acid Is Associated With Disturbed Functional Connectivity in the Hippocampus of Patients With Depression.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e08693}, doi = {10.1002/advs.202508693}, pmid = {41437183}, issn = {2198-3844}, support = {2024YFA1308200//National Key Research and Development Program of China/ ; 82571747//National Natural Science Foundation of China/ ; 82271570//National Natural Science Foundation of China/ ; BK20240095//Outstanding Youth Talent funding of Jiangsu Province/ ; GSP-LCYJFH12//Jiangsu Province High-Level Hospital Construction Funds to Zhongda Hospital Affiliated to Southeast University/ ; }, abstract = {Major Depressive Disorder (MDD) is characterized by abnormal metabolic profiles along the microbiome-gut-brain axis. Bile acids (BAs), a class of steroid compounds regulated by the host and microbes, are increasingly shown to become dysregulated in models of depression. However, the identity of key regulatory BA metabolite in patients with MDD and associated mechanism remain to be clarified. Here, a prospective observational study in patients with depression (n = 235) and control subjects (n = 232) for identifying functional BA metabolites regulating depressive behavior and brain functional connectivity is performed. Using comparative metabolomics assay, an increased level of taurocholic acid (TCA) in the serum of patients with MDD is observed, which is reversed by anti-depressant treatments. Transferring fecal microbiome from patients with MDD induced TCA accumulation to the hippocampus of recipient mice exhibiting depression-like behavior. TCA supplementation suppressed hippocampal neurogenesis, triggered microglial activation, and elicited depression-like behavior in mice, which are alleviated by a sphingosine-1-phosphate receptor 2 (S1PR2) antagonist. In patients with MDD, functional neuroimaging and spearman correlation analysis revealed that circulating TCA is strongly correlated with functional connectivity in the subregions of hippocampus. The results highlight the potential of harnessing TCA as a prognostic marker and therapeutic target for depression.}, } @article {pmid41437143, year = {2025}, author = {Yang, C and Yue, H and Sun, A and Feng, Z and Feng, H and Zhang, Y and Zhao, L and Zhou, J and Zhu, H and Wei, F}, title = {Intercropping-mediated enrichment of core microbiome enhances suppression of Verticillium wilt in cotton.}, journal = {Environmental microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40793-025-00840-0}, pmid = {41437143}, issn = {2524-6372}, support = {2024D14007//Tianshan Innovation Team Project/ ; TCYC2023TP02//Xinjiang Tianchi Talents Program/ ; 2022YFD1400300//National Key R&D Program of China/ ; }, abstract = {BACKGROUND: Verticillium wilt, caused by Verticillium dahliae Kleb., is a devastating soilborne disease threatening global cotton production. Intercropping is a sustainable agricultural practice known to suppress soilborne diseases, yet the microbiome-mediated mechanisms underlying its efficacy against Verticillium wilt remain poorly understood.

RESULTS: A three-year field trial (2019-2021) showed that intercropping cotton with mustard significantly reduced Verticillium wilt severity (32.11-39.2%), increased yield (13.88-23.22%), and lowered soil microsclerotia density. Intercropping reshaped soil microbial communities and enriched a core set of beneficial taxa compared to monocropping, generating more complex and cooperative rhizosphere networks during flowering and boll stage. We then constructed an intercropping-enriched synthetic community (IC-SynCom) from the enriched core microbiotas with multiple beneficial traits; this consortium, comprising Bacillus altitudinis strain CRB-021, Lysobacter firmicutimachus strain CRB-253, Rhizobium soli strain CRB-314, Enterobacter hormaechei strain CRB-070, and Pantoea sp. strain CRB-006, achieved the highest control efficacy at 72.83 ± 1.31%, promoted cotton growth, and outperformed single-strain inoculants. qRT-PCR further showed that IC-SynCom activated systemic plant defenses by the upregulation of key defense-related genes, including phenylalanine ammonia-lyase (GhPAL), cinnamate 4-hydroxylase (GhC4H1), pathogenesis-related protein 10 (GhPR10), peroxidase (GhPOD), and β-1,3-glucanase (Ghβ-1,3-glucanase), which are involved in salicylic acid signaling and lignin biosynthesis.

CONCLUSIONS: Our findings demonstrate that intercropping enhances soil's capacity to suppress Verticillium wilt by reshaping root-associated microbiomes. A core consortium of intercropping-enriched beneficial microbes (IC-SynCom) effectively suppresses Verticillium wilt through direct antagonism and activation of plant immunity. These results highlight the potential of microbiome-based strategies for sustainable management of soilborne diseases.}, } @article {pmid41437131, year = {2025}, author = {Orel, N and Fadeev, E and Celussi, M and Turk, V and Klun, K and Afjehi-Sadat, L and Herndl, GJ and Tinta, T}, title = {Down the drain: exploring wastewater's role in coastal microbiome transformations.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02298-1}, pmid = {41437131}, issn = {2049-2618}, support = {P1-0237//The Slovenian Research and Innovation Agency/ ; P4-0432//The Slovenian Research and Innovation Agency/ ; I 4978-B//Austrian Science Fund/ ; 10046144//INTERREG Italy - Croatia/ ; }, abstract = {BACKGROUND: Many coastal ecosystems worldwide are impacted by wastewater discharges, which introduce nutrients, pollutants, and allochthonous microbes that can alter microbiome composition and function. Although the severity and distribution of these impacts vary across regions, their potential consequences for key ecological processes remain a concern. The resilience and functional adaptability of native coastal microbiomes are still poorly understood. To study the immediate ecological impact of wastewater discharge on a coastal seawater microbiome, we conducted short-term microcosm experiments, exposing a coastal microbiome to two types of treated wastewater: (i) unfiltered wastewater containing nutrients, pollutants, and allochthonous microbes; and (ii) filtered wastewater containing only nutrients and pollutants.

RESULTS: By integrating multi-omics and metabolic assays, we show that wastewater-derived organic matter and nutrients (mostly ammonia and phosphate) did not alter the taxonomic composition of the coastal microbiota, but triggered reorganization of metabolic pathways in them. We observed enhanced metabolism of proteins, amino acids, lipids, and carbohydrates, particularly of the lineages Alteromonadales, Rhodobacterales, and Flavobacteriales. Glaciecola (Alteromonadales), a copiotroph with antagonistic traits, significantly contributed to these shifts. Conversely, allochthonous taxa like Legionellales and Pseudomonadales had minimal impact. Elevated phosphorus concentrations resulting from wastewater input reduced the synthesis of proteins linked to scavenging phosphorus from organic phosphorus compounds, including alkaline phosphatase activity in native Rhodobacterales and Flavobacteriales, with important ecological implications for phosphorus-depleted coastal ecosystems. Furthermore, the presence of wastewater caused a decline in relative abundance and metabolic activity of Synechococcus, potentially affecting carbon cycling. Yet, the coastal microbiome rapidly respired wastewater-derived dissolved organic carbon, resulting in bacterial growth efficiencies consistent with global coastal averages.

CONCLUSIONS: Our findings highlight the capacity of coastal microbiomes to withstand wastewater discharge, with critical implications for assessment of anthropogenic perturbations in coastal ecosystems. However, wastewater-driven changes in metabolic functions and niche utilization within the autochthonous microbial community, impacting phosphorus cycling and potentially affecting carbon cycling, may have long-term consequences for ecosystem functioning. Video Abstract.}, } @article {pmid41437105, year = {2025}, author = {Son, Y and He, P and Craft, EJ and Piñeros, MA and Baldwin, M and Wang, Z and Gu, AZ and Kao-Kniffin, J}, title = {Synergistic enhancement of Sorghum bicolor nutrient uptake and growth by microbiomes in enhanced biological phosphorus removal system and arbuscular mycorrhizal fungi.}, journal = {Environmental microbiome}, volume = {20}, number = {1}, pages = {155}, pmid = {41437105}, issn = {2524-6372}, support = {PS00298891//Fulbright Program/ ; 2019-67013-29364//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Understanding soil microbial interactions is essential for developing biofertilizers in regenerative agriculture. Polyphosphate-accumulating organisms (PAOs) play a pivotal role in enhanced biological phosphorus removal (EBPR) systems by sequestering phosphorus from wastewater and storing it as intracellular polyphosphate. However, their role in terrestrial phosphorus cycling remains poorly characterized, despite their potential to serve as a reservoir of plant-available phosphorus. This study investigates PAO-enriched microbiomes in the sorghum rhizosphere, focusing on their novel interactions with arbuscular mycorrhizal fungi (AMF). By integrating PAOs derived from EBPR biosolids and compost with AMF, we assessed their synergistic effects on plant growth and nutrient uptake in Sorghum bicolor (sorghum), as well as their broader influence on rhizosphere microbial traits and functional dynamics.

RESULTS: We employed plant biometry analysis, nutrient assays, [31]P NMR spectroscopy, single-cell Raman microspectroscopy (SCRS), and microbiome profiling to comprehensively evaluate rhizosphere microbial interactions and their effects on plant physiology and nutrient dynamics. [31]P NMR confirmed polyphosphate accumulation by PAOs derived from both compost and EBPR biosolids, demonstrating the soil adaptability of EBPR-derived PAOs. AMF showed enhanced synergy with EBPR-derived microbiomes, significantly enhancing sorghum growth, nutrient acquisition, and microbial diversity. Key PAOs, Thauera, Rhodanobacter, and Paracoccus, were successfully incorporated into the rhizosphere and positively correlated with improved phosphorus uptake. PICRUSt2 analysis indicated enrichment of microbial functions linked to motility and xenobiotic metabolism in EBPR-treated rhizospheres. SCRS revealed AMF-induced phenotypic shifts in EBPR-derived microbiomes, while network analysis showed that AMF reorganized community connectivity, fostering novel microbial interactions in EBPR-amended environments.

CONCLUSIONS: This study explored the interactions between AMF and microbiomes derived from EBPR biosolids, in comparison with those from compost, uncovering novel microbial synergies that enhance phosphorus uptake in Sorghum bicolor and promote plant productivity. The findings underscore the potential of targeted microbial co-inoculation such as integrating EBPR microbiomes with AMF as an innovative strategy for improving soil fertility and advancing biofertilizer development through microbial-driven nutrient recycling. By harnessing wastewater-derived phosphorus via PAOs, this approach offers a sustainable alternative to conventional fertilization, supporting regenerative agriculture, nutrient circularity, and the broader application of microbial biofertilizers in crop production.}, } @article {pmid41437084, year = {2025}, author = {Jiang, W and Chen, R and Song, L and Qin, L and Xu, X and Li, X and Zhao, L and Lyu, J and Wang, X and Wang, G and Chen, X and Liu, Y and Wang, M and Yin, C and Wang, Y and Mao, Z}, title = {From metabolic fingerprints to field solutions: engineering the apple rhizosphere microbiome via host-directed Bacillus recruitment for sustainable apple replant disease control.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02301-9}, pmid = {41437084}, issn = {2049-2618}, support = {CARS-27//China Agriculture Research System of MOF and MARA/ ; 2022TZXD0037//Key R&D program of Shandong Province/ ; 2023YFD2301003//National Key Research and Development Program/ ; }, abstract = {BACKGROUND: The rhizosphere microbiome, as the second genome of plant immunity, forms a critical ecological barrier in plant-pathogen interactions. However, its functional mechanism in resisting the replanting disease pathogenic Fusarium proliferatum MR5 in apples has not been systematically elucidated. This study employed an integrated multi-omics approach to investigate the rhizosphere mechanisms of resistant (CG935) and sensitive (M9T337) apple rootstocks, aiming to uncover the metabolic and microbial interactions underlying apple replant disease resistance.

RESULTS: Multiple omics joint analysis found that the infection of Fusarium proliferatum MR5 triggered the activation of a specific lysine biosynthesis pathway in resistant rootstocks, and the expression levels of key rate limiting enzymes aspartate kinase and dihydrodipicolinate synthase were significantly upregulated by 2.79 ~ 6.81 times compared to M9T337. Along with the metabolic reprogramming process, the efflux of lysine from the rhizosphere increased, and Bacillus with broad-spectrum antibacterial activity were specifically recruited, increasing its relative abundance by 40.73%. In vitro assays demonstrated that the recruited Bacillus suppressed Fusarium spore germination and disrupted mycelial growth through the production of antifungal compounds, including 2,4-di-tert-butylphenol and bacillomycin. Potted experiments have confirmed that the synergistic treatment of Bacillus and lysine significantly reduces the number of pathogenic Fusarium in the rhizosphere, increases soil enzyme activity, and reshapes a more stable rhizosphere bacterial community structure by enhancing the modularity (the degree of modularity in microbial network structure) of the microbial network. This collaborative strategy effectively alleviates the physiological damage of apple seedlings under replanting stress, resulting in a 31.18% increase in plant fresh weight. Field validation experiments further demonstrate that this strategy can promote the growth of replanted apple saplings and reduce the occurrence of apple replant disease.

CONCLUSIONS: Our findings elucidate an apple replant disease resistance mechanism in apple rootstocks involving lysine-mediated recruitment of protective Bacillus, which enhances rhizosphere microbiome stability and suppresses soil pathogenic Fusarium. Developed a technology for synergistic control of apple replant disease using Bacillus-lysine. The research results provide theoretical basis and practical solutions for green control of apple replant disease based on precise regulation of rhizosphere microbiome. Video Abstract.}, } @article {pmid41436928, year = {2025}, author = {Nath, S and Mittinty, M and Zilm, P and Santiago, PHR and Ketagoda, DKH and Jamieson, L and Weyrich, L}, title = {Super donor assessment tool for oral microbiome transplantation.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04630-z}, pmid = {41436928}, issn = {1471-2180}, support = {2019/GNT1187737//National Health and Medical Research Council/ ; }, abstract = {AIMS: Oral microbiome transplantation (OMT) involves transferring microbiota from donor to recipient. However, selecting suitable donors remains challenging due to a lack of standardised guidelines. This study developed a novel super donor assessment tool (SDAT) combining a multi-criteria decision-making (MCDM) process and an analytical hierarchical process (AHP) to identify OMT "super donors" for dental caries prevention.

METHODS: This cross-sectional study used four sequential screening phases with data from 93 healthy participants, capturing socio-demographics, lifestyle, dietary and oral health behaviours. The SDAT employed MCDM, AHP, combining criteria with normalised and weighted ranks to establish the top 10 donors for three models: "Optimal donor" (Model 1), "Ideal donor" (Model 2), and "Sub-optimal donor" (Model 3). Donor plaque samples underwent 16S ribosomal RNA amplicon sequencing for microbial profiling, examining alpha and betadiversity, differential abundance, and network analysis.

RESULTS: Alpha diversity analysis showed significant differences among groups (Kruskal-Wallis p < 0.001), with Model 1 showing the lowest diversity and Model 3 the highest. Beta diversity analysis using Permutational Multivariate Analysis of Variance revealed significant differences in microbial community composition (R² = 0.19, p = 0.001). Differential abundance analysis (False Discovery Rate < 0.05, controlling for age and sex) identified health-associated genera (Neisseria, Lautropia, Streptococcus, Veillonella) in Model 1, whereas Model 3 showed higher levels of disease-associated taxa (Treponema, Capnocytophaga). Network analysis revealed that Model 1 was organised around Actinomyces and Prevotella, Model 2 around Rothia and Haemophilus, and Model 3 was dominated by pathogenic taxa.

CONCLUSION: SDAT provides a systematic, transparent framework for super-donor selection, ensuring precision and reproducibility in donor rankings. The scoring system standardises the donor selection process, the effectiveness of donor screening, and reduces the risk of adverse events for OMT.}, } @article {pmid41436743, year = {2025}, author = {Prajapati, SK and Shukla, R and Kumar, V and Yadav, D and Lekkala, L and Szekeres, C and Ma, Y and Jain, S and Yadav, H}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e102998}, doi = {10.1002/alz70855_102998}, pmid = {41436743}, issn = {1552-5279}, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/immunology ; Aged ; Female ; *Cognitive Dysfunction/immunology/microbiology ; Middle Aged ; *Alzheimer Disease/immunology/microbiology ; Aged, 80 and over ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) pathogenesis has been linked to the microbiota-immune-brain axis; however, the relationship between gut microbiota, immune activity, and cognitive impairment remains unclear. Thus, this study examines the connection between intestinal microbial composition, immune cell phenotype, and cognitive function in older adults.

METHOD: Data and biological samples were obtained from participants aged ≥60 years (Control, n = 30; mild cognitive impairment (MCI), n = 30) from the MiaGB (Microbiome in Aging Gut and Brain) consortium, a multi-site, clinical study. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) scores, immunophenotyping through flow cytometry, stool microbiome analysis using whole-genome metagenomics, and bulk transcriptomics analysis was carried out.

RESULTS: The abundance of immune cells such as granulocytes, lymphocytes, T-cells, and NK cells was significantly decreased in MCI group. Interestingly, the levels of CD4+ were reduced while CD8+ cells increased in MCI participants compared to controls. Microbial profiling revealed distinct bacterial signatures, with MCI participants showing higher relative abundances of Eubacterium hallii, Parabacteroides distasonis, Eggerthella_sp_CAG_298, Dorea formicigenerans and Alistipes finegldii. Differential expression analysis of transcriptomics data identified 1632 upregulated and 240 downregulated genes. Gene ontology and pathway analysis revealed that upregulated genes are involved in several immune functions such as response to stimulus, adaptive immune response, lymphocyte, and T cell activation, while downregulated genes are linked to nervous system functions and signaling processes such as neuron projection. Transcriptomics analysis further highlighted that several downregulated genes are involved in the key pathways that participate in the neural functions.

CONCLUSION: These distinct bacteria, immune cells, and gene expression profiles suggest that alterations in immune cell populations, gene expression, and gut microbiota are associated with cognitive function in aging, highlighting potential interactions between the microbiota-immune-brain axis and cognitive impairment.}, } @article {pmid41436619, year = {2025}, author = {Do Nascimento, S and Theodosiou, AA and Sergaki, C}, title = {Microbiotoxicity: an under-recognised player in drug efficacy, toxicity, and health outcomes.}, journal = {npj antimicrobials and resistance}, volume = {3}, number = {1}, pages = {102}, pmid = {41436619}, issn = {2731-8745}, abstract = {The gut microbiome regulates immunity, inflammation, and metabolism. Disruption by antibiotic and non-antibiotic drugs, termed microbiotoxicity, may impair efficacy of treatments, including cancer immunotherapy and vaccination, and contribute to antimicrobial resistance (AMR). This review explores microbiotoxicity's clinical impacts, highlighting non-antibiotic drug effects. Further research into drug-microbiome interactions in future may help inform prescribing practices and drug development as a way to improve health outcomes, reduce toxicity, and support AMR stewardship.}, } @article {pmid41436524, year = {2025}, author = {Frey, DL and Helm, B and Guerra, M and Hagner, M and Lu, J and Dittrich, AS and Wege, S and Eberhardt, R and Herth, FJF and Sommerburg, O and Schultz, C and Dalpke, AH and Klingmüller, U and Mall, MA and Boutin, S}, title = {SputOMICs identifies common and distinct markers in cystic fibrosis and chronic obstructive pulmonary disease.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44418}, pmid = {41436524}, issn = {2045-2322}, abstract = {Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are muco-obstructive lung diseases. Knowledge of molecular processes has much improved therapeutic options in CF, whereas much less is known for COPD, a disease affecting an increasing number of patients. Here, we report a multilayer workflow integrating microbiome, inflammation and proteome profiling with clinical data to identify disease specific characteristics in sputum. Our proof-of-concept study shows that CF sputum is dominated by Pseudomonas and Staphylococcus, exhibits heightened neutrophilic inflammation, and a severe protease-antiprotease imbalance. In contrast, COPD displays heterogeneous microbiome composition, eosinophilic inflammation, and altered extracellular matrix remodeling. Proteome-based cellular deconvolution identifies disease-specific immune cell signatures, underscoring the complexity, especially in COPD. Multi-omics factor analysis suggests that matrisome and nucleotide metabolism changes may act as disease discriminators, though future confirmation in larger cohorts is needed. These findings highlight the potential of our integrated approach to uncover sputum biomarkers as tools for patient stratification and personalized therapeutic strategies in CF and COPD.}, } @article {pmid41436448, year = {2025}, author = {Manghi, P and Antonello, G and Schiffer, L and Golzato, D and Wokaty, A and Beghini, F and Mirzayi, C and Long, K and Gravel-Pucillo, K and Piccinno, G and Gamboa-Tuz, SD and Bonetti, A and D'Amato, G and Azhar, R and Eckenrode, K and Zohra, F and Giunchiglia, V and Keller, M and Pedrotti, A and Likhotkin, I and Elsafoury, S and Geistlinger, L and Blanco-Miguez, A and Thomas, AM and Zolfo, M and Ramos, M and Valles-Colomer, M and Tamburini, S and Asnicar, F and Jones, HE and Huttenhower, C and Carey, V and Davis, S and Pasolli, E and Oh, S and Segata, N and Waldron, L}, title = {Meta-analysis of 22,710 human microbiome metagenomes defines an oral-to-gut microbial enrichment score and associations with host health and disease.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-66888-1}, pmid = {41436448}, issn = {2041-1723}, support = {5R01CA230551//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; 5R01CA230551//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {Large public datasets of the human microbiome now exist but combining them for large-scale analysis is difficult due to a lack of standardization. We developed curatedMetagenomicData (cMD) 3, a uniformly processed collection of over 22,000 human microbiome samples with manually curated metadata from 94 studies and 42 countries. This large and diverse resource allows for meta-analysis of the links between microbes and human health. Through meta-analysis, we identified hundreds of microbial species and thousands of microbial functions significantly associated with a person's sex, age, body mass index, and disease status, and catalog these as references. We developed an "oral enrichment score" (OES) based on the relative abundance of bacteria typically found in the oral cavity and not in the gut. Higher OES in the gut is a consistent feature in individuals with disease, suggesting that the relative abundance of oral bacteria in the gut is a simple and quantifiable signal of altered microbiome health. These analyses identify modest but widely shared patterns in human microbiomes, serving as a reproducible and readily updatable reference.}, } @article {pmid41436256, year = {2025}, author = {Viganò, P and Abodi, M and Benaglia, L and Bolis, I and Casalechi, M and Ferraro, C and Li Piani, L and Reschini, M and Ruggiero, F and Salmeri, N and Somigliana, E and Horne, AW and Nap, AW and Dolmans, MM and , }, title = {Effectiveness of an anti-inflammatory diet before in vitro fertilisation in women with endometriosis: protocol for a randomised controlled trial.}, journal = {BMJ open}, volume = {15}, number = {12}, pages = {e108596}, doi = {10.1136/bmjopen-2025-108596}, pmid = {41436256}, issn = {2044-6055}, mesh = {Humans ; Female ; *Fertilization in Vitro ; *Endometriosis/complications/diet therapy ; *Infertility, Female/etiology/therapy/diet therapy ; Adult ; Randomized Controlled Trials as Topic ; Quality of Life ; Ovulation Induction/methods ; }, abstract = {INTRODUCTION: Endometriosis is a common, benign, chronic inflammatory disease with multiple consequences, from chronic pain to systemic comorbidities and poor quality of life. As it usually affects people of reproductive age, one of the most distressing consequences is infertility, which can be only partly overcome by medically assisted reproduction. Poor outcomes are, in fact, frequent adverse events. As no definitive therapy exists for endometriosis-related infertility, affected women often tend to try either complementary and alternative medicine or self-management strategies to improve their quality of life, with the hope of also enhancing their fertility. Among available options, dietary interventions are commonly explored, even if no robust evidence is available on the optimal type of diet and its effects on reproductive outcomes. This trial will investigate whether an anti-inflammatory dietary intervention can improve fertility outcomes in women affected by endometriosis undergoing in vitro fertilisation (IVF).

METHODS AND ANALYSIS: The DietAry interveNtion in ameliorating fertiliTy parameters in women with Endometriosis undergoing IVF (DANTE) study is a single-centre, randomised, controlled, non-pharmacological interventional trial in patients living with endometriosis who are infertile and require IVF. Participants will be allocated to either a 12-week intervention based on an anti-inflammatory diet or no diet before the beginning of controlled ovarian stimulation. Following baseline assessment, 438 participants aged <40 years with a diagnosis of infertility according to WHO criteria (ie, not conceiving after 12 months or more of regular unprotected intercourse) and a normal ovarian reserve will be randomly allocated to one of the two groups (1:1 ratio). In both groups, the dietary habits of participants will be assessed at baseline, and adherence to the intervention will be monitored throughout the study period via 24-hour recalls and food diaries. Participants will provide biological samples (peripheral blood, vaginal swabs and faeces) before and after the intervention to evaluate potential differences in inflammatory markers and microbiome composition between the two groups and across timepoints (before and after diet in the intervention group). Follicular fluid will be collected at the time of oocyte retrieval to describe potential difference in sex steroid levels. Patients will also complete questionnaires on quality of life, sexual function and symptom severity before and after the intervention to assess differences between the two groups and across time points. The primary outcome will be the rate of inadequate ovarian response (defined as the retrieval of ≤3 oocytes according to the Poseidon 2016 criteria) at the time of oocyte retrieval in the treatment versus the no-treatment groups. Secondary outcomes will include clinical pregnancy and live birth rates, IVF-related embryological outcomes, inflammatory marker levels in peripheral blood, vaginal and bowel microbiota features, steroid composition of follicular fluid, life quality and pain symptoms variation.

ETHICS AND DISSEMINATION: The study has received ethics approval from Comitato Etico Territoriale Lombardia 3 (#5587_18.12.2024). Results will be presented in peer-reviewed journals and at international conferences.

TRIAL REGISTRATION NUMBER: NCT06885125.}, } @article {pmid41436068, year = {2025}, author = {Yang, CY and Jalsrai, A and Hsieh, HM}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e101570}, doi = {10.1002/alz70855_101570}, pmid = {41436068}, issn = {1552-5279}, mesh = {Animals ; Mice ; *Alzheimer Disease/drug therapy/pathology ; Mice, Inbred C57BL ; *Neuroprotective Agents/pharmacology ; Disease Models, Animal ; Mice, Transgenic ; *Polysaccharides/pharmacology ; Male ; Maze Learning/drug effects ; *Plant Extracts/pharmacology ; RAW 264.7 Cells ; *Anti-Inflammatory Agents/pharmacology ; }, abstract = {BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by a progressive decline in cognitive functions. Key pathological features of AD include the accumulation of Aβ plaques, the formation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated Tau, and significant neuronal loss. Neuroinflammation is critical to the pathogenesis of AD, closely linked to the development of these pathological hallmarks and the progression of neuronal damage. Hedysarum, a traditional herbal medicine and dietary supplement with a long history of clinical application, is widely recognized for its health-promoting and disease-managing properties.

METHODS: In this study, we investigated the neuroprotective and anti-inflammatory potential of Hedysarum alpinum L. polysaccharide extracts (HAP) using two models, in vivo 5xFAD mice and in vitro LPS-induced RAW264.7 macrophages. The 4-month-old 5xFAD and wild-type (C57BL/6J) mice were orally administered with HAP (20 mg/kg) or saline vehicle daily for six weeks, respectively. Behavioral tests were conducted during the last two-week treatment to evaluate cognitive functions.

RESULTS: In the Barnes maze, the TG+HAP group exhibited a significantly shorter latency to locate the escape hole during the training phase compared to the TG+saline group. During the probe phase, the HAP-treated group also spent considerably more time in the target quadrant, indicating improved spatial learning and memory. Moreover, in the Y-maze test, 5xFAD mice showed a significantly reduced spontaneous alternation rate compared to wild-type mice, reflecting impaired short-term memory. However, HAP administration significantly improved the spontaneous alternation rate in 5xFAD mice. Furthermore, HAP effectively attenuated LPS-induced activation of the NLRP3 inflammasome in RAW264.7 macrophages by inhibiting the NFκB signaling pathway. HAP significantly reduced LDH release and gene expression levels of pro-inflammatory mediators, including IL-1β, IL-6, TNF-α, and iNOS.

CONCLUSIONS: Our findings demonstrate that HAP significantly reduces inflammation and improves cognitive function in 5xFAD mice. These beneficial effects could be mediated through the modulation of the microbiota-gut-brain axis, which will be further elucidate through analyzing of the gut microbiome composition.}, } @article {pmid41436038, year = {2025}, author = {Zhang, T and Peng, G}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e101496}, doi = {10.1002/alz70855_101496}, pmid = {41436038}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Alzheimer Disease/pathology/metabolism ; *Cognitive Dysfunction/pathology/metabolism ; Aged ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/blood ; *Basal Forebrain/pathology/diagnostic imaging ; Cognition/physiology ; Magnetic Resonance Imaging ; Aged, 80 and over ; }, abstract = {BACKGROUND: Emerging research highlights the role of the gut microbiome in the progress of Alzheimer's disease (AD). Alterations in serum bile acid (BA) profiles, reflecting gut microbial activity, have been observed in AD patients; however, the connection to cognitive decline is still poorly understood. This research aims to deepen our understanding of the complex mechanisms through which the gut microbiome and its metabolites influence cognitive function in AD patients.

METHOD: We analyzed data from 1,414 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 389 cognitively unimpaired controls, 754 mild cognitive impairment (MCI) individuals, and 271 AD patients. We examined 15 BA metabolites and 8 BA ratios to explore their correlations with volumes of the basal forebrain cholinergic system (BFCS) and cognitive performance. We also conducted mediation analyses to assess the role of BFCS in the impact of BA profiles on cognitive function, as well as the role of AD pathology in the effect of BA profiles on BFCS.

RESULT: Associations were observed between serum BA profiles, BFCS volumes, and cognitive performance, even after adjusting for demographic factors. The mediation analysis suggested the mediating role of the BFCS in the relationship between gut microbiota metabolism-related secondary-to-primary BA ratios and cognitive function. Furthermore, the influence of secondary-to-primary BA ratios on BFCS was modulated by tau pathology.

CONCLUSION: Our findings suggest that BFCS may modulate the relationship between BAs and cognitive function, with tau pathology potentially mediating the influence of BAs on BFCS. These results enhance our understanding of the intricate mechanisms through which the brain-gut axis modulates cognitive function in AD.}, } @article {pmid41436029, year = {2025}, author = {Huang, Z and Sekhon, VK and Guo, O and Newman, M and Sadeghian, R and Vaida, ML and Jo, C and Ward, D and Bucci, V and Haran, JP}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e100530}, doi = {10.1002/alz70855_100530}, pmid = {41436029}, issn = {1552-5279}, mesh = {Humans ; *Alzheimer Disease/diagnosis ; *Gastrointestinal Microbiome ; Female ; Male ; Aged ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a complicated neurodegenerative disorder influenced by dynamic interactions among clinical, microbial, and other complex underlying mechanisms. The Alzheimer's Disease Analysis Model Generation 1 (ADAM-1) is an innovative multi-agent large language model (LLM) framework proposed to deal with the complications of analyzing diverse and multi-modal datasets. ADAM-1 integrates clinical datasets, microbiome profiles, and existing Alzheimer's publications using retrieval-augmented generation (RAG) techniques supporting AI agents to enhance diagnostic and analytical capabilities offering unified and comprehensive insights into Alzheimer's disease prognosis.

METHOD: The study incorporates a multi-modal dataset with paired clinical and gut microbiome data from 102 nursing home residents, including 64 healthy controls (HC) and 38 individuals with AD, collected across four facilities in central Massachusetts as part of one of our previous studies. ADAM-1, built on the GPT-4o-mini-2024-07-18 model, integrates three AI agents designed for Alzheimer's binary classification: a computational agent for generating descriptive statistics, a summarization agent for synthesizing insights from the data and knowledge database, and a classification agent for performing binary predictions based on prior outputs. The knowledge database comprises 80,909 Alzheimer's-focused publications from PubMed. Classification performance was assessed using F1 scores across 15 randomized seeds, with comparisons to XGBoost as the baseline model. The study was conducted using Python 3.10.14 on an Ubuntu 24.04.1 LTS workstation with four 3090 GPUs.

RESULT: For Alzheimer's classification, ADAM-1 achieved a mean F1 score comparable to that of XGBoost (p = 0.0967, t-test) while demonstrating significantly reduced F1 score variance (p = 0.0083, F-test), indicating more stable performance across evaluations using 15 randomized seeds. The reduced variance in F1 scores emphasizes the reliability of ADAM-1 in handling relatively small sample data, a common scenario in clinical translational research.

CONCLUSION: ADAM-1 offers a robust and consistent platform for multi-modal data analysis in Alzheimer's research. The system's human-machine interaction through natural language queries enhances data interpretability, expanding and broadening researchers' insights in analyzing such complex datasets. Future versions of ADAM will include blood biomarkers and neuroimaging thus enabling more comprehensive and precise diagnostics, advancing the understanding of the complicated and dynamic underlying mechanisms of Alzheimer's disease progression.}, } @article {pmid41435933, year = {2025}, author = {Ganamurali, N and Sabarathinam, S}, title = {Digoxin-Induced Gut Dysbiosis: Mechanistic Links to Prostaglandin Dysregulation and Lipid Metabolic Imbalance.}, journal = {Prostaglandins & other lipid mediators}, volume = {}, number = {}, pages = {107055}, doi = {10.1016/j.prostaglandins.2025.107055}, pmid = {41435933}, issn = {1098-8823}, abstract = {Digoxin, a cardiac glycoside with established roles in heart failure and arrhythmia, increasingly exemplifies drug-microbiome-host interactions. Its bioavailability and efficacy are profoundly influenced by Eggerthella lenta-mediated reduction, producing inactive metabolites that reshape systemic physiology. Emerging evidence demonstrates that digoxin-induced gut dysbiosis perturbs arachidonic acid metabolism, altering cyclooxygenase-driven prostaglandin production and disrupting vascular tone and inflammatory homeostasis. These changes extend to lipid regulation, where reduced short-chain fatty acid production and bile acid derangements impair hepatic lipid utilization, promoting steatosis and metabolic dysfunction. This review integrates mechanistic insights into digoxin-microbiota interactions, prostaglandin pathway perturbation, and lipid imbalance, emphasizing their clinical significance and therapeutic implications for precision medicine in cardiovascular care.}, } @article {pmid41435858, year = {2025}, author = {Asadullin, A and Kashchenko, G and Klochev, A and Taldaev, A and Adonin, L and Smutin, D}, title = {Meta-analysis of sources and transmission pathways of Apis mellifera (Hymenoptera: Apidae) microbiota based on 16S sequencing data.}, journal = {Journal of insect science (Online)}, volume = {25}, number = {6}, pages = {}, doi = {10.1093/jisesa/ieaf093}, pmid = {41435858}, issn = {1536-2442}, support = {25-26-00381//Russian Science Foundation/ ; }, mesh = {Animals ; Bees/microbiology ; RNA, Ribosomal, 16S/analysis/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria/classification/genetics/isolation & purification ; Honey/microbiology ; }, abstract = {This study investigates the mechanisms governing the formation and transfer of microbial communities associated with the honey bee (Apis mellifera L.) superorganism, focusing on the interplay between plant, in-hive, and bee environments. By analyzing 16S rRNA sequencing data from multiple public datasets through bioinformatics and statistical modeling, we characterized the structure and transmission pathways of these microbiota. Our analysis reveals that each environment hosts a distinct and specialized microbial community, with significant barriers to free microbial exchange. Alpha and beta-diversity analyses confirmed the uniqueness of the bee gut microbiota and the mixed, intermediate nature of the honey microbiome. Structural equation modeling identified that direct microbial transfer from plants to bees is negligible. Instead, honey serves as an obligate intermediary and selective filter, with microorganisms transitioning from plants to honey before a lower-probability transfer to bees occurs. Furthermore, we identified key bacterial taxa, including Apilactobacillus kunkeei, Acinetobacter, and Pseudomonas, that potentially act as generalists capable of persisting across multiple environments. These findings underscore the possibility of the selective bacterial transfer between hives, which may play roles in both pathogens transfer and maintaining hive microbiome stability.}, } @article {pmid41435750, year = {2025}, author = {Maruyama, T and Ogawa, M and Nagai, R and Hirose, K and Iwata, S and Tanaka, G and Ito, T and Kamikawa, M and Kitazawa, H and Uemoto, Y}, title = {Impact of heritable and non-heritable gut microbiota on microbiability estimation and phenotype prediction of production traits in Duroc pigs.}, journal = {Animal : an international journal of animal bioscience}, volume = {20}, number = {1}, pages = {101727}, doi = {10.1016/j.animal.2025.101727}, pmid = {41435750}, issn = {1751-732X}, abstract = {Pig phenotypes are influenced by host genetics and the gut microbiota. However, the impacts of classification methods and the heritability of the gut microbiota on production traits in pigs remain unclear. Here, we evaluated the impacts of the gut microbiota with different classifications and heritabilities on the estimation of microbiability (i.e., the proportion of host phenotypic variance explained by the gut microbiota) and prediction of production traits in Duroc pigs. We identified the most effective microbial classification based on heritability and microbiability; determined the relationship between heritability of the microbiota and host phenotypic values; and investigated the impact of components of the gut microbiota with different heritabilities on microbiability estimation and phenotype prediction. In total, 961 Duroc pigs with both phenotypic and pedigree data were evaluated through bacterial 16S rRNA gene sequencing of the gut microbiotas from faecal samples. Microbiability for all traits was higher when estimated using amplicon sequence variants (ASVs) than when using other microbial classifications. Therefore, the ASV classification was used in subsequent analyses. The microbiability estimates of daily gain (DG) and backfat thickness (BF) (0.21 and 0.15, respectively) were higher than those of other traits, such as body measurement traits (range of 0.00-0.06). In total, 154 of 368 ASVs with high prevalence were significantly heritable in this population. Furthermore, 17 and 27 ASVs exhibited significant heritability and were associated with DG and BF, respectively. Microbiability estimates were high using heritable ASVs in DG (0.08) and using non-heritable ASVs in BF (0.09). Phenotype prediction using a model that included the sum of breeding values and heritable ASV effects had the highest prediction accuracy in DG (i.e., 0.45, compared with 0.20 for a model including breeding values alone). No difference was observed between heritable and non-heritable ASV effects in BF. Our results indicate that the gut microbiota explains a substantial portion of phenotypic variance, and microbial effects can be used to predict DG and BF. Our results indicate that it is important to differentiate between heritable and non-heritable ASVs when evaluating the impact of host genetics and the gut microbiota on host phenotypes in pigs.}, } @article {pmid41435605, year = {2025}, author = {Xu, Y and Yang, W and Yang, Z and Pan, Y and Zhu, Y and Shen, B and Chen, J}, title = {Differential and complementary effects of Baizhu and Fuling on spleen deficiency syndrome by regulating microbiota-gut-metabolite axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157690}, doi = {10.1016/j.phymed.2025.157690}, pmid = {41435605}, issn = {1618-095X}, abstract = {BACKGROUND: Atractylodes macrocephala Koidz. (commonly known as Baizhu, BZ) and Poria cocos (Schwan.) Wolf. (referred to as Fuling, FL) are frequently employed in the treatment of spleen deficiency syndrome (SDS) owing to their spleen-tonifying and dampness-eliminating properties. The combination of the two herbs, referred to as the BZ-FL herb pair, exhibited complementary and enhancing effects. Nevertheless, the distinct and complementary mechanisms and effects of BZ and FL individually remain inadequately understood.

PURPOSE: This study aimed to investigate the differential and complementary effects and underlying mechanisms of BZ and FL on SDS.

METHODS: The chemical components in BZ, FL, and the BZ-FL herb pair were qualitatively and quantitatively analyed using UHPLC-Q Exactive HF-X and UPLC-MS technique. SDS model rats were established by a combination of dietary and fatigue-inducing methods and then treated with BZ, FL, and the BZ-FL herb pair. In order to elucidate the effects on gastrointestinal motility, immune function, and water metabolism, the concentrations of gastrointestinal hormones, low-density lipoprotein, high-density lipoprotein, total cholesterol, serum protein levels, and albumin were measured. Additionally, the levels of IL-2, IgA, IL-4, IgG, and IFN-γ in colon tissue were quantified utilizing enzyme-linked immunosorbent assay (ELISA) and biochemical assays. Pathological changes were examined using hematoxylin and eosin staining, while immunofluorescence was used to measure the levels of the intestinal barrier proteins and aquaporins (Aqps) in colonic tissues. The levels of Aqps and cAMP/PKA/CREB signaling pathway were detected in colon and kidney tissues using western blot analysis. Untargeted metabolomics was used to analyze the serum and feces metabolic profile. The 16S rRNA gene high-throughput sequencing was performed to detect the gut microbiota composition in fecal samples.

RESULTS: The quantification of chemical components revealed that BZ significantly enhanced the dissolution of triterpene acids from FL. BZ, FL, and the BZ-FL herb pair effectively mitigated SDS by modulating gastrointestinal hormones, kidney and colon Aqps, and protein expression within the cAMP/PKA/CREB signaling pathway, while also enhancing intestinal barrier integrity. Serum metabolomics analysis demonstrated that BZ influenced bile acid biosynthesis, FL affected the citrate cycle and glycerophospholipid metabolism, and the BZ-FL herb pair impacted all these pathways. Gut microbiota analysis indicated that the efficacy of the BZ-FL herb pair in ameliorating SDS was associated with a preserved gut microbiome, characterized by the relative abundance of microbial taxa such as Escherichia-Shigella, Kurthia, and UCG-005. Fecal metabolomics analysis indicated that the BZ-FL herb pair synergistically enhances and complements each other by influencing metabolites in butanoate, arginine and proline, starch and sucrose, cysteine and methionine, purine, and propanoate metabolism. Moreover, correlation and comprehensive analyses identified a robust association among SDS phenotypes, serum metabolites, fecal metabolites, and microbial genera. In addition, the BZ-FL herb pair and BZ alone exhibited significantly greater regulatory effects on gastrointestinal function-related indicators compared to FL.

CONCLUSIONS: This study presents initial evidence of the differential and complementary effects of BZ and FL, analyzing their chemical compositions and their influence on water-fluid metabolism and the microbiota-gut-metabolites axis in SDS. These findings reflect the rationality and scientific basis of the compatibility theory. The study identified potential mechanisms of the BZ-FL herb pair in treating SDS, providing a reference for future research and clinical applications.}, } @article {pmid41435506, year = {2025}, author = {Souto-Silva, MV and Bispo, ECI and de Oliveira, NN and Pogue, R and Zonari, A and Saldanha-Araujo, F and Carvalho, JL}, title = {The cytokine-skin barrier axis in health and disease.}, journal = {Cytokine & growth factor reviews}, volume = {87}, number = {}, pages = {113-123}, doi = {10.1016/j.cytogfr.2025.12.009}, pmid = {41435506}, issn = {1879-0305}, abstract = {The skin barrier functions as both a structural defense and an immunological interface that integrates environmental, microbial, and systemic signals. Its disruption predisposes to cutaneous inflammation and contributes to systemic immune dysregulation. In this review, we provide an integrated analysis of how cytokine signaling regulates skin barrier integrity, highlighting both mechanistic insights and clinical implications across health and disease. We first revisit the architecture of the skin barrier and describe common insults that compromise its function, and the mechanisms by which these activate canonical signalling pathways-NF-κB, MAPK, JAK-STAT, and PI3K/Akt/mTOR-leading to the release of cytokines from keratinocytes and immune cells. Particular attention is given to cytokine families with direct relevance for epidermal physiology: IL-1 and IL-17 in antimicrobial defense and hyperinflammation; IL-20, IL-31, and type 2 cytokines in keratinocyte proliferation, differentiation, and barrier protein suppression; and TNF and interferons in amplifying inflammation and tissue injury. We also discuss how these cytokine networks drive systemic manifestations, linking skin barrier dysfunction to atopic dermatitis (AD), psoriasis, inflammaging, and metabolic disorders. Finally, we review therapeutic approaches that target cytokine signaling or restore barrier integrity, ranging from emollients and microbiome-based strategies to biologics and JAK inhibitors. By systematically reviewing the cytokine-barrier axis, this work highlights how modulation of cytokine signaling represents a promising avenue for clinical and preventive interventions in dermatology and systemic health.}, } @article {pmid41435214, year = {2025}, author = {Yoshida-Court, K and Teka, B and Cisneros Napravnik, T and Karpinets, T and El Alam, MB and Firdawoke, E and Chanyalew, Z and Mihret, A and Addissie, A and Gizaw, M and Lan, J and Haymaker, C and Duose, DY and Luthra, R and Colbert, LE and Jhingran, A and Kantelhardt, EJ and Kaufmann, AM and Abebe, T and Klopp, AH}, title = {Linking Microbiome Diversity and Immune Profiles in Ethiopian Patients With Cervical Cancer.}, journal = {JCO global oncology}, volume = {11}, number = {}, pages = {e2500060}, doi = {10.1200/GO-25-00060}, pmid = {41435214}, issn = {2687-8941}, mesh = {Humans ; *Uterine Cervical Neoplasms/immunology/microbiology ; Female ; Ethiopia ; *Microbiota/immunology ; Adult ; Middle Aged ; *Receptors, Antigen, T-Cell/immunology/genetics ; }, abstract = {PURPOSE: This study investigates the interplay between T-cell receptor (TCR) immune characteristics and microbiome profiles to explore the relationship between immune diversity and microbial composition in cervical samples from Ethiopia.

METHODS: Cervical specimens were collected from patients at Tikur Anbessa Specialized Hospital in Addis Ababa, and rural Butajira, south-central Ethiopia. Patient data, including age, human papillomavirus status, pathology, and TCR immune characteristics, were analyzed with a focus on the interactions between TCR profiles and microbiome compositions in malignant samples.

RESULTS: Three distinct TCR profiles were identified: Group 1 (TCR active) exhibited features of active immune engagement, including high diversity, clonal expansion, and repertoire richness. Group 2 (TCR restricted) showed reduced TCR diversity and expansion, suggesting a restricted repertoire. Group 3 (TCR balanced) had moderate diversity and clonal activity. TCR repertoire groups were linked with microbial diversity, with Group 1 (TCR active) showing the highest number of microbes (high operational taxonomic units and microbial diversity). Maximum TCR clonal expansion positivity associated with microbial richness, while Group 3 (TCR balanced) was linked to reduced microbial alpha diversity. Taxonomic analysis revealed specific organisms enriched in TCR repertoire group.

CONCLUSION: Variations in TCR profiles are linked to distinct microbial environments in cervical cancer with greater microbial richness in patients with greater maximum productive frequency. These findings underscore the interplay between TCR diversity, microbiome composition, and malignancy, offering insights into the potential implications for microbiome-targeted therapies and prognostic biomarkers in cervical cancer.}, } @article {pmid41435148, year = {2025}, author = {Katuwawala, KS and Fernando, WMADB and Bharadwaj, P and Martins, RN}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e098838}, doi = {10.1002/alz70855_098838}, pmid = {41435148}, issn = {1552-5279}, mesh = {Humans ; *MicroRNAs/metabolism ; *Alzheimer Disease/diagnosis/metabolism/genetics ; *Gastrointestinal Microbiome/physiology ; Biomarkers/metabolism ; Feces/chemistry ; Brain/metabolism ; }, abstract = {BACKGROUND: Alzheimer's Disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline and memory loss. Emerging research suggests that gut microbiota play a significant role in AD progression through mechanisms like neuroinflammation and neurotransmitter dysregulation. Fecal microRNAs (miRNAs) have gained attention as non-invasive biomarkers reflecting gut-brain communication, offering potential insights into disease pathogenesis and therapeutic targets. This review examines the significance of fecal miRNA profiles in AD, focusing on their role in early diagnosis, disease monitoring, and potential therapeutic intervention.

METHOD: A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2010 to 2023. Inclusion criteria were based on research articles investigating fecal miRNA expression in AD, miRNAs involved in gut-brain communication, and studies highlighting miRNAs as diagnostic or prognostic biomarkers. Search terms such as "Alzheimer's Disease," "fecal microRNA," "gut microbiome," "biomarkers," and "gut-brain axis" were used. A total of 40 studies, including both clinical and preclinical research, met the inclusion criteria and were reviewed.

RESULT: Key miRNAs such as miR-146a, miR-155, and miR-34a were consistently dysregulated, indicating their involvement in neuroinflammatory pathways and synaptic dysfunction. These miRNAs also influenced amyloid precursor protein (APP) processing and tau phosphorylation, critical factors in AD pathogenesis. Additionally, miR-132 and miR-181c were associated with cognitive decline and AD severity, suggesting their potential as non-invasive biomarkers for disease progression. Preclinical studies also demonstrated that dietary interventions and probiotics could modulate fecal miRNA expression, indicating potential therapeutic strategies targeting the gut microbiome.

CONCLUSION: Fecal miRNA profiles offer valuable insights into the gut-brain axis in Alzheimer's Disease and serve as promising non-invasive biomarkers for early diagnosis and disease monitoring. Altered miRNA expression reflects gut dysbiosis and neuroinflammatory responses, making them potential targets for therapeutic interventions. Future research should focus on validating these findings through large-scale clinical trials and exploring how dietary and probiotic treatments can modify miRNA expression to benefit AD patients. This review emphasizes the need for a multidisciplinary approach to better understand the role of the gut microbiome in neurodegenerative diseases and develop novel strategies for AD management.}, } @article {pmid41435039, year = {2025}, author = {Elorriaga, IT and Imatz, E and Ibarlucea, B and Cano, A and Sanmartín, E and Tueros, I and Ayala, U and de Heredia, AG and Zaldua, C and Zugaza, JL and Aleman, IT and Garcia-Sebastian, M and Martínez-Lage, P and Erramuzpe, A}, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e099250}, doi = {10.1002/alz70860_099250}, pmid = {41435039}, issn = {1552-5279}, mesh = {Humans ; Aged ; *Public Health ; Female ; Male ; Aged, 80 and over ; Biomarkers ; Middle Aged ; *Aging ; *Healthy Aging ; }, abstract = {BACKGROUND: The ITTHACA project is a collaborative initiative involving six research institutions from the Basque Country including Universities, Health, Technology and Basic Research Institutions. It builds upon the ongoing CITA GO-ON) CITA Go-On study, ClinicalTrials.gov, NCT04840030) cohort study, which adapts the Finnish FINGER [Ngandu, T., et al. 2015] model to the local context. ITTHACA focuses on enhancing healthy aging by identifying markers, prediction models and sensors for in vivo monitoring that allow the establishment and implementation of combined intervention strategies in the population.

METHOD: This one-year randomized-controlled trial (total n = 250; 125 control and 125 intervention), focused on 60-85-year-old males and females at risk of dementia, adopts a multimodal approach. Biomarker identification includes proteomics and metabolomics in biological fluids (blood) and 16S metagenomics and lipidomics in the gut microbiome (stool), as well as employing a FINGER-like mice model. Biosensor technology under development includes multi-channel bioimpedance spectroscopy for tissue analysis and electrochemical sensors for real-time detection of aging markers in biofluids. Predictive modeling integrates data from these analyses and multiple domains-cognition, cardiovascular health, voice, food texture perception and habits-to generate diagnostic tools that monitor biological aging and inform early interventions. A proof-of-concept study in an older population sample, with special attention to user experience, will evaluate the potential benefits of these findings in improving the quality of life for older adults.

RESULT: Not applicable. The ITTHACA project is ongoing, with outcomes expected to include validated biomarkers, novel biosensors, and predictive models that facilitate early interventions.

CONCLUSION: ITTHACA demonstrates the power of interdisciplinary collaboration in tackling the complex multidomain challenge of aging. By leveraging the expertise of complementary Basque Country Research Centers, this initiative is poised to produce innovative resources for prolonging healthy and autonomous living. The project's outcomes are expected to support new therapeutic strategies and socio-healthcare interventions that address the rising prevalence of aging-related conditions, including cognitive decline.}, } @article {pmid41434948, year = {2025}, author = {Kaiyrlykyzy, A and Zholdasbekova, G and Alzhanova, D and Kozhakhmetov, S and Kushugulova, A and Askarova, S}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e097791}, doi = {10.1002/alz70855_097791}, pmid = {41434948}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Alzheimer Disease/genetics/epidemiology ; Aged ; Kazakhstan/epidemiology ; Polymorphism, Single Nucleotide/genetics ; Gastrointestinal Microbiome ; Cytokines/blood ; Risk Factors ; Cohort Studies ; Middle Aged ; Apolipoproteins E/genetics ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia and a critical social issue. Its multifactorial nature necessitates evaluating risk factors in diverse populations.

METHODS: This study analyzed 181 AD patients and 244 controls in Kazakhstan, comparing clinical, genetic, and microbial traits.

RESULTS: In our cohort, significant dementia-associated variables included smoking, depression, dyslipidemia, insulin resistance, and liver dysfunction. AD patients had higher HDL, bilirubin, AST/ALT ratios, and lower ALT. Genetic analysis identified 13 SNPs linked to AD, notably in APOE, TOMM40, and MED12L genes involved in lipid metabolism, mitochondrial function, and gene transcription. APOE4 increased AD risk 1.9x, with higher prevalence in northern Kazakhstan (Astana). We also found specific alterations in the gut microbiome, specifically, a decreased Firmicutes/Bacteroidetes ratio, a reduced Bifidobacterium, and increased proteobacteria and inflammatory bacteria. The investigation of cytokine profiles demonstrated that pro-inflammatory cytokines such as IFN-γ, IL-6, TNF-β, MCP-1, and IL-17A were significantly elevated in AD patients, along with anti-inflammatory cytokines IL-4 and IL-1RA, suggesting a dysregulated inflammatory response in AD. Additionally, elevated serum adiponectin levels, observed at three times higher than in controls, were strongly correlated with multiple cytokines and specific microbial taxa, such as Actinobacteria and Acidomicrobiia, indicating a potential interplay between gut microbiota, adipose tissue, and neuroinflammation in AD.

CONCLUSION: These findings underscore the importance of considering bio-geographic and environmental factors in AD research. The study's outcomes may aid in further research and the development of personalized approaches for managing and treating AD in distinct geographical regions. Research support: Nazarbayev University Collaborative Research Program Grant [Funder Project Reference: 20122022CRP1602] and the Ministry of Higher Education and Science of the Republic of Kazakhstan Grant [Funder Project Reference: AP14871338].}, } @article {pmid41434766, year = {2025}, author = {Lwere, K}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e097665}, doi = {10.1002/alz70855_097665}, pmid = {41434766}, issn = {1552-5279}, mesh = {Humans ; *Alzheimer Disease/microbiology ; Cross-Sectional Studies ; *Gastrointestinal Microbiome/genetics ; Male ; *Cognitive Dysfunction/microbiology ; Female ; Aged ; *Dysbiosis/microbiology ; Uganda ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Feces/microbiology ; Phylogeny ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of global cognitive decline. However, its mechanisms remain poorly understood in sub-Saharan Africa (SSA), where genetic, dietary, and environmental factors differ significantly. Emerging evidence links the gut microbiota to AD through neuroinflammation and gut-brain axis dysfunction. This study investigated phylogenetic and compositional microbiome shifts in AD, Mild Cognitive Impairment (MCI), and healthy controls in Uganda, providing novel insights into microbial dysbiosis and its role in cognitive decline in low-resource settings.

METHOD: In this cross-sectional study, stool samples from 104 participants (AD: 77; MCI: 14; controls: 13) were analyzed using 16S rRNA sequencing (V3-V4 region), with DADA2 generating amplicon sequence variants (ASVs). Beta diversity was assessed using Weighted UniFrac (phylogenetic differences) and Bray-Curtis (compositional differences) metrics. Principal Coordinate Analysis (PCoA) was used to visualize clustering patterns, whereas group differences were assessed using Permutational Multivariate Analysis of Variance (PERMANOVA) at p < 0.05.

RESULT: Beta diversity analysis revealed distinct microbial shifts that were linked to cognitive decline. Weighted UniFrac PCoA showed clear clustering, with Axis 1 (39.46% variation) separating AD patients from controls and Axis 2 (16.28%) capturing within-group variability, particularly in AD. The MCI group occupied an intermediate position, reflecting the microbial gradient associated with cognitive decline. Confidence ellipses highlighted minimal overlap between AD and controls, whereas MCI partially overlapped with both groups, suggesting a transitional profile. Bray-Curtis PCoA confirmed compositional differences, with PC1 (28.66%) separating AD from controls and PC2 (14.44%) capturing MCI dispersion. PERMANOVA confirmed significant group-level differences (Weighted UniFrac: R² = 0.18, p = 0.001; Bray-Curtis: R² = 0.21, p = 0.001), with the strongest divergence between AD and controls (p = 0.001), and significant differences between AD and MCI (p = 0.005).

CONCLUSION: Distinct microbial shifts across AD, MCI, and control groups highlight the role of the gut microbiome in neurodegeneration. The transitional profile of MCI underscores its potential as an early marker of dysbiosis, supporting the development of microbiome-targeted strategies for the early detection and intervention of Alzheimer's disease.}, } @article {pmid41434746, year = {2025}, author = {Williams, C and Golden, A and Yadav, H and Masternak, MM and , }, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e100453}, doi = {10.1002/alz70860_100453}, pmid = {41434746}, issn = {1552-5279}, mesh = {Humans ; *Public Health ; *Gastrointestinal Microbiome ; *Patient Selection ; }, abstract = {BACKGROUND: Gut microbiota is crucial in nutrient extraction, metabolism, cognition, and immune function. Consequently, the increasing number of microbiome studies aims to link specific bacteria, fungi, and viruses with various cognitive disease outcomes. Unfortunately, clinical studies often exclude many older adults with Alzheimer's Disease and Related Dementia who are homebound or from racially/ethnically diverse populations. The homebound older adult population is estimated to be three times larger than the equally impaired and chronically ill nursing home population. People of color often hesitate to participate in clinical trials due to mistrust, logistical barriers, and lack of awareness. Recruiting a diverse group of patients has been challenging.

METHOD: We review the literature using CINAL, PubMed, Medline, PsycINFO, and Embase to highlight evidence-based strategies for promoting inclusivity among homebound and minority communities in microbiome studies. Additionally, we discussed the inclusion and exclusion criteria necessary for clinical trials.

RESULTS: We identified strategies such as community engagement, culturally appropriate assistance, mobile health units, and strategic partnerships with feedback mechanisms to improve recruitment and retention of underserved populations. We also discussed inclusion and exclusion criteria while highlighting factors that can confound results. While these criteria may complicate trials involving vulnerable populations, they are essential for optimizing outcomes. We must recognize and adequately support these populations while keeping these criteria in mind.

CONCLUSION: This review emphasized recruitment strategies for underrepresented groups in microbiome studies and underscores the importance of inclusion and exclusion criteria to ensure robust study results. Without inclusivity in microbiota clinical trials, we cannot effectively address health inequities or ensure the generalizability of findings. The complexity and long-term nature of these trials suggest that additional support for patients and caregivers may be necessary for participants with cognitive decline. Diverse participation helps uncover variations in disease prevalence, progression, and treatment responses among different populations, leading to more personalized and effective healthcare solutions. It also enhances the overall quality of research by incorporating a wide range of perspectives and experiences.}, } @article {pmid41434707, year = {2025}, author = {Dempsey, DA and Agarwal, P and Fernandez, S and Brosch, JR and Quirke, M and Graham-Dotson, Y and Gao, S and Clark, D and Apostolova, LG and Clark, DG and Farlow, MR and Mathew, S and Unverzagt, F and Wang, S and Diaz, E and Schimmel, L and French, R and Blach, C and Kaddurah-Daouk, RF and Saykin, AJ and Risacher, SL and , }, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e105690}, doi = {10.1002/alz70860_105690}, pmid = {41434707}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; Aged ; *Cognitive Dysfunction/diet therapy ; *Public Health ; Surveys and Questionnaires ; *Diet, Mediterranean ; Middle Aged ; Indiana ; Alzheimer Disease ; Self Report ; Reproducibility of Results ; Aged, 80 and over ; }, abstract = {BACKGROUND: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been associated with cognitive benefits and reduced risk of Alzheimer's disease. Adherence is typically assessed using comprehensive but time-consuming food frequency questionnaires (FFQs). We examined concurrent validity between a brief MIND diet screener and a more extensive FFQ.

METHODS: 94 participants (51 cognitively normal (CN), 31 subjective cognitive decline (SCD), 12 mild cognitive impairment (MCI)) from the Indiana Alzheimer's Disease Research Center (IADRC) who participated in the Alzheimer's Gut Microbiome Project (AGMP) completed both the self-reported 15-item MIND screener and computerized Vioscreen FFQ. For both measures, we used the same cutoff criteria to assign values of 0, 0.5, or 1 corresponding to low, medium, and high intake for the 'healthy' food groups and reverse correspondence for the 'unhealthy' food groups, which were then summed to generate a total MIND diet score (0-15) with higher scores indicating greater adherence. Agreement between the two methods was assessed using Pearson correlation, intraclass correlation coefficient (ICC) for absolute agreement and consistency, and a tertile-based cross-classification. ANOVA was used to test differences in MIND scores between diagnostic groups, adjusting for age, sex, and education.

RESULTS: The mean MIND diet score from the FFQ was 7.49 (range: 2.5-11), and from the screener was 10.05 (range: 5-13.5), with a mean 2.56-point difference showing consistently higher scores on the screener (Figure 1). The screener demonstrated moderate correlation with the FFQ score (r = 0.63, p <0.001, R2=0.40). Absolute agreement was low (ICC=0.34), while consistency was moderate (ICC=0.64) (Figure 2). In cross-classification, 19.15% of individuals were classified into disparate tertiles. A significant difference was observed between CN and MCI groups using both methods, but only the screener-derived score remained marginally significant after adjustments (p = 0.05) (Figure 3).

CONCLUSIONS: The MIND screener shows moderate correlation and consistency with the FFQ, with participants systematically reporting higher scores on the screener, indicating overestimation of their MIND diet score. While the screener does not capture detailed or food item specific dietary variations assessed by the FFQ, it is a valid tool for rapid estimation of MIND diet score and may be useful in research and clinical practice.}, } @article {pmid41434687, year = {2025}, author = {Hisham, HIH and Lim, SM and Ramasamy, K and Majeed, ABA and Shahar, S}, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e106306}, doi = {10.1002/alz70860_106306}, pmid = {41434687}, issn = {1552-5279}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; *Public Health ; Aged ; *Cognitive Dysfunction/microbiology/therapy ; *Frailty/microbiology/psychology ; *Dysbiosis/microbiology ; Exercise ; Feces/microbiology ; }, abstract = {BACKGROUND: Cognitive frailty (CF), a condition characterised by the co-occurrence of physical frailty and cognitive impairment, has been linked to dysregulated gut microbiota (i.e., dysbiosis) and increased intestinal permeability. Emerging evidence suggests that the gut microbiome plays a crucial role in maintenance of gut-brain barrier integrity, suppression of neuroinflammation, regulation of neurotransmitter production, and ultimately promotion of psychological health. This study aimed at examining the effects of a 6-month multidomain intervention (i.e., physical exercise, cognitive training, psychosocial training and nutritional guidance) on gut microbiota composition.

METHOD: A total of 27 CF participants (12 control; 15 intervention) were recruited and stool samples were collected for 16S rRNA sequencing. The stool samples were homogenised, and DNA was extracted, followed by PCR amplification, DNA library preparation, and sequencing. Statistical analysis was performed using GraphPad Prism. Normality was assessed using the Shapiro-Wilk Test, and differences between groups were analysed using the Ordinary One-way ANOVA Test. Correlations between genus abundance and psychosocial parameters were evaluated using Pearson's correlation analysis.

RESULT: Microbiota profiling revealed a significant increase of the Blautia genus in the intervention group (IV6, intervention after 6 months) when compared to the control group (C6, control after 6 months) (p = 0.0132), suggesting a positive shift in gut microbial balance following lifestyle modifications. The Blautia genus abundance was negatively correlated with depression (r = -0.4120, p = 0.0022) and loneliness scores (r = -0.3328, p = 0.0184), indicating its potential protective role against psychosocial factors. On the contrary, the Prevotella genera exhibited a positive correlation with depression scores (r = 0.2820, p = 0.04), reinforcing its association with neuroinflammation which disrupts neurotransmitter balance.

CONCLUSION: The present results highlight the positive impact of lifestyle interventions on gut microbial composition and their possible implications for psychosocial health in older adults with CF. The Blautia genus enrichment may serve as a biomarker or therapeutic target for improving psychosocial well-being in CF individuals. This warrants further investigation of the mechanistic pathways linking gut microbiota modifications with psychosocial outcomes.

FUNDING: This study is part of the Transforming Cognitive Frailty to Later-Life Self-sufficiency (AGELESS) project funded by the Ministry of Higher Education, Malaysia under the Long-Term Research Grant Scheme (LRGS/1/2019/UM/01/1/3).}, } @article {pmid41434599, year = {2025}, author = {Dinesh, D and Morgan, X and Scott, TM and Garelnabi, M and Mangano, KM and Noel, SE and Huttenhower, C and Tucker, KL and Palacios, N}, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e098660}, doi = {10.1002/alz70860_098660}, pmid = {41434599}, issn = {1552-5279}, mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome ; Aged ; *Public Health ; Puerto Rico/ethnology ; Prospective Studies ; Feces/microbiology/virology ; *Cognition/physiology ; Hispanic or Latino ; Boston ; Cross-Sectional Studies ; Dysbiosis ; *Virome ; Aged, 80 and over ; Middle Aged ; Alzheimer Disease ; White ; }, abstract = {BACKGROUND: Gut bacterial variations and dysbiosis may influence cognitive function via the microbiome-gut-brain-axis. Gut viruses may also, directly or indirectly, impact cognitive function by modulating the gut bacteria. Hispanics/Latinos, who may have unique microbiome characteristics, are at a higher risk of Alzheimer's disease and related dementia. There is a lack of research on the gut microbiome and, especially, the virome in Hispanics/Latinos. Here, we examined variations in the gut bacteriome and virome associated with cognitive function in the Boston Puerto Rican Health Study (BPRHS), a prospective cohort of older Puerto Rican adults residing in the Boston area.

METHOD: This study was conducted in 316 BPRHS participants with fecal metagenomic sequencing and cognitive assessments, summarized as a composite global cognitive score (GCS). Taxonomic profiling of the gut bacteriome was performed using MetaPhlAN 4.0. Gut virome profiles from shotgun sequencing were generated using BAQLaVa 1.0. Cross-sectional associations between bacterial and viral composition and GCS were assessed using alpha (Shannon) and beta (Bray-Curtis) diversity indices. Feature-wise testing was performed using multivariate linear regression (MaAsLin2) to identify bacterial and viral taxa associated with the GCS.

RESULT: Among 316 participants (mean age 68.7 years, 70.9% female), there were no differences in overall bacterial or viral composition, measured by alpha and beta diversity, based on GCS. In feature-wise analyses, adjusted for age, sex, and BMI, among participants with higher GCS (better cognitive function), we observed an enrichment of Faecalibacterium prausnitzii bacterium (β = 0.78, p = 0.01, FDR p = 0.22), and depletion of the phage Carjivirus communis (β = -1.07, p < 0.01, FDR p = 0.09).

CONCLUSION: The observed results suggest an enrichment of F. prausnitzii, a beneficial butyrate producing taxa, among participants with better cognitive function, and enrichment of Carjivirus communis, a Crassvirales dsDNA Bacteroidetes phage, among participants with worse cognitive function. A recent study reported an association between Bacteroidetes phages and amyloid β and Alzheimer's disease pathology. Gut viral variations may modulate gut bacteria, impacting cognitive function. Future work will test interactions of the gut bacteriome, virome and their functional pathways, as related to cognitive function in Puerto Rican adults.}, } @article {pmid41434434, year = {2025}, author = {de Souza, IC and de Lima, AMDL and Bastiani, M and Borelli, WD and Ebert, ELK and Barth, RA and Senger, JE and Schumacher-Schuh, AF and Moriguchi, EH and Senger, J and Bruscato, NM and Werle, BM and Zanella, L and Netson, LV and Detogni, A and Guerra, RR and Martins, AF and Barboza, JVC and Gaio, EJ and Zimmer, ER}, title = {Developing Topics.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 7}, number = {}, pages = {e108925}, doi = {10.1002/alz70861_108925}, pmid = {41434434}, issn = {1552-5279}, mesh = {Humans ; *Cognitive Dysfunction/microbiology ; Aged ; Male ; *Alzheimer Disease/microbiology ; Female ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Saliva/microbiology ; Aged, 80 and over ; *Dysbiosis/microbiology ; *Mouth/microbiology ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that ultimately leads to dementia. Emerging evidence suggests that oral dysbiosis may contribute to AD. The oral microbiota plays a crucial role in maintaining systemic health, and its imbalance has been associated with neurodegeneration. However, beyond the identification of individual taxa, the structure and dynamics of microbial communities-particularly their ecological interactions-remain poorly understood in AD. Here, we investigated abundance association networks of the oral microbiota across the AD continuum.

METHOD: Saliva samples collected from 12 elderly individuals classified as cognitively unimpaired (CU), having mild cognitive impairment (MCI), or having Alzheimer's disease (AD) were sequenced on the Illumina MiSeq™ platform, targeting the V3-V4 regions of the 16S rRNA gene. FASTQ files were processed using the DADA2 pipeline. Amplicon sequence variants (ASVs) were inferred, and taxonomic assignments were performed using the eHOMD 16S rRNA database. ASVs were normalized by rarefaction without replacement. Finally, normalized, centered log-ratio transformed abundance data were used to construct genus-level correlation networks for the CU, MCI, and AD groups.

RESULT: In CU individuals, Eikenella maintained exclusively positive associations with other microbial taxa (Figure 1). However, these interactions were significantly reduced or shifted toward negative relationships in individuals with AD. Notably, one of the most pronounced changes was the weakened association between Eikenella and Lachnospiraceae_G_3 in individuals with AD. Additionally, a positive relationship between Eikenella and Peptostreptococcaceae_XIG_1 observed in CU shifted to a negative relationship in the AD group. These specific microbial associations were not observed in the MCI group.

CONCLUSION: In summary, our results suggest a disruption in microbial synergy, which may reflect or potentially contribute to the underlying pathological mechanisms of AD. Network analysis may provide valuable insights into the dynamic changes within the oral microbiome across different stages of AD, thereby enhancing our understanding of the oral microbiome's role in neurodegenerative processes.}, } @article {pmid41434376, year = {2025}, author = {Blanco, EJ and Gonzalez, R and Perez, G and Piñero, J and Morales, H and Olivieri-Henry, G and Gonzalez, C and Godoy-Vitorino, F and Sepulveda, V}, title = {Developing Topics.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 7}, number = {}, pages = {e108947}, doi = {10.1002/alz70861_108947}, pmid = {41434376}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Aged ; *Alzheimer Disease/epidemiology/genetics/complications ; *Periodontitis/epidemiology ; Puerto Rico/epidemiology ; Hispanic or Latino ; *Periodontal Diseases/epidemiology ; Aged, 80 and over ; Severity of Illness Index ; White ; }, abstract = {BACKGROUND: Periodontal inflammation has been implicated in Alzheimer's Disease (AD) through systemic inflammatory and neurodegenerative pathways, including microbial dysbiosis and cytokine signaling and microbial infiltration. While the oral microbiome's role in cognitive decline has gained momentumrecently, there is limited research on these associations in Hispanic population, underrepresented in Alzheimer's research and facing disproportionately high burden of both dementia and oral disease.

OBJECTIVE: To evaluate the association between periodontal disease severity and clinical, cognitive, metabolic, and genetic factors in a cohort of Puerto Rican older adults with and without Alzheimer's Disease.

METHODS: We conducted a cross-sectional analysis of 43 community-dwelling participants enrolled in the Association-Gut-Microbiome-AD (IRB: 2290033626) study. Each underwent a full-mouth periodontal examination, including clinical attachment loss (CAL), probing depth (PD), and bleeding on probing (BOP) at six sites per tooth. Periodontal disease severity was classified using CDC-AAP 2012 case definitions: mild, moderate, or severe periodontitis based on interproximal CAL and PDthresholds. Predictor variables included age, BMI, insulin resistance (HOMA-IR), APOE-ε4 status, AD, and cognitive scores (MoCA and CDR). Bivariate analyses and Multinomial logistic regression were used to assess associations.

RESULTS: Eighty-one percent of participants met criteria for periodontitis, including 28% with severe and 49% with moderate disease. Age was the most consistent predictor of worsening periodontal inflammation (p < 0.01). CDR scores were significantly associated with greater severity in both bivariate (p < 0.01) and unadjusted models (CDR mild vs none: OR = 0.13; 95% CI, 0.02-0.86; p = 0.03). Severe periodontitis was more commonly observed in Alzheimer's, showing a higher odds ratio when compared to controls (OR = 2.75; p = 0.44) though not statistically significant. MoCA scores, APOE-ε4 status, BMI, and HOMA-IR were not significantly associated with periodontal severity.

CONCLUSION: Aging and dementia severity (CDR) were the strongest predictors of periodontal inflammation. These findings align with emerging literature linking oral microbial dysbiosis and neuroinflammatory mechanisms in AD. The use of standardized CDC-AAP definitions provided clinical rigor, and the elevated periodontitis prevalence observed in this cohort underscores the need for integrated oral-systemic care strategies in dementia prevention and management, particularly in underrepresented populations such as Puerto Rico.}, } @article {pmid41434102, year = {2025}, author = {Ngouongo, YJW and Muhammad, JA and Bernal, R and Satizabal, CL and Beiser, AS and Ramachandran, VS and Kautz, TF and Seshadri, S and Himali, JJ and Fongang, B}, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e103169}, doi = {10.1002/alz70860_103169}, pmid = {41434102}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Public Health ; *Cognition/physiology ; Feces/microbiology ; }, abstract = {BACKGROUND: Emerging evidence indicates a complex interplay between cardiovascular health, gut microbiome composition, and cognitive function. Life's Essential 8 (LE8), created by the American Heart Association, encompasses crucial cardiovascular health metrics. This study aimed to explore the relationship between LE8 adherence, gut microbiota, and cognition.

METHOD: We used stool samples, LE8 metrics, and cognitive assessment measures from a sample of 781 participants (mean age 54.9 years, 57.1% Female) from the Framingham Heart Study (generation3, New Offspring Spouses, and the Omni2 cohorts) at the 3[rd] examination (2016-2019). Associations between LE8 adherence, gut microbiome diversity, and cognitive performance were evaluated using multivariable linear regression models, adjusting for potential confounders. Mediation analysis was conducted to explore whether specific bacterial taxa mediated the relationship between LE8 adherence and cognitive performance.

RESULT: Participants with greater adherence to LE8 demonstrated significantly increased gut microbial diversity (α-diversity: Chao1, p = 0.0014; Shannon, p = 0.0071) and distinct microbial compositions (β-diversity: PERMANOVA p = 1e-4). Higher adherence to LE8 was related to an increased abundance of genera Barnesiella and Ruminococcus, while reduced abundance of Clostridium was associated with higher LE8 adherence. Greater gut microbial diversity (α-diversity: Chao1, p = 0.0012; Shannon, p = 0.0066), and beneficial genera like Oscillospira correlated with better global cognitive scores (GCS). Taxonomic overlap analyses revealed microbial taxa that simultaneously influence LE8 adherence and cognitive outcomes. Mediation analyses indicated that specific taxa, including Barnesiella and Lentisphaerae, mediated the link between higher LE8 adherence and better cognitive performance. These taxa could be key modulators in the gut-brain axis, connecting cardiovascular and brain health. Conversely, higher Clostridium abundance was associated with poorer cognitive performance.

CONCLUSION: This study highlights the interconnected relationship between cardiovascular health, gut microbiome diversity, and cognitive function. Higher adherence to LE8 was associated with favorable microbial profiles and better cognitive performance, with the gut microbiome serving as a critical mediator. These findings emphasize the importance of integrated lifestyle interventions that address cardiovascular and cognitive health simultaneously. To validate these results and refine therapeutic strategies, future research should prioritize longitudinal studies and randomized controlled trials that explore the causal pathways and clinical applications of these findings.}, } @article {pmid41433829, year = {2025}, author = {Nyame, I and Ngouongo, YJW and Ayele, BA and Djotsa, AN and Jian, X and Fonteh, AN and Seshadri, S and Himali, JJ and Fongang, B and , }, title = {Public Health.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 6}, number = {}, pages = {e096594}, doi = {10.1002/alz70860_096594}, pmid = {41433829}, issn = {1552-5279}, mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Sleep/physiology ; *Public Health ; Feces/microbiology ; *Cognition/physiology ; Aged ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The American Heart Association has identified eight metrics for improving heart and brain health, including sleep health. Recent studies highlight the strong link between sleep health, gut microbiome, and diseases like Alzheimer's. While sleep deprivation is known to affect gut microbiome and brain health, the specific impact of sleep health on gut microbiome and cognitive disorders remains largely unexplored.

METHOD: We analyzed stool samples and sleep metrics from 781 participants (mean age 54.9, 57.1% female) in the Framingham Heart Study to examine the effect of sleep on gut microbiome composition and cognitive performance. Using the V4 region of the 16S rRNA and Lefse analysis, we identified microbiome profiles related to sleep health. ANOVA assessed the sleep-cognitive performance relationship, while multivariable and differential abundance analyses explored the microbiome's link to cognitive function, controlling for age, sex, and education.

RESULT: Differences in bacterial diversity were observed between low, moderate, and high groups. Lefse analysis showed higher levels of aldenense, bolteae, symbiosium, and lavalense in the low group, while Butyrivibrio, putredinis, and Dorea were less abundant. ANOVA indicated a significant correlation between global cognitive scores and sleep metrics (p = 0.0024). Positive correlations were found between cognitive scores and Pseudobutyrivibrio and Ruminococcus, while negative correlations were observed with Barnesiella and Clostridium. At the species level, xylanivorans and lactaris were positively correlated, whereas boltea, callidus, and intestinihominis were negatively correlated with cognitive scores.

CONCLUSION: Our findings showed that individuals with good sleep scores had higher cognitive performance, while those with lower sleep scores had lower cognitive performance. The results also indicated an association between gut microbiome and sleep metric as well as between gut microbiome and cognitive performance. Finally, our work revealed that the taxa Clostridium and bolteae exhibited association with both sleep metric and cognitive performance. Further studies should be conducted to understand the effects of sleep metric on the relationship between gut microbiome and the risk of developing Alzheimer's Disease and Related Dementias (ADRD).}, } @article {pmid41432929, year = {2025}, author = {Garcia, M and Sadler, NC and Stohel, I and Zhao, S and Krishnamoorthy, S and Farris, Y and Reichart, NJ and Bagwell, CE and Zambare, N and McClure, R}, title = {Community Dynamics Drive Calcium Carbonate Production in an Enriched Consortium of Soil Microbes.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-025-02632-y}, pmid = {41432929}, issn = {1432-184X}, abstract = {Recently, there has been a focus on using soil microbes as a means to store carbon in the soil in the form of calcium carbonate, outcomes of which include soil stabilization and biocementation. The molecular processes involved in microbially induced calcium carbonate formation are known, but there is still a significant knowledge gap regarding how community interactions, emergent processes that are distinct from the roles of individual members, may drive the formation of carbonate. To answer these questions, we describe the development and application of a consortium of soil microbes consisting of one species each of the Rhodococcus, Microbacterium, and Curtobacterium genera and two species from the Bacillus genus. We term these five species cultivated together carbon storing consortium A (CSC-A). Growth assays show that only a subset of CSC-A members produces CaCO3 with Rhodococcus producing the most CaCO3 but the complete CSC-A produces significantly higher amounts of CaCO3 compared to the sum total carbonate produced by all member species. The development of CSC-A shows that CaCO3 production may be as much a community process as it is the contribution of individual species, requiring us to move beyond single species analysis to fully understand carbonate formation by microbial communities in nature. CSC-A will allow the scientific community to ask and answer key questions about the molecular interactions surrounding inorganic carbon formation in soil, an important knowledge gap that must be filled if we wish to stabilize soils and harness microbial processes for materials production.}, } @article {pmid41432837, year = {2025}, author = {Yu, F and Yan, Y and Chen, L and Song, L and Salama, ES and Su, S}, title = {Salivary microbiome and metabolome profiles associated with dental caries in Tibetan children from high-altitude regions.}, journal = {Odontology}, volume = {}, number = {}, pages = {}, pmid = {41432837}, issn = {1618-1255}, support = {2022LQTD57//Longyuan Youth Innovation and Entrepreneurship Talents/ ; Lzuyxcx-2022-145//Office of English Language Acquisition/ ; 2019-FWZX-03//Lanzhou University Special Research Project of Serving the Economic and Social Development of Gansu Province/ ; }, abstract = {This study investigated, for the first time, the salivary microbiome and metabolome profiles associated with dental caries in Tibetan children of mixed dentition residing in high-altitude areas. Moreover, a diagnostic model for caries was established by exploring the potential cariogenic mechanisms of identified biomarkers. Saliva samples were collected from 28 Tibetan children (aged 10.20 ± 0.67 years in the high caries [HC] group, n = 15; 10.38 ± 0.65 years in the caries-free [H] group, n = 13). Illumina 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) were employed to analyze microbial composition and metabolic profiles, respectively. Although alpha diversity showed no significant differences among groups, beta diversity analysis revealed distinct microbial and metabolic differences between the HC and H groups. Several bacterial genera exhibited significant variations and were strongly correlated with caries status. Salivary microbial and metabolic compositions differed significantly between Tibetan children with and without caries in high-altitude areas; differential biomarkers may serve as diagnostic or early-warning indicators of dental caries in this unique population. The identified microorganisms and metabolites could be used as non-invasive biomarkers or early warning markers for dental caries detection in Tibetan children in high-altitude areas. Moreover, the further exploration of their pathogenic roles will be helpful for the prevention and discovery of therapeutic drug targets of caries in Tibetan children at high altitude.}, } @article {pmid41432792, year = {2025}, author = {Basile, A and Spagoni, L and Visaggio, D and Riggio, FP and Bologna, MA and Mancini, E and Visca, P and Riccieri, A}, title = {The Putative Involvement of Bacterial Symbionts in Cantharidin Biogenesis: An Explorative Study in Meloidae Insects.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-025-02683-1}, pmid = {41432792}, issn = {1432-184X}, abstract = {Insect-microbes holobionts integrate host and microbial functions, with symbionts supporting nutrition, immunity, and defence, while producing metabolites, including beetle-derived compounds with therapeutic potential. Cantharidin is a toxic terpene produced by blister beetles (Coleoptera: Meloidae), endowed with defensive and pharmacological properties. Male insects produce and contain cantharidin in large quantities and transfer it to females upon mating. This study is aimed to gain information about the involvement of insect-associated bacteria in cantharidin biogenesis. To support the possibility that bacteria participate in cantharidin biogenesis, cantharidin antibacterial activity was assessed against six reference strains of representative species of Bacillota and Pseudomonadota from publicly available culture collections. All bacterial strains tolerated concentrations up to 600 µg/ml cantharidin in a standard antibacterial susceptibility test. To identify candidate bacterial lineages, 16S rRNA metataxonomic profiling of the V5-V6 region was performed in males and females from different Meloidae subfamilies and tribes. Analysis of the insect-associated microbiomes of the five cantharidin-producing species (Lydus trimaculatus, Meloe proscarabaeus, Mylabris variabilis, Hycleus polymorphus, Zonitis flava) revealed communities dominated by Pseudomonadota, with secondary contributions from Actinomycetota in Z. flava and M. proscarabaeus and Cyanobacteriota in the other host insects. Although overall community structure and composition did not differ significantly between sexes, a few taxa displayed consistent male-associated patterns, with Staphylococcus, Cutibacterium and one Enterobacteriaceae ASV resulting more abundant in males across all species. The intrinsic bacterial resistance to cantharidin, with both quantitative and qualitative differences in microbiome structure between male and female insects, makes the hypothesis of a putative involvement of bacteria in cantharidin biogenesis still viable.}, } @article {pmid41432724, year = {2025}, author = {Zhang, Z and Ye, B and He, J and Xiang, L and Li, S and Zhao, J and Chen, W and Zhang, Q and Zhao, W and Yang, J and Li, Y and Ju, J and Liu, Y and Xia, M}, title = {Microbial metabolites associated with healthy lifestyles in relation to metabolic syndrome and vascular health: a cross-sectional study.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0143325}, doi = {10.1128/msystems.01433-25}, pmid = {41432724}, issn = {2379-5077}, abstract = {UNLABELLED: Lifestyle behaviors influence the risk of metabolic syndrome (MetS) and affect vascular health. However, the interactions between gut microbiota and lifestyle behaviors in relation to MetS, as well as the specific microbial taxa and metabolites involved, remain unclear. Here, we aimed to investigate the associations among healthy lifestyle behaviors, gut microbiota, and MetS and to explore the potential mediating roles of microbially derived metabolites in these associations. A total of 1,342 participants with complete assessments of the Healthy Lifestyle Score (HLS), MetS, and vascular health were enrolled. Fecal samples were collected and subjected to metagenomic sequencing. Host genetic data were obtained using a high-density genotyping array, and plasma metabolites were quantified by liquid chromatography-mass spectrometry. Using generalized linear models, we found that increased abundances of Alistipes putredinis, Odoribacter splanchnicus, and Roseburia hominis were associated with higher HLS and a reduced risk of MetS. Eleven microbial metabolic pathways were independently correlated with both HLS and MetS. Furthermore, increased plasma levels of cinnamoylglycine and betaine, driven by enhanced microbial capacity for homolactic fermentation, were identified as potential microbial effectors associated with MetS and vascular health. These findings indicate that the association between HLS and MetS may involve modulation of the gut microbiota and their metabolites and highlight the potential to enhance the beneficial effects of healthy behaviors on MetS and vascular health through microbiota-modifying interventions.

IMPORTANCE: Metabolic syndrome raises the risk of heart disease and diabetes, yet practical levers to prevent it remain limited. We show that everyday healthy habits align with a gut microbial "signature" linked to better vascular health and lower metabolic risk. Using metagenomics, metabolomics, and genetic causal analyses, we identify specific bacteria (Alistipes putredinis, Odoribacter splanchnicus, and Roseburia hominis) and microbially produced molecules-especially cinnamoylglycine and betaine from enhanced homolactic fermentation-that may mediate these benefits. These findings connect lifestyle, the gut microbiome, and blood metabolites in a single framework, suggesting actionable biomarkers to monitor risk and potential microbiota-targeted strategies (diet and pre/probiotics) to improve cardiometabolic health. By highlighting concrete microbial pathways and metabolites, our work advances the path toward precision prevention and low-cost interventions for metabolic syndrome and vascular disease.}, } @article {pmid41432650, year = {2025}, author = {Peter Rimmer, and Zhang, F and Scott, G and , and Hold, GL and Gordon, M and Iqbal, TH and Hansen, R}, title = {The Gut Microbiome at the Onset of Inflammatory Bowel Disease: A Systematic Review and Unified Bioinformatic Synthesis.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.09.014}, pmid = {41432650}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Few studies describe gut microbiome signatures in treatment-naïve new-onset inflammatory bowel disease (IBD). We present a novel secondary bioinformatic reanalysis of sequence outputs mapped to the latest microbial taxonomy.

METHODS: MEDLINE and Embase searches were performed for microbiome studies in treatment-naïve IBD. Appraisal was completed with Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Available 16S ribosomal RNA sequence data sets were downloaded and missing data sets requested. Integrated data were run through a unified QIIME2 bioinformatics pipeline. Multivariable models adjusting for methodologic differences were developed using MaAsLin2.

RESULTS: There were 36 eligible studies; 18 contributed to bioinformatic reanalysis and 24 to supplementary meta-analysis. Samples from 1743 patients were included, comprising 678 from individuals with Crohn's disease (CD), 399 with ulcerative colitis (UC), 130 healthy controls (HCs), and 405 symptomatic controls (SCs); 990 of which were biopsy samples. Alpha diversity was reduced: feces-pediatric UC vs SCs, adult CD and UC vs HCs, and pediatric SCs vs HCs; pediatric biopsy samples-CD vs SCs, CD vs UC, and UC vs SCs. Beta diversity demonstrated clear distinctions between fecal and mucosal biopsy communities, least evident in UC, in addition to community separation by geography. Multivariate modeling revealed depletion of anaerobic and enrichment of aerobic and facultative anaerobic bacteria, alongside enrichment of oral genera across both CD and UC.

CONCLUSIONS: Core microbial perturbations at onset of CD and UC are depletion of anaerobes and enrichment of oxygen-tolerant, orally associated bacteria. As we place greater emphasis on early diagnosis and prediction of IBD risk, this finding may support innovative diagnostic approaches. Microbiome-targeted intervention and alteration of luminal oxygen availability may offer novel therapeutic avenues for new-onset patients and identified high-risk groups.}, } @article {pmid41432437, year = {2025}, author = {Bowerman, KL and Lu, Y and McRae, H and Volmer, JG and Zaugg, J and Pope, PB and Hugenholtz, P and Greening, C and Morrison, M and Soo, RM and Evans, PN}, title = {Metagenomic analysis of fecal microbiomes reveals genetic potential for diverse hydrogen management strategies in marsupials.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0160825}, doi = {10.1128/msystems.01608-25}, pmid = {41432437}, issn = {2379-5077}, abstract = {Methane is an end product of plant biomass digestion by gut microbiota, though the amount produced and/or released varies between hosts. On a per-unit-of-feed basis, macropodid marsupials (e.g., kangaroos) have been reported to emit less methane than ruminant livestock, despite a similar diet, although measurements exist for only a subset of macropodid species. Competition for hydrogen within the gut microbiome, particularly through alternative hydrogen sinks to methanogenesis, influences methane production; therefore, characterizing hydrogen management strategies within a host system can provide insights into methane emission profiles. In this study, we analyzed 33 fecal microbiomes of 14 marsupial species (predominantly captive animals) to provide the first systematic characterization of methanogen types and hydrogen-cycling genetic capacity across marsupial gut microbiomes. We recovered 1,394 metagenome-assembled genomes and identified host-associated bacterial signatures that varied significantly between marsupial species. Comparative analysis with fecal microbiomes from high- and low-methane-emitting mammals revealed that marsupials display heterogeneous hydrogen management strategies: some harbor elevated methanogenesis genes (mcrA, methanogen-specific hydrogenases), while others show enrichment of bacterial hydrogen-uptake hydrogenases and alternative electron acceptor pathways (nitrate/nitrite reduction, sulfite reduction). This predicted functional variation occurs both between and within marsupial families and gut types, suggesting that hydrogen management capacity may differ within taxonomic and anatomical classifications. These results demonstrate that marsupial gut microbiomes cannot be treated as a functionally homogenous group regarding methane emissions and highlight the need for species-specific measurements to accurately assess their methanogenic potential and inform ecological models of greenhouse gas production.IMPORTANCEHerbivorous marsupials such as kangaroos and wallabies have been reported to produce significantly lower methane emissions than ruminant livestock despite eating a similar diet, yet the microbial mechanisms underlying this difference remain poorly understood. Here, we conduct a comparative study of fecal microbiomes of 14 marsupial species to provide the first investigation of hydrogen-cycling genetic capacity across these animals. Through comparative analysis with fecal microbiomes of high- and low-methane-producing animals, we identify enrichment of bacterial genes for alternative hydrogen uptake and disposal pathways in some marsupials, supporting competition for hydrogen playing a role in the level of methane production. These data also indicate variation in hydrogen management between marsupials, including within species, suggesting methane emission capacity may vary at the level of the individual.}, } @article {pmid41432331, year = {2025}, author = {Tardo, DT and Cortes-Canteli, M and Fuster, V and Sachdev, PS and Kovacic, JC}, title = {The Heart-Brain-Metabolism Axis in Cardiovascular and Neurologic Disease.}, journal = {Journal of the American College of Cardiology}, volume = {86}, number = {25}, pages = {2663-2686}, doi = {10.1016/j.jacc.2025.09.1602}, pmid = {41432331}, issn = {1558-3597}, mesh = {Humans ; *Brain/metabolism/physiopathology ; *Cardiovascular Diseases/metabolism/physiopathology ; *Nervous System Diseases/metabolism/physiopathology ; *Heart/physiopathology ; *Myocardium/metabolism ; }, abstract = {The heart-brain axis has been widely acknowledged in medicine, but arguably it has not been particularly well understood until relatively recent times. For example, we have only recently come to appreciate the profound impact of the HBA on the development of vascular cognitive impairment and dementia (VCID). The complexity of these relationships is further reinforced by appreciating additional autonomic interconnectedness via the gut and metabolic pathways, as well as the spleen and immune pathways, in the form of the heart-brain-metabolism axis. Furthermore, the directionality of these pathways is complex, and all of these elements exert unique effects on the other. This multifaceted system is susceptible to pathologic processes involving multiple organ systems, namely, but not exclusively, the heart, vasculature, brain, autonomic nervous system, gut, and liver, with common clinical outcomes including VCID and cognitive frailty. In this state-of-the-art review, we explore the anatomic and physiologic interconnectedness between the heart, brain, gut, and metabolic systems. A focus has been placed on how relevant pathologic processes affect the cardiovascular and neurologic organ systems, as well as specific aspects of metabolism and the influence of the immune and gastrointestinal systems, all of which can contribute to both nervous system and cardiac dysfunction. Where relevant, we describe how therapeutic efforts should be focused on a preventative approach, with early identification of relevant cardiovascular and neurologic factors, to allow for the timely introduction of therapeutic measures to mitigate the risk of developing disease. Emerging approaches to cognitive risk prediction in cardiovascular disease include clinically accessible tools for older adults, brain imaging biomarkers linking stress-related neural activity to future cardiovascular events, and novel strategies such as gut microbiome modulation. Evidence supports the cognitive safety and potential neuroprotective benefit of statins, and ongoing trials and translational research aim to refine prevention through integrated cardiovascular, neurocognitive, and metabolic interventions.}, } @article {pmid41432253, year = {2025}, author = {Ricci, F and Hutchinson, T and Leung, PM and Nguyen-Dinh, T and Zeng, J and Jirapanjawat, T and Eate, V and Wong, WW and Cook, PLM and Greening, C}, title = {Chemosynthesis enables microbial communities to flourish in a marine cave ecosystem.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf286}, pmid = {41432253}, issn = {1751-7370}, abstract = {Chemosynthesis, an ancient metabolism that uses chemical compounds for energy and biomass generation, occurs across the ocean. Although chemosynthesis typically plays a subsidiary role to photosynthesis in the euphotic ocean, it is unclear whether it plays a more important role in aphotic habitats within this zone. Here, we compared the composition, function, and activity of microorganisms colonising the sediment of a marine cave at mesophotic depth, across a transect from the entrance to the interior. Microbes thrived throughout this ecosystem, with interior communities having higher diversity than those at the entrance. Analysis of 132 species-level bacterial, archaeal, and eukaryotic metagenome-assembled genomes revealed niche partitioning of habitat generalists distributed along the cave, alongside specialists enriched across the entrance and interior environments. Photosynthetic microbes and photosystem genes declined in the inner cave, concomitant with enrichment of chemosynthetic lineages capable of using inorganic compounds such as ammonium, sulfide, carbon monoxide, and hydrogen. Biogeochemical assays confirmed that the cave communities consume these compounds and fix carbon dioxide through chemosynthesis, with inner communities mediating higher cellular rates. Together, these findings suggest that the persistent darkness and low hydrodynamic disruption in marine cave sediments create conditions for metabolically diverse communities to thrive, sustained by recycling of inorganic compounds, as well as endogenous and lateral organic matter inputs. Thus, chemosynthesis can sustain rich microbial ecosystems even within the traditionally photosynthetically dominated euphotic zone.}, } @article {pmid41432144, year = {2025}, author = {Liu, J and Ni, H-B and Yu, M-Y and Qin, S-Y and Elsheikha, HM and Peng, P and Guo, L and Xie, L-H and Liang, H-R and Lei, C-C and Xu, Y and Tang, Y and Yu, H-L and Qin, Y and Liu, J and Sun, H-C and Zhang, X-X and Qiu, B}, title = {Comprehensive profiling of antibiotic resistance, virulence genes, and mobile genetic elements in the gut microbiome of Tibetan antelopes.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0144325}, doi = {10.1128/msystems.01443-25}, pmid = {41432144}, issn = {2379-5077}, abstract = {UNLABELLED: Tibetan antelopes, native to high-altitude plateau regions, play an important role in the local ecosystem. Their gut harbors antimicrobial-resistant microbes, including potential pathogens. To explore this, we analyzed 33,925 metagenome-assembled genomes (MAGs), including 7,318 from 68 Tibetan antelopes sequenced in our laboratory. We first profiled the composition of antibiotic resistance genes (ARGs) and then examined their associations with virulence factor genes (VFGs). In total, 2,968 ARGs were identified, conferring resistance to 23 antibiotic classes, with elfamycin resistance being most prevalent. Two ARGs were located on phage-derived sequences, though their phage taxonomy could not be resolved. ARGs were significantly correlated with VFGs, particularly genes linked to adherence and effector delivery systems. Given potential dissemination risks, we further assessed associations between ARGs and mobile genetic elements (MGEs), finding that insertion elements accounted for the largest number of ARG-MGE links. Comparative analysis with other plateau animals and humans revealed seven ARGs uniquely present in Tibetan antelopes. In summary, this study provides the first comprehensive overview of ARG composition in Tibetan antelope gut microbiomes, establishing a baseline for future hypothesis-driven studies and antimicrobial resistance surveillance in wildlife.

IMPORTANCE: Investigating the drug resistance of Tibetan antelope (Pantholops hodgsonii) gut microbiota serves as a critical biological indicator for assessing the impact of human activities (particularly antibiotic contamination) on the fragile ecosystem of the Qinghai-Tibet Plateau. This study untangles the invasion of antibiotic resistance genes (ARGs) into remote conservation areas, suggesting that Tibetan antelopes may act as potential vectors for ARG dissemination across plateau environments. Such findings not only highlight threats to wildlife health but also provide an ecological warning regarding the pervasive environmental risks posed by the global antimicrobial resistance crisis in natural ecosystems.}, } @article {pmid41431940, year = {2026}, author = {Zhang, L and Wang, C and Zhang, X and Li, G and Sheng, Z}, title = {Identification of key gut microbiota and microbial QTL in contributing to the significant differences in body weight between two Chinese local chicken breeds.}, journal = {Animal genetics}, volume = {57}, number = {1}, pages = {e70060}, doi = {10.1111/age.70060}, pmid = {41431940}, issn = {1365-2052}, support = {XM202403//Open Research Fund of Tianjin Key Laboratory of Animal Molecular Breeding and Biotechnology/ ; 2021YFD1300100//National Key R&D Program of China/ ; 2021BBA234//Key Research and Develpment Project of Hubei province/ ; HBZY2023B007//the Supporting High Quality Development of Seed Industry Fund Project of Hubei Province/ ; 2023BAA029//Major Program (JD) OF Hubei province/ ; }, mesh = {Animals ; *Chickens/genetics/microbiology/growth & development ; *Gastrointestinal Microbiome/genetics ; *Quantitative Trait Loci ; *Body Weight/genetics ; Genome-Wide Association Study/veterinary ; China ; Phenotype ; Male ; }, abstract = {Previous studies have identified genetic loci that are associated with both feed conversion efficiency and gut microbiota in chickens, suggesting that interactions between the host genome and gut microbiota may influence chicken growth. However, the number of microbial QTL and gut microbiota associated with chicken body weight remains largely unknown. To further explore the impact of host-gut microbiota interactions on chicken body weight and to identify gut microbiota associated with chicken body weight, this study strictly controlled environmental interference and obtained phenotypic, genotypic, and gut microbiota composition data from 100 Langshan and Tibetan chickens (with significant differences in body weight) raised under identical standardized housing conditions. Through genome-wide association studies of chicken body weight, microbiome genome-wide association studies, and Mendelian randomization analysis, we have identified 145 microbial QTL as instrumental variables and screened out seven genera that have a significant causal relationship with chicken body weight, including the genera Blautia and Faecalibacterium. This study identified potential molecular and microbial markers associated with chicken body weight, offering a valuable theoretical framework for enhancing economic efficiency in poultry production.}, } @article {pmid41431830, year = {2025}, author = {Bakirtas, A and Kiykim, A and Baskin, AK and Anil, H and Bozkurt, HB and Cimen, SS and Demirkale, ZH and Esenboga, S and Ogulur, I and Ardicli, S and Cagdas, D and Kistler, W and Yuksel, H and Akdis, CA}, title = {A Survey on Environmental Protective and Risk Factors and Awareness Related to Epithelial Barrier Integrity, Microbiome and Allergic Diseases.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.70190}, pmid = {41431830}, issn = {1398-9995}, } @article {pmid41431826, year = {2025}, author = {Quintero, GA and Clay, OK}, title = {How to search for microbiomes: the example of bacteria in gallbladder bile.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/17460913.2025.2601522}, pmid = {41431826}, issn = {1746-0921}, abstract = {Questions surrounding the presence or absence of microbiomes in sites of the human body with at most low bacterial biomass in health are still not fully resolved. We begin with the notion of microbiome as "micro-biome," a community of several species, versus microbiota as simply "living things," and return to the pioneer epoch of biome research, which in one sense could be viewed as beginning already around 1800. Applying the biome notion to bacteria in sites of the human body, we find concordance with more recent attempts to test what is and what is not a (core) microbiome in practice. The biome perspective is then applied to a double question that has been addressed, without a consensus answer so far: (1) does the healthy gallbladder typically have a stable microbiota, and (2) do gallbladder microbiota, in either health or (gallstone) disease, qualify as microbiomes in the sense considered here?}, } @article {pmid41431748, year = {2025}, author = {Donnelly, CP and Zi, L and Li, L and Laukens, K and Cuypers, B and Prinsen, E and Okla, MK and Reynaert, S and Verbruggen, E and Asard, H and Beemster, GTS and AbdElgawad, H}, title = {The soil microbiome contributes to the adaptation of grassland plant species to increasingly persistent precipitation regimes by inducing transcriptomic, metabolic, and structural changes.}, journal = {The New phytologist}, volume = {}, number = {}, pages = {}, doi = {10.1111/nph.70788}, pmid = {41431748}, issn = {1469-8137}, support = {GOA: RegimeShift//University of Antwerpen/ ; }, abstract = {Climate change is leading to more persistent precipitation regimes (PRs) featuring prolonged dry and wet periods in Northern Europe. Plants and plant communities can acclimatize, reducing the impact of repeated exposures to extreme PRs. We addressed the hypothesis that PR adaptations by the soil microbiome contribute to the acclimatization of plants. We used soils from grassland mesocosms exposed to a 1-d (1SPR) or a 30-d (30SPR) wet/dry cycle to investigate how soil legacy affects the response of four grassland plant species to subsequent PR events. During the 40-d experiment, 5-d PR (5PR) treatments reduced growth compared with 1-d (1PR) samples, independent of soil legacy. The 30SPR treatment altered soil fungal communities, influencing plant responses, with Plantago and Phleum showing significant stress adaptations when compared with 1SPR. Integrating genome-wide transcriptional, physiological, and biochemical analyses enabled us to propose a mechanistic model showing how soil 30SPR influences four grassland plant species by activating common mechanisms, including redox signaling pathways and stress hormones (jasmonic acid, ethylene, and abscisic acid) under 5PR. These responses lead to cell wall reinforcement through increased lignin and callose, enhancing resilience. Overall, these findings underscore the role of soil legacy in helping grassland plants adapt to potential future PR variations.}, } @article {pmid41431686, year = {2025}, author = {Alnek, K and Bärenson, A and Aasmets, O and Janson, H and Talja, I and Laht, B and Vorobjova, T and Kirss, A and Cinek, O and Uibo, R and Tagoma, A and , }, title = {Mother and child stool bacteriomes 1-2 years postpartum: Associations with maternal history of gestational diabetes and child atopic dermatitis.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114087}, pmid = {41431686}, issn = {2589-0042}, abstract = {Gestational diabetes mellitus (GDM) may contribute to the onset of immune-mediated diseases in offspring. This observational study included women belonging to the GDM risk group and aimed to investigate the gut bacteriomes of the mothers with and without recent history of GDM, and those of their children resulting from index pregnancies. Stool and blood samples were collected within one week at 1-2 years postpartum from mother-child pairs. Stool bacteriome 16S rDNA sequencing data were compared with maternal history of GDM, human leukocyte antigen (HLA) haplotypes, metabolic biomarker levels, and children's atopic dermatitis diagnosis, allergen-specific immunoglobulin E (IgE) levels, HLA haplotypes, intestinal fatty acid-binding protein and metabolic biomarker levels, and antibodies to food proteins. The GDM status, atopic dermatitis and IgE positivity were associated with the children's gut bacterial composition. These results indicate that GDM affects children's gut bacteriome composition even 1-2 years after birth.}, } @article {pmid41431379, year = {2026}, author = {Al-Btoosh, S and Donnelly, RF and Kelly, SA}, title = {Microbes and medicines: interrelationships between pharmaceuticals and the gut microbiome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2604867}, doi = {10.1080/19490976.2025.2604867}, pmid = {41431379}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Probiotics ; *Bacteria/drug effects/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Pharmaceutical Preparations/metabolism ; Prebiotics ; Biotransformation ; }, abstract = {The human gut microbiome plays a critical role in modulating pharmacological and toxicological responses to medications. With a gene pool vastly exceeding that of the human host, the gut microbiome acts as a metabolically active organ capable of transforming, inactivating, or accumulating drugs. This review explores the bidirectional interplay between prescription medicines and the gut microbiome, encompassing three key mechanisms: direct biotransformation by microbial enzymes, indirect modulation of host metabolism and signaling pathways, and drug bioaccumulation within microbial cells. Particular attention is given to six major drug classes: immunotherapeutics, chemotherapeutics, antidepressants, statins, hypoglycemics, and antihypertensives. The ways in which individual microbial profiles can influence therapeutic outcomes are also reviewed. We examined how common non-antibiotic pharmaceuticals can significantly alter microbial diversity and promote antimicrobial resistance. Strategies to enhance drug efficacy through microbiome modulation, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), are critically assessed. Experimental models ranging from in vitro batch and chemostat systems to animal and clinical studies are compared in terms of their utility for studying drug‒microbiome interactions. Finally, emerging evidence suggesting the gut microbiota composition may serve as a predictive biomarker for personalized medicine and therapeutic success is highlighted. Understanding and harnessing the complex interrelationships between medicines and microorganisms could offer novel avenues to optimize treatment outcomes and mitigate adverse drug effects.}, } @article {pmid41431145, year = {2025}, author = {Porchia, DD and Wang, Y and Zhou, Z and Chen, M and Porges, EC and Cohen, RA and Ghare, S and Barve, S and Cook, RL and Li, Z}, title = {Cannabis use, microbial diversity and Dialister abundance in older adults with HIV: A cross-sectional study.}, journal = {HIV medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/hiv.70180}, pmid = {41431145}, issn = {1468-1293}, support = {R01DA042069/DA/NIDA NIH HHS/United States ; U24AA029959/AA/NIAAA NIH HHS/United States ; }, abstract = {OBJECTIVES: People with HIV frequently experience gastrointestinal symptoms linked to dysbiosis, impaired mucosal barrier integrity and persistent immune activation. Cannabis is widely used for symptom management by people with HIV, but its effects on the gut microbiome are unclear.

METHODS: We conducted a cross-sectional analysis of 63 people with HIV (mean age 59.4 years; 71.4% Black or Hispanic) enrolled in the Marijuana Associated Planning and Long-term Effects study and its microbiome and Alzheimer's substudies, which included participants with and without mild cognitive impairment (MCI). Participants provided faecal samples for 16S rRNA sequencing. Cannabis use was quantified using a validated Timeline Followback. Alpha diversity was estimated using the Shannon index, beta diversity with Bray-Curtis dissimilarity and permutational multivariate analysis of variance (PERMANOVA), and genus-level abundance using the IFAA method. All models were adjusted for age, sex and education.

RESULTS: Higher cannabis consumption showed a statistically significant association with reduced alpha diversity (β = -0.062 per 50-mg Tetrahydrocannabinol (THC) per use-day; 95% confidence interval [CI]: -0.12 to -0.004; p = 0.038). No statistically significant differences in beta diversity were observed between high and low-to-no groups (p = 0.35). At the genus level, Dialister abundance showed a statistically significant dose-dependent association with cannabis use, with a 14.4% reduction in abundance per 50-mg increase in THC per use-day (q = 0.034).

CONCLUSION: Cannabis consumption in older people with HIV, including those with and without MCI, was associated with lower microbial diversity and reduced Dialister abundance, a taxon with dual roles in mucosal integrity and gastrointestinal symptom modulation. Reduced alpha diversity and Dialister depletion are notable given links to impaired mucosal barrier integrity, microbial translocation and systemic immune activation in HIV. These findings suggest cannabis may modify HIV-associated dysbiosis, warranting further longitudinal studies to disentangle symptomatic benefits from long-term impacts on mucosal health and systemic inflammation.}, } @article {pmid41431112, year = {2025}, author = {Wang, M and Qin, S and Wu, C and Li, H and Li, H and Yu, J}, title = {Microbiome-Metabolomics Insights into the Brain-Gut Homeostasis of d-gal Induced Aging Mice To Reveal the Antiaging Effects of Lactoferrin and Its Digesta.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c11706}, pmid = {41431112}, issn = {1520-5118}, abstract = {Lactoferrin (LF) plays a positive role in attenuating aging. In this study, LF obtained using different processing methods (freeze-dried: F and spray-dried: S) and its gastrointestinal digesta (XF and XS) were supplemented in d-gal-induced mice to explore their antiaging effects. The results showed that LF and its digesta (LFs) effectively ameliorated cognitive decline. Mechanistically, LFs prevented neuronal and synaptic injury by restoring redox balance, inhibiting the activation of microglia and astrocytes, and activating the cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway. Additionally, LFs increased the tight junction proteins and mucin-2, regulated the gut microbiota, particularly enriching bacteria in Firmicutes and restoring the Firmicutes/Bacteroidota ratio to maintain intestinal homeostasis. Meanwhile, LFs altered phospholipids (PLs) and other metabolites involved in glycerophospholipid metabolism such as arachidonic acid. Correlation analysis showed a significant association among metabolites, microbiota, and behaviors. These results indicated that LF and especially its digesta exert antiaging effects through multitarget pathways involving neuronal protection, neuroinflammation suppression, and microbiota-gut-brain axis regulation.}, } @article {pmid41430778, year = {2026}, author = {Alula, KM and Nguyen, TT and de Zoeten, EF}, title = {Regulation of intestinal regulatory T cells via stress response pathways in inflammatory bowel disease.}, journal = {Autoimmunity}, volume = {59}, number = {1}, pages = {2602715}, doi = {10.1080/08916934.2025.2602715}, pmid = {41430778}, issn = {1607-842X}, mesh = {Humans ; *Inflammatory Bowel Diseases/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Endoplasmic Reticulum Stress/immunology ; Unfolded Protein Response/immunology ; Animals ; Signal Transduction/immunology ; *Intestinal Mucosa/immunology/metabolism ; Gastrointestinal Microbiome/immunology ; *Intestines/immunology ; }, abstract = {Cell stress, including endoplasmic reticulum (ER) stress, heat shock, and hypoxia, plays a pivotal role in cellular homeostasis and immune regulation, particularly in the intestine. ER stress, a key aspect of cell stress, triggers the unfolded protein response (UPR) to restore balance by managing misfolded proteins or inducing apoptosis if unresolved. The activation of these stress responses has emerged as a critical contributor to intestinal inflammation in conditions like inflammatory bowel disease (IBD). Regulatory T cells (Tregs), vital for maintaining mucosal immune tolerance, are strongly influenced by cellular stress, with the UPR shaping their stability, metabolic programming, and function. Microbial dysbiosis and reduced short-chain fatty acids (SCFAs) disrupt these adaptive pathways, further impairing Treg function. In this review, we explore how UPR signaling shapes Treg metabolism and intestinal inflammation. Identifying gaps in UPR-mediated adaptation and stress thresholds, we thus propose microbiome- and ER-stress-based therapeutic strategies as putative strategies for restoring immune balance in IBD.}, } @article {pmid41430711, year = {2025}, author = {Juul, SE and Comstock, BA and Mayock, DE and German, K and Feltner, J and Irvine, J and Lagerquist, E and Heagerty, PJ}, title = {Darbepoetin plus slow-release IntraVenous Iron to decrease transfusions and improve iron status and neurodevelopment in preterm infants (DIVI): study protocol for a randomized, blinded phase II trial.}, journal = {Trials}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13063-025-09374-9}, pmid = {41430711}, issn = {1745-6215}, support = {R01HD107003//National Institute of Child Health and Human Development/ ; }, abstract = {BACKGROUND: Infants born preterm are at high risk of anemia, red blood cell transfusions, and iron deficiency, all of which may negatively influence long-term neurodevelopment. To ameliorate these complications of prematurity, we developed a Phase II trial to determine whether treatment with an erythropoietic-stimulating agent, darbepoetin (Darbe), plus a slow-release intravenous (IV) iron preparation (ferumoxytol (FMX) or low-molecular-weight iron dextran (LMW-ID)) might decrease transfusions while maintaining iron sufficiency.

METHODS: This single-center study is a parallel design, prospective, randomized controlled Phase II trial of 120 infants born 24-0/7 to 31-6/7 weeks of gestation cared for in the University of Washington Neonatal Intensive Care Unit. After informed consent, infants less than 72 h of age are randomized to one of five treatment groups: (1) Oral iron (standard care), n = 40, or weekly Darbe 10 µg/kg/dose IV or SQ plus; (2) FMX - 10 mg/kg/dose IV, n = 20; (3) FMX - 20 mg/kg/dose IV, n = 20; (4) LMW-ID - 10 mg/kg/dose IV, n = 20; or (5) LMW-ID - 20 mg/kg/dose IV, n = 20. Infants will be followed to 2-year corrected age with sequential developmental testing. Our primary outcome is ferritin level at 34-36 weeks postmenstrual age. Secondary outcomes include other hematologic assessments, drug safety, evaluation of the gut microbiome, and neurodevelopment to 2 years corrected age.

DISCUSSION: This trial will determine whether darbepoetin plus a slow-release IV iron preparation is safe, which iron preparation and dose best maintain iron sufficiency and decrease or eliminate transfusions, whether IV iron will result in a more diverse, less pathogenic microbiome when compared to oral iron supplementation, and, finally, whether these treatments affect neurodevelopment to 2 years corrected age.

TRIAL REGISTRATION: National Clinical Trial (NCT) NCT05340465. Registered on March 1, 2022.}, } @article {pmid41430556, year = {2025}, author = {Luo, Y and Yang, Y}, title = {Network and machine learning integration reveals gut microbiome biomarkers in pediatric IBD.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {797}, pmid = {41430556}, issn = {1471-2180}, } @article {pmid41430427, year = {2025}, author = {De Santis, A and Bevilacqua, A and Corbo, MR and Speranza, B and Francavilla, M and Gatta, G and Carucci, F and Sinigaglia, M}, title = {A statistical approach to model soil microbiota versus heavy metals: a case study on soil samples from Foggia, Southern Italy.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-32485-x}, pmid = {41430427}, issn = {2045-2322}, abstract = {Heavy-metal (HM) contamination undermines soil functions and food safety, while risk appraisals often rely on chemical indices that can be unstable in the presence of extremes and only indirectly reflect biological integrity. We present an integrative framework that couples standardized contamination metrics with soil microbiome profiling to deliver stable, interpretable classifications and actionable bioindicators. Twelve peri-urban soils from Southern Italy were analysed for potentially toxic elements, including Arsenic (As), Cadmium (Cd), Chromium (Cr), Copper (Cu), Nickel (Ni), Lead (Pb), and Zinc (Zn) and profiled by shotgun metagenomics. We introduce a Standardized Ecological Risk index (SPERI) that preserves the ranking conveyed by conventional composites yet reduces outlier leverage. SPERI strongly agreed with Improved Potential Ecological Risk Index (IPERI) while stabilizing variance (R[2] = 0.896) and improved between-site comparability. Along the contamination gradient, community structure shifted consistently: families such as Pseudomonadaceae, Xanthomonadaceae and Rhodospirillaceae increased with risk, whereas Geodermatophilaceae and Nocardiaceae declined. Simple decision-tree models trained on family-level relative abundances reliably separated SPERI classes and repeatedly selected Zn- and Cd-enriched sites as primary split drivers, aligning microbial signals with chemical risk. By combining open, reproducible analytics with jointly chemical- and microbiome-informed endpoints, this workflow improves the interpretability and transferability of ecological risk assessment and supports targeted remediation and monitoring in contaminated agro-ecosystems.}, } @article {pmid41430336, year = {2025}, author = {Bertrand, C and Marmeisse, R and Martin, MC and Binet, F}, title = {Interplay between host and environmental filters drives plant-associated microbiomes in the remote sub-Antarctic Kerguelen Islands.}, journal = {Environmental microbiome}, volume = {20}, number = {1}, pages = {154}, pmid = {41430336}, issn = {2524-6372}, abstract = {BACKGROUND: Plants evolve as holobionts, ecological and evolutionary units made up of the host plant and its associated microbiota, which shape plant fitness and adaptive capacity. Isolated ecosystems with low biodiversity and plant cover, such as the fellfields of the remote sub-Antarctic Kerguelen Islands, represent ideal open-air laboratories to disentangle the drivers affecting plant-microbiome interactions. In such pristine environments, endemic plant species and their microbiota have coevolved in isolation possibly since the last ice age. In this study, we investigated the bacterial and fungal communities associated with different soil-plant compartments of two phylogenetically distant endemic plants, the Poaceae Poa kerguelensis and the Brassicaceae Pringlea antiscorbutica, in fellfields with contrasted pedoclimatic conditions.

RESULTS: Using 16S rRNA gene and Internal Transcribed Spacer (ITS) region metabarcoding, we identified a strong soil-plant compartment effect affecting microbial communities, with bacterial and fungal α-diversity higher in bulk and rhizospheric soils and progressively decreasing in roots and above-ground compartments. The microbiota of the different soil-plant compartments studied differ in their recruitment patterns. The bacterial communities of the aerial parts of P. antiscorbutica were less dependent on those of the underground parts compared to those of P. kerguelensis. We also showed that the microbiota of distinct plant species and their different soil-plant compartments respond differently to pedoclimatic variables, with a greater impact of climatic variables over soil ones on aboveground bacterial microbiomes than on belowground microbiomes.

CONCLUSIONS: Our results highlight the dual role of environmental variability and of the identity of the host on the recruitment and diversity of plant microbiomes in the isolated studied ecosystems. As plant holobionts are part of the global biogeochemical ecosystem functioning, our results suggest that plant species-specific microbial recruitment strategies and differential vulnerability to environmental factors should be included in predicting sub-Antarctic ecosystem response to global warming.}, } @article {pmid41430309, year = {2025}, author = {Aladejana, OM and Ayorinde, DF}, title = {The intersection between human metapneumovirus and the respiratory microbiome.}, journal = {Virology journal}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12985-025-02872-x}, pmid = {41430309}, issn = {1743-422X}, abstract = {Human metapneumovirus is one of the viral causes of respiratory illness that can range from mild to life-threatening diseases. In December 2024, there was news about increased cases of human metapneumovirus (HMPV) in China, when 6.2% and 5.4% of positive respiratory illnesses and admissions, respectively, were linked to HMPV, surpassing adenovirus, rhinovirus, and COVID-19. There have been concerns about it becoming another epidemic, and by implication, a pandemic, especially as the world is gradually recovering from COVID-19 and its devastating impacts. Currently, there is no directly acting antiviral drug targeting HMPV, and this has left a gap in its treatment and management, especially in the young, elderly, and immunocompromised, who are prone to having severe manifestations. As the immune system is crucial in fighting and eliminating the infection, modulating the immune system directly or indirectly can treat HMPV. The lung that was initially known to be sterile is now found to house different populations of microorganisms, including bacteriome, virome, and mycobiome. The lung microbiome modulates HMPV infection. The presence of pathobionts like H. influenzae enhances HMPV infection and severity. The detection of the microbiome was made possible by the advent of cutting-edge technologies like next-generation sequencing and bioinformatics tools. The combination of Recombinase Polymerase Assay, CRISPR-Cas12a, and Fluorescence Assay has been used in the rapid detection of HMPV in China. The microbiome plays a crucial role in shaping the immune system. Exploring such can be a way of managing HMPV. Probiotics, prebiotics, and postbiotics are ways in which the microbiota can be manipulated to limit adverse drug reactions. These can be explored in HMPV diagnosis, treatment, and prevention.}, } @article {pmid41430301, year = {2025}, author = {Wikki, I and Palmu, J and Kauko, A and Havulinna, A and Jousilahti, P and Lahti, L and Knight, R and Salomaa, V and Niiranen, T}, title = {Prospective association between the gut microbiota and incident pneumonia: a cohort study of 6419 individuals.}, journal = {Respiratory research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12931-025-03453-w}, pmid = {41430301}, issn = {1465-993X}, support = {330887//Research Council of Finland/ ; 321351, 354447//Research Council of Finland/ ; }, abstract = {BACKGROUND: Previous animal studies have identified the protective capacity of the gut microbiota against respiratory infections. Nevertheless, the prospective association between human gut microbiota and pneumonia risk remains unknown.

OBJECTIVES: To evaluate the links between gut microbiota and incident pneumonia in a representative population sample.

METHODS: We performed shotgun metagenome sequencing on stool samples from 6419 FINRISK 2002 participants. Participants were followed up for incident pneumonia using nationwide health register data. We employed multivariable-adjusted Cox regression models and permutational multivariate analysis of variance (PERMANOVA) to assess the association of gut microbiome alpha diversity, compositional variation (beta diversity), and taxonomic composition with pneumonia risk.

RESULTS: Altogether, 685 patients (10.7%) developed pneumonia during a mean follow-up of 17.8 years. Alpha diversity was not associated with incident pneumonia (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.93 - 1.08), whereas community composition was (PERMANOVA R[2] = 0.03%; P = 0.02). We observed an inverse association between the relative abundance of butyrate-producing bacteria and incident pneumonia (HR per 1-SD increase 0.91; 95% CI 0.85-0.98). The relative abundance of Bacteroides_F pectinophilus, Eubacterium_G ventriosum, Agathobaculum butyriciproducens, Butyribacter intestini, Eubacterium_I ramulus, CAG-1427 sp000435675, and CAG-603 sp900066105 were inversely associated with pneumonia risk. The relative abundance of Clostridium_AQ innocuum was positively correlated with pneumonia risk.

CONCLUSIONS: The gut microbiota composition, and especially the relative abundance of butyrate-producing bacteria, was associated with lower pneumonia risk in the population. These findings warrant further studies to investigate whether microbiome modulation to increase short chain fatty acid production through diet, prebiotics, or probiotics could reduce pneumonia risk.}, } @article {pmid41430289, year = {2025}, author = {Williams, GM and Hoedt, EC and Duncanson, K and Gan, L and Prakoso, E and Talley, NJ and Beck, EJ}, title = {Inverse associations between Mediterranean diet constituents and the gut microbiota in metabolic-associated steatotic liver disease (MASLD): a case-control study.}, journal = {Nutrition & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12986-025-00939-8}, pmid = {41430289}, issn = {1743-7075}, abstract = {BACKGROUND: Dietary therapy, specifically for weight loss, is currently considered first-line therapy for metabolic-associated steatotic liver disease (MASLD). However, increasing recognition of the role of the gut-liver axis in MASLD highlights potential for microbiota-modulating dietary therapy to improve outcomes. This study aimed to explore dietary variables relevant to gut microbiota in MASLD.

METHODS: Twenty-five adults with MASLD and 25 healthy controls were recruited using a retrospective case-control design and characterised using 3-day dietary intake records, clinical markers, and shotgun metagenomic sequencing.

RESULTS: MASLD participants consumed less dietary fibre (p = < 0.01), very long chain omega-3 fatty acids (p = 0.02), nuts and seeds (p = 0.03), whole grains (p < 0.01) and vegetables (p = 0.04). Participants with MASLD had lower abundance of Alistipes senegalensis (r=-0.01, p = 0.04), Coprococcus eutactus (r=-0.07, p = 0.006), Faecalibacterium (r=-0.02, p < 0.001), and higher abundance of Ruminococcus torques (r = 0.04, p = 0.02), and less expression of functional pathways associated with ethanol production, methionine, folate and branched-chain amino acid metabolism. Bacterial species and functional pathways more abundant in MASLD were positively associated with intake of added sugars and saturated fat, and negatively associated with unsaturated fatty acid and dietary fibre intake.

CONCLUSIONS: Microbiota characteristics differ between individuals with and without MASLD, and this is influenced by dietary intake. Future translation-focused research investigating dietary interventions and the gut-liver-axis in MASLD are warranted.}, } @article {pmid41430245, year = {2025}, author = {Kardish, MR and Agans, RT and Barbato, RA and Doherty, SJ and Goodson, MS and Karl, JP and Kokoska, R and Liechty, ZS and McNeal, ND and Racicot, K and Steel, JJ and Sweet, C and Tuck, SM and Leary, DH}, title = {Meeting report of the eight annual Tri-Service Microbiome Consortium Symposium.}, journal = {BMC proceedings}, volume = {20}, number = {Suppl 2}, pages = {2}, pmid = {41430245}, issn = {1753-6561}, abstract = {The Tri-Service Microbiome Consortium (TSMC) was created to foster and enhance cooperation, collaboration, and communication of microbiome research among Department of Defense (DoD) researchers and their collaborators. The 8th Annual TSMC Symposium was held in Colorado Springs, CO on 25-26 September 2024 and featured oral and poster presentations and discussions centered on microbiome-related topics within four broad thematic areas: 1) Surveillance; 2) Health and Performance; 3) Enablers; and 4) Remediation. Collectively this meeting promoted sharing of methods, experiments, and findings across DoD affiliated microbiome research and promoted future and ongoing collaborations. This report summarizes the proceedings of the 8th Annual TSMC Symposium.}, } @article {pmid41430101, year = {2025}, author = {Zhou, F and Pan, Y and Zhan, J and Li, X and Yu, S and Tang, L}, title = {Continuous cropping drives assembly process of soil microbial community to alter keystone taxa causing challenges.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04595-z}, pmid = {41430101}, issn = {1471-2180}, support = {2022YFD1901503//National Key Research and Development Program of China/ ; 2022YFD1901503//National Key Research and Development Program of China/ ; 202202AE090025//Major Science and Technology Special Project of Yunnan Province/ ; }, abstract = {BACKGROUND: Healthy soil is crucial for maintaining the sustainability of soil ecosystem services and ensuring food security. The soil microbiome serves as a key indicator of soil health. However, long-term continuous monoculture significantly adversely affects the diversity and functioning of soil microbial communities, posing a serious threat to sustainable agricultural development. Therefore, making it crucial to understand the microbial mechanisms underlying these challenges.

METHODS: In this study, tobacco was subjected to different planting durations: 1 year (CR), 5 years (CC5), 10 years (CC10), and 15 years (CC15). The rhizosphere microbial community assembly process, composition, keystone taxa, and their relationship to continuous cropping challenges were analyzed.

RESULTS: The rhizosphere bacterial community structure of tobacco after 5 years of continuous cropping was significantly separated from other treatments, while no significant separation was observed in the fungal community. Further investigation into the assembly processes of microbial communities under different continuous cropping durations revealed that bacterial community assembly processes exhibited differences, whereas no significant differences were observed in fungal community assembly processes. Specifically, the rhizosphere bacterial community in CC5 was predominantly shaped by deterministic assembly processes, explaining its structural distinctiveness from other treatments. Co-occurrence network analysis revealed that the number of nodes and edges in bacterial-fungal interactions decreased by 22.70% and 79.86%, respectively, in CC5 compared with CR. Differential microbial abundance identified a significant decline in key microbes (Rhodanobacter, Ellin6067, Frankiales, and Setophoma) alongside a marked increase in the abundance of genus Verticillium in CC5 relative to CR. RDA indicated these bacterial genera correlated negatively with pathogen accumulation and disease incidence but postively with yield These relationships potentially constituted the primary driver for exacerbated continuous cropping obstacles in CC5. In CC10, bacterial community assembly was primarily dominated by stochastic processes. Although the number of network nodes and edges increased by 21.96% and 204.73%, respectively, compared to CC5, they remained lower than those in CR. By extending the continuous cropping to 15 years, the bacterial community assembly was shaped by stochastic processes. Compared with CC5, the number of network nodes and edges in CC15 increased by 34.39% and 405.44%, respectively, with beneficial microbes (Rhodanobacter, Ellin6067, Frankiales, and Setophoma) showing remarkable abundance recovery and pathogenic fungi like Verticillium declining, ultimately resulting in microbial community characteristics approximating those observed in the CR.

CONCLUSIONS: The bacterial community in CC5 was driven by deterministic assembly processes, resulting in a distinct structure. The complexity and stability of the co-occurrence network significantly decreased, accompanied by a higher abundance of harmful microbes and a lower abundance of beneficial microbes, which exacerbated the continuous cropping obstacles. In contrast, after 15 years of continuous cropping, the bacterial community assembly shifted to stochastic processes and trans-kingdom co-occurrence network complexity and stability strengthened, beneficial microbes increased, and continuous cropping challenges alleviated.}, } @article {pmid41430013, year = {2025}, author = {Wolfgang, A and Temme, N and Tilcher, R and Schumann, M and Berg, G}, title = {Wireworm-Associated Microbial Communities and their Implications on Biological Control.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-025-02672-4}, pmid = {41430013}, issn = {1432-184X}, abstract = {Wireworms (larvae of different click beetles, Elateridae) are significant soil-borne pest species that can cause severe crop losses. They are difficult to control, and biocontrol using entomopathogenic fungi (EPF) display variable field efficacy. To understand microbial interactions and improve biological control, we studied the interplay between insect and soil microbiota in four wireworm species (Agriotes spp.) at temporal and spatial scales. We found that microbiota associated with wireworms are species-specific and primarily soil-derived. Our results further indicate that ectosymbiotic bacterial community composition on wireworm cuticles is relatively stable over time in specimens not deceasing from spontaneous entomopathogen infection. Therefore, successful microbiome homeostasis on cuticles appears to be correlated with long-term survival of wireworms in soil. Interestingly, EPF were prevalent but low-abundant in all wireworm species as well as in soils. Therefore, we analyzed immune priming effects by low-abundant EPF in soil. Mortality was higher in naïve wireworms than in wireworms pre-exposed to EPFs, and molting frequency increased, indicating both developmental adaptations and immune priming as strategies for EPF avoidance in wireworms. This work disentangles the key components of wireworm microbiomes and highlights the importance of microbial interactions for biocontrol. Biocontrol of wireworms could be improved by considering their species-dependency in microbiome homeostasis as well as physiological and behavioral adaptations to soil-borne pathogens. The potential functional synergies between EPF and soil microbes need further exploration.}, } @article {pmid41429881, year = {2025}, author = {Hanzely, P and Holm, K and Bjørnholt, JV and Melum, E and Hov, JR and Rasmussen, H}, title = {Efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) in human microbiota-associated mouse models.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-32072-0}, pmid = {41429881}, issn = {2045-2322}, support = {802544/ERC_/European Research Council/International ; }, abstract = {The gut microbiome has gained significant interest due to its association with immune dysregulation, allergies, autoimmune conditions, metabolic disorders, and inflammation-associated malignancies. Understanding underlying mechanisms requires appropriate in vivo models, such as human microbiota-associated mouse models to study the microbiota-host interactions. This study compared the efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) from a single donor in C57BL/6J germ-free mice as these methods are often used interchangeably. Using 16S rRNA sequencing, we quantified colonisation efficacy in luminal and tissue samples from orally- (n = 6) and rectally- (n = 6) colonised mice. We detected 84 genera in the FMT sample, 17 of which were not transferred at all, while additional 7 genera were found exclusively in rectally-colonised mice. A significantly higher proportion of amplicon sequence variants (ASVs) (33% vs. 26%; P < 0.05) and genera (32% vs. 25%; P < 0.05) were absent in orally- compared to rectally-colonised group. Some taxa showed different relative abundances in human vs. mouse samples (e.g. Alistipes and Bacteroides relatively more abundant in mice while Faecalibacterium considerably decreased). Beta diversity analysis revealed greater similarity between FMT and tissue samples irrespective of the administration route, with distinct separation of the tissue and luminal samples. Overall, rectal administration yielded more overlapping genera and ASVs with FMT, highlighting that it could have advantages compared with oral administration for microbiota establishment studies.}, } @article {pmid41429716, year = {2025}, author = {Węgrzyn, A and Bloch, S and Węgrzyn, G}, title = {Employing bacteriophages to combat cancer.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1880}, number = {6}, pages = {189485}, doi = {10.1016/j.bbcan.2025.189485}, pmid = {41429716}, issn = {1879-2561}, mesh = {Humans ; *Neoplasms/therapy/diagnosis/immunology/genetics ; *Bacteriophages/genetics ; Cancer Vaccines/therapeutic use/immunology ; Animals ; *Phage Therapy/methods ; }, abstract = {Bacteriophages are viruses infecting bacterial cells; therefore, their application in cancer research may initially appear counterintuitive. Nevertheless, bacteriophages have been employed in the development of numerous advanced biotechnological tools, which has led to the emergence of multiple approaches utilizing them for improved cancer diagnostics and novel therapeutic strategies. Unlike other recently published reviews in this field, this paper does not emphasize technological principles or focus on specific cancer type. Instead, we provide a broad overview of innovative concepts and highlight recent advances in the use of bacteriophages in anti-cancer research. In particular, we discuss their roles in: (i) early cancer diagnosis and detection of tumorigenic mutations, (ii) elimination of bacteria that promote carcinogenesis and modulation of the microbiome influencing tumor growth, (iii) development of anti-cancer vaccines, (iv) modulation of cancer-related immune responses, (v) targeted delivery of anti-cancer drugs, and (vi) genetic modification of cancer cells through therapeutic DNA delivery.}, } @article {pmid41429281, year = {2025}, author = {Zhao, Z and Ju, Y and Gao, B and Yu, Y and Ur Rehman, K and Jiménez, N and Gago-Ferrero, P and Subirats, J and Matamoros, V and Wang, D and Li, Q and Zheng, L and Huang, F and Yu, C and Zhang, J and Cai, M}, title = {Functional microbial consortia augmented black soldier fly larvae achieve high efficiency ammonia mitigation during chicken manure bioconversion.}, journal = {Bioresource technology}, volume = {}, number = {}, pages = {133848}, doi = {10.1016/j.biortech.2025.133848}, pmid = {41429281}, issn = {1873-2976}, abstract = {Animal manure management frequently generates substantial ammonia (NH3) emissions, posing serious environmental and health concerns. Black soldier fly larvae (BSFL) bioconversion technology offers a promising solution by converting manure into valuable insect-derived protein and fat, while partially mitigating NH3 release. In this study, a functional microbial consortium (comprising Gordonia sp. AY-3, Lysinibacillus macroides F1, and Lactobacillus plantarum L7) from black soldier fly larvae (BSFL) frass and the larval gut was screened and developed to synergistically enhance BSFL productivity and reduce NH3 emissions. Results showed that optimal performance was achieved at an inoculation ratio of 2:1:1, which significantly reduced NH3 emissions by 37 % and increased larval fresh weight, dry weight, and bioconversion efficiency by 9 %, 9 %, and 12 %, respectively, compared with the control treatment. Functional gene analysis revealed a 37 %-52 % upregulation in nitrification (nxrAB) and denitrification genes (norBC, nosZ, nirK, nirS). Microbiome profiling indicated significant increases in Lactobacillus, Pseudomonas, and Bacteroides populations. Further pilot-scale validation demonstrated a 33 % reduction in environmental NH3 emissions. The daily average NH3 concentration decreased from 55 to 37 mg/m[3], along with a 4 % increase in BSFL fresh weight. Functional gene analyses showed that the consortium enhanced nitrogen assimilation via glutamine synthetase-glutamate synthase (GS-GOGAT) pathways, and upregulated denitrification-related genes. Overall, this BSFL bioconversion combined with microbial augmentation provides an effective strategy for reducing NH3 pollution while enhancing the efficiency of organic waste conversion.}, } @article {pmid41429263, year = {2025}, author = {Huang, J and Zhang, Y and Li, Q and Wang, M and Zhou, H and Su, H and Sun, X}, title = {Anti-PD-L1 improves barrier function and reduces CD103[+] DC cell accumulation by regulating gut and lung microbiota and its metabolites to alleviate asthma in juvenile mice.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {100944}, doi = {10.1016/j.bj.2025.100944}, pmid = {41429263}, issn = {2320-2890}, abstract = {BACKGROUND: Programmed death ligand 1 (PD-L1) was found to play an important role in maintaining tolerance and immune balance, and its mechanism of action on asthma still needs to be further clarified. We aim to block P MATERIAL AND METHODS: in a juvenile asthma model, PD-L1 blockers were used to inhibit the expression of PD-L1 in vivo. By evaluating parameters that reflect airway hyperresponsiveness, airway inflammation, tissue damage, intestinal barrier function, and microbiome changes in mice, the impact of PD-L1 blockade on various physiological and immune indicators in asthma models is fully revealed.

RESULTS: PD-L1 blockade reduces leukocyte infiltration in the lungs, including eosinophils, decreased levels of IgE and IgG1, and restored Th1/Th2 imbalance by reducing IL-4, IL-13, and GATA-3 while increasing IFN-γ. In addition, PD-L1 blockade significantly decreased levels of IL-17A/F and increased IL-10. Histological analysis of the lungs showed that PD-L1 blockade attenuated airway inflammatory cell infiltration and mucus hyperproduction. Further testing showed that the intestinal barrier function was improved after PD-L1 blockade. Mechanistic studies revealed that PD-L1 blockade improved microbiota composition in the lungs and gut, increased Lactobacillus, SCFA, and reduced LPS. As well as induced the downregulation of CD103[+] DCs in lung. Correlation analysis showed that airway inflammation is negatively correlated with SCFA and positively correlated with LPS, and barrier function is negatively correlated with LPS.

CONCLUSIONS: PD-L1 blockade alleviated asthmatic airway inflammation by modulating gut and lung microbiota, improving intestinal barrier function, increasing SCFA levels, reducing LPS and CD103[+] DCs activity.}, } @article {pmid41429213, year = {2025}, author = {Jopling, E and Metcalfe-Roach, A and Turvey, SE and Mandhane, P and Brett Finlay, B and LeMoult, J and , }, title = {The infant gut microbiome and the intergenerational transmission of psychiatric risk.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106232}, doi = {10.1016/j.bbi.2025.106232}, pmid = {41429213}, issn = {1090-2139}, abstract = {Elevated stress during the prenatal period is associated with increased psychiatric risk among children. However, less is known about the mechanisms through which this intergenerational transmission of risk occurs. The early life microbiome is one candidate mechanism through which maternal stress during the prenatal period could impact offspring mental health, with a growing body of literature highlighting the importance of the early life microbiome in mental health across the lifespan. This study leverages Canada's largest deeply phenotyped birth cohort to elucidate the mechanistic associations between maternal prenatal stress, dynamic changes in the microbiome across the first year of life, and child internalizing symptoms. Analytic sample size with use of full information maximum likelihood methodology was 2,985. Analyses indicated that early diversification of the early life microbiome significantly mediated the relation between higher maternal perceived stress during pregnancy and increased internalizing symptoms among offspring at 5 years of age. Crucially, microbial taxa impacted by early diversification of the microbiome implicated the immune system. This work supports maturational dynamics of the microbiome as one mechanism through which prenatal stress is biologically embedded to impact offspring's later mental health. By linking several burgeoning areas of research, this study lays the groundwork for future multidisciplinary work examining the intergenerational transmission of psychiatric risk through the microbiome.}, } @article {pmid41429111, year = {2025}, author = {Santos, LNA and Souza, RBMS and Fernandes, EL and Lima, LS and Silva, HL and Volpe, LM and Oliveira, SG and Félix, AP}, title = {A therapeutic gastrointestinal diet improves nutrient digestibility and modulates fecal microbiota and metabolites in dogs.}, journal = {American journal of veterinary research}, volume = {}, number = {}, pages = {1-10}, doi = {10.2460/ajvr.25.09.0346}, pmid = {41429111}, issn = {1943-5681}, abstract = {OBJECTIVE: To evaluate the effects of a therapeutic gastrointestinal diet on the apparent digestibility coefficients (ADCs), metabolizable energy (ME), and palatability of the diet, fermentative metabolites, and fecal microbiome of dogs.

METHODS: Sixteen 1-year-old healthy Beagles were used. All animals consumed a control diet for healthy adult dogs for 20 days. On day 21, 8 dogs changed to a therapeutic gastrointestinal diet (test diet), and 8 dogs continued receiving the control diet for 35 days. Fresh feces were collected on days 0, 3, 15, and 30 after changing to the test diet for pH, fermentative metabolites, and microbiota analysis. Feces were collected for ADCs and ME analysis of the diets (days 31 through 35). The palatability of the control and test diets was compared at the end of the study.

RESULTS: The test diet presented greater ADCs of nutrients and ME and resulted in lower fecal pH and greater fecal concentrations of ammonia, total biogenic amines, total short-chain fatty acids, and butyrate. β-Diversity analysis revealed distinct fecal microbiome profiles between the diets on days 3, 15, and 30, with a greater abundance of Turicibacter and Faecalibacterium and lower Streptococcus in the test group. Dogs preferred the test to the control diet in the palatability test.

CONCLUSIONS: The test diet presented high ADCs of nutrients, high palatability, and beneficially modulated the fecal microbiome and fermentative metabolites of dogs.

CLINICAL RELEVANCE: Providing a highly digestible and palatable diet with functional ingredients may contribute to the treatment of gastrointestinal disorders of dogs.}, } @article {pmid41429080, year = {2025}, author = {Castillo-Ilabaca, C and Jessen, GL and Aranda, M and Fernández, C and Méjanelle, L and Gutiérrez, MH and Pantoja-Gutiérrez, S}, title = {Evidence for priming-enhanced microbial degradation of polycyclic aromatic hydrocarbons in marine sediments.}, journal = {Marine pollution bulletin}, volume = {224}, number = {}, pages = {119163}, doi = {10.1016/j.marpolbul.2025.119163}, pmid = {41429080}, issn = {1879-3363}, abstract = {Priming effect is the enhanced microbial degradation of refractory organic carbon in the presence of labile organic matter. It has been proposed to explain the disappearance of supposedly recalcitrant terrestrial organic matter that reaches the coastal ocean. Here, we experimentally evaluated whether labile organics boosts the degradation of persistent pollutants, phenanthrene and pyrene (polycyclic aromatic hydrocarbons, PAHs). Microcosm incubations were conducted during 11 and 50 days using marine surface sediments from Concepción Bay, a PAH-impacted upwelling ecosystem in central Chile, and the Almirante Montt Gulf, a rather pristine Patagonian Fjord. Addition of yeast extract enhanced the degradation of phenanthrene and pyrene by 14-170 %, while microalgal extract increased the decay rate constant of phenanthrene by 67 %. PAH degradation was accompanied by a pronounced enrichment of hydrocarbonoclastic bacteria, which increased approximately 840-fold (average Log2FC = 9.7) with rather pristine Patagonian sediments but only 12-fold increase (average Log2FC = 3.6) in PAH-impacted Concepción Bay sediments. The broader shift in microbial community structure detected in Patagonian fjords coincides with low ambient PAH contents, as expected in unpopulated areas. Considering the long record and intensity of industrial activity off Concepción Bay and the surrounding area, we suggest that those sediments contain a core microbiome with a toolkit of potential enzymes involved in PAH-degradation pathways capable of processing high inputs of PAHs. This finding may imply that coastal marine sediments store microbial capacity for degradation of contaminants induced by a long history of PAH emissions, and this ability can be further enhanced by exposure to primers.}, } @article {pmid41428895, year = {2026}, author = {Vijayan, N and Briseño, J and Simakov, O and Nyholm, SV}, title = {Maintaining microbiota across diverse symbiotic organs in Euprymna scolopes: Insights into shared immune responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {1}, pages = {e2512903122}, doi = {10.1073/pnas.2512903122}, pmid = {41428895}, issn = {1091-6490}, support = {IOS2247195//NSF (NSF)/ ; 9349 and 12342//Gordon and Betty Moore Foundation (GBMF)/ ; 945026//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; }, mesh = {Animals ; *Symbiosis/immunology ; *Decapodiformes/microbiology/immunology/genetics ; Female ; *Microbiota/immunology ; Aliivibrio fischeri/physiology ; Transcriptome ; Carrier Proteins ; }, abstract = {Many animals have multiple organs or tissues that are colonized by diverse microbiota. The female Hawaiian bobtail squid, Euprymna scolopes, has two organs with distinct symbiotic communities: the accessory nidamental gland (ANG) and the light organ (LO). The ANG hosts a bacterial consortium, whereas the LO has a binary relationship with Vibrio fischeri, housed in extracellular crypt spaces as part of the central core (CC). To understand how the host maintains distinct symbiotic communities, we used transcriptomics to identify immune-related genes that are uniquely and similarly expressed in the ANG and LO-CC compared to organs without a known microbiota. Genes such as peptidoglycan recognition proteins EsPGRP2 and EsPGRP3, cathepsin-Z, alkaline phosphatase, and acidic phospholipase exhibited significant upregulation in the symbiotic organs compared to other tissues like gills, skin, mantle, optic lobe, ovaries, and brain. Moreover, EsPGRP2 displayed distinct localization patterns within the ANG, inversely correlating with bacterial presence, whereas the protein was colocalized with V. fischeri in the LO-CC. Notably, 10 different galaxins (EsGal) were uniquely highly expressed in both the ANG and LO-CC, with EsGal1 messenger RNA predominantly localized to the LO-CC epithelium, while EsGal2 and EsGal3 were primarily found in the epithelia of ANG tubules. Furthermore, antimicrobial assays using partial peptides derived from EsGal1 and EsGal2 showed varying and distinct patterns of inhibitory activity for these peptides. In summary, our findings identify similar immune gene families expressed across functionally distinct symbiotic organs in E. scolopes, suggesting that common immunomodulatory factors may maintain distinct symbiotic niches in the host.}, } @article {pmid41428865, year = {2025}, author = {Rutkowski, N and Yang, B and Gray-Gaillard, E and Ruta, A and Mejías, JC and Patatanian, M and Cherry, C and Celik, N and Stivers, KB and Ramanujam, S and Price, NL and Housseau, F and Pardoll, DM and Sears, CL and Elisseeff, JH}, title = {Antibiotic-induced microbiota depletion impairs the proregenerative response to a biological scaffold.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {52}, pages = {e2510841122}, doi = {10.1073/pnas.2510841122}, pmid = {41428865}, issn = {1091-6490}, support = {DGE2139757//NSF | NSF Graduate Research Fellowship Program (GRFP)/ ; DGE1746891//NSF | NSF Graduate Research Fellowship Program (GRFP)/ ; K99AG081564/GF/NIH HHS/United States ; }, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology/adverse effects ; *Gastrointestinal Microbiome/drug effects/immunology ; Mice ; Dysbiosis/immunology/chemically induced ; *Tissue Scaffolds ; Mice, Inbred C57BL ; Male ; Macrophages/immunology ; Female ; Interleukin-4/metabolism ; CD4-Positive T-Lymphocytes/immunology ; }, abstract = {Therapeutic biological scaffolds promote tissue repair primarily through the induction of type 2 immunity. However, systemic immunological factors, including aging, sex, and previous infections, can modulate this response. The gut microbiota is a well-established modulator of immune function across organ systems, yet its influence on type 2-mediated repair remains underexplored. Here, we establish a bidirectional relationship between the gut microbiota and biological scaffold-mediated tissue repair. Utilizing a conventionalized germ-free mouse, we demonstrate that scaffold implantation induces compositional and functional changes in the gut microbiome, particularly affecting amino acid biosynthesis. Additionally, in a model of antibiotic-induced microbiota depletion, we show that dysbiosis disrupts key immune regulators of type 2 immunity, including reductions in eosinophils, proregenerative macrophages, and interleukin-4 (IL-4)-producing CD4[+] T cells. At 6 wk post-scaffold implantation, we observed a significant decrease in myocytes with centrally located nuclei alongside an upregulation in profibrotic gene expression with antibiotic treatment. These findings provide insights into the influence of the gut microbiota on type 2-mediated tissue repair.}, } @article {pmid41428827, year = {2025}, author = {De Sotto, R and Aggarwal, N and Tham, EH and Chang, MW}, title = {Machine Learning in Microbiome Research and Engineering.}, journal = {ACS synthetic biology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acssynbio.5c00273}, pmid = {41428827}, issn = {2161-5063}, abstract = {Microbiomes, complex communities of microorganisms and their genetic material, hold immense potential for addressing global challenges in diverse sectors, including healthcare, agriculture, and bioproduction. Engineering these intricate ecosystems, however, necessitates a comprehensive understanding of the complex web of microbial interactions. The emergence of machine learning (ML) has revolutionized microbiome research, offering powerful tools to analyze massive data sets, uncover hidden patterns, and predict microbial behavior. ML algorithms have demonstrated remarkable success in identifying and characterizing microbial communities, predicting interactions between organisms and optimizing the design of microbial communities for specific functions. This Perspective examines the transformative applications of ML in the context of microbiome engineering, encompassing both microbiome data analysis and the targeted manipulation of microbial communities. These techniques employ a variety of strategies, including the manipulation of quorum sensing molecules, antimicrobial peptides, growth conditions, the introduction of probiotics, and the utilization of bacteriophages. By integrating ML with experimental approaches, researchers are pushing the boundaries of microbiome engineering, paving the way for novel applications in diverse fields. However, it is important to acknowledge the challenges that ML algorithms face, such as the limited availability of high-quality, large-scale data sets, the inherent complexity of biological systems, and the need for improved integration of experimental and computational methods. This perspective further discusses the future perspectives of the field, highlighting expected developments in data generation, algorithm development, and interdisciplinary collaboration. These advancements hold the key to unlocking the full potential of microbial communities for addressing pressing global challenges.}, } @article {pmid41428801, year = {2025}, author = {Sauša, S and Zodāne, A and Kumar, S and Plūme, J and Baranova, J and Kozlova, T and , and Saušs, H and Kloviņš, J and Pīrāgs, V and Mitravinda, KS and Kistkins, S and Brīvība, M}, title = {Rapid and Selective Gut Microbiome Modulation by Polyherbal Formulation in Type 2 Diabetes.}, journal = {Endocrine connections}, volume = {}, number = {}, pages = {}, doi = {10.1530/EC-25-0463}, pmid = {41428801}, issn = {2049-3614}, abstract = {BACKGROUND: Metformin, the first-line treatment for type 2 diabetes, often induces gastrointestinal side effects, affecting treatment adherence. Recent research suggests that the gut microbiome mediates both the efficacy and tolerability of metformin. This study evaluates the effect of a polyherbal formulation, used as an add-on to metformin, on the gut microbiota in patients with type 2 diabetes and metformin intolerance.

METHODS: We report preliminary findings from the first 7-day intervention phase of an ongoing randomized, placebo-controlled, crossover trial (NCT06846138) in 27 adults with type 2 diabetes. Participants received either polyherbal formulations or a placebo alongside metformin for 7 days. Stool samples were collected pre- and post-intervention for shotgun metagenomic sequencing. Microbial diversity, composition, and pathway functions were analyzed using Kraken2, Bracken, and HUMAnN3. Continuous glucose monitoring was used to assess glycemic metrics.

RESULTS: No significant alpha-diversity changes were observed; however, beta-diversity differed significantly between arms (PERMANOVA R2 = 0.04, p = 0.04). In the polyherbal formulation group, 17 species changed post-treatment (FDR < 0.25), with significant increases in six Bifidobacterium spp. (e.g., B. adolescentis, B. ruminantium). In contrast, the placebo group showed no major microbial shifts. Polyherbal formulation also altered 10 microbial pathways (FDR < 0.25). Continuous glucose monitoring revealed no short-term changes in glycemic levels.

CONCLUSION: Short-term polyherbal formulation co-administration significantly modulates gut microbiota, promoting beneficial taxa like Bifidobacterium in metformin-treated type 2 diabetes patients. This supports the potential role of the polyherbal formulation in microbiome-targeted strategies to improve metformin tolerability and effectiveness.}, } @article {pmid41428602, year = {2025}, author = {Zhang, Y and Chen, W and Wang, B and Rehman, KU and van Huis, A and Henawy, AR and Cai, M and Zheng, L and Ren, Z and Huang, F and Zhang, J}, title = {Enhancing Salmonella Inhibition in Black Soldier Fly Larvae (Hermetia illucens L.) Conversion by Bioaugmentation With Gut Microbiota.}, journal = {Microbial biotechnology}, volume = {18}, number = {12}, pages = {e70242}, doi = {10.1111/1751-7915.70242}, pmid = {41428602}, issn = {1751-7915}, support = {31770136//National Natural Science Foundation of China/ ; 2662022SKYJ006//Fundamental Research Funds for the Central Universities/ ; 2662023DKPY003//Fundamental Research Funds for the Central Universities/ ; 2022hszd013//Major Project of Hubei Hongshan Laboratory/ ; 2024BCA006//Hubei Province Technological Innovation Plan Project/ ; }, mesh = {Animals ; Larva/microbiology ; *Gastrointestinal Microbiome ; *Salmonella/growth & development ; Manure/microbiology ; *Diptera/microbiology ; Chickens ; Bacillus ; Metagenomics ; *Antibiosis ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {Black soldier fly larvae (BSFL) can efficiently convert organic waste into biomass and reduce pathogenic bacteria in organic waste. The microbial composition of the substrate and the gut of BSFL is a pivotal factor in determining the efficacy of BSFL in pathogen elimination. However, there are insufficient data on the gut microbiology of BSFL in relation to pathogen inhibition. To address this gap, we investigated the dynamics of Salmonella during the conversion of chicken manure by BSFL and examined the role of intestinal bacterial communities and core bacteria in reducing Salmonella levels. The results indicate that BSFL treatment can reduce the amount of Salmonella in chicken manure, with the gut microbiome of the BSFL playing a crucial role in this reduction. Combining metagenomic analysis with culturomics methods, we isolated 158 strains from the larval gut, in which seven gut bacteria belonging to the genus Bacillus can promote BSFL to reduce Salmonella. In reinoculation and validation experiments, the combination of BSFL and Bacillus velezensis A2 enhanced the elimination of Salmonella from chicken manure and larvae. This study provides insight into how BSFL can reduce pathogenic bacteria in chicken manure and suggests that pairing BSFL with functional microorganisms can improve the biosafety of organic waste conversion by BSFL.}, } @article {pmid41428567, year = {2025}, author = {Khromova, AM and Timerzyanov, MI and Valeeva, YV and Khaertynova, IM and Endaltseva, KM and Siraeva, ZY}, title = {[The study of the meconial microbiota for the purposes of forensic science and practice].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {68}, number = {6}, pages = {47-51}, doi = {10.17116/sudmed20256806147}, pmid = {41428567}, issn = {0039-4521}, mesh = {Humans ; *Meconium/microbiology ; Infant, Newborn ; *Gastrointestinal Microbiome/physiology ; *Forensic Sciences/methods ; Female ; Pregnancy ; *Microbiota ; }, abstract = {UNLABELLED: The issue of the effect of prenatal and perinatal pathological processes on the intestinal microbiome of the fetus and newborn requires increased attention.

OBJECTIVE: To analyze the results of scientific research reflecting the influence of the intestinal microbiome of a newborn on the stages of postembryonic development.

MATERIAL AND METHODS: A search for contemporary scientific studies relevant to the review's objectives was conducted in the scientific citation systems eLibrary (RSCI), Web of Science, PubMed, and Scopus. Thirty-three publications relevant to the review's subject matter were analyzed and included in the list.

RESULTS AND CONCLUSION: The idea of meconium non-sterility due to maternal-fetal transplantental microbial transition has been confirmed. The diagnostic value of detecting violations of the taxonomic composition of the microbiome lies in optimizing disease prevention and treatment strategies.}, } @article {pmid41428256, year = {2025}, author = {Sivarajan, D and Pothayi, V and Devasia, SC and Ramachandran, B}, title = {Impact of dietary composition on behavioural expression and gut microbiome dynamics in zebrafish.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {478}, number = {1}, pages = {13}, pmid = {41428256}, issn = {1432-2013}, support = {CSIR-UGC-JRF-905/2018//University Grants Commission/ ; (ECR/2018/002479)//DST-SERB, India/ ; }, mesh = {Animals ; *Zebrafish/microbiology/physiology ; *Gastrointestinal Microbiome/physiology ; *Behavior, Animal/physiology ; *Diet ; Brain/physiology ; *Animal Feed ; Aggression ; }, abstract = {Diet is a key physiological factor shaping brain function and gut microbiota, which together form the dynamic gut-brain axis. This bidirectional communication system plays a pivotal role in regulating behavioural outcomes. Therefore, it is worth investigating various behavioural aspects and connecting them with gut microbial dynamics shaped by differential dietary composition. Using zebrafish, we examined the effects of monotypic and combined diets of live feed and commercial feed on behavioural outcomes, morphometry, and gut microbiota. After chronic dietary intervention, fish receiving a mixed diet (Artemia, pellet, and spirulina) showed behavioural profile with enhanced exploration, reduced anxiety-like behaviour, and moderate aggression, alongside a balanced gut microbial composition. In contrast, monotypic diets produced distinct effects: Artemia-only fish displayed reduced boldness, heightened anxiety, and pathogenic microbial enrichment, while pellet-only fish showed greater growth but increased aggression. These findings highlight the importance of mixed feeding regimens for maintaining healthy gut-brain-behaviour interactions and support zebrafish as a model for studying diet-microbiota-behaviour relationships.}, } @article {pmid41427854, year = {2025}, author = {Wang, Y and Yu, J and Gao, L}, title = {Targeting Intratumoral Bacteria for Cancer Nanotherapeutics.}, journal = {ACS applied materials & interfaces}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsami.5c16720}, pmid = {41427854}, issn = {1944-8252}, abstract = {Intratumoral microbiota has emerged as a key modulator of cancer progression and therapeutic response, significantly influencing treatment outcomes. Although conventional microbiome-modulating approaches such as antibiotic administration can enhance cancer treatment efficacy, they frequently lead to inconsistent therapeutic results and disrupt beneficial microbial communities. Nanotechnology, with its capacity for precise interactions at microscopic and molecular scales, offers a promising solution for selectively regulating tumor-associated microbiota and reshaping the tumor microenvironment. This review elucidates current knowledge by conducting a comprehensive analysis of the literature, with a focus on classifying the antibacterial mechanisms of nanotechnology against intratumoral bacteria into physical, chemical, and biological modalities, and further discusses the precision design of nanomaterials, therapeutic outcomes, and antimicrobial mechanisms within each modality. Furthermore, we discuss challenges in precise targeting and safety, examine the translational progress of nanotechnology-based antimicrobial strategies, and propose future directions for research and clinical application.}, } @article {pmid41427744, year = {2025}, author = {Burnside, M and Helliwell, E and Treerat, P and Rozendal, T and Merritt, J and Baker, JL and Kreth, J}, title = {Comparative characterization reveals conserved and divergent ecological traits of oral corynebacteria.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0297325}, doi = {10.1128/spectrum.02973-25}, pmid = {41427744}, issn = {2165-0497}, abstract = {Corynebacteria are abundant members of the oral microbiome and increasingly recognized as key structural organizers of supragingival biofilms. Despite their prevalence, the ecological roles and phenotypic traits of many oral corynebacterial species remain poorly defined. Here, we isolated and characterized two new strains, Corynebacterium durum JJ2 and Corynebacterium argentoratense MB1, and compared them with previously characterized and published Corynebacterium durum JJ1 and reference strain Corynebacterium matruchotii ATCC 14266. Phenotypic assays revealed that C. durum strains displayed robust aggregation, thick biofilm formation, and extensive extracellular polymeric substance (EPS) networks, whereas C. argentoratense MB1 and C. matruchotii ATCC 14266 formed thinner biofilms with minimal EPS production. All four strains secreted extracellular membrane vesicles capable of inducing chain elongation in Streptococcus sanguinis, underscoring a conserved interspecies signaling function. Genomic analysis demonstrated close relatedness between C. durum and C. matruchotii, while C. argentoratense MB1 was more distantly related, with a reduced genome, fewer metabolic pathways, and the absence of nitrate reductase genes, consistent with its inability to grow under anaerobic conditions. These findings suggest that C. argentoratense MB1 may represent a less specialized or transient inhabitant of the oral cavity, whereas C. durum and C. matruchotii are well adapted to the oral niche. Together, this study expands our understanding of phenotypic diversity, metabolic capacity, and interspecies interactions among selected oral corynebacteria, highlighting their potential importance as biofilm organizers and contributors to oral microbial ecology.IMPORTANCEOral corynebacteria contribute to the structural and ecological stability of supragingival communities. Yet, their species-level functions remain poorly defined. By isolating and characterizing new strains of Corynebacterium durum and Corynebacterium argentoratense, and comparing them with reference strains including Corynebacterium matruchotii, we provide new insight into their phenotypic diversity, metabolic capacity, and ecological roles. Our results demonstrate that C. durum strains form robust biofilms enriched in extracellular polymeric substances, while C. argentoratense produces thinner biofilms and lacks the genomic features required for anaerobic growth, suggesting a less specialized or transient role in the oral cavity. Importantly, we show that extracellular membrane vesicles secreted by all tested strains promote chain elongation in Streptococcus sanguinis, highlighting a conserved mechanism of interspecies communication. These findings advance our understanding of how oral corynebacteria contribute to biofilm organization and microbial homeostasis and position them as critical but understudied players in oral microbial ecology.}, } @article {pmid41427732, year = {2025}, author = {O'Brien, CE and Frese, SA and Cernioglo, K and Damian-Medina, K and Mitchell, RD and Casaburi, G and Melnyk, RA and Henrick, BM and Smilowitz, JT}, title = {Randomized, placebo-controlled trial reveals the impact of dose and timing of Bifidobacterium infantis probiotic supplementation on breastfed infants' gut microbiome.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0051825}, doi = {10.1128/msphere.00518-25}, pmid = {41427732}, issn = {2379-5042}, abstract = {UNLABELLED: A dysfunctional gut microbiome has become increasingly common in infants born in high-income countries as Bifidobacterium strains no longer dominate the gut microbiome. Probiotics containing Bifidobacterium infantis have been used in breastfed newborns to successfully restore the gut microbiome; however, no studies to date have demonstrated this effect in older breastfed infants whose gut microbiomes are transitioning toward stability and maturity. This is a 9-week randomized controlled trial wherein 2-4 months old exclusively breastfed infants (n = 40) received 0 CFU/day B. infantis EVC001 (placebo), 4.0 × 10[9] CFU/day B. infantis EVC001 (low), 8.0 × 10[9] CFU/day B. infantis EVC001 (medium), or 1.8 × 10[10] CFU/day B. infantis EVC001 (high) in equal allocation for 28 consecutive days beginning on day 8. Stool samples were collected on study days 7, 10, 14, 21, 28, 35, 42, and 63. Fecal B. infantis levels were significantly higher in all supplement groups compared with placebo on day 28 and day 63. On day 28, fecal B. infantis levels were significantly higher in infants who received any (low, medium, and high) dose compared with baseline. The abundance of fecal Bifidobacteriaceae significantly increased nearly 2-fold in response to B. infantis EVC001 supplementation. No matter the dose, probiotic supplementation with B. infantis in 2- to 4-month-old exclusively breastfed infants resulted in colonization until at least 1 month post-supplementation.

IMPORTANCE: This study found that supplementing exclusively breastfed infants with a probiotic, Bifidobacterium infantis EVC001, between 2 and 4 months of age can successfully restore beneficial bacteria in their gut, even after the newborn period. Although previous research showed this effect in newborns, this is the first study to demonstrate that older infants, whose gut microbiomes are typically more stable, can still benefit. The probiotic was effective at all tested doses, with higher levels of B. infantis and overall Bifidobacteriaceae in infants' stool during and even 1 month after supplementation. This study demonstrates that B. infantis can take hold in the gut and potentially improve gut health in older breastfed babies, offering a promising approach to support infant health in settings where beneficial gut bacteria are often missing.

CLINICAL TRIALS: This study was registered at clinicaltrials.gov as NCT03476447.}, } @article {pmid41427714, year = {2025}, author = {Bell, AG and Cable, J and Temperton, B and Tyler, CR}, title = {Assessment of the effectiveness of host depletion techniques for profiling fish skin microbiomes and metagenomic analysis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0183825}, doi = {10.1128/spectrum.01838-25}, pmid = {41427714}, issn = {2165-0497}, abstract = {UNLABELLED: Microbiomes on fish mucosal surfaces play crucial roles in nutrient absorption, immune priming, and defense, and disruptions in these microbial communities can lead to adverse health outcomes, including disease. Studying fish microbiomes relies on sequencing microbiota within mucosal-rich samples; however, nucleic acid extraction from these samples is composed predominantly of host DNA, making subsequent bioinformatic processes difficult. Host depletion techniques address this issue by either selectively degrading host DNA before sequencing or retaining bacterial DNA post-extraction. However, their application to fish mucosal samples has been largely unexplored. Here, we assessed the efficacy of various host depletion techniques on fish skin mucosal swabs via either selectively removing CpG-methylated (predominantly eukaryotic) DNA or selectively lysing eukaryotic cells before DNA extraction. Surprisingly, none of the existing methods we assessed effectively reduced host DNA to be practically useful. Furthermore, some methods introduced a bias toward certain bacterial taxa, including the Bacilli class and the Proteobacteria phylum. Our findings illustrate that the currently available host depletion techniques are largely ineffective for reducing host DNA in fish mucosal samples. This poses a major limitation for developing an understanding of the functional composition of fish mucosal microbiomes, as enriching microbiota (and excluding host DNA) is fundamental for cost-effective metagenomic studies and facilitating more accurate analyses of the microbiota metabolome and proteome.

IMPORTANCE: Microbial communities on fish mucosal surfaces are vital for immune function and disease resistance. However, sequencing these communities is hindered by the dominance of host DNA in mucosal samples, which can exceed 99% of total nucleic acids. While host depletion techniques are routinely used in human and mammalian systems to enrich microbial DNA, their efficacy on fish samples remains uncharacterized. In this study, we assessed multiple commercial and published host depletion methods on fish skin microbiomes. None significantly reduced host DNA to levels suitable for high-quality metagenomic sequencing, and some introduced taxonomic bias. We suggest methodological reasons, including differences in fish cell structure and mucus composition compared to mammalian systems, that may explain these shortcomings. Based on our findings, we propose protocol modifications and highlight key areas for improvement. This work identifies critical limitations and offers a foundation for developing optimized host depletion strategies tailored to fish mucosal microbiome research.}, } @article {pmid41427705, year = {2025}, author = {Wang, J and Qu, R and Huang, W and Chen, Y and Li, Y and Lin, Q and Wu, Z and Yan, H and Yu, T and Wang, C and Ren, X and Wang, X and Wu, J}, title = {Progressive and concordant alterations in transcriptional and gut microbiota across aortic valve calcification severity.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0213725}, doi = {10.1128/spectrum.02137-25}, pmid = {41427705}, issn = {2165-0497}, abstract = {UNLABELLED: Calcific aortic valve disease (CAVD) is a common disorder associated with substantial morbidity and mortality. Although the gut microbiome has complex associations with cardiovascular disease, its variation across the calcification spectrum in CAVD remains poorly defined. We profiled aortic-valve transcriptomes from 31 patients spanning graded calcification and paired these with matched stool microbiome profiles. We identified subtle yet widespread transcriptional changes in mild CAVD (m-CAVD), consistent with a progressive relationship between calcification burden and gene-expression remodeling. At the community level, the gut microbiome in m-CAVD exhibited an intermediate configuration between non- and higher-calcification profiles, suggesting an early shift in the gut ecosystem along the disease continuum. At the genus level, we identified 11 taxa associated with stage; notably, Anaerococcus increased with calcification burden, whereas Rheinheimera declined across stages. These results refine the pathophysiology landscape of CAVD by connecting stage-dependent valvular transcriptional changes with coordinated shifts in the gut microbiome and indicate that early, microbiome-targeted interventions may be promising.

IMPORTANCE: Calcific aortic valve disease is a common valvular heart disease. Due to the difficulty in sampling arterial calcified tissues, research on the interaction between their gene expression and the gut has been limited. In this study, by analyzing the transcriptional profiles of calcified aortic valve tissues from patients with different levels of calcification and the characteristics of their corresponding gut microbiota, we identified consistent features between lesion gene expression and gut microbiota variation. This provides important evidence for the association between the gut microbiota and disease development stages, offering a new perspective for understanding disease progression and early intervention.}, } @article {pmid41427586, year = {2026}, author = {Newman, KL and Standke, AK and James, G and Vendrov, KC and Inohara, N and Bergin, IL and Higgins, PDR and Rao, K and Young, VB and Kamada, N}, title = {Miniature bioreactor arrays for modeling functional and structural dysbiosis in inflammatory bowel disease.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2604875}, doi = {10.1080/19490976.2025.2604875}, pmid = {41427586}, issn = {1949-0984}, mesh = {*Dysbiosis/microbiology ; Humans ; *Gastrointestinal Microbiome ; Animals ; Mice ; *Bioreactors/microbiology ; Feces/microbiology ; *Inflammatory Bowel Diseases/microbiology ; Clostridioides difficile/growth & development ; Colitis, Ulcerative/microbiology ; Disease Models, Animal ; Crohn Disease/microbiology ; Female ; Male ; Interleukin-10/genetics/deficiency ; Bacteria/classification/isolation & purification/genetics ; Mice, Inbred C57BL ; }, abstract = {Alterations in the gut microbiota, known as gut dysbiosis, are associated with inflammatory bowel disease (IBD). There is a need for model systems that can recapitulate the IBD gut microbiome to better understand the mechanistic impact of differences in microbiota composition and its functional consequences in a controlled laboratory setting. To this end, we introduced fecal samples from patients with Crohn's disease (CD) and ulcerative colitis (UC), as well as from healthy control subjects, to miniature bioreactor arrays (MBRAs) and analyzed the microbial communities over time. We then performed two functional assessments. First, we evaluated the colitogenic potential of the CD microbiotas in genetically susceptible germ-free IL-10-deficient mice and found that colitogenic capacity was preserved in a bioreactor-cultivated CD microbiota. Second, we tested impaired colonization resistance against Clostridioides difficile in UC microbiotas using the MBRA system and found that UC microbiotas were innately susceptible to C. difficile colonization while healthy microbiotas were resistant, consistent with what is seen clinically. Overall, our results demonstrate that IBD microbiotas perform comparably to healthy donor microbiotas in the MBRA system, successfully recapitulating microbial structure while preserving IBD-specific functional characteristics. These findings establish a foundation for further mechanistic research into the IBD microbiota using MBRAs.}, } @article {pmid41427415, year = {2025}, author = {Bernate, E and Shi, Y and Franck, E and Crofts, TS}, title = {A functionally selected Acinetobacter sp. phosphoethanolamine transferase gene from the goose fecal microbiome confers colistin resistance in E. coli.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.09.693354}, pmid = {41427415}, issn = {2692-8205}, abstract = {Polymyxins are last-resort antibiotics for infections caused by multidrug resistant Gram-negative bacteria such as Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii . This makes the rise of bacteria exhibiting polymyxin E (colistin) resistance, largely through modification of lipid A moieties, concerning and suggests that it is important to document potential sources of the corresponding resistance genes. This study searched for potential emerging colistin-resistance genes from the environment by investigating a previously performed functional metagenomic selection for colistin resistance of a goose fecal microbiome. We found that the selection captured Acinetobacter sp. DNA fragments which all contained eptA genes. We confirmed their ability to confer significant colistin resistance in E. coli via modification of lipid A in the outer membrane. Furthermore, we found evidence for mobilization of closely related eptA genes in Acinetobacter strains, marking them as potential mcr genes or their precursors. This study highlights the goose fecal microbiome as a potential source for colistin resistance in the environment.}, } @article {pmid41427374, year = {2025}, author = {Suzuki, E and Deleray, V and Zemlin, J and Kousha, A and Nonoguchi, H and Sun, D and Tsai, CM and Zuffa, S and Kvitne, KE and Dorrestein, PC and Tsunoda, SM and Nizet, V and Liu, GY and Askarian, F}, title = {Effect of Perinatal Ampicillin or Amoxicillin/Clavulanate Exposure on Maternal and Infant Gut Microbiome, Metabolome, and Infant Responses to the 20-valent Pneumococcal Conjugate Vaccine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.08.692990}, pmid = {41427374}, issn = {2692-8205}, abstract = {Emerging studies suggest that antibiotics can disrupt the gut microbiome and alter vaccine-induced immune responses, but the specific consequences of early-life exposure on neonatal immune development remains poorly understood. Here, we examined how two antibiotics frequently used in perinatal care, broad-spectrum ampicillin (AMP) and the extended-spectrum combination amoxicillin/clavulanate (AMOX/CLAV), administered during gestation and lactation, influence neonatal gut microbiome composition, fecal metabolome profiles, and responses to the 20-valent pneumococcal conjugate vaccine (PCV20). Maternal treatment with AMOX/CLAV, but not AMP, significantly reduced PCV-specific IgG titers at 4-and 6-weeks post-prime immunization compared to untreated controls. Exclusive exposure to AMOX/CLAV also impaired neutrophil-mediated opsonophagocytic killing, indicating diminished antibody functionality. These effects were transient, with immune parameters normalizing by week 8 post-prime immunization. Metabolomic and microbiome profiling revealed that maternal AMP and AMOX/CLAV differentially perturbed specific metabolite classes including bile acids, N -acyl lipids, and indole-derivatives, as well as key commensal taxa including Bacteroidales and Coriobacteriales within the gut microbiota. Together, these findings reveal a previously underappreciated maternal-offspring route of antibiotic influence that transiently disrupts neonatal vaccine responsiveness through microbiome and metabolome alterations. These results highlight maternal antibiotic exposure as a modifiable factor shaping early-life immunity.}, } @article {pmid41426949, year = {2025}, author = {Allshouse, T and Amendano, M and Caruso, B and Del Campo, R and Murphy, G and Shaffer, L and Steinberg, E and Sullivan, A and Stowe, E}, title = {The Microbiota of Homemade Tepache Includes Antibiotic-Resistant Microorganisms.}, journal = {microPublication biology}, volume = {2025}, number = {}, pages = {}, pmid = {41426949}, issn = {2578-9430}, abstract = {Tepache is a traditional, homemade Mexican drink made by fermenting pineapple rinds. The natural probiotic bacteria in tepache are said to promote a healthy gut microbiome. This study assessed the microbial community in homemade tepache for diversity, survival in simulated gastric fluid, and antibiotic resistance. Simulated gastric passaging reduced total community numbers but the community density was not strongly impacted by exposure to tetracycline. Metagenomic analysis reveals a community dominated by Bacillus, Meyerozyma and Talaromyces. These results indicate that consuming home fermented beverages may provide helpful probiotic bacteria but could also expose the gut microbiome to antibiotic resistance genes.}, } @article {pmid41426590, year = {2025}, author = {Zhang, J and Xu, X and Chen, L and Yang, X and Matsubara, JK and Tian, Y and Liu, J and Jin, X and Chang, H and Xu, M and Zhu, C and Wang, X and Ren, L and Xie, J and Liu, J and Liu, G and Lu, M and Wang, X and Du, L and Ma, Z and Liu, X and Zhao, H and Chen, W and Huo, X and Zheng, G and Xie, C and Xu, C and Zhang, X and Qi, W and Feng, Z}, title = {Circulating microbiome profiling in transjugular intrahepatic portosystemic shunt patients: 16S rRNA vs. shotgun sequencing.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1662837}, pmid = {41426590}, issn = {2296-858X}, abstract = {BACKGROUND AND AIM: Current efforts to characterize the circulating microbiome are constrained by the lack of standardized protocols for isolating and sequencing microbial communities in blood. To address this challenge, our study compared 16S rRNA (V3-V4 region) and shotgun metagenomic sequencing for circulating microbiome detection.

MATERIALS AND METHODS: After obtaining ethics committee approval and informed consent, samples were aseptically collected from 10 patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedures. Shotgun metagenomic reads were taxonomically classified using the Kraken2-Bracken pipeline. 16S rRNA (V3-V4) data were analyzed through an ASV-based approach, with USEARCH for denoising and VSEARCH for taxonomic annotation. The results from both sequencing methods were then systematically compared.

RESULTS: Shotgun metagenomic sequencing generated 7,024,580,376 raw reads (mean depth: 234,152,679.2 reads/sample), while 16S rRNA sequencing produced 6,612,678 raw reads (mean depth: 220,422.6 reads/sample). 16S rRNA amplicon sequencing captured a broader range of microbial signals. Although the taxonomic profiles from both sequencing methods showed limited overlap, the core microbiota common to both were still identified. These conserved core microbial communities exhibited stable α- and β-diversity indices across separate vascular compartments.

CONCLUSION: In our study, 16S rRNA amplicon sequencing captured more diverse microbial signals than shotgun metagenomics. A stable microbial community structure was observed across vascular compartments, suggesting a homogeneous microbial composition throughout the circulatory system.}, } @article {pmid41426531, year = {2025}, author = {Jijón, G and Hough, C and Gedris, D and Frandsen, PB and Chaston, JM}, title = {Gut microbiome composition of Trichoptera larvae across functional feeding groups: a case study from the Provo River, Utah, USA.}, journal = {ZooKeys}, volume = {1263}, number = {}, pages = {165-177}, pmid = {41426531}, issn = {1313-2989}, abstract = {Diet is known to be a major factor in the gut microbiome of many groups of insects. Larvae from the insect order Trichoptera have varied feeding behaviors, encompassing all functional feeding groups, making them an excellent group for studying the links between diet and gut microbe community variation. However, no previous study has examined these links in caddisflies. Here, we characterize the gut microbiome composition of four caddisfly genera belonging to four different functional feeding groups over two sampling periods using 16S metabarcoding. We found that the sampling date had the strongest influence on gut microbiome variation. Host functional feeding groups and phylogeny also influenced gut community composition; however, improved sampling is necessary to confirm this relationship. Our preliminary results point to interesting differences among larvae from different feeding groups and suggest future areas for research, including performing species-level identification of the caddisfly larvae, using more taxa within and between functional feeding groups, using temporal and larval stage-matched replicates, assessing the degree of microbiome residency in caddisfly guts, and performing deeper sequencing.}, } @article {pmid41426377, year = {2025}, author = {Li, Z and Zhang, Y and Luo, X and Wang, Y and Peng, L and Zou, L}, title = {Dynamic relationships between bilirubin concentrations and the gut microbiota in the neonatal period: A pilot prospective cohort study.}, journal = {Pediatric investigation}, volume = {9}, number = {4}, pages = {347-360}, pmid = {41426377}, issn = {2574-2272}, abstract = {IMPORTANCE: Understanding the dynamic interplay between gut microbiota development and bilirubin metabolism may provide new insights into the pathophysiology of neonatal jaundice. Identifying microbial taxa associated with bilirubin fluctuations could help inform early prediction and microbiota-targeted interventions for hyperbilirubinemia.

OBJECTIVE: To investigate the correlation between dynamic changes in the gut microbiota and bilirubin concentrations during the neonatal period.

METHODS: Bilirubin concentrations were monitored daily throughout the neonatal period. Fecal samples were collected from neonates on days 1, 3, 7, 14, 21, and 28 after birth. The composition of the gut microbiome was assessed by 16S rRNA gene amplicon sequencing of the fecal samples. Within-subject, same-day associations between transcutaneous bilirubin (TcB) and genus-level abundance were quantified using a repeated-measures correlation.

RESULTS: Thirty neonates were included in the final analysis. Among the top-30 genera, six exhibited false discovery rate significant, same-day within-subject associations with TcB under the repeated-measures correlation framework (|rrm| ≥0.30). Changes in the abundances of the genera Streptococcus (r rm = +0.416, 95% confidence interval [CI] 0.272-0.543, P = 2.084 × 10[-7]; P-adj = 3.126 × 10[-6]) and Rothia (r rm = +0.340, 95% CI 0.187-0.476; P = 3.134 × 10[-5]; P-adj = 1.567 × 10[-4]) were positively correlated with bilirubin concentrations throughout the neonatal period. In complementary cross-sectional analyses centered on meconium, additional genus-bilirubin correlations were identified for TcB measured on postnatal days 3-7 and for the neonatal TcB peak, with multiplicity controlled separately for each endpoint.

INTERPRETATION: A correlation was found between dynamic changes in the gut microbiome and bilirubin concentrations during the neonatal period. The identified genera might be potential markers or targets for intervention for neonatal jaundice.}, } @article {pmid41426333, year = {2025}, author = {Turgeman, I and Henick, BS and Mezquita, L}, title = {Editorial: Nature and nurture in early onset lung cancer.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1750797}, pmid = {41426333}, issn = {2234-943X}, } @article {pmid41426250, year = {2025}, author = {Dai, YK and Li, DY and Cong, LL and Liao, Y and Wang, XC and Fan, JW and Chen, WJ and Fan, CH and Ma, T and Wu, YJ}, title = {Mechanism of Chronic Atrophic Gastritis: A 20-Year Bibliometric Analyses.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {17457-17475}, pmid = {41426250}, issn = {1178-7031}, abstract = {BACKGROUND AND PURPOSE: Chronic atrophic gastritis (CAG), affecting approximately 20-30% in high-risk populations, contributes to significant morbidity and mortality due to its progression to gastric cancer. Despite two decades of research into its pathogenesis, the vast body of literature has not yet been systematically mapped. A comprehensive bibliometric analysis mapping the field's evolution, collaborative networks, and knowledge gaps remains lacking. Therefore, we conduct a 20-year bibliometric analysis (2005-2024) of research on the mechanism of CAG to identify seminal works, emerging themes, evaluate global collaboration networks, and highlight translational challenges and opportunities.

PATIENTS AND METHODS: Data were retrieved from the Web of Science Core Collection (WoSCC) spanning from January 1, 2005, to December 31, 2024. Bibliometric analysis was performed using CiteSpace and VOSviewer to analyze publication trends, influential authors and institutions, keyword clusters, and citation bursts.

RESULTS: A total of 954 papers were identified, with China leading in publication output (41.51%), followed by the USA (15.20%). The USA demonstrated high centrality in international collaboration. Key journals included WORLD J GASTROENTERO and GASTROENTEROLOGY. Prolific authors such as Liu Yuetao and co-cited authors like CORREA P were identified. Keyword analysis revealed "Helicobacter pylori" as the most prominent term, with clusters focusing on traditional Chinese medicine, macrophage biology, and gastric intestinal metaplasia.

CONCLUSION: The study highlights the significant research output and collaboration in CAG, emphasizing the importance of interdisciplinary approaches and international partnerships. Future research should focus on integrating traditional knowledge with modern mechanistic studies and addressing emerging themes such as microbiome dysbiosis and precision medicine.}, } @article {pmid41426219, year = {2025}, author = {Jeong, JY and Park, SH and Kim, M and Kang, HK and Park, NG}, title = {Comparative gut microbiota, growth performances, and cytokine indices in broiler chickens with or without litter.}, journal = {Journal of animal science and technology}, volume = {67}, number = {6}, pages = {1328-1342}, pmid = {41426219}, issn = {2055-0391}, abstract = {Developmental patterns of the gut microbiota are important for improving chicken health and productivity. However, the influence of litter and litter microbes on cecal microbiota is still unclear. This study aimed to identify broiler cecal microbiota at different ages according to litter usage in cage (without litter) and conventional (with litter) conditions. The cecal contents of the broilers from each group were collected from 1-5 wk. The development and function of the gut microbiota were evaluated using 16S rRNA gene sequencing. The final body weight of the chickens was higher in the cage group than that in the conventional group. In particularly, α-diversity was higher at 3 wk than that at 1 wk. The phyla Firmicutes predominated at 3 wk. In contrast, the abundance of Bacteroidetes and fibrinolytic bacteria increased significantly at 1 and 2 wk compared to that at 3 and 5 wk. Corynebacterium was the most abundant genus in the conventional group after 3 wk. In conclusion, the cecal microbiota are influenced by environmental factors, such as cage, which improves the chicken gut environment.}, } @article {pmid41425942, year = {2025}, author = {Li, Z and Peng, X and Wang, Q and Guo, L and Liu, S and Xu, L}, title = {Host sweet preference modulates the salivary microbiome and its divergent associations with plaque-associated and non-plaque-related oral diseases.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1732083}, pmid = {41425942}, issn = {1664-302X}, abstract = {BACKGROUND: Microorganisms play a critical role in the progression of oral diseases. However, it remains unclear whether the frequency of sweet consumption influences the salivary microbiota in both plaque-associated and non-plaque-related oral diseases.

METHODS: Based on salivary microbiome analysis, unstimulated saliva samples were collected from university students aged 17-20, including healthy controls (HC), dental caries (DC), and dental fluorosis (DF) groups, under different sweet consumption frequencies. Microbiota potentially critical in disease development were identified.

RESULTS: No significant differences in α- and β-diversity were observed among the three groups. However, distinct microbial structures at the genus and species levels were evident under different sweet consumption conditions. Under high sweet consumption, the caries group exhibited enrichment of microbiota closely associated with sugar metabolism and acid production (e.g., Streptococcus, Rothia), while Ralstonia was significantly enriched in the caries group, suggesting its potential role in high-sweet-induced caries development. Under low sweet consumption, the healthy control group showed enrichment of taxa such as Stenotrophomonas, potentially linked to ecological stability, whereas the dental fluorosis group demonstrated significant enrichment of Fastidiosipila, reflecting specific fluoride-induced selective pressure on the microbiome. This study indicates that although sweet consumption frequency did not significantly alter overall microbial diversity, it reshaped the oral microbiota structure in a disease-specific context. The caries group was more prone to developing a cariogenic microbial profile under high-sugar conditions, while the fluorosis group exhibited unique ecological adaptive characteristics.}, } @article {pmid41425940, year = {2025}, author = {Zheng, B and Wang, L and Sun, S and Yuan, X and Liang, Q}, title = {The molecular interplay between the gut microbiome and circadian rhythms: an integrated review.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1712516}, pmid = {41425940}, issn = {1664-302X}, abstract = {This integrated review synthesizes current evidence on the molecular interplay between the gut microbiome and circadian rhythms, emphasizing a sophisticated bidirectional communication system crucial for maintaining metabolic, immune, and neurological homeostasis. The host circadian clock orchestrates microbial composition and function through rhythmic changes in feeding-fasting cycles, hormone secretion, immune responses, and bile acid metabolism. In return, microbial metabolites, including short-chain fatty acids such as butyrate, secondary bile acids like lithocholic acid, and tryptophan derivatives, act as timing cues that influence core clock gene expression via epigenetic mechanisms, receptor-mediated signaling (GPR41/43, FXR), and neuroendocrine pathways. Disruption of this finely tuned dialogue, known as chronodisruption, often driven by modern lifestyles, predisposes individuals to a range of pathologies, including metabolic syndrome, inflammatory bowel disease (IBD), neurodegenerative disorders, and cancer. The review also evaluates promising chronotherapeutic interventions such as time-restricted eating (TRE), targeted probiotic use, and chronopharmacology, which aim to resynchronize host-microbe rhythms and restore physiological balance. Elucidating these mechanisms provides a foundational framework for developing personalized health strategies that target the gut-clock axis.}, } @article {pmid41425933, year = {2025}, author = {Zhai, C and Sun, W and Li, Y and Han, H and Zhang, Y and Ma, B}, title = {Pre-release environmental acclimation enhances wild adaptability of endangered Kaluga sturgeon (Huso dauricus): insights from digestive, immune, and gut-microbiome perspectives.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1720688}, pmid = {41425933}, issn = {1664-302X}, abstract = {INTRODUCTION: Pre-release environmental acclimation is an effective strategy for improving post-stocking survival and restoring wild genetic resources in hatchery-reared juveniles. However, environmental acclimation protocols for the endangered Kaluga sturgeon (Huso dauricus) are currently non-existent.

METHODS: Here, cultured H. dauricus were transferred to a tributary of the Songhua River in autumn and exposed to an in-situ environmental acclimation protocol for 30 days. Subsequently, a hatchery control (HK) and seven environmental acclimation groups-HC1 (day 2), HC2 (day 5), HC3 (day 10), HC4 (day 15), HC5 (day 20), HC6 (day 25) and HC7 (day 30)-were monitored for feeding rate, digestive and immune enzyme activities, immune-gene expression, and gut microbiota change.

RESULTS: During the initial phase of wild conditioning, feeding rate remained negligible until HC2 group, then increased to 66%, 88.89% and 100% in groups HC4, HC5 and HC6, respectively. Meanwhile, digestive enzyme activities stabilized between groups HC4 and HC5, and immune enzyme activities in the wild-conditioned sturgeon were markedly higher than those of the control group. In addition, compared with the control group, the pro-inflammatory cytokine Interleukin-6 (IL-6) was significantly up-regulated, whereas the anti-inflammatory genes Interleukin-10 (IL-10) and Transforming growth factor-beta (TGF-β) were significantly down-regulated in HC4 group (P < 0.05). At the phylum level, the dominant microbiota shifted from Pseudomonadota to Bacillota by day 20 (HC5 group) and thereafter remained stable.

DISCUSSION: This study provides a theoretical framework for characterizing the physiological and biochemical responses of H. dauricus during environmental acclimation and provides a scientific basis for conserving its wild genetic resources.}, } @article {pmid41425932, year = {2025}, author = {Quijia-Pillajo, J and Chapin, LJ and Owen, JS and Altland, JE and Jones, ML}, title = {Fertilization influences the substrate, rhizosphere, and endosphere bacteriome of Petunia × hybrida.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1719754}, pmid = {41425932}, issn = {1664-302X}, abstract = {INTRODUCTION: In controlled environment agriculture (CEA), soil is replaced with soilless substrates that have poorly understood microbiome dynamics. We investigated the rhizosphere and endosphere bacteriome of Petunia × hybrida 'Picobella Blue' (Picobella) and 'Wave Purple' (Wave) grown in a soilless substrate (80% sphagnum peat and 20% perlite) under three fertilization rates (25, 100, and 200 mg·L[-1] N).

METHODS: Plant growth was assessed with the TraitFinder phenotyping platform, shoot dry weight, and nutrient analysis. Bacteriomes were profiled by 16S rRNA amplicon sequencing from unplanted substrate, bulk substrate, rhizosphere, and endosphere samples.

RESULTS: Both cultivars grew largest and healthiest at 200 mg·L[-1] N. Picobella fertilized with 100 and 200 mg·L[-1] N were equally green, whereas Wave was greenest at 200 mg·L[-1] N. Distinct bacteriomes were observed across unplanted substrate, rhizosphere, and endosphere. In unplanted substrate, fertilizer rate shaped bacterial community composition but not alpha diversity. In the rhizosphere, pH changes driven by fertilization strongly influenced bacterial community structure and reduced diversity. Endosphere and rhizosphere communities were further shaped by cultivar and fertilization rate.

DISCUSSION: These findings highlight nutrient management as a key driver of bacteriome dynamics across the substrate-plant continuum, underscoring the complex interactions between fertilization, plant genotype, and microbial communities in soilless culture.}, } @article {pmid41425929, year = {2025}, author = {Li, P and Yu, J and Li, T and Gong, X and Li, L and Cui, Y and He, J and Li, B and Wu, S and Guan, Q and Zhang, Z and Dai, X and Li, Z}, title = {The metabolite ILA of Akkermansia muciniphila improves AP-related intestinal injury by targeting and inhibiting CASP3 activity.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1669383}, pmid = {41425929}, issn = {1664-302X}, abstract = {OBJECTIVE: Acute Pancreatitis (AP) is a common acute abdominal disease in clinical practice. The gut microbiome is recognized as a key regulator in the development of acute pancreatitis. Akkermansia muciniphila (AKK) is recognized as a functional probiotic strain and has a beneficial effect on the progression of many diseases. However, the role of the AKK in the development of AP remains unclear. Here, we evaluated the potential contribution of AKK to AP.

DESIGN: Relative abundance of gut microbial AKK in AP was evaluated. A rat model of acute pancreatitis was established by retrograde pancreatic duct infusion of sodium taurocholate. Non-targeted and targeted metabolomics analysis were used for metabolites analysis.

RESULTS: We first found that the relative abundance of gut microbial AKK in AP patients was significantly reduced compared with that in healthy subjects. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably alleviates AP-related intestinal injury in AP rat models. Metabolomics studies found that the live AKK was able to generate Indole-3-lactic acid (ILA). ILA exerted a protective effect against AP-related intestinal injury, and significantly reduce inflammatory cell activation and pro-inflammatory factor overproduction. The mechanistic study revealed that ILA inhibits the apoptosis of intestinal epithelial cells by suppressing the activity of CASP3, and improves the role of intestinal barrier dysfunction in the AP model.

CONCLUSION: We revealed that ILA, derived from live AKK, may act as a novel endogenous agonist for CASP3. ILA may serve as a new potential treatment method for intestinal injury in AP after successfully translating its efficacy into clinical practice.}, } @article {pmid41425928, year = {2025}, author = {Rodríguez-Moreno, A and Martín-Blázquez, S and de Heredia, UL and Soto, Á and Lázaro, E}, title = {Impact of simulated microgravity in short-term evolution of an RNA bacteriophage.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1680651}, pmid = {41425928}, issn = {1664-302X}, abstract = {INTRODUCTION: Microgravity is a critical environmental factor in space that can alter microbial physiology and virus-host interactions. Understanding these effects is essential for planetary protection and crew health during long-term missions. Bacteriophage Qβ, an RNA virus infecting Escherichia coli F+ strains, provides a relevant model due to its potential presence in the human gut microbiome and its well-characterized evolutionary dynamics.

METHODS: We simulated microgravity using a custom-built 3D-clinostat and compared Qβ infections in semisolid medium under standard gravity and simulated microgravity. Twelve evolutionary lines were propagated for ten serial transfers under four experimental conditions combining bacterial growth and infection environments. Viral titers were quantified by plaque assay, and consensus sequences were determined by Sanger sequencing.

RESULTS: Initial infections under simulated microgravity yielded significantly lower viral titers than those in standard gravity, likely due to hindered phage diffusion and delayed infection initiation. After ten transfers, mutation C2011A (amino acid substitution T222N in the A1 virus protein) was fixed in all lines evolved under simulated microgravity but remained absent or polymorphic in standard gravity lines. Under simulated microgravity, the mutation increased virus titers and promoted faster initiation of infections in semisolid medium. However, those effects were not appreciable in normal gravity.

DISCUSSION: Our findings highlight the adaptability of Qβ and the potential impact of microgravity on phage-host interactions, offering insights into virus evolution in extraterrestrial conditions and its implications for space missions and planetary protection.}, } @article {pmid41425927, year = {2025}, author = {Qin, R and Li, C and Yuan, X and Chen, Y}, title = {Microbiome-targeted Alzheimer's interventions via gut-brain axis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1729708}, pmid = {41425927}, issn = {1664-302X}, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options, underscoring the need for novel therapeutic targets. The gut-brain axis has emerged as a critical bidirectional communication system, with growing evidence establishing gut dysbiosis as a causal factor in AD pathogenesis. This dysbiosis, characterized by a reduction in beneficial microbes and an increase in pro-inflammatory taxa, compromises intestinal and blood-brain barrier integrity, promoting systemic inflammation and the translocation of neurotoxic agents like lipopolysaccharide (LPS). Consequently, the balance of key microbial metabolites is disrupted, reducing neuroprotective short-chain fatty acids (SCFAs) and indoles while elevating inflammatory mediators, which collectively exacerbate neuroinflammation, amyloid-β (Aβ) deposition, and tau pathology. This review evaluates promising interventions, including probiotics, anti-inflammatory diets, exercise, and phytochemicals that can restore microbial balance, enhance barrier function, and improve cognitive outcomes in preclinical and early clinical studies. However, clinical translation is hindered by an overreliance on animal models, short-term studies, and insufficient mechanistic insight. Future research must prioritize large-scale human trials, multi-omics integration to elucidate signaling pathways, and personalized approaches that account for host genetics and baseline microbiome composition to fully harness the therapeutic potential of the gut-brain axis for AD.}, } @article {pmid41425925, year = {2025}, author = {Sukchawalit, R and Goryluk-Salmonowicz, A and Hobman, JL and Popowska, M}, title = {Editorial: Impacts of metal and xenobiotic-induced stress on antibiotic resistance in microbial communities.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1745065}, doi = {10.3389/fmicb.2025.1745065}, pmid = {41425925}, issn = {1664-302X}, } @article {pmid41425919, year = {2025}, author = {Kasani, PH and Yun, CH and Cho, KH and Jeong, SJ}, title = {Neonatal gut microbiota stratification and identification of SCFA-associated microbial subgroups using unsupervised clustering and machine learning classification.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1668451}, pmid = {41425919}, issn = {1664-302X}, abstract = {BACKGROUND: The neonatal gut microbiome plays a critical role in infant health through the production of short-chain fatty acids (SCFAs). However, the organization of SCFAs-producing microbial communities in neonates remains poorly characterized. This study applied unsupervised clustering and machine learning to classify microbial subgroups associated with SCFAs production, providing insight into their composition and metabolic potential.

METHODS: This study recruited 71 mother-infant pairs from Kangwon National University Hospital and Bundang CHA Hospital, collecting meconium samples within five days postpartum. Microbial diversity was analyzed by 16S rRNA gene sequencing (V3-V4 region) at the genus level, and SCFAs were quantified from the same samples. To identify functionally distinct microbial subgroups, K-Means, Agglomerative, Spectral, and Gaussian Mixture Model clustering were applied. Clustering validity was assessed using Silhouette Score, Calinski-Harabasz Index, Davies-Bouldin Index, and Prediction Strength Validation, with t-distributed Stochastic Neighbor Embedding (t-SNE) visualization to evaluate cluster separation. SCFAs distributions across clusters were compared, while random forest and logistic regression models were used to classify SCFAs-associated microbial clusters through Receiver Operating Characteristic curves (ROC).

RESULTS: The clustering analysis identified distinct microbial subgroups linked to SCFAs production, with Agglomerative clustering outperforming K-Means in capturing functionally relevant structures. Cluster 1 had higher SCFAs levels, enriched in Bacteroides, Prevotella, and Enterococcus, while Cluster 2 exhibited lower SCFAs concentrations with a more heterogeneous composition. The introduction of a third cluster in multi-class analysis revealed an intermediate metabolic profile, suggesting a continuum in microbial metabolic function. Classification analysis confirmed random forest model superiority, achieving ROC score of 91.05% (Agglomerative) and 87.74% (K-Means) in binary classification, and 92.98% (Agglomerative) and 89.84% (K-Means) in multi-class classification, demonstrating RF's strong predictive ability for SCFAs-based clusters.

CONCLUSION: Unsupervised clustering combined with classification analysis effectively predict SCFAs-associated subgroups and paving the way for future research on longitudinal tracking and functional genomic integration in early-life metabolic health.}, } @article {pmid41425837, year = {2025}, author = {Oladele, P and Johnson, TA}, title = {Trehalose and maltodextrin preserve microbial community structure in freeze-dried fecal samples for fecal microbiota transplantation.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf204}, pmid = {41425837}, issn = {2730-6151}, abstract = {Fecal microbiota transplantation (FMT) is a promising approach for restoring gut microbial balance in both humans and animals. However, the logistical limitations of transplanting fresh fecal samples have increased interest in freeze-dried (lyophilized) fecal material as a transplant inoculum. While lyophilization facilitates storage, it can compromise bacterial viability, which is essential for FMT effectiveness. Lyoprotectants are often used to protect bacterial cultures during freeze-drying, but their effect on complex microbial communities remains unclear, as they may preferentially preserve some taxa over others. This study investigated the impact of four lyoprotectants-mannitol, maltodextrin, trehalose, and a maltodextrin-trehalose mixture-on bacterial viability and community structure in pig fecal samples post-lyophilization. Propidium monoazide (PMA) treatment combined with 16S rRNA sequencing (PMAseq) was used to differentiate viable from non-viable bacteria. In the total community (without PMA), microbial profiles appeared similar across treatment groups. However, when focusing on the viable community (PMA-treated), lyoprotectant choice significantly influenced the post-lyophilization community composition. Gram-negative bacterial viability was especially sensitive to lyophilization. Trehalose and maltodextrin preserved bacterial viability and community structure more effectively than mannitol. Mannitol-treated samples had reduced viable bacterial cells and altered community composition, while trehalose and maltodextrin better maintained diversity and structure of the viable (PMA-treated) communities. Taken together, lyoprotectants have differential effects on microbial composition during lyophilization. Among those tested, trehalose and maltodextrin best preserved both viability and community structure, making them promising candidates for FMT applications. Future research should explore optimizing lyoprotectant formulations to enhance microbiome stability and functional outcomes.}, } @article {pmid41425836, year = {2025}, author = {Yin, X and Ang, LP and Zhu, RL and Azarbad, H and Ni, HH and Chai, ML and Liu, C and Kong, F and Liu, LJ and Liu, SL and Ma, Y and Zhou, HD and Luo, ZS and He, XK and Ye, LX and Li, H and Shu, L}, title = {Host-specific and environmental core bacteria differentially shape the stability and function of the Sphagnum phyllosphere.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf221}, pmid = {41425836}, issn = {2730-6151}, abstract = {Sphagnum mosses maintain peatland ecosystem stability through intimate associations with their microbiomes. As the foundational component of these communities, the core microbiome enables ecosystems to resist, absorb, and recover from environmental changes, yet the roles and processes of Sphagnum core members remain poorly understood, particularly in subtropical ecosystems. Here, we identified different components of core microbiomes and found that host-specific and environmental core microbiomes differentially shape the stability and function of Sphagnum phyllosphere bacteria by examining vertical stratification within a litter-Sphagnum-soil system in a subtropical mountain forest. Sphagnum harbors a microbial community that is significantly distinct from its surrounding environment (i.e. litter and soil), with community assembly primarily driven by deterministic processes, whereas litter and soil communities are more strongly shaped by stochastic processes. Sphagnum host-specific core taxa, enriched in carbon- and nitrogen-cycling lineages (i.e. Ca. Eremiobacterota), stabilized microbial composition, whereas environmental core taxa enhanced interaction strength and network robustness, and these groups responded differently to environmental filters (e.g. pH and elevation). Our framework highlights that core microbiomes are not functionally homogeneous, but instead reflect contrasting strategies that collectively shape ecosystem stability.}, } @article {pmid41425703, year = {2025}, author = {Feng, Y and Yang, H and Liang, G and Chen, J and Li, T and Wang, Y and Chang, J and Li, Y and Yang, M and Zhou, X and Wang, Z and Ge, C}, title = {Immune Checkpoint Inhibitors Combined with Oncolytic Virotherapy: Synergy, Heterogeneity, and Safety in Cancer Treatment.}, journal = {Oncology research}, volume = {33}, number = {12}, pages = {3801-3836}, pmid = {41425703}, issn = {1555-3906}, mesh = {Humans ; *Oncolytic Virotherapy/methods/adverse effects ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects/pharmacology ; *Neoplasms/therapy/immunology ; Combined Modality Therapy ; Tumor Microenvironment/immunology/drug effects ; Oncolytic Viruses/immunology ; Immunotherapy/methods ; Animals ; }, abstract = {Immune checkpoint inhibitor (ICI) has limited efficacy in the treatment of immune "cold" tumors. Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1 (PD-L1) expression, the ORR is only 5%-8% compared with 30%-40% of "hot" tumors. This article reviews the synergistic mechanism, clinical efficacy and optimization strategy of oncolytic virus (OVs) combined with ICIs in the treatment of refractory malignant tumors. Systematic analysis of mechanistic interactions across tumor types and clinical trial data demonstrates that OVs transform the immunosuppressive microenvironment by inducing immunogenic cell death and activating innate immunity. Concurrently, ICIs enhance adaptive immunity by reversing T-cell exhaustion and expanding T-cell diversity. Clinical trials in melanoma, head and neck cancer and breast cancer showed superior efficacy. The Objective Response Rate (ORR) of combination therapy was 39%-62%, while the ORR of ICI monotherapy was 18%. Treatment heterogeneity is mainly attributed to virus-related factors, including targeting specificity and replication efficiency, tumor characteristics, such as antigen presenting ability and mutation load, and host immune status, including pre-existing antiviral antibodies and microbiome composition. This combined approach represents a paradigm shift in cancer immunotherapy, which effectively transforms immune "cold" tumors into "hot" tumors through the continuous activation of innate and adaptive immune responses. In the future, it is expected to improve the therapeutic effect of treatment-resistant malignant tumors through the integration of immune regulatory molecules, accurate biomarkers to guide the treatment scheme and triple combination strategy by a new generation of engineering viruses.}, } @article {pmid41425618, year = {2025}, author = {Fuller-Shavel, N and Davies, EJ and Peleg Hasson, S}, title = {Nutritional strategies in supporting immune checkpoint inhibitor, PI3K inhibitor, and tyrosine kinase inhibitor cancer therapies.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1670598}, pmid = {41425618}, issn = {2296-861X}, abstract = {Nutritional status of patients undergoing cancer treatment has been associated with cancer therapy and survival outcomes across multiple therapy types. Targeted therapies, including immune checkpoint inhibitors (ICIs), phosphatidylinositol 3-kinase (PI3K) inhibitors and EGFR-tyrosine kinase inhibitors (TKIs), are both influenced by and themselves influence the patients' nutritional and metabolic status. Precision nutrition approaches that address specific aspects of targeted therapies, from minimizing toxicities and treatment resistance to potential therapeutic synergies, offer an important avenue to optimize clinical outcomes for patients receiving targeted oncological treatments as a part of an overall precision integrative oncology approach. Optimizing ICI treatment may necessitate gastrointestinal microbiome modulation and managing systemic inflammation with a variety of dietary approaches under study, including the Mediterranean diet, increasing fiber and fermented food intake, fasting and fasting mimicking diet and the ketogenic diet. Supplementation approaches using live biotherapeutics alongside ICIs predominate over prebiotic, postbiotic and synbiotic studies, which require further attention and investment, alongside human research on mycotherapy and fucoidan-based combinations. Optimizing PI3K treatment tolerance requires close attention to monitoring and managing glycemic control through nutrition, lifestyle and pharmacological intervention as necessary, and in supporting patients with EGFR-TKIs both nutritional prehabilitation and close attention to managing gastrointestinal toxicities is paramount. Rational individualized approaches based on detailed and dynamic clinical assessment of patient-, cancer- and treatment-related factors, using validated prognostic scores and biomarkers, are needed to maximize the potential of precision nutrition now and in future trials in this arena.}, } @article {pmid41425608, year = {2025}, author = {Yaghoubi Khanghahi, M and AbdElgawad, H and Curci, M and Garrigues, R and Korany, SM and Alsherif, EA and Verbruggen, E and Spagnuolo, M and Addesso, R and Sofo, A and Beemster, GTS and Crecchio, C}, title = {Transcriptomic, biochemical, and microbiome assessments into drought and salinity tolerance in durum wheat mediated by plant growth-promoting bacteria.}, journal = {Physiology and molecular biology of plants : an international journal of functional plant biology}, volume = {31}, number = {12}, pages = {2121-2143}, pmid = {41425608}, issn = {0971-5894}, abstract = {UNLABELLED: This study investigates the efficacy of plant growth-promoting bacteria (PGPB) in improving stress tolerance in plants by analyzing the molecular and biochemical bases in durum wheat grain. An experiment was conducted where soil and seeds were inoculated with PGPB, under drought and salinity stress. 16 S rRNA sequencing indicated no change in grain bacterial communities in response to biofertilizers and stress. However, a genome-wide analysis identified 153 up-regulated and 33 down-regulated plant genes in response to PGPB, predominantly enriched in stress-related biological processes. These genes specifically encode for proteins involved in metabolite interconversion enzyme, chaperone, protein modifying enzyme, and transporters, which are functionally related groups assisting protein folding in the cell under stress conditions. Moreover, pathway analysis confirmed related changes at the metabolite and enzyme activity levels. In this regard, PGPB-treated plants exhibited heightened activity of both enzymatic and non-enzymatic (e.g., thioredoxins, peroxiredoxins, etc.) antioxidants under stress, showcasing significant enhancements ranging from + 27% to + 283% and + 36% to + 266%, respectively. Further elucidation of biochemical pathways revealed alterations in the activation of non-antioxidant enzymes in PGPB-treated plants, exemplified by increased activities of glutamate synthase (40-44%) and decreased activities of protein-tyrosine-phosphatase (29-31%) under both stresses, as well as elevated activities of anthocyanidin reductase (91%) and lipoxygenases (18%) specifically under drought. Overall, the present research highlighted the potential of beneficial bacteria in improving plant stress tolerance, especially under drought, through shifting transcriptome expression of plant genes and employing multiple protective strategies which can complement each other.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-025-01686-z.}, } @article {pmid41425546, year = {2025}, author = {Müller, L and Di Benedetto, S}, title = {Immunosenescence and inflammaging: Mechanisms and modulation through diet and lifestyle.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1708280}, pmid = {41425546}, issn = {1664-3224}, mesh = {Humans ; *Immunosenescence ; *Inflammation/immunology/metabolism ; *Life Style ; *Diet ; Animals ; Gastrointestinal Microbiome/immunology ; *Aging/immunology ; }, abstract = {Aging is associated with profound alterations in the immune system, characterized by immunosenescence and inflammaging, which together compromise host defense, promote chronic low-grade inflammation, and contribute to the development of age-related diseases. Immunosenescence involves thymic involution, hematopoietic stem cell skewing, accumulation of senescent immune cells, and impaired adaptive and innate responses. Inflammaging arises from persistent activation of innate immune pathways, senescence-associated secretory phenotype (SASP) signaling, metabolic dysregulation, and age-related alterations in the gut microbiome. These processes are interconnected through feedback loops and network-level interactions among immune, metabolic, and microbial systems, creating a self-perpetuating cycle of immune dysfunction and systemic inflammation. Emerging evidence indicates that immunosenescence and inflammaging can be modulated through integrative strategies that combine nutrition, microbiome modulation, and lifestyle interventions to sustain immune resilience across the lifespan. Nutrient-specific strategies, including polyphenols, omega-3 fatty acids, and micronutrients, regulate oxidative stress, cytokine signaling, and immune cell metabolism. Holistic dietary patterns such as the Mediterranean diet, caloric restriction, and microbiome-supportive diets enhance gut barrier integrity, modulate systemic inflammation, and improve adaptive immunity. Lifestyle factors, including regular physical activity, adequate sleep, and stress reduction, further support immune resilience. Personalized nutrition and lifestyle strategies, guided by immunobiological profiling, enable tailored approaches to mitigate immune aging. Collectively, these insights highlight a multidimensional framework for understanding and modulating immunosenescence and inflammaging. Integrating dietary, lifestyle, and pharmacological strategies offers a promising path toward enhancing immune function, reducing chronic inflammation, and promoting healthy longevity.}, } @article {pmid41425113, year = {2025}, author = {Wang, D and Zhang, J and Wang, B and Gao, J and Zhang, G}, title = {Current Trends and Future Insights on Rosacea Treatment: A Bibliometric Analysis.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {18}, number = {}, pages = {3397-3412}, pmid = {41425113}, issn = {1178-7015}, abstract = {BACKGROUND: Rosacea involves immune, neurovascular, and microbial factors, but its complex mechanisms are poorly understood, hindering effective treatment development. This study aims to examine research trends and significant contributions in the treatment of rosacea.

METHODS: Publications related to rosacea treatment were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using VOSviewer, CiteSpace, and the R package "bibliometrix".

RESULTS: By June 7, 2024, 1389 English-language publications published between 1970 and 2024 were identified for analysis. The leading research countries were the United States (446 articles) and China (149 articles), with the Central South University (95 articles) being the most productive institution. Key journals included Journal of the American Academy of Dermatology (impact factor = 12.8) and the British Journal of Dermatology (impact factor = 11). James Q. Del Rosso was identified as a major contributor (h-index = 20). Keywords cluster analysis revealed five prominent themes: 1) pharmacological treatment and clinical trials, 2) epidemiology and associated risk factors, 3) pathophysiology and pathogenesis, 4) skin barrier function and related dermatoses, and 5) laser and physical therapies. Representative terms of emerging trends include "pathogenesis", "pathophysiology", and "standard classification", suggesting increasing focus on immune dysregulation, neurovascular mechanisms, and microbiome-related pathways. These insights indicate that future rosacea treatment research may shift toward targeted, mechanism-based therapeutic strategies.

CONCLUSION: This study underscores the dynamic landscape of research in rosacea treatment, synthesizes current areas of emphasis, and forecasts future trends. Future developments in rosacea research may concentrate on integrating precision medicine approaches by linking molecularly defined pathogenic mechanisms with standardized classification systems, thereby facilitating targeted and multidisciplinary treatment strategies.}, } @article {pmid41424975, year = {2025}, author = {Ma, L and Wang, H and Jin, Q and Sun, Z and Yu, S and Zhang, Y}, title = {The Gut-Liver Axis: Molecular Mechanisms and Therapeutic Targeting in Liver Disease.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {7531-7546}, pmid = {41424975}, issn = {1178-7074}, abstract = {The gut microbiota, often termed the "second genome", demonstrates profound therapeutic potential through its intricate biological network connecting multiple distal organs. Although microbial diversity is strongly correlated with intestinal health, its systemic implications on overall physiological homeostasis remain incompletely understood. This review synthesizes the latest evidence from clinical trials, randomized controlled trials (RCTs), systematic reviews, and meta-analyses to elucidate the biological pathways and therapeutic applications of the gut-liver axis. Through comprehensive schematic illustrations, we delineate the molecular mechanisms underlying bidirectional gut-liver communication, including microbial metabolite signaling, immune modulation networks, and enterohepatic circulation dynamics. Although interventional studies have confirmed the beneficial physiological effects of microbial modulation, current mechanistic insights are predominantly derived from animal models with limited clinical translation. While large-scale cohort studies with long-term follow-up data remain imperative, the existing evidence strongly supports the clinical value of microbiome-targeted strategies for treating hepatic diseases and related complications. These findings establish a critical theoretical framework for the development of next-generation microbial therapeutics targeting the gut-liver axis. The novelty of this review lies in its systematic classification of gut microbiota and their metabolites in the pathogenesis and treatment of various liver diseases, its detailed elaboration on signaling pathways, and its dedicated focus on the role of Traditional Chinese Medicine (TCM) in modulating the gut-liver axis.}, } @article {pmid41424906, year = {2025}, author = {Goswami, A and Ghosh, S and Bandyopadhyay, A and Saha, RG and Sengupta, P and Bhuniya, U and Mandal, P}, title = {Comparative Analysis of Vaginal Microbiome Associated with Oncogenic HPV Infection Among Different Ethnic Groups of Women of the Eastern Region of India.}, journal = {Indian journal of microbiology}, volume = {65}, number = {4}, pages = {1877-1890}, pmid = {41424906}, issn = {0046-8991}, abstract = {The study aimed to identify the influence of vaginal bacterial composition on HPV infection among tribal women of the eastern region of India compared to non-tribal women of the same region. For this study, 13 tribal women and 12 non-tribal women were recruited. DNA was isolated from vaginal swab samples, and subsequently, 16S rRNA gene analysis was performed. We identified two distinct clusters of samples based on taxonomic profiling and bacterial diversity. One cluster belonged to HPV negative samples and the other to HPV16/18 positive samples. The abundance of three bacterial species was significantly lower (p value < 0.05) among oncogenic HPV positive samples (mean abundance = 4.33, 0, and 0, respectively) compared to HPV negative samples (mean abundance = 29.71, 45.73, and 19.01, respectively) irrespective of their ethnicities, such as Lactobacillus amylolyticus, Bacillus coagulans, and Costridium sensu stricto. HPV16/18 positive samples also represent the differential microbiome composition between the two ethnic groups of women. Ethnicity specific variations in human vaginal microbiome composition might be recommended for geographically tailored microbiome-based therapeutic strategies.}, } @article {pmid41424898, year = {2025}, author = {Chattopadhyay, P and Biswas, I and Banerjee, G}, title = {Analysing the Metagenomic Dynamics of Soil Microbiota Affected by Tea Pruning and Skiffing Methods in Tea Plantations of Dibrugarh, Assam, India.}, journal = {Indian journal of microbiology}, volume = {65}, number = {4}, pages = {2015-2020}, pmid = {41424898}, issn = {0046-8991}, abstract = {Beginning with the centralization of young tea (Yt) to encourage low branch growth, subsequent light pruning (LP) and deep skiffing (DS) techniques are employed to promote branch spread, ensuring an ideal leaf area index and manageable plucking height. This study investigates the effects of LP and DS compared to Yt on soil biota, a previously unexplored topic. Soil samples from Yt, LP, and DS sites within the Rajgarh Tea Estate in Assam, India, were analyzed for standard parameters and metagenomic DNA using Illumina sequencing. While all samples exhibited a clay loam texture with minimal parameter variation, significant variations in soil phyla abundance were observed. Acidobacteria dominated across all samples, but linear discriminant analysis revealed distinct phyla compositions. At the genus level, Geobacter, Verticiella, and Glaciihabitans were most abundant in S11, S7, and S9 samples, respectively. However, the relative abundance of phyla in the soil samples from Yt, LP, and DS sites varies significantly. But the difference in bacterial community at genus level resolution was not significant at p value 0.05 level. These findings indicate that pruning and skiffing primarily impact on the relative abundance of soil phyla, not microbial diversity. Understanding the soil microbiota in relation to tea cultivation practices through metagenomics can pave the way for developing new microbial consortia for an integrated crop management system in tea cultivation.}, } @article {pmid41424782, year = {2025}, author = {Xu, M and Yu, Y and Li, L and Zhao, K and Lai, J and Wei, L and Ge, L}, title = {Rhein ameliorates inflammation, gut dysbiosis, and renal injury in obesity-related glomerulopathy mice.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1654062}, pmid = {41424782}, issn = {1663-9812}, abstract = {OBJECTIVE: Obesity-related glomerulopathy (ORG) lacks targeted therapies. Rhein, a bioactive anthraquinone from Rhei Radix et Rhizoma, was evaluated for its effects on inflammation, renal function, and gut microbiota in high-fat diet-induced ORG mice.

METHODS: C57BL/6J mice were fed a 60% fat diet for 12 weeks to establish ORG, followed by 300 mg/kg/day rhein free intake for 12 weeks. Serum cytokines (IL-6, TNF-α), renal histopathology, and 16S rRNA microbiome sequencing were analyzed.

RESULTS: Rhein significantly reduced body weight (P < 0.001), serum triglycerides (P < 0.01), and proteinuria (P < 0.001), while improving glomerular lesions. It also markedly lowered serum levels of IL-6, TNF-α, and creatinine. 16S rRNA sequencing revealed that rhein restored gut microbiota diversity (e.g., Chao1 index increased from 303.58 to 425.78) and reversed the Firmicutes/Bacteroidetes imbalance (76.86%-62.15%). Analysis of similarities (ANOSIM) further confirmed a significant difference in microbial community structure between the Rhein and Model groups (R = 0.926, p = 0.008).

CONCLUSION: Rhein mitigates ORG progression is associated with anti-inflammatory, lipid-lowering, and microbiota-modulating mechanisms, offering a novel therapeutic strategy.}, } @article {pmid41424704, year = {2025}, author = {Araújo, JPM and Przelomska, NAS and Smith, RJ and Drechsler-Santos, ER and Alves-Silva, G and Martins-Cunha, K and Hosoya, T and Luangsa-Ard, JJ and Perrigo, A and Repullés, M and Matos-Maraví, P and Woods, R and Pérez-Escobar, OA and Antonelli, A}, title = {A new species of Purpureocillium (Ophiocordycipitaceae) fungus parasitizing trapdoor spiders in Brazil's Atlantic Forest and its associated microbiome revealed through in situ "taxogenomics".}, journal = {IMA fungus}, volume = {16}, number = {}, pages = {e168534}, pmid = {41424704}, issn = {2210-6340}, abstract = {Our planet is inhabited by an estimated 2.5 million species of fungi, of which fewer than 10% have been scientifically described. Some of the most understudied yet remarkable fungal species are those capable of parasitizing arthropods, notably insects and spiders. Here, we explore the hidden diversity of a spider-attacking (araneopathogenic) fungus and its associated microbiome in one of the world's most biodiverse yet threatened biomes, the Atlantic Forest. We apply a field-based "taxogenomic" approach, comprising the integration of classical fungal taxonomy and genomic characterization of a sample's endogenous, associated, and incidental DNA. The data we produced in the field reveal a new species of Purpureocillium fungus belonging to the P. atypicola group, parasitizing trapdoor spiders, and provide a snapshot of its associated bacterial and fungal microbiota. Molecular, morphological, and ecological data support P. atypicola as a complex of cryptic species infecting a variety of ecologically distinct spider species globally. We call for consolidated efforts to accelerate and facilitate the publication of both new species and the characterization of the genomic composition of their associated taxa.}, } @article {pmid41424695, year = {2025}, author = {Wang, X and Yue, R and Wen, J and Wu, H and Zhou, X and Chen, Y and Luo, L and Lin, S and Ai, Q and He, Y and Zhao, W}, title = {Alanyl-Glutamine Attenuates Soybean Meal-Induced Intestinal Dysfunction and Growth Retardation in Largemouth Bass (Micropterus salmoides).}, journal = {Aquaculture nutrition}, volume = {2025}, number = {}, pages = {7842137}, pmid = {41424695}, issn = {1365-2095}, abstract = {This study investigated the mitigating effects of alanyl-glutamine (AG) on soybean-meal-induced enteritis (SBMIE) in largemouth bass (Micropterus salmoides). Three experimental diets were prepared: a fishmeal (FM) diet as a positive control, a 50% soybean meal (SBM) replacement FM protein (SBM50) diet as a negative control, and the SBM50 diet supplemented with 1% AG (SBM50 + 1% AG). Fish (initial weight: 10.20 ± 0.20 g) were distributed into three groups in triplicate (25 fish per tank) and fed for 8 weeks. Results demonstrated that the SBM50 + 1% AG group exhibited markedly higher final body weight, weight gain rate, and specific growth rate compared to the SBM50 (p < 0.05). The SBM50 + 1% AG group markedly elevated serum levels of free glycine, lysine, and total essential amino acids compared to the FM group (p < 0.05). In addition, the SBM50 + 1% AG group markedly increased the intestinal plica height (PH) and goblet cell numbers compared to the SBM50 group (p < 0.05). Pathological alterations, including villous atrophy, nuclear pyknosis, mitochondrial matrix dissolution, and inner membrane disruption, were shown in the SBM50 group, all of which were ameliorated by AG supplementation. In addition, the addition of AG significantly reduced Caspase3 activity compared to the FM group (p < 0.05). Microbiome analysis revealed dietary AG significantly increased α-diversity and the proliferation of potentially beneficial taxa (Bacteroidota, Bacteroides, and Prevotella) (p < 0.05). Transcriptomics showed dietary AG upregulated intestinal barrier-related pathways (including focal adhesion, cell adhesion molecules, and adherens junction), along with tight junction gene expression (zo-1, claudin-3, and filamin-B). In conclusion, high dietary SBM inclusion impairs growth performance and induces intestinal inflammation in largemouth bass. Dietary AG effectively mitigates SBMIE by remodeling the intestinal microbiota, enhancing intestinal barrier integrity, and modulating immune responses.}, } @article {pmid41424621, year = {2025}, author = {Shangguan, Y and Zhu, J and Ye, J and Korpelainen, H and Li, C}, title = {Selenium phytofortification: enhanced stress resistance and nutraceutical enrichment in horticultural crops.}, journal = {Horticulture research}, volume = {12}, number = {12}, pages = {uhaf236}, pmid = {41424621}, issn = {2662-6810}, abstract = {As a bridge between human health and plant nutrition, Selenium (Se) phytofortification represents a promising strategy for achieving a safe and effective dietary Se supplementation. Due to chemical similarities, Se absorption, transformation, and storage in crops primarily follow the sulfur metabolic pathway. Se enhances horticultural crop resilience against abiotic and biotic stresses by: (i) boosting antioxidant capacity, (ii) inducing hormonal cascades, (iii) promoting the accumulation of key metabolites (e.g. amino acids, flavonoids), (iv) strengthening cellular functions, and (v) harnessing plant-microbiome interactions. In horticultural crops, most Se exists in organic forms, such as selenoamino acids, selenoproteins, selenium-polysaccharides, and selenium-polyphenols, which contribute to unique quality traits. Additionally, Se regulates the synthesis of core nutrients, including amino acids, flavonoids, phenolic compounds, soluble sugars, mineral elements, alkaloids, and volatile compounds. It also extends postharvest shelf life by delaying senescence and deterioration. Current phytofortification strategies focus on enhancing bioavailable Se in edible parts through agronomic interventions and plant breeding. Artificial Se fertilization is the most common agronomic approach, classified by the application method (soil fertilization, foliar spraying, hydroponic supplementation, and seed soaking) and fertilizer type (inorganic, organic, nano-Se, and biosynthesized fertilizers). Optimizing plant species, fertilization methods, dosage, timing, and elemental synergies maximize phytofortification efficiency.}, } @article {pmid41424618, year = {2025}, author = {Pandey, SN and Goyal, K and Rana, M and Menon, SV and Ray, S and Ali, H and Kumbhar, PS and Disouza, J and Singh, SK and Gupta, G and Wong, LS and Kumarasamy, V and Subramaniyan, V}, title = {Microbiome-derived bile acids as endogenous regenerative mediators in liver repair.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {681-690}, pmid = {41424618}, issn = {2352-3204}, abstract = {The liver's extraordinary capacity for self-repair is often compromised by chronic injury, fibrosis, or extensive resection, creating an urgent need for innovative regenerative therapies to restore liver function. Emerging evidence suggests that microbiome