@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.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Aging/physiology/immunology
*Dysbiosis/microbiology/physiopathology/complications
Sarcopenia/microbiology

@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).},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

Humans
*Alzheimer Disease/immunology/metabolism
Aged
Male
Female
*Gastrointestinal Microbiome
Feces/microbiology/chemistry
*Cognitive Dysfunction/immunology/metabolism
Metabolomics
Aged, 80 and over

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

Animals
*Balaenoptera/microbiology
*Microbiota
*Bacteria/genetics/classification/isolation & purification
High-Throughput Nucleotide Sequencing
*Respiratory System/microbiology
RNA, Ribosomal, 16S/genetics
Phylogeny

@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.},
}

Humans
Female
Male
*Gastrointestinal Microbiome/genetics
*Apolipoprotein E4/genetics
Aged
*Biomarkers
*Alzheimer Disease/genetics/microbiology
Feces/microbiology
Middle Aged

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

Humans
*Heart Failure/microbiology/metabolism/physiopathology
*Gastrointestinal Microbiome/physiology
Disease Progression
Dysbiosis/microbiology
Probiotics
Methylamines/metabolism
Animals

@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.},
}

Humans
*Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism
*Liver Neoplasms/therapy/microbiology/immunology/metabolism
*Bacteria/metabolism
Tumor Microenvironment/immunology
Animals

@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.},
}

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

@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.},
}

Humans
*Gastrointestinal Microbiome
*Coumarins/metabolism
*Molybdenum/metabolism
Inflammatory Bowel Diseases/microbiology/metabolism
*Bacteria/enzymology/metabolism/genetics
*Bacterial Proteins/metabolism/genetics
Xanthine Oxidase/metabolism/genetics

@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.},
}

Humans
*Longevity/physiology
*Skin Aging/physiology
Artificial Intelligence
*Dermatology/methods/trends
*Geroscience/methods
Biomarkers/metabolism
Skin/microbiology
Translational Research, Biomedical
*Aging/physiology
Microbiota

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

Humans
*Autism Spectrum Disorder/genetics/etiology/epidemiology
Genetic Predisposition to Disease
Environmental Exposure/adverse effects

@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.},
}

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

@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.},
}

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