@article {pmid41284401,
year = {2025},
author = {Giorgi, M},
title = {Gut Health and the Microbiome: The Hidden Drivers of Obesity.},
journal = {Rhode Island medical journal (2013)},
volume = {108},
number = {12},
pages = {15-18},
pmid = {41284401},
issn = {2327-2228},
mesh = {Humans ; *Obesity/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Energy Metabolism ; Animals ; },
abstract = {Obesity is a complex disease that spreads globally as a pandemic which affects all human activities from basic daily functions to advanced medical conditions that transform entire communities. The core factors of dietary excess and sedentary lifestyles continue to drive obesity but scientific evidence demonstrates that the gut microbiome plays a crucial role in regulating energy balance and body fat as well as metabolic wellness. High-throughput sequencing technology has transformed our understanding of this problem while showing how gut microbial communities affect nutrient absorption and host metabolism while protecting us from increased systemic inflammation. These new discoveries are emergent and promising to help us understand how to manage this complex multifactorial condition. This review examines the developing mechanisms through which gut microbes affect obesity while assessing preclinical and human study evidence and discussing potential therapeutic approaches to modify the microbiome for obesity treatment and its related conditions.},
}

Humans
*Obesity/microbiology/therapy
*Gastrointestinal Microbiome/physiology
Energy Metabolism
Animals

@article {pmid41284313,
year = {2025},
author = {Armstrong, E and Seo, E and Boyachuk, B and Loutfy, M and Smith, G and Falutz, JM and Klein, M and Coburn, B and Walmsley, S and Zhabokritsky, A and , },
title = {Gut microbiome and healthy aging in HIV: data from the correlates of healthy aging in geriatric HIV (CHANGE HIV) cohort.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000004412},
pmid = {41284313},
issn = {1473-5571},
abstract = {OBJECTIVES: Despite longer life expectancies, those aging with HIV experience increased comorbidity and other health challenges relative to the general population. Alterations in the composition of the gut microbiome are associated with increased immune activation and aging, but few studies have explored the association of the gut microbiome with adverse age-related outcomes in people living with HIV. We assessed the relationship between gut microbiome composition and healthy aging in HIV.

DESIGN/METHODS: The CHANGE HIV study is a Canadian cohort of people aged 65 and older, which aims to investigate correlates of healthy aging in HIV. Rectal swabs were collected at enrolment from a subset of 158 consenting participants, which we analyzed with 16S rRNA gene sequencing to characterize the gut microbiome. Healthy aging was quantified using the Rotterdam Healthy Aging Score (HAS) and categorized as healthy (13-14), intermediate (11-12), and poor (0-10). We collected other markers of healthy aging including cognition, frailty, and demographics.

RESULTS: Gut microbiome diversity did not differ based on HAS category, although some disease-associated bacteria were enriched in participants with lower HAS. Gut microbiome diversity did not differ based on age or frailty status. Lower HAS score group was associated with lower household income, poorer nutrition and cognition, and earlier year of HIV infection.

CONCLUSION: Gut microbiome composition was not associated with healthy aging as defined by the HAS, although there were weak associations between HAS and disease-associated bacterial genera. Interventions that target social circumstances may provide greater improvements in health among aging persons with HIV.},
}

@article {pmid41283989,
year = {2025},
author = {Peterson, BM and Rudloff, I and Deen, NS and Di Simone, SK and Nataraja, RM and Toldi, G and Pacilli, M and Garrick, SP and Cho, SX and Nold, MF and Forster, SC and Nold-Petry, CA},
title = {The microbiome's hidden influence: preclinical insights into inflammatory responses in necrotizing enterocolitis.},
journal = {Seminars in immunopathology},
volume = {47},
number = {1},
pages = {41},
pmid = {41283989},
issn = {1863-2300},
mesh = {Humans ; *Enterocolitis, Necrotizing/microbiology/etiology/immunology/therapy/metabolism ; *Gastrointestinal Microbiome/immunology ; Animals ; Infant, Newborn ; Infant, Premature ; Disease Susceptibility ; Disease Models, Animal ; Inflammation ; Probiotics/therapeutic use ; Dysbiosis ; },
abstract = {Necrotizing enterocolitis (NEC) is the most common surgical emergency in preterm infants; nonetheless, besides supportive measures, no treatment is available. NEC significantly increases length of hospitalization of preterm infants, causes severe morbidity and up to 70% mortality. Despite limited understanding of the underlying mechanisms, prematurity, dysbiosis and an underdeveloped immune system are known to increase the risks of developing NEC. The low weight of preterm infants (often < 2000 g) and unpredictable progression of NEC hinder clinical research; hence, most of our mechanistic understanding of NEC pathophysiology has arisen from animal models. Recent advances in bacterial genomic analyses highlighted the intestinal microbiome's key role in NEC, strengthening the concept that this disease results from an interaction between the patient's developing immune system and their microbiome. This notion is supported by the moderate effect of probiotics in preventing NEC. Here, we review the current knowledge on how the immune system interacts with the intestinal microbiome in early life, including in relation to NEC, describe the current evidence from cohort studies, clinical trials, in vivo and in vitro models used to study NEC, and methods to modulate the immune system and microbiome in early life. Knowledge on the early-life microbiome and immune system in health and diseases, including NEC, can be harnessed to develop novel and urgently needed immunomodulatory and microbiota-based therapeutics.},
}

Humans
*Enterocolitis, Necrotizing/microbiology/etiology/immunology/therapy/metabolism
*Gastrointestinal Microbiome/immunology
Animals
Infant, Newborn
Infant, Premature
Disease Susceptibility
Disease Models, Animal
Inflammation
Probiotics/therapeutic use
Dysbiosis

@article {pmid41283692,
year = {2025},
author = {Zhang, S and Easwaran, M and Elafify, M and Mahmoud, AA and Wang, X and Ahn, J},
title = {Prophages and their interactions with lytic phages in the human gut microbiota and their impact on microbial diversity, gut health, and disease.},
journal = {Applied and environmental microbiology},
volume = {},
number = {},
pages = {e0189925},
doi = {10.1128/aem.01899-25},
pmid = {41283692},
issn = {1098-5336},
abstract = {Bacteriophages (phages), the dominant prokaryotic viruses that specifically target bacteria in the human gut microbiome, play a crucial role in maintaining intestinal balance, regulating bacterial populations, and preserving microbial diversity within the gut microbiota. While prophages can enhance bacterial virulence and antibiotic resistance, potentially posing health risks, they also provide beneficial functions, including enhancing host fitness, promoting immune modulation, and contributing to ecosystem resilience, which supports intestinal homeostasis. Human gut microbiota is essential for various physiological functions, including digestion, vitamin synthesis, immune modulation, and protection against pathogens. Dysbiosis, or microbial imbalance, is associated with various disorders such as inflammatory bowel disease, obesity, diabetes, and mental health disorders. Consequently, prophages are important considerations for developing therapies to prevent intestinal diseases. Recently, there has been significant interest in prophage induction in the gut due to its functional impacts on microbial dynamics, gut health, and disease modulation. Prophage induction can be regulated by diet, antibiotics, metabolites, gut health, lifestyle, and intestinal environments. However, compared with lytic phages, prophages remain underexplored, leaving gaps in our understanding of their functions within the gut. Therefore, further research is needed to fully elucidate the complex interactions between phages, prophages, and the gut microbiota, and their effects on health and disease. This knowledge could inform the development of phage-based therapies and improve therapeutic strategies for gut health.},
}

@article {pmid41283679,
year = {2025},
author = {Ahearn-Ford, S and Kakaroukas, A and Young, GR and Nelson, A and Abrahamse-Berkeveld, M and van Elburg, RM and Smith, D and Berrington, JE and Embleton, ND and Stewart, CJ},
title = {Spatiotemporal development of late and moderate preterm infant gut and oral microbiomes and impact of gestational age on early colonization.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0066725},
doi = {10.1128/msystems.00667-25},
pmid = {41283679},
issn = {2379-5077},
abstract = {Microbiome research focusing on late and moderate preterm infants (LMPT; 32 to 36 weeks gestation) is limited, despite rising LMPT births, large healthcare burdens, and increased risks of multiple morbidities, potentially microbially related. In this longitudinal cohort study, 16S rRNA gene sequencing was used to analyze 371 stool and 402 saliva samples from 160 LMPT infants, collected at five time points between birth and 12 months corrected age (CA), to describe spatial and temporal variability in gut and oral microbiomes. Paired stool and saliva samples (n = 337) were analyzed for potential microbial relationships. Early LMPT samples (up to 60 days of life; DOL) were also compared with data from seven extremely preterm infants (EP; <28 weeks gestation; stool n = 14, saliva n = 14). LMPT stool and saliva were composed of distinct microbial communities at each time point, and both sample types showed increasing alpha diversity over time. Stool was initially dominated by Escherichia/Shigella, Klebsiella, and Streptococcus, with Bifidobacterium becoming dominant from term equivalent age (TEA). Contrarily, saliva was dominated by Streptococcus throughout the first year, with early contributions from Staphylococcus and later Veillonella. LMPT infants had higher stool and lower saliva diversity compared with EP infants. Both sample types from EP infants were taxonomically distinct from LMPTs, with Escherichia/Shigella dominating both EP sample types throughout the first 60 DOL. The results highlight the unique trajectories of LMPT microbiomes and emphasize the role of gestational maturity in shaping microbial communities.IMPORTANCEThe oral and gut microbiome develops from birth and plays important roles in health. This has been well studied in extremely preterm infants (EP; born <32 weeks gestation) and term infants (born >38 weeks gestation), but there is a paucity of research describing oral and gut microbiome development in late and moderate preterm infants (LMPT; 32 to 36 weeks gestation). Our study analyzed microbiome development in 160 LMPT infants from birth to 12 months corrected age. The results showed distinct microbial communities in stool and saliva, with increasing alpha diversity and niche specification over time. LMPT infants' gut microbiome became dominated by Bifidobacterium by month 3, while the oral community was consistently dominated by Streptococcus. These results highlight that LMPT infants have gut and oral microbiome development that is more like term infants than EP infants, which has important implications for the care of LMPT infants.},
}

@article {pmid41283667,
year = {2025},
author = {Zhang, J and Meng, F and Sun, Y and Xu, W and Wu, S and Su, X},
title = {Phylo-Spec: a phylogeny-fusion deep learning model advances microbiome status identification.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0145325},
doi = {10.1128/msystems.01453-25},
pmid = {41283667},
issn = {2379-5077},
abstract = {The human microbiome is crucial for health regulation and disease progression, presenting a valuable opportunity for health state classification. Traditional microbiome-based classification relies on pre-trained machine learning (ML) or deep learning (DL) models, which typically focus on microbial distribution patterns, neglecting the underlying relationships between microbes. As a result, model performance can be significantly affected by data sparsity, misclassified features, or incomplete microbial profiles. To overcome these challenges, we introduce Phylo-Spec, a phylogeny-driven deep learning algorithm that integrates multi-aspect microbial information for improved status recognition. Phylo-Spec fuses convolutional features of microbes within a phylogenetic hierarchy via a bottom-up iteration and significantly alleviates the challenges due to sparse data and inaccurate profiling. Additionally, the model dynamically assigns unclassified species to virtual nodes on the phylogenetic tree based on higher-level taxonomy, minimizing interferences from unclassified species. Phylo-Spec also captures the feature importance via an information gain-based mechanism through the phylogenetic structure propagation, enhancing the interpretability of classification decisions. Phylo-Spec demonstrated superior efficacy in microbiome status classification across two in silico synthetic data sets that simulate the aforementioned cases, outperforming existing ML and DL methods. Validation with real-world metagenomic and amplicon data further confirmed the model's performance in multiple status classification, establishing a powerful framework for microbiome-based health state identification and microbe-disease association. The source code is available at https://github.com/qdu-bioinfo/Phylo-Spec.IMPORTANCEThe human microbiome profoundly influences health and disease, but current computational tools often overlook the evolutionary relationships among microbes, leading to incomplete or inaccurate interpretations of complex microbial data. Phylo-Spec provides a new way to understand the microbiome by combining microbial abundance, taxonomy, and phylogeny within a unified deep learning framework. This model not only improves the accuracy of health status classification but also highlights key microbial contributors linked to disease. By capturing both microbial diversity and evolutionary context, Phylo-Spec bridges the gap between bioinformatics and biological insight, offering a powerful and interpretable approach for advancing microbiome-based diagnostics and precision medicine.},
}

@article {pmid41283475,
year = {2025},
author = {Ahmed, A and Li, S and Yu, JJ and Shao, WH},
title = {Immunopathogenesis of Systemic Lupus Erythematosus: Interplay of Innate and Adaptive Immunity, Microbiome Dysbiosis, and Emerging Therapeutic Targets.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {32},
number = {4},
pages = {},
doi = {10.3390/pathophysiology32040061},
pmid = {41283475},
issn = {1873-149X},
abstract = {Systemic lupus erythematosus is a multifactorial autoimmune disease characterized by the dysregulation of both innate and adaptive immunity, resulting in chronic inflammation, autoantibody production, and multi-organ damage. Innate immune dysfunction involves macrophages, neutrophils, plasmacytoid dendritic cells, natural killer cells, and the complement system, which collectively amplify autoimmunity through defective clearance of apoptotic cells, overproduction of pro-inflammatory cytokines, and abnormal type I interferon signaling. Adaptive immune abnormalities, including skewed T-cell subsets, impaired regulatory T and B cells, and autoreactive B-cell hyperactivity, further perpetuate pathogenic autoantibody generation. Gut microbiota dysbiosis contributes to SLE pathogenesis via Th17 activation, loss of mucosal tolerance, and molecular mimicry mechanisms. This review synthesizes current knowledge on the immunopathogenesis of SLE, emphasizing the interplay between innate and adaptive immunity and integrating evidence from both human and experimental murine models to provide a comprehensive understanding of disease mechanisms.},
}

@article {pmid41283232,
year = {2025},
author = {George, MY and Gamal, NK and Mansour, DE and Famurewa, AC and Bose, D and Messiha, PA and Cerchione, C},
title = {The Gut Microbiome Role in Multiple Myeloma: Emerging Insights and Therapeutic Opportunities.},
journal = {Hematology reports},
volume = {17},
number = {6},
pages = {},
doi = {10.3390/hematolrep17060056},
pmid = {41283232},
issn = {2038-8322},
abstract = {Multiple myeloma is a hematological cancer depicted by the proliferation of plasma cells within the bone marrow, causing immune dysfunction and other abnormalities. The gut microbiome, the microbial community in the gastrointestinal tract, was found to modulate systemic immunity, inflammation, and metabolism. Although the interplay between gut microbiome and multiple myeloma has been found in recent research, there is a gap in knowledge linking the effect of the microbiome on the pathogenesis and treatment of multiple myeloma. The imbalance in the gut microbiome, dysbiosis, may influence multiple myeloma pathogenesis through immune modulation and inflammation. Certain microbial species have been associated with multiple myeloma progression, complications, and therapeutic responses to treatment. Moreover, microbiome-derived metabolites, short-chain fatty acids, can influence the immune circuits associated with multiple myeloma progression. Understanding the bidirectional relationship between multiple myeloma and gut microbiota may provide insights into enhanced treatment and the development of new microbiome-based interventions. The current review provides a comprehensive highlight of current evidence linking the gut microbiome with multiple myeloma, demonstrating its significant roles in the development, progression, and treatment of multiple myeloma. Additionally, it focuses on the therapeutic potential of modulating the gut microbiome as a novel adjunct strategy in multiple myeloma management.},
}

@article {pmid41283171,
year = {2025},
author = {Ping, Y and Zhao, X and Lv, L and Meng, W and Meng, Y and Ruan, G and Cheng, Y and Xiao, Z and Tian, Y and Chen, M and Chen, L and Yi, A and Tang, Z and Li, N and Chen, D and Wei, Y},
title = {Gut microbiota and metabolic signatures of anxiety in ulcerative colitis: a cross-sectional study.},
journal = {Therapeutic advances in gastroenterology},
volume = {18},
number = {},
pages = {17562848251393419},
pmid = {41283171},
issn = {1756-283X},
abstract = {BACKGROUND: Patients with ulcerative colitis (UC) usually experience anxiety symptoms that seriously affect their quality of life, treatment, and prognosis. Dysbiosis of the gut microbiota plays an important role in UC and mental illness. However, little is known about the role of the gut microbiota in UC patients with anxiety.

OBJECTIVES: To identify the gut-microbiome and fecal metabolome profiles uniquely associated with comorbid anxiety in UC patients and to explore potential biomarkers for diagnosis.

DESIGN: A cross-sectional, two-group comparative study.

METHODS: To study the underlying association between them, we recruited 126 UC patients in this study, including 78 with anxiety and 48 without anxiety. A total of 102 fecal samples were collected for metagenomic sequencing and metabolome sequencing. Microbial diversity, differential gut microbiota, functional pathways, and metabolites were analyzed. Multivariable logistic regression was used to identify independent risk factors associated with anxiety in UC patients, while Spearman correlation was employed to explore microbe-metabolite interactions and the performance of potential biomarkers.

RESULTS: We found that disease severity, steroid usage, and abdominal pain may promote the occurrence of anxiety. Compared to UC patients without anxiety, UC patients with anxiety had low fecal microbial community diversity, with an increase in the species Haemophilus sp. HMSC71H05 and Corynebacterium durum, and a decrease in the species Roseburia intestinalis (RI), Bifidobacterium longum (BL), and Enterococcus hirae. The metabolic pathways driven by the gut microbiota were disrupted. Moreover, the levels of most metabolites (such as L-kynurenine) were increased in the feces, while the levels of a few metabolites decreased, including indole-2-carboxylic acid, N-demethylmirtazapine, and tauroursodeoxycholic acid.

CONCLUSION: Our research further revealed that these gut microbiota and metabolites are highly correlated. This study provides a new perspective for understanding the occurrence and development of anxiety in UC patients, suggesting that RI and BL may serve as potential candidate biomarkers to diagnose UC patients with anxiety.},
}

@article {pmid41282988,
year = {2025},
author = {Jia, S and Gu, W and Jiang, L and Zhang, Y and Fu, X and Yin, J and Zhou, Y},
title = {Effect of rainfall on metagenomics in a sewage environment in Hongta District, Yuxi city, Yunnan Province.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e20199},
pmid = {41282988},
issn = {2167-8359},
mesh = {*Sewage/microbiology/virology ; China ; *Metagenomics ; *Rain ; Bacteria/genetics/classification/isolation & purification ; *Microbiota ; Archaea/genetics/isolation & purification ; },
abstract = {BACKGROUND: Hongta District of Yuxi city is located in the central region of Yunnan Province, Southwest China. Previous studies have shown a high prevalence of enteric infectious diseases in the area, which may be related to sewage discharge. However, there has been no systematic analysis of the microbiome in sewage in this area. In this study, we investigated environmental sewage in Hongta District, Yuxi city, Yunnan Province.

METHODS: Surveillance was conducted in Hongta District, Yuxi city, for a period of one year. At both its urban and rural sites, sewage samples were collected for metagenomic sequencing.

RESULTS: The results revealed that in the sewage samples, bacteria accounted for 98.31% of the total microbiome, followed by Archaea (1.05%), Viruses (0.30%) and Eukaryota (0.34%). At the phylum level, Proteobacteria was the taxon with the highest relative abundance, accounting for 57.57% of all samples, followed by Firmicutes (17.17%), Bacteroidetes (12.23%), Actinobacteria (7.10%), and Synergistetes (1.45%). At the genus level, the taxa with the highest relative abundances of all the microbiomes were Acidovorax (6.63%), Pseudomonas (4.98%), Acinetobacter (4.23%), Comamonas (3.85%), and Aliarcobacter (2.78%). The diversity of the samples grouped by site and rainfall formed their own clusters, but only the compositions of different taxa grouped by rainfall significantly differed (P = 0.038 at the family, P = 0.019 at the genus and P = 0.005 at the species level). In general, the abundance of several taxa at the family, genus and species levels in the dry season group was higher (P < 0.05) than that in the rainy season group according to the Kruskal-Wallis test. The relative abundance s of most virulence genes were higher at urban sites than at rural sites, while those in the rainy season was higher than those in the dry season. The distribution of antibiotic resistance genes (ARGs) in urban and rural sewage was significantly different (P = 0.018). The relative abundance of multidrug resistance genes in urban sewage was higher than that in rural sewage, and the relative abundance of most resistance genes in the dry season group was higher than that in the rainy season group.

CONCLUSIONS: In general, the abundance and distribution features of the sewage microbial communities in the Hongta District of Yuxi city were affected by site and rainfall factors, with significant regional and temporal specificity. Strengthening the surveillance of environmental sewage and improving discharge methods are highly important for ensuring public health security.},
}

*Sewage/microbiology/virology
China
*Metagenomics
*Rain
Bacteria/genetics/classification/isolation & purification
*Microbiota
Archaea/genetics/isolation & purification

@article {pmid41282978,
year = {2025},
author = {Han, X and Liu, H and Bai, X and Li, D and Wang, T and Zhong, H and Yao, Y and Sun, J},
title = {Insights into antibiotic resistomes from metagenome-assembled genomes and gene catalogs of soil microbiota across environments.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e20348},
pmid = {41282978},
issn = {2167-8359},
mesh = {*Soil Microbiology ; *Metagenome ; China ; *Microbiota/genetics ; *Drug Resistance, Microbial/genetics ; Anti-Bacterial Agents/pharmacology ; *Bacteria/genetics/drug effects ; Metagenomics ; },
abstract = {Antibiotic resistance poses a significant global health threat, and soil is recognized as a critical reservoir for antibiotic resistance genes (ARGs). To investigate soil microorganisms in the areas where both humans and common domestic animals (such as pigs and chickens) are present and active. In this study, we employed metagenomic sequencing to investigate the soil resistome across four Chinese provinces-Yunnan, Guizhou, Sichuan, and Jiangsu. From 111 soil samples, we generated metagenome-assembled genomes (MAGs) and gene catalogs to analyze microbial community composition, ARG distribution, and mobile genetic elements (MGEs). Our results revealed notable regional differences in microbial communities and ARG profiles. Pseudomonadota and Actinomycetota were the dominant phyla across samples, and ARG abundance was significantly higher in Sichuan, Yunnan, and Jiangsu compared to Guizhou. We also identified microbial taxa likely serving as ARG vectors, suggesting potential for horizontal gene transfer. Functional annotation indicated that metabolic functions, particularly carbohydrate and amino acid metabolism, were predominant, which may be associated with the composition of organic matter in the soil environment. Multidrug resistance genes are widespread in soil microbial communities and may spread through food chains or soil-water-plant systems, posing potential ecological and public health risks. MGEs showed significant regional variation and play a key role in the horizontal spread of ARGs. Together, these findings provide new insights into the soil antibiotic resistome and offer a foundation for developing targeted strategies to manage environmental antibiotic resistance.},
}

*Soil Microbiology
*Metagenome
China
*Microbiota/genetics
*Drug Resistance, Microbial/genetics
Anti-Bacterial Agents/pharmacology
*Bacteria/genetics/drug effects
Metagenomics

@article {pmid41282808,
year = {2025},
author = {Porchia, DD and Wang, Y and Zhou, Z and Chen, M and Porges, EC and Cohen, RA and Ghare, S and Barve, S and Cook, RL and Li, Z},
title = {Cannabis use, microbial diversity, and Dialister abundance in older adults with HIV: a cross-sectional study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.03.25339401},
pmid = {41282808},
abstract = {OBJECTIVES: People living with HIV (PLWH) frequently experience gastrointestinal symptoms linked to dysbiosis, impaired mucosal barrier integrity, and persistent immune activation. Cannabis is widely used for symptom management by PLWH, but its effects on the gut microbiome are unclear.

METHODS: We conducted a cross-sectional analysis of 63 PLWH (mean age 59.4 years; 71.4% Black or Hispanic) enrolled in the Marijuana Associated Planning and Long-term Effects study and its microbiome substudy. Participants provided fecal samples for 16S rRNA sequencing. Cannabis use was quantified using a validated Timeline Followback. Alpha diversity was estimated using the Shannon index, beta diversity with Bray-Curtis dissimilarity and PERMANOVA, and genus-level abundance using the IFAA method. Models adjusted for sex, age, and education.

RESULTS: Higher cannabis consumption was significantly associated with reduced alpha diversity (β = -1.23, p =0.038). No significant differences in beta diversity were observed between high and low-to-no groups (p =0.35). At the genus level, Dialister abundance showed a significant dose-dependent association with cannabis use, with a 14.4% reduction in abundance per 50 mg increase in THC per use-day (q=0.034). Reduced alpha diversity and Dialister depletion are notable given links to impaired mucosal barrier integrity, microbial translocation, and systemic immune activation in HIV.

CONCLUSION: Cannabis consumption in PLWH was associated with lower microbial diversity and reduced Dialister abundance, a taxon with dual roles in mucosal integrity and gastrointestinal symptom modulation. These findings suggest cannabis may modify HIV-associated dysbiosis, warranting further longitudinal studies to disentangle symptomatic benefits from long-term impacts on mucosal health and systemic inflammation.},
}

@article {pmid41282762,
year = {2025},
author = {Zhao, Y and Naidoo, J and Conroy, M and Ferri, JT and Gills, JJ and Chen, KY and White, JR and Glass, S and Assan, WO and Peloza, K and Schollenberger, MD and Sharfman, WH and Marrone, KA and Forde, P and Brahmer, J and Anagnostou, V and Pardoll, DM and Murray, J and Lipson, EJ and Sears, CL and Shaikh, FY},
title = {Primary resistance to ICI-based regimens is associated with early longitudinal changes in the fecal microbiome and loss of microbial stability.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.01.25336378},
pmid = {41282762},
abstract = {While immune checkpoint inhibitors (ICI)-based regimens and chemo-immunotherapy combinations (chemo-ICI) are now first-line therapy for patients with metastatic non-small cell lung cancer (NSCLC), the number of patients who experience a sustained response to treatment remains limited. The majority of patients will not benefit from initial treatment (primary resistance) or develop progressive disease after an initial period of response (acquired resistance). Microbiome-based biomarkers offer an opportunity to identify patients who may have a poor response to ICI-based regimens using non-invasive methods, and potentially, then the microbiota may be amenable to therapy-enhancing alteration. However, a deep understanding of the longitudinal dynamics of gut microbial features in patients treated with ICIs in NSCLC, a feature of likely importance for microbiome-based therapeutics, remains limited. In this study, we show that patients with NSCLC who experience primary resistance to an ICI-based regimen show a loss of intra-individual microbiome stability in the first 4 months during treatment with an ICI-based regimen, independent of antibiotic exposure. Loss of microbiome stability was validated in a second tumor type in patients with melanoma. To identify key microbial species associated with progression, recursive feature elimination with random forest classifiers was used to identify temporally associated microbial species associated with disease progression. An index of these progression-associated species was able to predict clinical outcomes based on pre-treatment fecal samples, with further validation on an independent cohort. Together, our data show that microbial instability may be an early indicator of ICI-resistance in patients with NSCLC and melanoma, with the potential to be developed into biomarkers of primary resistance to ICI-based regimens.},
}

@article {pmid41282761,
year = {2025},
author = {Yaghjyan, L and Goel, N and Heine, J and Byrd, DA and Forsyth, SE and Fowler, E and Egan, KM},
title = {Fecal sample biobanking for breast cancer research focused on the gut microbiome.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.31.25339256},
pmid = {41282761},
abstract = {BACKGROUND: Gut microbiome is an emerging potentially modifiable contributor to breast health, including breast cancer (BCa). To advance prevention research in this area, we established a prospective biobanking cohort of cancer-free women.

METHODS: Eligible women were ≥40 years old, had no cancer history and no recent antibiotic use. Women were enrolled during screening mammography visits at three imaging centers in Florida (February 2021-June 2024), completed a BCa risk factor survey, and underwent body measurements. We collected digital mammograms and stool/urine/saliva samples. Optionally, women completed NIH's Diet History Questionnaire and a neighborhood stress questionnaire. Mammographic breast density (MBD) was assessed using established computerized approaches.

RESULTS: We recruited 733 cancer-free women (49% Caucasian, 21% African American, 26% Hispanic, and 4% from mixed/other races). The average age was 60 years (range 40-92); the majority (68.3%) were postmenopausal. BCa risk factor, neighborhood stress and diet questionnaires were completed by 97%, 65% and 58% of participants, respectively. Urine, saliva, and mammograms were available for all women; 83% also returned stool samples.

CONCLUSIONS: We have established a representative cohort of screen-aged women with comprehensive BCa risk factor data, biospecimen collection, and MBD.

IMPACT: This unique resource provides opportunity for future gut microbiome-focused BCa prevention research.},
}

@article {pmid41282717,
year = {2025},
author = {Evans, EM and Mayday, MY and Pearce, EM and Iwanaga, K and Ly, NP and Church, GD and Reyes, G and Simon, MR and Blum, J and Kim, H and Mu, J and Baez-Maidana, J and Auletta, JJ and Shaw, PJ and Kreml, EM and Martin, PL and Duncan, CN and Rowan, CM and Godder, K and Hurley, C and Cuvelier, GDE and Qayed, M and Abdel-Azim, H and Keating, AK and Fitzgerald, JC and Hanna, R and Killinger, JS and Hume, JR and Quigg, TC and Castillo, P and Satwani, P and Moore, TB and Dvorak, CC and Zinter, MS},
title = {Upper and Lower Respiratory Tract Compartmentalization in Pediatric Stem Cell Transplantation.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.15.25336763},
pmid = {41282717},
abstract = {RATIONALE: Lung injury after hematopoietic stem cell transplantation (HCT) occurs due to infection, chemotherapy toxicity, and alloreactive inflammation. Analyses of bronchoalveolar lavage (BAL) fluid have revealed dominant pathobiologic signatures, but minimally-invasive diagnostics are needed.

OBJECTIVES: To determine whether microbiome and gene expression perturbations are shared along the respiratory tract or isolated to the alveoli in pediatric HCT patients with lung injury.

METHODS: We performed bulk RNA sequencing on 189 paired nasal and BAL samples from 160 patients enrolled at 28 children's hospitals (2016-2021). Microbial and human transcripts were compared using multivariable models accounting for age, sex, and paired sampling.

MEASUREMENTS AND MAIN RESULTS: BAL and nasal transcriptomes differed across 13,698 genes, 48 cellular components, and network interactions linking inflammation, reactive oxygen species, and immunometabolism. Minimal BAL-nasal correlation was observed in gene expression levels (median ρ=0.03, IQR -0.03 to 0.08) or fractional abundance of key cells such as neutrophils and CD8+ T-cells. BAL microbiomes harbored fewer commensal bacteria and more fungi and DNA viruses. BAL bacterial RNA was associated with diminished immune signaling whereas nasal bacterial RNA aligned with inflammatory gene expression. Further, only BAL microbial RNA was linked to transcriptional shifts in epithelial injury response, keratinization, and collagen deposition. Finally, BAL commensal microbiome depletion, epithelial injury, and immune dysregulation signatures were associated with death or ≥7 days of mechanical ventilation in 30% of patients, whereas nasal samples provided minimal prognostic information.

CONCLUSIONS: These data support alveolar compartmentalization in pediatric HCT and emphasize the ongoing need for minimally-invasive but informative diagnostics.},
}

@article {pmid41282695,
year = {2025},
author = {Lande, SJ and Stephney, LM and Ramirez, LGA and Nesbeth, PC and Hartman, TJ and Jones, DP and Valvi, D and Hechenbleikner, EM and Lin, E and McConnell, RS and Chatzi, VL and Alvarez, JA and Ziegler, TR},
title = {Dietary Macronutrient Intake and the Gut Microbiome in Adults Undergoing Bariatric Surgery for Obesity.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.28.25338397},
pmid = {41282695},
abstract = {Limited information linking dietary intake to gut metagenomic data in bariatric surgery patients is available. We examined whether there were correlations between macronutrient intake and the gut microbiome and related gene pathways prior to and following bariatric surgery. Participants were 29 adults living with obesity undergoing bariatric surgery (93% females). Three-day food records were analyzed prior to and after surgery to estimate mean daily intakes of macronutrients to derive measures of diet quality [glycemic index, added sugar intake, and the Healthy Eating Index 2015 (HEI-2015)]. Pre- and post-operative stool samples were sequenced using whole-genome shotgun sequencing to identify changes in microbial composition. Diversity indices and differential abundance were calculated, and correlations between dietary intake and outcomes were assessed using linear regression and machine learning models. At the phylum level, pre-operative Synergistetes abundance was positively correlated with soluble fiber intake, and Proteobacteria was inversely linked with HEI-2015 scores. Post-operatively, Lentisphaerae was inversely correlated with dietary glycemic index. The change in Verrucomicrobia abundance was inversely correlated with the change in glycemic index, and the change in Fusobacteria abundance was positively correlated with the change in glycemic index. The changes in several functional gene pathways were positively linked to the change in HEI-2015 scores, the change in soluble fiber intake, and the change in insoluble fiber intake. In adults undergoing bariatric surgery, intakes of specific macronutrients pre-operatively and as a function of the change after surgery were correlated with several microbial phyla, genera, and nutrient-related functional gene pathways.},
}

@article {pmid41282530,
year = {2025},
author = {Shoji, F and Kawabata, T and Kosai, K and Fujishita, T and Toyozawa, R and Shimamatsu, S and Ito, K and Taguchi, K and Yamaguchi, M},
title = {Intratumoral microbiome is associated with the response to cancer immunotherapy in lung cancer patients with high PD-L1 expression.},
journal = {Immuno-oncology technology},
volume = {28},
number = {},
pages = {101066},
pmid = {41282530},
issn = {2590-0188},
abstract = {BACKGROUND: High expression of tumoral programmed death-ligand 1 (PD-L1) [high PD-L1 tumor proportion score (TPS)] is a predictive biomarker of response to cancer immunotherapy in lung cancer; however, its predictiveness is insufficient. Recently, resident microbiomes in several organs including the lung have been demonstrated to control host immunity but their role in the response to cancer immunotherapy is still unknown.

MATERIALS AND METHODS: This single-center, retrospective study analyzed 32 high PD-L1-TPS lung cancer patients treated with immune checkpoint inhibitors (ICI). We carried out shotgun metagenome sequencing using frozen tumor tissues, then analyzed the correlation between the intratumoral microbiota and response to ICI therapy.

RESULTS: In this study, only 56.3% of patients with high PD-L1-TPS showed response to ICI therapy. Among 11 significant compositional differences in intratumoral microbiota observed in ICI responders, there was significantly longer progression-free survival (PFS) in patients with abundant Tetrasphaera and Mesorhizobium. Of patients with these abundant microbiota, 83.3% showed response to ICI therapy and all patients without these microbiota were ICI nonresponders (P = 0.0050). There were significant differences among three groups classified by the abundance of g_Tetrasphaera and g_Mesorhizobium (PFS, P = 0.0016 and overall survival, P = 0.0013). Twenty pathway modules were enriched in ICI responders and eight were enriched in ICI nonresponders.

CONCLUSIONS: This study revealed the specific compositions of intratumoral microbiota as demonstrating relevance to response to ICI therapy in high PD-L1-TPS lung cancer patients. The intratumoral microbiota components Tetrasphaera and Mesorhizobium may have a key role in determining the response to cancer immunotherapy for lung cancer.},
}

@article {pmid41282255,
year = {2025},
author = {Norloff, E and Coker, K and Tusneem, S and Dixon, CT and Zhu, K and Graves, CL},
title = {Chronic Early Life Stress Alters the Microbial and Transcriptional Profile of the Zebrafish Gut.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7491371/v1},
pmid = {41282255},
issn = {2693-5015},
abstract = {Chronic early life stress (ELS) is appreciated to potently shape a myriad of biological outcomes later in life and has been associated with fertility deficits and the onset of gastrointestinal dysfunction in humans. Further, recent longitudinal cohort studies demonstrate that multigenerational adversity impacts the gut microbiome composition in early childhood, highlighting the gut-brain axis as an important target of ELS. Building on our recently published work demonstrating that ELS alters the neuroimmune profile of the developing zebrafish gut, our goal here was to establish a model of multigenerational ELS in zebrafish and determine cumulative stress impacts on fertility, gut microbial composition and the transcriptional landscape of the developing gut. Wild-type zebrafish were exposed to chronic ELS beginning at 5 dpf until 30 dpf according to our recently published stress paradigm for a total of four successive generations. We compared stressed and unstressed groups from either stressed or unstressed lineages and found that chronic ELS was associated with reduced egg viability and profound changes to the gut microbiome. RNA-sequencing revealed ELS-associated differential expression of more than 800 genes in founder generations. Altogether our data demonstrate that zebrafish are a powerful model for exploring neuroimmune interactions at mucosal surfaces across generations.},
}

@article {pmid41282186,
year = {2025},
author = {Chen, S and Cui, L and Zuo, B and Zhao, J and Walker, ED},
title = {Tannic Acid Shaped Microbiome Composition in Midguts and Rearing Microcosms of Aedes triseriatus (Say).},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7706154/v1},
pmid = {41282186},
issn = {2693-5015},
abstract = {Tannic acid (TA), a polyphenol derived from plants, often accumulates in water-holding containers where mosquitoes develop. Yet, its effects on mosquito gut microbiota remain poorly understood, representing an important knowledge gap. Because mosquito-associated microbiota are vital for host development, nutrition, and immunity, uncovering how TA shapes these microbial communities may yield new insights into mosquito biology and vector control strategies. In this study, we conducted a comparative analysis of bacterial communities in Aedes triseriatus midguts and rearing microcosms with or without TA supplement. Addition of TA at 0.35 mg/mL caused up to 50% larval Ae. triseriatus mortality, whereas combined supplementation with TA and kanamycin (100 µg/mL) increased mortality to 75% relative to controls. TA treatment significantly reduced microbial Chao 1 richness and Shannon diversity in larval and adult mosquito guts, while water and leaf samples were not affected. Distinct microbial community structures were observed between TA-treated and control groups across larvae, adults, water, and leaf surfaces. Pseudomonadota and Bacteroidota dominated all samples, with TA increasing the relative abundance of Pseudomonadota while decreasing Bacteroidota. Notably, Pseudomonas was enriched in TA-treated water, leaf surfaces, and larval midguts, suggesting a role in tannic acid detoxification. PICRUSt functional predictions indicated enrichment of carbohydrate and amino acid metabolism and membrane transport pathways under TA exposure, reflecting adaptive microbial responses to TA stress. Our findings highlighted how TA shapes mosquito microbiota and habitat quality, offering potential avenues to manipulate microbial communities as a biocontrol strategy for mosquito larvae.},
}

@article {pmid41282140,
year = {2025},
author = {Gascoigne, N and Wojciech, L and Prasad, M and Brzostek, J and Rybakin, V and Hoerter, J and Hou, B and Tung, D and Chua, YL and Ampudia, J and Rai, A and Chodaczek, G and Fu, G and Pettersson, S},
title = {The role of Themis in development of type 2 diabetes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7943370/v1},
pmid = {41282140},
issn = {2693-5015},
abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder driven by chronic inflammation and immune dysregulation, particularly within adipose tissue. This study investigates the role of the T cell-specific protein Themis in modulating immune-metabolic interactions that contribute to T2D pathogenesis. Using high-fat diet (HFD)-induced obesity models, we demonstrate that Themis -deficient (KO) mice exhibit accelerated weight gain, glucose intolerance, and insulin resistance compared to wild-type (WT) controls. These metabolic abnormalities are linked to functional alterations in the CD8[+] T cell compartment, including site-specific clonal expansion and reshaping of the T cell receptor (TCR) repertoire within adipose tissue, suggesting antigen-driven activation. Additionally, Themis deficiency leads to significant shifts in gut microbiome composition, characterized by reduced diversity and increased abundance of Firmicutes , particularly Clostridium species. However, fecal microbiota transplantation from Themis KO mice into germ-free WT hosts failed to recapitulate the full T2D phenotype, underscoring the dominant role of intrinsic immune dysfunction over microbial dysbiosis. These findings highlight a synergistic interplay between adaptive immunity and the microbiome in shaping metabolic outcomes and suggest that T cells play a central role in responses that influence T2D progression. Our data advocate for a more integrated approach to T2D research, incorporating genetic, immunological, and microbial factors.},
}

@article {pmid41282059,
year = {2025},
author = {Wright, G and Cook, M and Xu, M and Morici, M and Travin, D and Wang, W and Klepacki, D and Chhabra, N and Rao, V and Sahile, H and Hackenberger, D and Safdari, H and Berger, M and Corazza, M and Bond, A and Guitor, A and Tertigas, D and Wang, L and Schaenzer, A and Ejim, L and Yarlagadda, V and Gomez, J and Surette, M and Av-Gay, Y and Dhar, N and Hung, D and Vázquez-Laslop, N and Mankin, A and Wilson, D},
title = {Saskemycin, a potent and selective antimycobacterial agent targeting a unique site on the ribosome.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7820265/v1},
pmid = {41282059},
issn = {2693-5015},
abstract = {Tuberculosis is the deadliest bacterial disease on the planet. The months-long regimen of multiple antibiotics required to treat tuberculosis profoundly affects the microbiome and leads to the development of antimicrobial resistance. Furthermore, non-tuberculous mycobacterial infections pose an increasing clinical challenge. Consequently, there is a growing need for new narrow-spectrum mycobacteria-targeting antibiotics with different mechanisms of action. Here, we report the discovery and characterization of a natural glycolipid antibiotic, saskemycin (SKM), which demonstrates potent and highly selective activity against mycobacteria. Genome sequencing, chemical analysis, and isotope feeding strategies reveal the unique structure and biosynthetic origin of SKM. SKM binds to the small ribosomal subunit at a site not targeted by any of the clinically relevant antibiotics acting on the ribosome. Bound to the ribosome, SKM corrupts the decoding center in a unique way, preventing stable binding of aminoacyl-tRNA in the A site and inhibiting translation in a sequence context-specific manner. Self-resistance in the producing organism is conferred by methylation of a single 16S rRNA nucleotide by SasO and SasN rRNA methyltransferases. These enzymes are orthologs of the ubiquitous RsmC and SpoU methyltransferases found in most bacterial genera but absent in mycobacteria, rationalizing SKM's exquisite selectivity. The discovery of SKM provides an entry point for the development of selective, microbiome-sparing antimycobacterial antibiotics with a unique structure, binding site, and mechanism of action.},
}

@article {pmid41282040,
year = {2025},
author = {Ariestine, DA and Sari, DK and Siahaan, L and Widyawati, T and Rusda, M and Sari, MD and Sofyani, S and Amin, MM},
title = {Impact of Areca Catechu Kombucha on Inflammatory Markers and Gut Microbiota - a Review.},
journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)},
volume = {79},
number = {5},
pages = {411-416},
pmid = {41282040},
issn = {1986-5961},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammation ; *Kombucha Tea ; *Aging/physiology ; Biomarkers ; Antioxidants/pharmacology ; },
abstract = {BACKGROUND: Understanding the aging process has become one of the global concerns as the world faces the new challenges of an aging population. Central to this phenomenon is cellular senescence, marked by an irreversible growth arrest due to cellular damage. Gut microbiome is a dynamic community of microorganisms influenced by diet, environmental exposures, and aging.

OBJECTIVE: This research highlights the significant impact of gut microbiota composition on overall health, particularly in older adults, where deterioration in microbial diversity can lead to adverse health outcomes. Kombucha, a fermented tea beverage, has emerged as a potential gut microbiota modulator, offering antioxidant properties and digestive support. Specifically, Kombucha derived from Areca catechu shows promise in modulating inflammatory markers and gut microbiota composition.

METHODS: This review synthesizes current literature on the relationship between aging, frailty, and gut health, with a particular focus on gut microbiota composition and chronic inflammation, referred to as "inflammaging." We specifically investigate the potential of Kombucha, a fermented tea beverage, to modulate gut microbiota and inflammatory markers.

RESULTS: Kombucha, a fermented tea beverage, has emerged as a potential gut microbiota modulator, offering antioxidant properties and digestive support. Specifically, Kombucha derived from Areca catechu shows promise in modulating inflammatory markers and gut microbiota composition. This review synthesizes current literature on the interplay between aging, frailty, and gut health-focusing on the role of gut microbiota and chronic inflammation ("inflammaging")-to elucidate the therapeutic potential of Kombucha in promoting gut health and mitigating age-related decline, thereby contributing to a deeper understanding of its role in the aging process.

DISCUSSION: This research elucidates the therapeutic potential of Kombucha in promoting gut health and mitigating age-related decline, contributing to a deeper understanding of its role in the aging process. The interplay between gut microbiota and chronic inflammation highlights the importance of dietary interventions in managing health in aging populations.

CONCLUSION: Kombucha presents a viable strategy for modulating gut health and addressing the challenges of aging, emphasizing the need for further exploration of its benefits in older adults.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Inflammation
*Kombucha Tea
*Aging/physiology
Biomarkers
Antioxidants/pharmacology

@article {pmid41281446,
year = {2025},
author = {Liu, Y and Hassan, H and Brooks, TR and VanLith, C and Cooley, M and Elgozair, M and Ahmed, FY and Giama, NH and Campbell, NA and Su, L and Tai, YL and Ren, J and Zhou, H and Roberts, LR},
title = {Blood and tissue dysregulated bile acids and short-chain fatty acids in cholangiocarcinoma.},
journal = {JHEP reports : innovation in hepatology},
volume = {7},
number = {12},
pages = {101467},
pmid = {41281446},
issn = {2589-5559},
abstract = {BACKGROUND & AIMS: Dysregulated bile acid (BA) homeostasis has been implicated in the initiation and progression of cholangiocarcinoma (CCA). The aim of this study was to investigate the roles of circulating and tumor BAs, oxysterols, short-chain fatty acids (SCFAs), transcriptomic changes, and stool microbiota composition in CCA, and their potential diagnostic and therapeutic implications.

METHODS: We used ultra-performance liquid chromatography-tandem mass spectrometry to quantify BAs, oxysterols, and SCFAs in serum from patients with benign focal nodular hyperplasia (n = 27), primary sclerosing cholangitis (PSC; n = 20), intrahepatic CCA (iCCA; n = 29), and extrahepatic CCA (eCCA; n = 35), and in tumor and adjacent non-tumor iCCA (n = 30) and eCCA (n = 26) tissues. Publicly available liver transcriptome and gut microbiome datasets were analyzed to assess BA metabolic pathway activity and related gene expression profiles.

RESULTS: Total primary conjugated BA levels and the taurine-to-glycine ratio of conjugated BAs were significantly elevated in the serum of patients with PSC and CCA compared to controls with focal nodular hyperplasia (p <0.05). Transcriptomic analysis revealed a significant downregulation of GLYAT and BAAT, key genes involved in glycine and taurine conjugation, in PSC and CCA (p <0.05). Hepatic oxysterol levels were increased concomitantly with BAs in patients with CCA. Among SCFAs, butyric acid was positively correlated with conjugated BAs in the serum of patients with iCCA, whereas acetic acid was negatively correlated with BAs in the serum of patients with non-PSC-eCCA (p <0.05). Conjugated BAs were positively correlated with carbohydrate antigen 19-9 levels in patients with iCCA and non-PSC-eCCA.

CONCLUSIONS: Profound alterations in serum and tissue levels of primary and taurine-conjugated BAs occur during cholangiocarcinogenesis. Further elucidation of the mechanisms regulating BA and oxysterol metabolism in CCA may offer new avenues for diagnosis and therapy.

IMPACT AND IMPLICATIONS: Cholangiocarcinomas (CCAs) are aggressive malignancies with limited therapeutic options. Although CCA cells exhibit distinct metabolic profiles, investigating their regulation through the enterohepatic axis remains challenging. In this study, targeted metabolomics was used to analyze bile acid (BA) profiles in serum and liver tissue, serum short-chain fatty acids, and hepatic oxysterol levels in patients with intrahepatic and extrahepatic CCA, compared to controls with focal nodular hyperplasia and primary sclerosing cholangitis. Liver transcriptome analysis revealed differentially expressed genes involved in BA metabolism in patients with primary sclerosing cholangitis and CCA. Correlations were also examined between BAs, oxysterols, short-chain fatty acids, clinical features, and microbiome components implicated in CCA development. These findings provide new insights into BA dysregulation in CCA and establish a foundation for the development of novel diagnostic biomarkers and therapeutic strategies.},
}

@article {pmid41281345,
year = {2025},
author = {Kabwe, M and Tucci, J and Dashper, S and Binte Mohamed Yakob Adil, SS and Petrovski, S},
title = {Characterisation of novel Fusobacterium nucleatum bacteriophages and their efficacy in disrupting pathogenic dual-species biofilms.},
journal = {Journal of oral microbiology},
volume = {17},
number = {1},
pages = {2584952},
pmid = {41281345},
issn = {2000-2297},
abstract = {BACKGROUND: The targeted manipulation of the microbiome using bacteriophages represents a novel approach for addressing antibiotic resistance and polymicrobial diseases.

OBJECTIVE: To isolate and characterise bacteriophages for key bacteria associated with pathogenic periodontal biofilms.

DESIGN: Using standard microbiological and bioinformatics techniques, this study isolated and characterized lytic (FNU2 and FNU3) and temperate (FNU4) bacteriophages specific to Fusobacterium nucleatum, a key bacterium in oral biofilms linked to periodontitis and a range of cancers.

RESULTS: Morphological and genomic analyses revealed distinct features, with FNU2 and FNU3 classified as Latrobevirus and FNU4 as an unclassified Caudoviricetes. Comparative bioinformatic analysis revealed various defence and anti-defence systems in bacterial hosts and bacteriophages, highlighting complex interactions. Functional assays demonstrated the efficacy of these bacteriophages in disrupting single-species F. nucleatum biofilms and dual-species biofilms of F. nucleatum and Porphyromonas gingivalis.

CONCLUSION: These findings highlight the potential of F. nucleatum-specific bacteriophages as precise tools for microbiome modulation in chronic diseases such as periodontitis and cancer.},
}

@article {pmid41281344,
year = {2025},
author = {Xu, M and He, Z and Zhou, J and Zhao, J and Tian, X and Cheng, Q and Lin, Y and Xin, H and Mou, C and Xue, Q and Luo, B},
title = {Altered oral microbiomes in patients with prolonged disorders of consciousness.},
journal = {Journal of oral microbiology},
volume = {17},
number = {1},
pages = {2577220},
pmid = {41281344},
issn = {2000-2297},
abstract = {BACKGROUND: The host microbiome is increasingly recognized as a key modulator of brain function and disease progression, yet the role of the oral microbiome in patients with prolonged disorders of consciousness remains underexplored.

METHODS: This study characterized oral microbiota differences among pDoC patients (n = 89) in the vegetative state (VS), the minimally conscious state (MCS), and emerging from the MCS (EMCS), with a particular focus on the impact of antibiotic use. We used 16S ribosomal RNA sequencing to profile oral microbiota in patients with different levels of consciousness.

RESULTS: β-diversity was significantly reduced in the VS group compared to the EMCS group. Differential abundance analysis identified five taxa (i.e., species Streptococcus danieliae, species Corynebacterium durum, family Lachnospiraceae, species Phocaeicola abscessus, and species Campylobacter showae) that exhibited significant differences between VS and EMCS, suggesting they were potentially involved in regulating oral microbial dysbiosis and brain-microbiome interactions. Antibiotic treatment induced pronounced microbial shifts in the VS group, while no such effect was observed in the MCS or EMCS groups. Prognostic models built using differential and dominant microbiota panels demonstrated strong predictive performance, achieving areas under the curve of 0.820 and 0.920, respectively.

CONCLUSIONS: These findings highlight oral microbiome alterations in pDoC and their potential relevance to disease progression, emphasizing the importance of microbiome-informed clinical strategies.},
}

@article {pmid41280932,
year = {2025},
author = {Qian, Y and Chen, Y and Liu, L and Wu, T and Chen, X and Ma, G},
title = {Depression and anxiety in inflammatory bowel disease: mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1676160},
pmid = {41280932},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/psychology/microbiology/therapy/immunology ; *Anxiety/therapy/etiology/epidemiology ; *Depression/therapy/etiology/epidemiology ; Animals ; *Brain-Gut Axis ; Dysbiosis ; *Brain/immunology/metabolism ; },
abstract = {Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), represents a group of chronic, relapsing intestinal inflammatory disorders with incompletely understood etiology. Depression and anxiety, as prevalent psychiatric conditions, exhibit rising incidence rates; notably, IBD patients demonstrate heightened susceptibility to these disorders compared to the general population, thereby exacerbating disease burden and increasing risks of adverse clinical outcomes. Emerging evidence reveals shared pathophysiological mechanisms between IBD and depression/anxiety. This review specifically addresses depression and anxiety within the IBD disease context, integrating recent epidemiological evidence and risk factors. Centered on the gut-brain axis framework, we examine mechanistic underpinnings through two interconnected pathways: gut dysbiosis and neuroimmune interactions mediated by inflammatory cytokines and neurotransmitters. Finally, we explore therapeutic interventions for depression and anxiety in IBD based on these mechanistic insights, aiming to advance clinical and public health management strategies.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Inflammatory Bowel Diseases/psychology/microbiology/therapy/immunology
*Anxiety/therapy/etiology/epidemiology
*Depression/therapy/etiology/epidemiology
Animals
*Brain-Gut Axis
Dysbiosis
*Brain/immunology/metabolism

@article {pmid41280921,
year = {2025},
author = {Li, X and Yuan, Q and Huang, H and Wang, L},
title = {Gut microbiota in irritable bowel syndrome: a narrative review of mechanisms and microbiome-based therapies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1695321},
pmid = {41280921},
issn = {1664-3224},
mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Animals ; Prebiotics/administration & dosage ; },
abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and its pathogenesis remains unclear. Dysbiosis of the gut microbiota is associated with IBS. The gut microbiota may modulate IBS symptoms via the epithelial barrier, mucosal immunity, microbial metabolites (e.g., short-chain fatty acids and bile acids), and gut-brain signaling. Currently, dietary approaches, probiotics, prebiotics, rifaximin, and fecal microbiota transplantation show variable benefit; effects are strain-/context-dependent and evidence certainty varies, with adverse-event reporting inconsistent. This narrative review takes a subtype-aware, mechanism-first perspective to summarize microbiota functions, symptom links, and intervention evidence with safety considerations. This review offers new perspectives and insights for precision treatment and microbiome research in IBS.},
}

Humans
*Irritable Bowel Syndrome/therapy/microbiology/immunology
*Gastrointestinal Microbiome/immunology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Dysbiosis/therapy
Animals
Prebiotics/administration & dosage

@article {pmid41280856,
year = {2025},
author = {Oluwole, OA and Campos, EVR and de Oliveira, JL and Fraceto, LF},
title = {Integrating the Nano-Phyto-Micro Triad for Climate-Resilient and Sustainable Agriculture.},
journal = {ACS omega},
volume = {10},
number = {45},
pages = {53702-53721},
pmid = {41280856},
issn = {2470-1343},
abstract = {The convergence of nanotechnology, plant hormones, and plant-associated microbiomes offers a transformative approach for climate-resilient and sustainable agriculture. This perspective examines how nanocarriers can improve the delivery and stability of natural hormones and microbiome-compatible compounds, addressing challenges such as low bioavailability, environmental degradation, and nontargeted effects. Plant hormones, such as auxins, gibberellins, and salicylic acid, play essential roles in stress responses and growth regulation, while beneficial microorganisms contribute to nutrient cycling, pathogen resistance, and resilience against abiotic stresses. However, their practical application remains limited due to their instability and inconsistent performance under field conditions. Recent advancements have demonstrated that innovative nanomaterials, such as polymeric, lipid-based, or silica nanoparticles, can enable the controlled release, targeted delivery, and environmental protection of these compounds. For example, chitosan-based nanoparticles increase root colonization by beneficial microbes and enhance systemic resistance in tomatoes and maize. This review synthesizes the current knowledge and emerging technologies at the nano-phyto-micro interface, highlighting synergistic mechanisms and gaps in regulation, formulation, and large-scale applications. We advocate integrated research strategies that combine omics approaches, advanced formulations, and real-world validations to unlock the full potential of this triad. Aligning nanotechnology with nature-based solutions may pave the way for low-input, high-efficiency farming systems tailored to changing climates.},
}

@article {pmid41280693,
year = {2025},
author = {Velo-Suarez, L and Guilloux, CA and Le Berre, R and Gouriou, S and Rault, G and Mottier, D and Meijer, L and Héry-Arnaud, G},
title = {Use of microbiome analysis as a complementary endpoint in clinical trials.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113754},
pmid = {41280693},
issn = {2589-0042},
abstract = {The ROSCO-CF study evaluated the safety and effect of oral R-roscovitine in people with cystic fibrosis chronically colonized by Pseudomonas aeruginosa. While no direct impact on the respiratory pathogen was detected, lung and gut microbiomes were analyzed to explore broader effects of the treatment. Sputum and fecal samples collected before and after treatment were examined using 16S rDNA sequencing. Despite overall stability in alpha diversity, dose-dependent shifts in beta diversity suggested subtle restructuring of microbial communities. Temporal analyses indicated emerging patterns in microbial coordination at higher doses. Specific taxa, such as Tannerella and Granulicatella elegans, showed increased abundance, while Streptococcus decreased with dose. These results suggest that R-roscovitine may influence microbial dynamics in a personalized and dose-dependent manner, supporting the inclusion of microbiome profiling as an exploratory endpoint in clinical trials.},
}

@article {pmid41280675,
year = {2025},
author = {Aatsinki, AK and Lamichhane, S and Isokääntä, H and Sen, P and Kråkström, M and Alves, MA and Keskitalo, A and Munukka, E and Karlsson, H and Perasto, L and Lukkarinen, M and Oresic, M and Kailanto, HM and Karlsson, L and Lahti, L and Dickens, AM},
title = {Dynamics of gut metabolome and microbiota maturation during early life.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113596},
pmid = {41280675},
issn = {2589-0042},
abstract = {Early-life gut microbiome-metabolome crosstalk plays a crucial role in maintaining host physiology. The microbially produced metabolites often convey effects on host health and physiology. This study investigates the gut metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and polar metabolites, and their relationship to gut microbiota composition in a birth cohort of 670 children. Samples were collected at 2.5 (n = 272), 6 (n = 232), 14 (n = 289), and 30 months (n = 157) of age. We identified the trajectories of the fecal metabolome that relate to the maturation of the early-life gut microbiota. We found that prevalent gut microbial abundances were associated with microbial metabolite levels, particularly in 2.5-month-old infants. Here, the abundances of early colonizers, e.g., Bacteroides, Escherichia, and Bifidobacterium, were associated with microbial metabolites, especially secondary BAs, particularly in breastfed infants. Our results suggest that early-life gut microbiota associates with changes in metabolome composition, particularly BAs, which may have physiological implications.},
}

@article {pmid41280427,
year = {2025},
author = {Soni, PK and Kala, A and Agarwal, P and Deka, R and Rahman, H and Vijayalakshmy, K and Chaudhary, LC},
title = {Taxonomic and functional shifts in the rumen microbiome of buffalo calves under long-term strategic supplementation of phyto-feed additives.},
journal = {Frontiers in veterinary science},
volume = {12},
number = {},
pages = {1647762},
pmid = {41280427},
issn = {2297-1769},
abstract = {INTRODUCTION: The present study aimed to understand the shift in the rumen microbiome of buffaloes fed diets with and without phyto-additives. The rationale was based on the hypothesis that plant-based additives can modulate the microbial population in the rumen, potentially reducing methane production and enhancing fiber degradation. Given the possibility that prolonged use of the same additives may lead to microbial adaptation and diminished efficacy, the study also investigated the effects of periodically switching additives.

METHODS: Three male buffalo calves were fed a control diet, while another three received additive-supplemented diets. Two additive formulations were used: FAI (a blend of garlic Allium sativum, ajwain Trachyspermum ammi, harad Terminalia chebula, and soapnut Sapindus mukorossi) and FAII (ajwain oil). The additives were alternated every 15 days to prevent microbial adaptation. After 21 days of feeding, rumen liquor samples were collected 2 hours post-feeding for metagenomic analysis. The study included both in vivo and in vitro assessments of rumen fermentation.

RESULTS: Metagenomic analysis revealed that dominant bacterial phyla included Prevotella, Bacteroides, Succiniclasticum, Fibrobacter, Clostridium, Alistipes, Ruminococcus, and Butyrivibrio, with over 50 bacterial species consistently present across all animals. The main archaeal phylum was Euryarchaeota (>85%), along with notable presence of Candidatus_Bathyarchaeota and Thaumarchaeota. At the genus level, Methanomicrobium and Methanobrevibacter each accounted for approximately 30% of the archaeal community, followed by Methanosphaera, Methanosarcina, and Methanomassiliicoccus. While total abundances of Archaea and Bacteroidota were not significantly different among groups, specific taxa within these phyla showed marked changes.

DISCUSSION: The inclusion of phyto-additives in the buffalo diet influenced the rumen microbiome composition by reducing methanogen populations, particularly Methanobrevibacter, and enhancing fiber-degrading microbial communities. These microbial shifts were associated with improved fiber utilization and decreased methane emissions. Rotating the additives every 15 days appeared to sustain their efficacy over time, potentially by preventing microbial adaptation. This approach may offer a sustainable strategy to optimize rumen function and reduce enteric methane emissions in ruminants.},
}

@article {pmid41280414,
year = {2025},
author = {Wei, WY and Zhou, XP and Yang, XL and Zong, Y and Shi, K and Li, JM and Diao, NC and Du, R and Zeng, FL},
title = {Effects of dietary supplementation of Poria cocos polysaccharides on intestinal barrier, immune function, and growth of Hyla rabbits.},
journal = {Frontiers in veterinary science},
volume = {12},
number = {},
pages = {1643620},
pmid = {41280414},
issn = {2297-1769},
abstract = {INTRODUCTION: Optimal rabbit health, which significantly influences growth and development, depends on three key factors: a robust immune system, proper intestinal function, and balanced gut microbiota. Poria cocos polysaccharide (PCP), the primary bioactive component of Poria cocos, exhibits multiple pharmacological properties with demonstrated benefits for animal health.

METHODS: 320 Hyla rabbits were randomly allocated to four dietary groups: a control group receiving a basal diet and three experimental groups supplemented with 0.1, 0.2%, or 0.3% PCP. The growth performance of the rabbits was measured on day 21 and day 42. At the end of the experimental period, growth performance was evaluated, and samples of serum, thymus, liver, spleen, kidney, duodenum, cecum, and cecal content were collected. These samples were used to assess serum biochemical parameters, antioxidant capacity, organ indices, immune function, intestinal permeability, intestinal morphology, microbial composition, and short-chain fatty acid (SCFA) concentrations.

RESULTS: The results showed that the PCP supplementation significantly enhanced growth performance and immune organ indices in Hyla rabbits. Compared with the control group, PCP was able to significantly increase serum levels of total protein (p < 0.05), albumin (p < 0.05), glucose (p < 0.05), total antioxidant capacity (p < 0.05), catalase (p < 0.05), glutathione peroxidase (p < 0.01), Immunoglobulin A (p < 0.05), Immunoglobulin G (p < 0.001), Immunoglobulin M (p < 0.01), and Interleukin-10 (p < 0.01), and down-regulate serum levels of total cholesterol (p < 0.05), triglyceride (p < 0.05), malondialdehyde (p < 0.01), Interleukin-6 (p < 0.05), diamine oxidase, D-lactate, and endotoxin (p < 0.05). And PCP significantly increased villus length (p < 0.05) and villus-to-crypt ratio (p < 0.01), as well as duodenum-related intestinal gene expression (p < 0.05) in the duodenum and cecum, and decreased crypt depth in the duodenum and cecum (p < 0.01). In addition, PCP significantly increased the concentration of short-chain fatty acids and improved the structure of gut microbiota.

CONCLUSION: In conclusion, these data suggest that PCP can be used as a potential tool to enhance growth performance by improving serum biochemistry, antioxidant capacity, immunity, gut barrier function, and gut flora composition in Hyla rabbits.},
}

@article {pmid41280320,
year = {2025},
author = {Shackelford, BB and Kedir, K and Babiker, A and Sintayehu, B and Negash, AA and Abdissa, A and Taye, WA and Beyene, E and Woodworth, MH and Hennink, MM},
title = {Knowledge and Acceptability of Fecal Microbiota Transplantation Among Patients, Caregivers, and Health Care Providers in Ethiopia.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf676},
pmid = {41280320},
issn = {2328-8957},
abstract = {BACKGROUND: Malnutrition and antimicrobial-resistant infections are major causes of morbidity and mortality in low-income countries. These conditions have been associated with the gut microbiome, although little is known about the acceptability of microbiota therapies such as fecal microbiota transplantation (FMT). We explored the acceptability of FMT among health care providers (HCPs) and patients in Addis Ababa, Ethiopia.

METHODS: In this qualitative study, we purposively sampled patients with bacterial infections and acute malnutrition, caregivers, and HCPs at two hospitals. Eight focus group discussions were held. Amharic and English discussion guides covered knowledge of FMT and perceived barriers or facilitators for uptake. Data were transcribed and translated into English when necessary. MAXQDA software was used for a thematic analysis, with trained researchers closely reading transcripts to identify issues, develop a codebook, iteratively code data, and assess intercoder agreement. Description, comparison, and categorization were conducted to discern core themes, and validity checks ensured that findings were grounded in the data.

RESULTS: HCPs indicated a general willingness to prescribe FMT, provided that there was sufficient evidence supporting its efficacy and safety and they were confident on patient adherence. Patient acceptability of FMT was categorized along a continuum from those who were unconvinced, persuadable, amenable, and accepting of salvage treatment.

CONCLUSIONS: FMT may be acceptable for HCPs and patients in Addis Ababa, although interventions are needed to enhance acceptance among some groups, such as marketing it as standard medication, obtaining endorsement by religious leaders, providing multiple formulations, and/or providing thoughtful health communication.},
}

@article {pmid41280278,
year = {2026},
author = {Zhou, ZY and Yin, QJ and Basnet, BB and Li, ZY and Li, G and Emam, M and Wu, QH and Wang, H and Wei, B},
title = {Amplicon-based prediction of secondary metabolic potential of microbiomes facilitates natural product discovery.},
journal = {Synthetic and systems biotechnology},
volume = {11},
number = {},
pages = {385-396},
pmid = {41280278},
issn = {2405-805X},
abstract = {The rapid exploration of natural products not only expands chemical diversity but also plays a vital role in drug discovery by identifying bioactive agents (e.g., antibiotics), revealing novel biological mechanisms, and providing new therapeutic opportunities. However, traditional techniques require extensive resources to screen and prioritize bacteria capable of producing valuable compounds from complex environmental samples. Here, we introduce the PSMPA (Predicting the Secondary Metabolism Potential using Amplicons) pipeline, designed to assess the secondary metabolic potential of microbiomes by estimating the abundance of biosynthetic gene cluster (BGC) classes based on 16S rRNA gene amplicons. This approach facilitates early-stage selection of samples and strains with high potential for novel compound production. We applied PSMPA to microbiome samples from marine environments (seawater, mangrove sediment, and intertidal flat sediment), leading to the identification of a promising Marinobacterium strain YM272 and the discovery of maripanthiones, a new class of sulfur-containing natural products. By enabling early identification of promising strains or samples, PSMPA accelerates novel natural product discovery and enhances the utility of amplicon sequencing for functional analysis. The web version of PSMPA is available at https://www.psmpa.net/.},
}

@article {pmid41280275,
year = {2026},
author = {Qi, X and Zhang, Y and Sun, Z and Wang, G and Ling, F},
title = {A simplified synthetic microbial community enhances resistance of crucian carp (Carassius auratus) to Aeromonas hydrophila infection through host immune activation.},
journal = {Synthetic and systems biotechnology},
volume = {11},
number = {},
pages = {407-418},
pmid = {41280275},
issn = {2405-805X},
abstract = {Bacterial diseases represent a major bottleneck in the sustainable development of aquaculture. The gut microbiota plays a vital role in host growth and health, including the enhancement of disease resistance. Although substantial progress has been made in elucidating the mechanisms of disease resistance in fish, the precise role of the gut microbiota in enhancing pathogen resistance in aquatic animals remains poorly understood. In this study, crucian carp (Carassius auratus) were used as a model to investigate the role of intestinal microbiota in modulating resistance to Aeromonas hydrophila. Individual crucian carp exhibited distinct clinical phenotypes following A. hydrophila infection. Specifically, significant differences were observed in the composition of the intestinal microbiota between fish displaying mild symptoms and those exhibiting severe phenotypic manifestations (α diversity: p < 0.01; β diversity: p = 0.001). Fecal microbiota transplantation (FMT) experiments demonstrated that fish with mild symptoms conferred enhanced resistance to A. hydrophila when their intestinal contents were transplanted into other individuals (p = 0.006). Further microbial analysis identified Cetobacterium (p = 0.013), Paraclostridium (p < 0.01), and Pseudomonas (p < 0.01) as key differential taxa. A simplified microbial community comprising these three strains was subsequently constructed. Feeding experiments confirmed that administration of this community significantly improved host resistance to A. hydrophila (p < 0.05) by activating intestinal immune responses and reinforcing the gut barrier. Overall, our findings underscore the potential of the microbial community as a novel strategy for disease prevention and control in aquaculture, providing a theoretical foundation for the development of microbiome-based therapies in fish health management.},
}

@article {pmid41280114,
year = {2025},
author = {Dirks, B and Mohr, AE and Corbin, KD and Carnero, EA and Smith, SR and Whisner, CM and Rittmann, BE and Krajmalnik-Brown, R},
title = {Microbial Feast or Famine: dietary carbohydrate composition and gut microbiota metabolic function.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.27.684932},
pmid = {41280114},
issn = {2692-8205},
abstract = {Diet composition plays a major role in shaping the structure and function of the gut microbiota and influencing host health. While numerous studies have investigated the impact of macronutrient type and quantity on microbiota using in vitro systems, animal models, and human participants, most of these studies focused primarily on microbial-community composition and lacked the functional information that can be gained from transcript-level analyses. In this exploratory analysis, we use metatranscriptomic data to gain a functional perspective on how dietary composition is associated with the gut microbiota and hypothesized implications for host physiology. Data were derived from a tightly controlled, randomized cross-over feeding study conducted in a metabolic ward, where participants consumed two isocaloric and eucaloric diets differing in food processing and fiber content: A Western Diet (WD) limited in fiber, resistant starch, and whole foods and a Microbiome Enhancer Diet (MBD) composed of fiber-rich, whole foods. Our prior findings showed that a WD lead to a resource-limited microbiota enriched in mucin-degrading bacteria that resorted to metabolizing host-derived organic material, while the MBD supported a resource-replete microbiota that primarily metabolized dietary fiber. The objective of this work was to explore these findings more deeply using bioinformatic analyses of metatranscriptomic data. Our analysis showed increased transcription of fiber-degrading enzymes in the MBD and mucin-degrading enzymes in the WD. While in this analysis functional diversity of the gut microbiome was not affected, differences in resistant-starch and fiber content shifted the types of metabolic processes being actively transcribed. The MBD promoted biosynthetic and carbohydrate-fermenting pathways, while the WD was characterized by enzymes for host-glycan and protein degradation. Furthermore, the MBD-supported ecosystem benefits host health via enhanced SCFA production and reduced reliance on host glycan degradation. The WD fostered increased mucin and protein breakdown pathways that yield metabolites that may harm the gut barrier and systemic metabolism.},
}

@article {pmid41280098,
year = {2025},
author = {Poyet, M and Rühlemann, M and Schaan, AP and Ma, Y and Moitinho-Silva, L and Wacker, EM and Jebens, H and Patel, L and Nguyen, LTT and Zimmer, A and Plichta, D and McDonald, D and Stevens, C and Agyei, A and Afihene, MY and Asibey, SO and Awuku, YA and Badiane, AS and Ching, LS and Corzett, C and Deme, A and Dominguez-Rodrigo, M and Duah, A and Fezeu, A and Froment, A and Gibbons, S and Girard, C and Hooker, J and Ibrahim, F and Iqaluk, D and Juimo, V and Kettunen, P and Lafosse, S and Lango-Yaya, E and Lehtimäki, J and Lim, YAL and Mabulla, A and Mahachai, V and Mohamed, RS and Moniz, K and Mwikarago, IE and Nartey, YA and Ndiaye, D and Noel, M and Onyekwere, C and Pin, TM and Plymoth, A and Roberts, L and Ruokolainen, L and Rusine, J and Segurel, L and Shapiro, BJ and Sigwazi, S and Sistiaga, A and Valles, K and Vatanen, T and Vilaichone, RK and Rosenstiel, P and Baines, J and Franke, A and Ellinghaus, D and Knight, R and Daly, M and Xavier, RJ and Alm, EJ and Groussin, M},
title = {Industrialization drives convergent microbial and physiological shifts in the human metaorganism.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.20.683358},
pmid = {41280098},
issn = {2692-8205},
abstract = {Understanding how host lifestyle and industrialization shape the human gut microbiome and intestinal physiology requires multimodal analyses across diverse global host contexts. Here, we generate multivariate data from the Global Microbiome Conservancy cohort, including gut microbiome, IgA-sequencing, host genotyping, diet, lifestyle and fecal biomarker profiles, to investigate host-microbiome interactions across gradients of industrialization and geography. We show that industrialization is associated with homogenized microbial compositions, reduced microbial diversity, and lower community stability, independent of host confounders. We further show that industrialization is linked to elevated markers of gut stress, increased IgA secretion, and altered patterns of IgA-bacteria interactions. Finally, we show that microbiome-based disease predictors trained on industrialized populations lose accuracy in less industrialized cohorts, highlighting limited cross-population transferability. Together, our results suggest profound restructuring of host-microbiome interactions due to industrialized lifestyles, and emphasize the need for inclusive, globally representative data to improve translational microbiome applications across diverse human populations.},
}

@article {pmid41280077,
year = {2025},
author = {Diaz, L and Kong, AX and Zhang, P and Chi, J and Pham, K and Johnson, M and Eno, A and Douglas, I and Mao, Y and MacDonald, JW and Cui, JY and Bammler, T and Gu, H and Geng, Y},
title = {Butyrate rescues chlorpyrifos-induced social deficits through inhibition of class I histone deacetylases.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41280077},
issn = {2692-8205},
abstract = {Chlorpyrifos (CPF) is a widely used organophosphate pesticide effective through inhibiting acetylcholinesterase, which leads to the accumulation of acetylcholine and continuous nerve stimulation. In addition to its well-known acute toxicity, exposure to CPF has also been linked to chronic conditions such as an increasing risk of autism spectrum disorder (ASD) and adverse effects on gut health, including disturbances to the gut microbiome and metabolism. However, the underlying mechanism of CPF's contribution to ASD remains unclear, and the roles of the gut microbiome and gut metabolites in CPF-induced neurodevelopmental toxicity remain elusive. Using a high-throughput social behavior assay, we found that embryonic exposure to CPF induced lasting social deficits in zebrafish. Through a small-scale screen of common health beneficial gut microbiome metabolites, we discovered that butyrate effectively rescued CPF-induced social deficits. RNA sequencing of zebrafish brain tissues revealed that early exposure to CPF induced a lasting suppression of neuronal genes, including many ASD risk genes, and elevated expression of circadian genes. Butyrate partially reversed the suppression of key neuronal genes. Butyrate is a non-selective inhibitor of histone deacetylases (HDACs). Through a series of loss-of-function experiments utilizing CRISPR-Cas9-induced knockouts and selective chemical inhibitors, we found that the class I HDAC, HDAC1, most likely mediates butyrate's rescue effect. Metabolomics analysis detected changes in several nitrogen metabolism-related pathways in the zebrafish gut following CPF exposure. Metagenomics analysis revealed an increase in abundance of the denitrifying bacteria Pseudomonas and a reduction in the nitric oxide-sensitive bacteria Aeromonas in the CPF-exposed zebrafish gut microbiome. Our results connect CPF-exposure with changes in the gut microbiome, metabolome, epigenetics, gene expression, and behavior, inspiring a novel hypothesis for the underlying molecular mechanisms of CPF-induced neurodevelopmental toxicity. In the long run, our findings may help elucidate how CPF exposure contributes to autism risk and inspire therapeutic developments.},
}

@article {pmid41280015,
year = {2025},
author = {Fulcher, JA and Hoff, NA and Li, F and Mukadi, P and Musene, K and Gerber, SK and Halbrook, M and Mwamba, GN and Kabamba, M and Tobin, NH and Muyembe-Tamfum, JJ and Aldrovandi, GM and Rimoin, AW},
title = {Gut microbiome associations with poliovirus vaccine seroconversion in children in the Democratic Republic of the Congo.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.13.682144},
pmid = {41280015},
issn = {2692-8205},
abstract = {BACKGROUND: Despite efforts to increase global immunization, vaccination seroconversion in low and middle income countries (LMICs) is often lower than in high income countries (HICs). The reasons for this disparity are not fully understood. Given the role of the gut microbiome in immune development, we investigated the relationship between the gut microbiome and polio vaccine seroconversion in children in the Democratic Republic of the Congo (DRC).

METHODS: This cross-sectional analysis included children ages 6-24 months old (n=90) enrolled in the DRC. Vaccine history was obtained from health records and/or self-report and poliovirus serostatus surveyed using dried blood spots. Nutritional status was evaluated using anthropomorphic measures. Microbiome profiling (16S rRNA gene) was performed and associations with poliovirus serostatus and malnutrition were examined.

RESULTS: The average age of the study population was 13.6 months (SD=5.6) with 58% female. Poliovirus seropositivity was 65.5% and 22% of the children were malnourished. We found that presence of Campylobacter and Veillonella , especially at an early age, was associated with low poliovirus vaccination seroconversion. These bacterial taxa differed from those associated with malnutrition.

CONCLUSIONS: The presence of enteropathogens such as Campylobacter at a young age could be an important factor contributing to low vaccination seroconversion in children in LMICs.},
}

@article {pmid41279994,
year = {2025},
author = {Jiang, T and Shen, Y and Li, X and Kozlowski, MJ and Jeffrey, PD and Groves, JT and Rabinowitz, JD and Conway, JM},
title = {Engineering auxin degradation into root-associated bacteria promotes plant growth.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.25.684584},
pmid = {41279994},
issn = {2692-8205},
abstract = {Overproduction of indole-3-acetic acid (IAA) by rhizosphere bacteria disrupts auxin homeostasis and induces root growth inhibition (RGI) in plants. Bacteria from the genus Variovorax mitigate this effect by degrading IAA, and in our prior work we identified the iad locus as being required for this activity. Here, we refine our understanding of the iad pathway using bacterial genetics, metabolomics, and isotope tracing to assign roles to individual Iad pathway enzymes and show that IadDE, though resembling a Rieske dioxygenase, functions instead as a monooxygenase that initiates catabolism via a novel intermediate. Guided by these insights, we installed chromosomal iad cassettes into root-associated commensals (Polaromonas MF047 and Paraburkholderia MF376), creating the first engineered bacteria that reprogram rhizosphere auxin homeostasis in microbially complex environments to benefit the plant. In natural soil, engineered Paraburkholderia enhanced plant biomass, and community profiling revealed no significant differences in microbiome composition between engineered and wild type treatments, supporting that auxin degradation conferred plant benefit without broader disruption of the rhizosphere community. Together, this work refines the pathway logic of microbial auxin degradation and demonstrates that commensals can be rationally engineered to deliver auxin-balancing functions in complex rhizosphere microbiomes. More broadly, it provides a framework for leveraging mechanistic insight to engineer plant-associated commensals that enhance plant growth, laying the foundation for deployment in agricultural settings.},
}

@article {pmid41279986,
year = {2025},
author = {Hensen, T and Khatib, L and Patel, L and McDonald, D and González, A and MahmoudianDehkordi, S and Blach, C and , and Knight, R and Kaddurah-Daouk, R and Thiele, I},
title = {Personalised whole-body modelling links gut microbiota to metabolic perturbations in Alzheimer's disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.28.685084},
pmid = {41279986},
issn = {2692-8205},
abstract = {The human gut microbiome has been linked to metabolic disturbances in Alzheimer's disease (AD). However, the mechanisms by which gut microbes might influence metabolic dysfunction in AD remain poorly understood. Previously, we used constraint-based metabolic modelling to associate an increased risk of AD with altered production of microbiome-derived metabolites. In this study, we investigated whether these previous results can also be identified in AD patients. Therefore, we created personalised whole-body metabolic models from gut metagenomics samples from 34 AD dementia patients, 51 individuals with mild cognitive impairments, and 298 healthy controls. These in silico models were profiled to predict the metabolic influences of gut microbiomes on blood metabolites with previously reported alterations in AD. We found an increased capacity of AD host-microbiome co-metabolism to produce S-adenosyl-L-methionine, L-arginine, creatine, taurine, and formate in the blood of AD dementia patients and patients with mild cognitive impairments. The metabolic predictions were then mechanistically linked to gut microbial changes in AD. This analysis identified that increased relative abundances of Bacteroides uniformis and Bacteroides thetaiotamicron were key factors driving the predicted metabolic changes. Furthermore, the predicted altered microbial influences on blood metabolites were also associated with allelic variations in the APOE risk gene in healthy individuals, which confirmed our previous findings. In conclusion, we identified blood metabolites whose perturbations in AD may be influenced by gut microbiota and predicted the key microbial drivers for these metabolic influences. These findings may facilitate the development of microbiome-informed treatments of AD.},
}

@article {pmid41279985,
year = {2025},
author = {Aleman, J and Vernetti, L and Schurdak, ME and DeBiasio, R and LaRocca, G and Yechoor, VK and Taylor, DL and Stern, AM and Miedel, MT},
title = {Recapitulation of clinical and molecular hallmarks of lipid-induced hepatic insulin resistance in a zonated, vascularized human liver acinus microphysiological system during metabolic dysfunction-associated steatotic liver disease (MASLD) progression.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.02.686163},
pmid = {41279985},
issn = {2692-8205},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts ca. 30% of the global population and is very heterogeneous making it a challenge to produce therapeutics. The heterogeneity arises from genetics, co-morbidities, the microbiome and lifestyle. To help address this challenge, we have refined the human vascularized liver acinus microphysiological system (vLAMPS), which provides an all-human platform for drug development, in line with recently updated federal requirements for the use of New Approach Methodologies (NAMs). By introducing clinically relevant media perturbations and employing several diverse and reproducible in situ and systemic measurements, we show that the vLAMPS can recapitulate key structural and functional aspects of normal physiology, acinus zonation, and all stages of MASLD progression including stellate cell activation and fibrosis. Importantly, in this study we also demonstrate that several hallmarks of lipid-induced hepatic insulin resistance paralleled MASLD progression. These included diminution of insulin receptor substrate 2 (IRS2) protein, compromised insulin receptor mediated insulin clearance, enhanced pericentral lipid accumulation, increased VLDL secretion, and enhanced hepatic glucose output mediated by increased periportal nuclear translocation of FOXO1. These results suggest that the mechanisms underlying MASLD progression in vLAMPS are clinically relevant and support the tenable hypothesis that the hepatic insulin resistant state plays both a causal and consequential role in a vicious cycle driving disease progression.},
}

@article {pmid41279900,
year = {2025},
author = {Li, L and Smardz, M and Soh, D and Marsh, PD and Hoare, A and Diaz, PI},
title = {The Impact of Serum on a Complex Synthetic Community Model of the Subgingival Microbiome.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.07.681017},
pmid = {41279900},
issn = {2692-8205},
abstract = {Despite rapid advances in characterizing the human microbiome, the ecological pressures shaping its transitions from healthy to diseased states remain poorly resolved. This is particularly true for periodontitis, a slow-progressing chronic inflammatory disease associated with well-defined shifts in the subgingival microbiome. Here, we report the development of a complex synthetic community model of the subgingival microbiome, designed for systematic interrogation of ecological factors that drive community restructuring. The model includes 22 prevalent and abundant subgingival species maintained in mucin-rich medium under microaerophilic, continuous culture conditions, in a chemostat. Using this system, we interrogated the impact of serum, as a surrogate for the inflammatory exudate, on community structure and function. Through integrated 16S rRNA gene sequencing, metatranscriptomics, and metabolomics, we found that serum was not required for a community with a periodontitis-like configuration to establish, but its presence intensified features of dysbiosis. Serum increased total biomass, promoted polymicrobial aggregate formation, promoted nitrogen and protein metabolism thereby modifying the environmental pH towards alkalinity, and introduced nitrosative stress. Serum also modified the community metatranscriptome in ways that paralleled microbiome activities in human periodontitis. Serum, however, decreased community diversity by disproportionally conferring a competitive advantage to the pathogen Porphyromonas gingivalis . This synthetic community model has revealed serum as a key nutritional pressure that modulates subgingival microbiome ecology and may perpetuate dysbiosis.},
}

@article {pmid41279814,
year = {2025},
author = {Lucas, A and Reale, M and Wolf, YI and Duong, B and Zhang, Y and Wickramasinghe, J and Behlman, L and Jones, SM and Higgins, S and Moustafa, AM and Elbasir, A and Amaravadi, R and Mitchell, T and Huang, A and Auslander, N},
title = {Taxonomy-free fecal microbiome profiles enable robust prediction of immunotherapy response and toxicity in melanoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.06.686285},
pmid = {41279814},
issn = {2692-8205},
abstract = {The gut microbiome has been causally linked to the efficacy of immune-checkpoint inhibitor therapy (ICI), prompting numerous clinical trials of microbiome-targeting strategies. Yet, mechanisms by which gut microbiota shape immune responses remain elusive as taxonomic biomarkers have failed to generalize across multiple cohorts. In this study, we develop a taxonomy-agnostic framework to identify microbial biomarkers of ICI response and immune-related adverse event (irAE) occurrence from metagenomic sequencing. Applying this approach to four independent melanoma cohorts from clinical centers across the United States, we uncover gut microbial proteins produced by diverse bacterial taxa that consistently predict ICI response. Notably, we uncover a previously uncharacterized operon involved in cellular redox homeostasis that is encoded by different bacteria and reliably predicts irAE occurrence. We further validated the predictive power of this operon in a prospectively sequenced melanoma cohort. Our results demonstrate that taxa-agnostic microbial protein biomarkers are robust, generalizable, and provide a path towards pretreatment risk stratification for melanoma patients initiating ICI therapy.},
}

@article {pmid41279663,
year = {2025},
author = {Li, Y and Diaz-Tang, G and Han, S},
title = {Human gut Bifidobacteria strains regulate host longevity via shared and divergent mechanisms in C. elegans.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279663},
issn = {2692-8205},
abstract = {The human gut microbiome influences many aspects of host aging physiology. However, it is not clear how distinct bacterial strains interact with host aging pathways and different healthspan metrics. To investigate this question, we chose Bifidobacteria as our bacterial model. The Bifidobacteria genus contains diverse species that are enriched in both human infants and centenarians, suggesting that they may confer "youthful" effects in aging adults. We selected eleven strains from nine Bifidobacteria species that are commonly detected in human fecal samples. Using our human anaerobic gut bacteria-C. elegans aging platform, we examined 1) individual Bifidobacteria strains' contribution to lifespan and healthspan and 2) their genetic interactions with the conserved, longevity-associated transcriptional regulators. We identified two B. longum and B. infantis strains that most strongly increased lifespan and stress resistance. Notably, these two strains act through shared (e.g., ATFS-1/ATF5, HSF-1/HFS1, and SKN-1/NRF2) and yet strain-specific pathways (e.g., NHR-49/PPARα for B. infantis) to enhance both lifespan and oxidative stress protection. Lastly, both strains activate a panel of genes involved in molecular chaperone, antioxidant, and lipid remodeling activities, serving as candidate cytoprotective mechanisms for further investigations. In summary, this study establishes a framework of dissecting the mechanistic links between human anaerobic gut bacteria and conserved host aging pathways that can be applicable beyond Bifidobacteria. While the connections between gut microbiome and aging in humans are complex, our approach provides the beginning steps to uncover strain-level interactions that may ultimately inform targeted probiotic strategies for promoting healthy aging.},
}

@article {pmid41279627,
year = {2025},
author = {Rodriguez, MT and Olmstead, SJ and McLaurin, KA and Mactutus, CF and Booze, RM},
title = {S-Equol: A Novel Therapeutic For HIV-1-Associated Gastrointestinal Dysbiosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.05.686823},
pmid = {41279627},
issn = {2692-8205},
abstract = {HIV-1 infection affects approximately 38.4 million people around the world. The advent of combination anti-retroviral therapy (cART) has greatly improved the quality of life of infected individuals; however, roughly 50% of these individuals will still experience HIV-1-associated neurocognitive disorders (HAND). Additionally, the gastrointestinal microbiome has been reported to be dysbiotic in HIV-1 infected individuals, regardless of adherence to cART. Current research has pointed to the gut-brain-microbiota axis as a potential target to treat both cognitive deficits and microbial changes. The present study investigated S-Equol (SE) as a potential therapeutic for HAND by modulating the gastrointestinal microbiome. The study included 21 HIV-1 Tg rats and 21 F344 control animals to test the effect 0.2mg SE has on cocaine-maintained responding on a PR schedule of reinforcement. Gastrointestinal microbiome alterations between genotypes were found at the phylum and genus level, regardless of treatment group, and SE treatment had both main effects and interactions with genotype. Prevotella_UCG_001 was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes.},
}

@article {pmid41279619,
year = {2025},
author = {Weingarden, AR and Dahlberg, FS and Broude, CN and Meng, X and Jain, S and Weakley, AM and Cabrera, AV and Dileepan, T and Fischbach, MA and Jenkins, MK},
title = {Gut microbial composition modulates food-specific CD4 [+] T cells in food allergy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.27.684919},
pmid = {41279619},
issn = {2692-8205},
abstract = {The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4 [+] T cells are affected by gut microbial composition. Here, we report that food allergy severity differs between mice obtained from two different specific pathogen-free mouse vendors (Jackson Labs [Jax] and Taconic Biosciences [Tac]). Mice from Tac develop diarrhea and anaphylaxis after fewer allergen exposures than mice from Jax. Using food allergen peptide:MHCII tetramers, we also find that Tac mice have fewer allergen-specific regulatory T cells in the small intestine compared to mice from Jax. In addition, Tac mice have a greater abundance of small intestinal mucosal mast cells and increased intestinal permeability. The increased food allergy severity phenotype is transferable via co-housing, which corresponds to a shift in Jax microbial communities towards those found in Tac mice. Our findings demonstrate for the first time that food allergen-specific Treg cells can be modulated by gut microbial community composition, which in turn is correlated to food allergy severity.},
}

@article {pmid41279522,
year = {2025},
author = {Arnold, J and McClure, S and Glazier, J and Ahan, RE and Shakya, S and Villegas, D and Chen, TL and Fuerte-Stone, J and McGann, R and Mimee, M},
title = {Engineering butyrate-producing Lachnospiraceae to treat metabolic disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.08.687059},
pmid = {41279522},
issn = {2692-8205},
abstract = {Engineering native gut bacteria offers a route to persistent, programmable therapeutics, yet many dominant taxa remain genetically intractable. Lachnospiraceae are a prevalent and abundant family in the human gut microbiome, possessing metabolic functions generally associated with health [1] . Despite their promise as engineered live biotherapeutics, genetic manipulation of Lachnospiraceae remains challenging. Here, we develop a modular toolkit for Lachnospiraceae engineering, including constitutive and inducible expression and chromosomal integration systems. Applying this toolkit to the native commensal Coprococcus comes , we program secretion of the mammalian cytokine interleukin-22 (IL-22) in the mouse intestinal tract where it elicits ileal transcriptional responses consistent with cytokine signaling. In a mouse model of metabolic associated steatotic liver disease, IL-22-secreting C. comes improves glucose homeostasis and attenuates hepatic steatosis. This work demonstrates that a native Lachnospiraceae chassis can be genetically programmed to modulate host metabolic and immune physiology. The toolkit provides a generalizable foundation for Lachnospiraceae-derived microbiome therapeutics and for probing causal links between Lachnospiraceae gene programs and host phenotypes.},
}

@article {pmid41279320,
year = {2025},
author = {AbuSalim, JE and Olszewski, K and Youssef, S and Hunter, CJ and MacArthur, MR and Henneberg, A and Ryseck, RP and Opitz, CA and Donia, MS and Rabinowitz, JD},
title = {Many circulating indole and phenol metabolites are host derived.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.05.680522},
pmid = {41279320},
issn = {2692-8205},
abstract = {Indole and phenol metabolites are typically thought to be products of bacterial digestion of tryptophan (indoles) and phenylalanine or tyrosine (phenols). Interest in controlling gut microbial production of these metabolites has continually grown as they have important physiological impacts, with indoles agonizing AhR signaling, and phenols being associated with healthy body weight. While there is a growing wealth of research into which bacteria produce these metabolites, host contribution to their circulating pools has not been adequately characterized. Here, through stable isotope tracing in cell culture and mice, we show that mammalian cells can make aryl-pyruvates, -lactates, -acetates, and -carboxylic acids. Levels of these metabolites in mice and human patients are insensitive to perturbations of the microbiome. In contrast, bacterial metabolism is required to synthesize aryl-propionates and free indole, phenol, and cresol. Overall, we show that host metabolism is a primary contributor to circulating indole and phenol metabolite pools.},
}

@article {pmid41279291,
year = {2025},
author = {Camargo, AP and Baltoumas, FA and Ndela, EO and Fiamenghi, MB and Merrill, BD and Carter, MM and Pinto, Y and Chakraborty, M and Andreeva, A and Ghiotto, G and Shaw, J and Proal, AD and Sonnenburg, JL and Bhatt, AS and Roux, S and Pavlopoulos, GA and Nayfach, S and Kyrpides, NC},
title = {A genomic atlas of the human gut virome elucidates genetic factors shaping host interactions.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.686033},
pmid = {41279291},
issn = {2692-8205},
abstract = {Viruses are key modulators of human gut microbiome composition and function. While metagenomic sequencing has enabled culture-independent discovery of gut bacteriophage diversity, existing genomic catalogues suffer from limited geographic representation, sparse taxonomic classification, and insufficient functional annotation, hindering detailed investigation into phage biology. Here, we present the Unified Human Gastrointestinal Virome (UHGV), a collection of 873,994 viral genomes from globally diverse populations that addresses these limitations. UHGV provides high-quality virome references with extensive host predictions, comprehensive functional annotations, protein structures, a classification framework for comparative analysis, and a web portal to facilitate data access. Using UHGV to profile worldwide metagenomes, we found that host range breadth is strongly associated with phage prevalence. Additionally, we identified diversity-generating retroelements and DNA methyltransferases as key factors enabling phage populations to access diverse hosts, revealing how specific genomic features contribute to global phage distribution patterns. UHGV is available at http://uhgv.jgi.doe.gov.},
}

@article {pmid41279255,
year = {2025},
author = {Plominsky, AM and Oliver, A and Henriquez-Castillo, C and Podell, S and Minich, JJ and Augyte, S and Lowell-Hawkins, J and Sims, NA and Allen, EE},
title = {Detoxifying and depolymerizing microorganisms reveal intertwined guild collaborations in the gut microbiome of a generalist macro-algivorous fish.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.04.686673},
pmid = {41279255},
issn = {2692-8205},
abstract = {UNLABELLED: The biotransformation of macroalgal biomass represents a major catabolic challenge due to its structurally diverse polysaccharides and inhibitory polyphenols. Unlike terrestrial lignocellulosic substrates, macroalgae polysaccharides contain multiple monomer types, branching patterns, and sulfation states. Additionally, macroalgae polyphenols have been shown to inhibit both microbial growth and their catalytic enzymes. While herbivorous fishes have evolved specialized gut microbiota to process these substrates, the enzymatic pathways remain poorly characterized, with few experimentally validated polysaccharide utilization loci or biochemically defined marine sulfatases, and limited understanding of polyphenol degradation. Here, we developed in vitro microcosms, based on the gut microbiome of the generalist macro-algivorous fish Kyphosus cinerascens , to temporally resolve the activity of the microbial guilds involved in macroalgal polysaccharide and polyphenol transformation. First, parallel cDNA/DNA amplicon sequencing were employed to distinguish the natural active fraction from transient gut microbiome taxa. Four media combinations were able to propagate between 96% to 99% of the active hindgut microbial families, reproducing the cooperative degradation dynamics observed in vivo . Metagenomic and metatranscriptomic profiling of these four optimized in vitro microcosms served as models to assess the stepwise functional successions occurring in the natural gut microbiome. Early Gammaproteobacteria expressed enzymes linked to polyphenol detoxification and alginate degradation, followed by Bacillota, Bacteroidota, and Verrucomicrobiota guilds targeting more recalcitrant sulfated polysaccharides and polyphenols. Together, these results identified temporal and taxonomic coordination as key features of macroalgal biomass deconstruction, providing an experimentally tractable model for discovering novel carbohydrate-active enzymes and elucidating poorly understood pathways of marine polyphenol degradation.

IMPORTANCE: Seaweed represents a source of sustainable biomass for various applications, but scalable industrial methods struggle to break down seaweed biomass into intermediate products due to the complexity of its constituents. Fish of the genus Kyphosus feed on different seaweed types by leveraging gastrointestinal bacteria to neutralize inhibitory polyphenols and convert their polysaccharides into simple sugars. This study identifies microbial groups that are transcriptionally active in natural fish hindgut microbiomes to propagate these active microbial communities in vitro . This enabled assessing how distinct microbial guilds act in succession to transform complex polysaccharides and polyphenols. Notably, this is the first study to assess the biotransformation capacities of macroalgal polyphenols by complex in vitro hindgut microbiomes of a generalist herbivorous fish. These findings advance our ecological understanding of cooperative degradation in marine gut symbioses and establish a tractable platform for discovering new enzymes and pathways with potential applications in algal biomass utilization.},
}

@article {pmid41279230,
year = {2025},
author = {Mahalingam, S and Carulli, EM and Mao, J and Stephens, KK and Erickson, JA and Winuthayanon, W},
title = {Vaginal epithelial estrogen receptor α coordinates glycogen deposition, microbial stability, and pH regulation in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.29.685365},
pmid = {41279230},
issn = {2692-8205},
abstract = {UNLABELLED: Estrogen plays a central role in regulating the vaginal environment, but the specific contribution of epithelial estrogen receptor α (ESR1) to microbial and biochemical homeostasis has not been fully defined. In our previous work, we showed that epithelial ESR1 is indispensable for estrogen-induced epithelial proliferation, cornification, and MUC1 expression. Here, using mice with conditional deletion of Esr1 in vaginal epithelial cells, called epithelial Esr1 [d/d] , we extend these findings to demonstrate that epithelial ESR1 also regulates glycogen deposition, luminal pH, and microbial stability. Compared to control littermates, epithelial Esr1 [d/d] mice reduced glycogen abundance, elevated vaginal pH, and a compositional shift in the vaginal microbiome, marked by enrichment of Comamonadaceae and loss of Lactobacillus species, without significant differences in alpha diversity. These changes parallel features of postmenopausal dysbiosis in women. Together, our findings identify epithelial ESR1 as a master regulator of multiple pathways that sustain vaginal homeostasis, integrating epithelial metabolism, barrier function, and host-microbe interactions. This work provides a mechanistic framework to understand postmenopausal vaginal dysbiosis and suggests epithelial estrogen signaling as a potential therapeutic target for genitourinary syndrome of menopause.

SIGNIFICANCE STATEMENT: The vaginal environment is essential for reproductive and gynecologic health, yet the mechanisms by which estrogen shapes this niche remain incompletely understood. We show that epithelial estrogen receptor α (ESR1) regulates glycogen deposition, luminal pH, and microbial composition in the murine vagina. Loss of epithelial ESR1 reduced glycogen and increased luminal pH without altering overall microbial diversity, but shifted community structure toward enrichment of Comamonadaceae , a family associated with neutral to mildly alkaline environments. These findings identify epithelial ESR1 as a key regulator of the metabolic and physicochemical conditions that maintain vaginal microbial balance and provide a mechanistic framework for understanding postmenopausal dysbiosis.},
}

@article {pmid41279171,
year = {2025},
author = {Okyere, L and Fulvio, AD and Gaulke, C},
title = {Long Term Culture of Germ-Free Zebrafish Using Gamma-Irradiated Feeds.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.09.681431},
pmid = {41279171},
issn = {2692-8205},
abstract = {UNLABELLED: Host associated microbiota play essential roles in regulating digestion, nutrient acquisition, immunity, and xenobiotic metabolism. Disruption of these communities is linked to numerous diseases and health defects though causal mechanisms underpinning these associations remain unclear in most cases. Gnotobiotic zebrafish provide a scalable low-cost in vivo model that is increasingly used to resolve causality in host-microbiota interactions. However, reliance on live diets limits the use of gnotobiotic zebrafish to early life stages where body systems and microbial communities are incompletely developed. As a result, many important host-microbiota interactions may be unable to be studied in this model system. Here we tested a simple method for long-term husbandry of gnotobiotic zebrafish using gamma-irradiated chow diets and evaluated effects on growth, gene expression, and microbial community composition. In conventionally reared animals, gamma irradiated diets did not affect growth or survival and only modestly impacted microbial community composition and diversity. In contrast, gnotobiotic zebrafish maintained on sterile irradiated diets for 55 days post fertilization were smaller, weighed less, and exhibited aberrant genes expression profiles relative to controls. These genes were enriched for pathways, related to immune response, xenobiotic metabolism, organ development, liver function, and lipid metabolism, with many expression patterns linked to the abundance of specific microbial taxa. Together, these findings establish a practical protocol for long-term maintenance of gnotobiotic zebrafish and extend the utility of this model to study microbiome-dependent effects on host physiology, and development beyond early larval stages of life.

IMPORTANCE: While the gnotobiotic zebrafish have been a powerful model for interrogation of host-microbiota interactions, their use has been limited to early life stages due to complications of long-term husbandry. To address this limitation, we developed a simple protocol that enables rearing germ-free zebrafish well beyond larval stages. Germ free fish exhibit physiological and developmental defects that mirror those described in mammalian counterparts supporting a conserved role for microbiota in vertebrate development and physiology. Our protocol provides a method to investigate microbial influences on adaptive immunity, metabolism, and chronic disease processes in zebrafish not possible with current methodologies. Given the rapid and simple methods for gnotobiotic derivation and the large number of transgenic animal lines available for zebrafish we anticipate this model will accelerate mechanistic discovery of microbial impacts on host health.},
}

@article {pmid41278968,
year = {2025},
author = {Mahen, KK and Massey, WJ and Orabi, D and Brown, AL and Jaramillo, TC and Burrows, AC and Horak, AJ and Dutta, S and Mrdjen, M and Mouannes, N and Varadharajan, V and Osborn, LJ and Ye, X and Yarbrough, DM and Grubb, T and Zajczenko, N and Hohe, R and Banerjee, R and Linga, P and Laungani, D and Hajjar, AM and Sangwan, N and Dwidar, M and Buffa, JA and Swanson, GR and Wang, Z and Brown, JM},
title = {Gut Microbe-Derived Trimethylamine Shapes Circadian Rhythms Through the Host Receptor TAAR5.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.03.647082},
pmid = {41278968},
issn = {2692-8205},
abstract = {UNLABELLED: Elevated levels of the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) are associated with cardiometabolic disease risk. However, the mechanism(s) linking TMAO production to human disease are incompletely understood. Initiation of the metaorganismal TMAO pathway begins when dietary choline and related metabolites are converted to trimethylamine (TMA) by gut bacteria. Gut microbe-derived TMA can then be further oxidized by host flavin-containing monooxygenases to generate TMAO. Previously, we showed that drugs lowering both TMA and TMAO protect mice against obesity via rewiring of host circadian rhythms. Although most mechanistic studies in the literature have focused on the metabolic end product TMAO, here we have instead tested whether the primary metabolite TMA alters host metabolic homeostasis and circadian rhythms via trace amine-associated receptor 5 (TAAR5). Remarkably, mice lacking the host TMA receptor (Taar5 [-/-]) have altered circadian rhythms in gene expression, metabolic hormones, gut microbiome composition, and diverse behaviors. Also, mice genetically lacking bacterial TMA production or host TMA oxidation have altered circadian rhythms. These results provide new insights into diet-microbe-host interactions relevant to cardiometabolic disease, and implicate gut bacterial production of TMA and the host receptor that senses TMA (TAAR5) in the physiologic regulation of circadian rhythms in mice.

HIGHLIGHTS: Mice lacking the host TMA receptor (Taar5 [-/-] [)] have altered circadian rhythms. Taar5 [-/-] mice have altered innate behaviors in a time of day dependent manner. The normal circadian oscillations in the gut microbiome are dysregulated in Taar5 [-/-] mice. Genetic deletion of bacterial TMA production or host TMA oxidation shapes circadian rhythms.},
}

@article {pmid41278862,
year = {2025},
author = {Liu, J and Coker, MO and Osazuwa-Peters, N and Peter, O and Idemudia, NL and Schlecht, NF and Obuekwe, O and Eki-Udoko, FE and Bromberg, Y},
title = {Whole Metagenome Sequencing: not Deep Enough for Complete Microbial Function Recovery.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.04.685665},
pmid = {41278862},
issn = {2692-8205},
abstract = {BACKGROUND: Whole metagenome shotgun sequencing (WMS) is widely used to profile microbial function. However, technical variability in sequencing and analysis often obscures true biological patterns. Large-scale studies are particularly susceptible to batch effects, such as differences in sequencing depth and platform and annotation strategies, as well as sample-to-flow-cell assignments. However, the relative effects of these factors on functional inference in such studies have yet to be systematically evaluated.We analyzed oral-rinse WMS data from a study cohort including 671 Nigerian youths aged 9-18, sequenced on two Illumina platforms. Microbial molecular functionality encoded in these data were annotated using the mi-faser/Fusion pipeline, to capture the broad functional repertoire, and HUMAnN 3/EC numbers pipeline to characterize curated enzymatic activities. We then quantified how technical factors and batch effects shaped the recovery of microbial functionality.

RESULTS: Three findings of our work were most salient. First, we observed that the choice of annotation strategy traded off between breadth and specificity of functional coverage. Second, we found that low-prevalence functions were disproportionately lost at shallow sequencing depths, indicating that in e.g. case-control studies with few representatives of the minor class, sequencing depth could critically impact study resolution. Finally, using our newly developed model relating sequencing depth to functional recovery, we demonstrated that increasing sequencing depth does not directly or proportionally improve functional recall. That is, at as little as 10% of this study's sequencing depth, 30% of the estimated complete microbiome functional repertoire was detectable. However, even at the full depth used in this study, we were only able to recover an estimated 60% of that complete functional repertoire.

CONCLUSIONS: Together, these findings and our depth-to-function mapping framework provide practical guidelines for the design and interpretation of WMS studies. Coordinating sequencing depth planning with annotation strategy, experimental design, and rigorous batch control is thus essential for robust detection of microbial functions and for ensuring reproducible microbiome insights.},
}

@article {pmid41278757,
year = {2025},
author = {Luo, RS and Kille, B and Vaughan, EE and Clark, JR and Maresso, AW and Nute, MG and Treangen, TJ},
title = {Strainify: Strain-Level Microbiome Profiling for Low-Coverage Short-Read Metagenomic Datasets.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.10.681738},
pmid = {41278757},
issn = {2692-8205},
abstract = {MOTIVATION: Strain-level microbiome profiling has revealed key insights into microbial community composition and strain dynamics. However, accurate strain-level analysis remains challenging due to limited linkage information, ambiguous read mapping, and complicating factors such as genome similarity, sequencing depth, and community complexity. These challenges are especially pronounced for short-read metagenomic data when estimating the relative abundances of multiple strains, a task critical for genotype-phenotype association studies.

RESULTS: To address this gap, we present Strainify, which enables accurate strain-level abundance estimation from short-read metagenomes with as little as 1% genome coverage. Specifically, Strainify combines (1) identification of informative variants via core genome alignment, (2) filtering of confounding variants via a window-based test, and (3) maximum likelihood estimation of strain abundances. A Shannon entropy-weighted version of the model further improves robustness in noisy, low-coverage settings by downweighting sites with low information content. Across simulated communities of varying complexity, Strainify consistently outperformed existing approaches. On mock community sequencing data, Strainify's estimates aligned more closely with reference abundances. When applied to a longitudinal gut microbiome dataset, Strainify successfully recapitulated the reported temporal dynamics of Bacteroides ovatus strain groups, demonstrating its ability to recover biologically meaningful patterns from real-world metagenomes. Together, these results establish Strainify as a robust and versatile solution for accurate strain-level abundance estimation in short-read, low-coverage microbiome studies.

AVAILABILITY: The Strainify code and results are available at: https://github.com/treangenlab/Strainify.},
}

@article {pmid41278751,
year = {2025},
author = {Adams, AND and Griffin, LE and Burnie, J and Powers, J and Causey, A and Glick, VJ and Gavitt, M and Richmond-Buccola, D and Kim, C and Ahmad, M and Jackson, M and Keiser, G and Cheng, JL and Kumar, A and Fernando, LD and Vlach, J and Orzalli, MH and Corbett-Helaire, KS and Decout, A and Azadi, P and Gopinath, S},
title = {Gram-positive bacterial cell wall components inhibit herpes simplex virus infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.02.686169},
pmid = {41278751},
issn = {2692-8205},
abstract = {The role of the mucosal microbiome in viral infections remains unclear. Genital herpes, caused by herpes simplex virus 1 and 2 (HSV-1 and HSV-2), is among the most prevalent sexually transmitted infections worldwide. Despite evidence linking vaginal Lactobacillus to protection against sexually transmitted viruses, the specific microbial components and mechanisms that mediate this defense are not well understood. Here, we show that multiple cell wall components from diverse gram-positive bacteria, including lactobacilli, inhibit HSV-1 and HSV-2 infection in cells and in a mouse model of genital herpes infection. Peptidoglycan (PG) and lipoteichoic acid (LTA), both major components of the gram-positive bacterial cell wall, significantly reduced HSV infectivity in vitro and improved survival and disease outcomes in mice. We further showed that Lactobacillus crispatus surface layer proteins SlpA and SlpB bind HSV-1 and inhibit infection. Antiviral effects of cell wall components were dose-dependent, relied on intact PG structure, and, in the case of PG and LTA, were independent of TLR2-mediated host signaling. Collectively, our findings identify a species-independent antiviral function for gram-positive bacterial cell wall components against HSV and suggest that the composition of the mucosal microbiome may play an underappreciated role in suppressing mucosal herpes infection in humans.},
}

@article {pmid41278627,
year = {2025},
author = {Pandey, S and Abu, YF and Singh, P and Roy, S},
title = {Cross-Fostering with control dams rescues Gut Dysbiosis and Chromatin-associated Transcriptional Changes in Offspring of Opioid-Exposed Dams.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.07.687278},
pmid = {41278627},
issn = {2692-8205},
abstract = {Prenatal opioid exposure disrupts gut homeostasis and causes gastrointestinal complications in offspring, but the mechanisms remain unclear. Here using a murine model of prenatal hydromorphone exposure, we examined gut microbiota, intestinal injury, transcriptomic signatures, and chromatin accessibility. Exposed pups displayed marked dysbiosis, epithelial damage, and upregulation of inflammatory gene programs accompanied by relaxed ileal chromatin. Cross-fostering to opioid-naïve dams restored microbial diversity, reestablished metabolite-producing taxa, and reversed injury-associated transcriptional and chromatin changes. Fecal microbiota transplantation from exposed dams recapitulated intestinal injury, indicating a microbiome-driven mechanism. These findings reveal a novel gut-microbiome-epigenome axis underlying opioid-induced injury and highlight early microbial intervention as a potential strategy to mitigate developmental harm.},
}

@article {pmid41278623,
year = {2025},
author = {Arif, S and Nirmalan, S and Alazizi, A and Mair-Meijers, H and Agyei, A and Afihene, MY and Asibey, SO and Awuku, YA and Duah, A and Plymoth, A and Nartey, Y and Roberts, L and Valles, K and Ibrahim, F and Lim, YAL and Pin, TM and Onyekwere, C and Rusine, J and Mwikarago, IE and Alm, EJ and Poyet, M and Groussin, M and Luca, F and Blekhman, R},
title = {Host transcriptional responses to gut microbiome variation arising from urbanism.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.26.683539},
pmid = {41278623},
issn = {2692-8205},
abstract = {Gut microbiomes of urban communities are compositionally different from their rural counterparts, and are associated with immune dysregulation and gastrointestinal disease. However, it is unknown whether these compositional differences impact host physiology, and through what mechanisms. Here, we used human colonic epithelial cells to directly compare host transcriptional changes induced by gut microbiomes from urban versus rural communities. We co-cultured host cells with live, stool-derived gut microbiomes from Rwanda, Ghana, Nigeria, Malaysia, and the United States, and quantified transcriptional responses using RNA-seq. We found that urban microbiomes affected innate immune pathways, including TNF signaling and bacterial antigen recognition. We also found that high-diversity microbiomes elicited a stronger host transcriptional response, while low-diversity microbiomes triggered epithelial restructuring and glycolysis. Finally, specific taxa driving these effects, including Bifidobacterium adolescentis and Bacteroides dorei , correlated with lifestyle factors such as diet. These findings demonstrate that urbanization-associated microbiome changes directly influence host epithelial gene expression.},
}

@article {pmid41278477,
year = {2025},
author = {Chang, L and Liu, Y and Li, H and Yan, J and Wu, W and Chen, N and Ma, C and Zhao, X and Chen, J and Zhang, J},
title = {Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1717696},
pmid = {41278477},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Cirrhosis/microbiology/metabolism/pathology ; Dysbiosis/microbiology ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Animals ; },
abstract = {Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid (SCFA)-producing taxa, particularly Lachnospiraceae and Ruminococcaceae. Meta-analyses indicate that fecal butyrate levels decrease by 40-70%, accompanied by a two- to fourfold increase in endotoxin concentrations. Bile acid profiling demonstrates an approximately 50% reduction in secondary bile acids and significant suppression of FXR/TGR5 signaling, whereas tryptophan metabolism shifts toward the kynurenine pathway, weakening epithelial defense and exacerbating portal hypertension. Clinically, dysbiosis and microbial translocation are associated with higher MELD scores, and patients in the lowest quartile of microbial diversity have a threefold increased risk of hepatic encephalopathy or spontaneous bacterial peritonitis. Microbiome-targeted interventions-including lactulose, rifaximin, probiotics or synbiotics, fecal microbiota transplantation, and bile acid modulators-restore community balance in 70-85% of clinical trials, although efficacy and safety vary by etiology and baseline microbiota composition. Integrated microbiome-metabolome models achieve areas under the curve (AUCs) of 0.82-0.90 for noninvasive classification and early detection of cirrhosis. Collectively, these findings underscore reproducible, quantitative microbiome-metabolite alterations and outline a roadmap for microbiome-informed precision care that connects mechanistic insight with clinical application, emphasizing the need for longitudinal and multi-ethnic validation.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Liver Cirrhosis/microbiology/metabolism/pathology
Dysbiosis/microbiology
Bile Acids and Salts/metabolism
Fatty Acids, Volatile/metabolism
Animals

@article {pmid41278444,
year = {2025},
author = {Gembillo, G and Soraci, L and Visconti, L},
title = {Unveiling the gut-kidney dialogue in diabetic kidney disease.},
journal = {World journal of diabetes},
volume = {16},
number = {11},
pages = {112440},
pmid = {41278444},
issn = {1948-9358},
abstract = {Emerging evidence suggests that intestinal dysbiosis and chronic low-grade inflammation play a critical role in the development and progression of diabetic kidney disease (DKD), particularly in the elderly. Reduced microbial diversity, loss of beneficial genera and over-representation of pathogenic bacteria are closely associated with declining kidney function. There is a possible causal relationship between specific gut microbiota profiles and DKD. Experimental models also show that gut-derived metabolites and altered intestinal permeability can promote renal inflammation, fibrosis and metabolic dysfunction. This editorial discusses the implications of these findings for future research and clinical practice, emphasizing the growing potential of microbiota-targeted therapies. Understanding the gut-kidney axis could ultimately open up new avenues for precision nephrology and metabolic care.},
}

@article {pmid41278153,
year = {2025},
author = {Zhang, LK and Gu, WC and Chen, J},
title = {Unveiling Yiyi Fuzi Baijiang powder: Microecological and network pharmacology approach to ulcerative colitis treatment.},
journal = {World journal of gastroenterology},
volume = {31},
number = {42},
pages = {111708},
pmid = {41278153},
issn = {2219-2840},
mesh = {*Colitis, Ulcerative/drug therapy/microbiology/chemically induced/pathology ; Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects/genetics ; Network Pharmacology ; Molecular Docking Simulation ; Mice ; Disease Models, Animal ; Dextran Sulfate/toxicity ; Humans ; Male ; Powders ; Colon/pathology/drug effects/microbiology ; Signal Transduction/drug effects ; },
abstract = {BACKGROUND: Yiyi Fuzi Baijiang powder (YFB), a classic Chinese medicine, significantly affects ulcerative colitis (UC). However, it remains unclear whether YFB plays a therapeutic role by improving the intestinal flora of UC patients and its active ingredients.

AIM: To explore the mechanisms of action of YFB in treating UC.

METHODS: A mouse model of UC was established by drinking 2.5% dextran sulfate sodium (DSS). Mice were treated with YFB. 16S rDNA sequencing was used to detect changes in intestinal flora and perform functional predictions. Corresponding target genes of core active ingredients in YFB and UC were obtained using multiple database retrievals and then used to predict the mechanism of overlapping targets. After screening core ingredients and target genes, AutoDock software was used for molecular docking, and the best binding target was selected to verify binding activity.

RESULTS: YFB improved DSS-UC mice by restoring body weight, reducing disease activity index, increasing water and food intake, and alleviating diarrhea and local histopathological damage. YFB enhanced beta diversity, decreased pathogenic bacteria such as Turicibacter and Clostridium_sensu_stricto_1, and increased probiotics such as unclassified_f_Lachnospiraceae and Akkermansia. However, it also reduced anaerobic probiotics such as Ruminococcus, Enterorhabdus and Bifidobacterium. Network pharmacology identified 17 pathways, with cancer and adipocytokine signaling pathways showing significant differences in predicting intestinal microbial function. Molecular docking revealed that nuclear factor kappa-B inhibitor A, RELA and NFKB1, and colchamine, morusin and orotinin had docking scores > 5.0.

CONCLUSION: YFB treats UC by reducing harmful bacteria and boosting probiotics to restore intestinal balance, while potentially influencing signaling pathways.},
}

*Colitis, Ulcerative/drug therapy/microbiology/chemically induced/pathology
Animals
*Drugs, Chinese Herbal/pharmacology/therapeutic use
*Gastrointestinal Microbiome/drug effects/genetics
Network Pharmacology
Molecular Docking Simulation
Mice
Disease Models, Animal
Dextran Sulfate/toxicity
Humans
Male
Powders
Colon/pathology/drug effects/microbiology
Signal Transduction/drug effects

@article {pmid41278045,
year = {2025},
author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A},
title = {Retraction: Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {r206},
doi = {10.7759/cureus.r206},
pmid = {41278045},
issn = {2168-8184},
abstract = {[This retracts the article DOI: 10.7759/cureus.85054.].},
}

@article {pmid41277978,
year = {2025},
author = {Blaiotta, G and Ciliberti, I and Aponte, M and Romano, R},
title = {Impact of predation on the bacterial community structure of Mediterranean mussels during depuration.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1647926},
pmid = {41277978},
issn = {1664-302X},
abstract = {The Mediterranean mussel (Mytilus galloprovincialis) is the most valuable shellfish farmed and consumed in the Western Mediterranean. Like any other filter-feeding organism, mussels are exposed to a wide range of microorganisms. Before consumption, bivalves are subject to depuration to purge the gastrointestinal content, thus minimizing the risk of pathogens' circulation. Over time, this strategy revealed several shortcomings, most notably concerning Vibrio spp. In this study, the potential use of autochthonous predatory bacteria as a biocontrol strategy to mitigate Vibrio spp. overgrowth in mussels during depuration was evaluated. Moreover, a polyphasic approach based on conventional and culture-independent strategies was used to assess the impact of predation and of depuration on the mussel microbiome during controlled depuration studies. The depuration greatly impacted the bivalve microbiota, jeopardizing its innate resilience. Moreover, the addition of a bacterial predator strain to mussels resulted in the disturbance of the microbiome. Therefore, even though the biotechnological application of bacterial predation in this context may appear promising when monitored by culture-dependent methods, the effect on the mollusks' microbiome does not seem to be easily predictable, above all when mussels are subject to depuration after the harvest.},
}

@article {pmid41277975,
year = {2025},
author = {Wang, B and Li, W and Xue, N and Xi, R and Wang, Y and Fang, L and Wang, Q and Liang, X and Xiao, Y and Yang, X and Wu, X},
title = {Co-application of biochar and compost enhanced soil carbon sequestration in urban green space.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1707894},
pmid = {41277975},
issn = {1664-302X},
abstract = {The mechanism of biochar and compost as soil amendments in urban green spaces remains unclear. Using Euonymus kiautschovicus as a model system, this study established eight treatment gradients, 0 (CK), single biochar applications: 4% (BC4), 8% (BC8), 12% (BC12), 7.5% compost (COM), and their combinations BCC4 (BC4 + 7.5% COM), BCC8 (BC8 + 7.5% COM), BCC12 (BC12 + 7.5% COM). Through metagenomic sequencing and metagenome-assembled genomes (MAGs) analysis, we investigated soil microbiome structure, carbon sequestration functional genes, and their interactions in response to amendments. The combined application of medium-low dose biochar (4-8%) with compost significantly optimized the physicochemical properties and microbial functions in soils. Compared to single amendments, hybrid treatments synergistically enhanced soil moisture content. Specifically, BCC8 increased by 27% compared to the CK, organic carbon levels reached 12.8 g/kg with BCC12, and available nutrients showed 45% higher available phosphorus with BCC4. Metagenomic analysis revealed that hybrid treatments reshaped microbial community structure, with BCC8 significantly enriching Acidobacteria (8.72%) and Nitrospira (1.42%), driving an increased abundance of carbon fixation genes. Among key carbon fixation pathways, the reductive tricarboxylic acid cycle (rTCA) exhibited the highest gene abundance (mean 15.03), dominated by MAG176. The Calvin-Benson-Bassham (CBB) cycle displayed broad adaptability, with MAG59 identified as a core carbon-fixing strain. This study has significant implications for the application of biochar-compost combinations in carbon management of urban green spaces.},
}

@article {pmid41277974,
year = {2025},
author = {Yang, R and Jia, M and Xu, Y and Wu, Z and Wu, D and Gui, Y},
title = {Correction: Microbiome and metabolome integrated analysis: exploring potential diagnostic approaches for Parkinson's disease using tongue coating samples.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1721341},
doi = {10.3389/fmicb.2025.1721341},
pmid = {41277974},
issn = {1664-302X},
abstract = {[This corrects the article DOI: 10.3389/fmicb.2025.1621468.].},
}

@article {pmid41277963,
year = {2025},
author = {Dwan, C and Das, A and O'Toole, PW and O'Callaghan, TF and Meehan, D and Hennessy, D and Irish, H and Buckley, F and Lahart, B},
title = {Evaluating the rumen microbial community of genetically divergent spring-calving dairy cows grazing grass-only or grass-clover swards at different stages of the grazing season.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1642486},
pmid = {41277963},
issn = {1664-302X},
abstract = {The current study used a culture-independent methodology to investigate the rumen microbiome composition in two genetically divergent groups of spring-calving dairy cows, high (€218) and low (€157) Economic Breeding Index (EBI), grazing two sward treatments-perennial ryegrass (grass-only) or perennial ryegrass and white clover (grass-clover)-at three time points across spring, summer, and autumn of a single grazing season. The analysis indicated that the EBI status had no significant effect on the rumen microbial community within the statistical power of this study. Beta diversity between the microbiomes was different (p < 0.001) between the two sward treatments only in autumn, when the clover proportion was highest (50.2%). Season had a significant effect on microbiome beta diversity across sward treatments (p < 0.001). There were only minor differences in the composition of the rumen microbiomes between the two sward treatments. Many bacterial genera were differentially abundant between spring and the two later time points. Bacterial genera that were more abundant in spring were positively correlated with rumen propionate levels, while those more abundant in summer and autumn were negatively correlated with propionate and positively correlated with acetate and butyrate. Methanogenic archaeal abundance was greater in summer and autumn compared to spring, and they were negatively correlated with propionate and positively correlated with methane (CH4) production. The results of this study demonstrate that genetic selection using the EBI does not affect the rumen microbial community and the core rumen microbial community is similar in cows grazing either grass-only or grass-clover swards. The results also demonstrate that the rumen bacterial community shifts across the grazing season, providing more favorable conditions for methanogenesis in summer and autumn compared to spring.},
}

@article {pmid41277959,
year = {2025},
author = {Zhang, S and Li, J and Li, L and Yuan, X},
title = {Gut microbiota on cardiovascular diseases-a mini review on current evidence.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1690411},
pmid = {41277959},
issn = {1664-302X},
abstract = {The gut microbiome has emerged as a critical modulator of cardiovascular disease (CVD) risk, offering a novel frontier for therapeutic intervention. This mini-review synthesizes current evidence on how probiotic-like bacteria and their metabolites mediate protective physiological mechanisms against CVD. Drawing from both animal models and human clinical trials, we elucidate the biological pathways, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acid metabolism, through which the gut microbiota influences hypertension, atherosclerosis, and heart failure. Furthermore, we examine microbiota-based strategies such as dietary modification, fecal microbiota transplantation (FMT), and pharmacological agents aimed at restoring microbial homeostasis. Despite promising mechanistic insights, human trials have yet to consistently demonstrate significant clinical benefits in reversing CVD outcomes via gut microbiota modulation. This review underscores the necessity of moving from correlation to causation, highlighting current limitations and future prospects for leveraging gut microbiome research in the development of personalized, effective therapeutic strategies for cardiovascular diseases.},
}

@article {pmid41277956,
year = {2025},
author = {Chen, Q and Huang, D and Liu, J and Jia, N and Shen, Z and Pei, C and Chen, C and Liu, Y and Wang, Y and Shi, S and Yi, R and He, Y and Wang, F and Wang, Z},
title = {The gut microbiota in high-altitude medicine: intersection of hypoxic adaptation and disease management.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1705487},
pmid = {41277956},
issn = {1664-302X},
abstract = {High-altitude exposure impacts hundreds of millions globally, posing a unique health challenge due to extreme stressors including hypobaric hypoxia and intense ultraviolet radiation. The gut microbiota, a microbial community residing in the intestinal tract, plays a pivotal role in maintaining host health through homeostasis. Emerging evidence highlights the gut microbiome's dual roles in facilitating host adaptation to high-altitude environments and in mediating maladaptive responses. This review explores the potential changes and mechanisms of the gut microbiota and its metabolites in mediating host adaptation and pathogenesis related to high-altitude exposure, alongside summarizing effective strategies for targeted microbiota modulation to prevent and treat altitude-related disorders. Furthermore, we discuss the influence of microbiota on drug metabolism in high-altitude populations and its potential role as diagnostic and prognostic biomarkers. Although current research remains exploratory, the gut microbiome has garnered significant interest in high-altitude medicine. With advancing investigations, microbiota-targeted interventions may emerge as critical breakthroughs for altitude disease management, paving the way for improved human adaptation to extreme environments and precision health strategies for plateau populations.},
}

@article {pmid41277831,
year = {2025},
author = {Rahmdel, S and Türkoglu, T and Nikjoo, N and Babaali, E and Moradi Mirhesari, D and Nega, M and Brüggemann, H and Huang, L and Witte Paz, M and Nieselt, K and Götz, F},
title = {Beyond commensalism: genomic insights into micrococcin P1-producing Staphylococcus chromogenes.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0073325},
doi = {10.1128/msphere.00733-25},
pmid = {41277831},
issn = {2379-5042},
abstract = {UNLABELLED: Staphylococcus chromogenes (S. chromogenes) is a predominant non-aureus staphylococcal species colonizing the teat skin and mammary gland of dairy ruminants. Although often linked to mild or subclinical mastitis, specific strains may also play protective roles against major udder pathogens. In this study, we characterized two S. chromogenes isolates (4S77 and 4S90) that displayed antimicrobial activity against Gram-positive bacteria. Complete genome sequencing revealed a conserved, plasmid-encoded biosynthetic gene cluster for the thiopeptide bacteriocin micrococcin P1 (MP1). All genes necessary for MP1 biosynthesis, modification, export, and immunity were identified, and compound production was confirmed by high-performance liquid chromatography and liquid chromatography-mass spectrometry. Comparative analysis with publicly available S. chromogenes genomes revealed that the MP1 cluster appears unique to these isolates. Both strains showed full phenotypic susceptibility to tested antibiotics, despite 4S90 carrying the lnuA gene, which did not confer detectable resistance under standard conditions. Classical staphylococcal toxin genes were also absent. Virulence gene profiling revealed a conserved repertoire of colonization- and persistence-associated genes, including factors involved in adhesion, capsule formation, and iron acquisition, but no markers of aggressive pathogenicity. Mobile genetic elements, including prophages and genomic islands, were common but did not carry antimicrobial resistance or virulence genes, suggesting a low risk of transmission of new pathogenic traits to the endogenous microbiome, including opportunistic bacteria. These findings suggest that MP1-producing S. chromogenes strains combine antimicrobial functionality with low virulence potential, highlighting their potential ecological role as protective commensals on the teat skin and in the broader mammary ecosystem of dairy ruminants.

IMPORTANCE: Staphylococcus chromogenes is one of the most prevalent bacteria isolated from the mammary glands of dairy animals and is primarily considered a causative agent of subclinical mastitis. However, certain strains may also act as microbial competitors that inhibit more harmful pathogens. In this study, we identified two goat-derived S. chromogenes strains that produce micrococcin P1 (MP1), a potent antimicrobial compound effective against Gram-positive bacteria, including major mastitis pathogens. Genomic and phenotypic analyses revealed that these strains possess low virulence potential and retain antibiotic susceptibility, suggesting a possible protective role within the mammary microbiome. This is the first report of MP1 production in this species. Our findings highlight the functional diversity within S. chromogenes and suggest its potential application in microbiota-based strategies for mastitis prevention and antimicrobial stewardship in livestock.},
}

@article {pmid41277829,
year = {2025},
author = {Russell, MM and Sosa-Moreno, A and Zhang, L and Comstock, SS},
title = {Associations of diet, race, and other environmental factors with antimicrobial resistance genes in the gut bacterial communities of pregnant women and 3-month-old infants.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0044525},
doi = {10.1128/msphere.00445-25},
pmid = {41277829},
issn = {2379-5042},
abstract = {The emergence of pathogens resistant to antimicrobials has become a forefront concern for clinicians and patients alike. Antimicrobial resistance (AMR) is exacerbated by the misuse and overuse of antibiotics. Pregnant women and their infants are an important area of focus, as antibiotic use during this vulnerable period of development may generate reservoirs of AMR genes, which would contribute to future risk. Identifying the extent of antibiotic use and its association with ARG composition and persistence within this window is crucial. We sought to characterize the gut resistomes of 3-month-old infants (n = 212) and pregnant women in their third trimester (n = 99) to assess ARG burden in these populations. For a subset of women and their infants (n = 33 pairs), we explored overlap of ARG. Preliminary analyses demonstrated that pregnant women and infants had markedly different resistome communities and identified other environmental and demographic characteristics to be associated with univariate differences in infant ARG composition. When controlling for the race of the mother, infant diet, and infant antibiotic exposure since birth, delivery by cesarean section was associated with increased diversity of ARG relative to the diversity of ARG in the samples from vaginally born infants. Cesarean-born infants had increased richness of aminoglycoside ARG and increased diversity of beta-lactamase and tetracycline ARG relative to vaginally born infants. Furthermore, infants consuming any formula had increased overall richness and diversity of ARG in multivariate analyses. This study provides further insight into how diet and method of delivery are associated with resistome composition within the first 3 months of infant microbiome development.IMPORTANCEPregnancy and the first 3 months of life are vulnerable periods for antibiotic exposure and subsequent development of antimicrobial resistance (AMR). AMR is an increasingly worrisome problem for global public health. The full repertoire of AMR genes present in the gut collectively is referred to as the resistome. Herein, the associations between a variety of demographic and environmental factors, including race of the pregnant women, sex of the infant, mode of delivery, amount of breast milk consumed in infant diet, and antibiotic exposure during the first 3 months of life, with resistome composition are reported. Infants consuming any formula had a greater richness and diversity of ARG overall, and cesarean-born infants had greater diversity of ARG within their resistomes. These findings give insight into the early seeding of the infant resistome, which is crucial to understanding how the resistome develops throughout life.},
}

@article {pmid41277738,
year = {2025},
author = {Bertoldi, CS and Moraes Ballejos Nunes, MV and Moreira, MFS and Drehmer, M},
title = {Association Between Maternal Obesity and Gestational Diabetes Mellitus With the Human Milk Microbiome: A Systematic Review.},
journal = {Journal of human lactation : official journal of International Lactation Consultant Association},
volume = {},
number = {},
pages = {8903344251389600},
doi = {10.1177/08903344251389600},
pmid = {41277738},
issn = {1552-5732},
abstract = {BACKGROUND: Evidence on the beneficial effects of microorganisms in human milk is emerging. Obesity and gestational diabetes mellitus appear to be related to alterations in the maternal gut microbiota and human milk composition. However, knowledge about the influence of maternal obesity and gestational diabetes mellitus on the human milk microbiota remains limited.

RESEARCH AIM: To summarize and systematically assess the evidence on the influence of obesity and gestational diabetes mellitus on the diversity and/or composition of the human milk microbiota.

METHOD: A systematic review following PRISMA guidelines was conducted. Searches were performed in the MEDLINE, Cochrane Database of Systematic Reviews, Web of Science, and EMBASE, as well as in ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The ROBINS-E tool was used to assess the risk of bias. Out of 1,473 studies identified and 24 protocol records, eight studies were selected for final analysis.

RESULTS: Exposure to gestational diabetes mellitus and maternal obesity were associated with changes in the human milk microbiota's diversity and/or composition. Lactating women exposed to obesity had a higher prevalence of Staphylococcus and a lower prevalence of Bifidobacterium in their milk. Those exposed to gestational diabetes mellitus had a higher prevalence of Staphylococcus, Gemella, and Prevotella. Findings regarding bacterial phyla prevalence were inconclusive.

CONCLUSION: Based on the findings presented in this systematic review, it is not yet possible to draw definitive conclusions regarding the true influence of maternal obesity and/or gestational diabetes mellitus on the diversity or composition of the human milk microbiota.},
}

@article {pmid41277537,
year = {2025},
author = {Liu, C and Wang, X and Zhang, Z and Wang, W and Wang, T and Zhao, Y and Wang, M and Chen, WH},
title = {GMrepo v3: a curated human gut microbiome database with expanded disease coverage and enhanced cross-dataset biomarker analysis.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkaf1190},
pmid = {41277537},
issn = {1362-4962},
support = {2024YFA0918500//National Key Research and Development Program of China/ ; 5001170159//Hubei Province/ ; 202505AF350080//Yunnan Expert Workstation/ ; },
abstract = {GMrepo (Gut Microbiome Data Repository) is a curated and consistently annotated database of human gut metagenomes, designed to improve data reusability and enable cross-project and cross-disease comparisons. In this latest release, GMrepo v3 has been expanded to 890 projects and 118 965 runs/samples, including 87 048 16S rRNA and 31 917 metagenomic datasets. The number of annotated diseases has increased from 133 to 302, allowing more comprehensive disease-related microbiome analyses. We systematically identified microbial markers between phenotype pairs (e.g. healthy versus diseased) at the project level and compared them across datasets to detect reproducible signatures. As of this release, GMrepo v3 includes 1299 marker taxa (726 species and 573 genera) associated with 167 phenotype pairs, derived from 275 carefully curated projects. To assess marker stability, we developed the Marker Consistency Index (MCI), which summarizes the prevalence and directional consistency of markers across studies. Among 400 markers showing altered abundances in ≥10 projects, 143 were consistently enriched in healthy controls (MCI > 75%), while 85 were enriched in diseases (MCI < 25%). A marker-centric interface enables users to explore marker behavior across diseases. The GMrepo v3 database is freely accessible at https://gmrepo.humangut.info.},
}

@article {pmid41277418,
year = {2025},
author = {Guggeis, MA and Andreani, NA and López-Agudelo, VA and Tran, F and Kadibalban, AS and Moors, KA and Marinos, G and Saboukh, A and Harris, D and Falk-Paulsen, M and Weber-Stiehl, S and Järke, L and Sommer, F and Welz, L and Bang, C and Franke, A and Chung, CJ and Bronowski, C and Schuchardt, S and Künzel, S and Aden, K and Schreiber, S and Kaleta, C and Baines, JF and Rosenstiel, P},
title = {Cross-species engraftment biases and metabolic divergence in gnotobiotic mice humanized with ulcerative colitis microbiota.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2581445},
doi = {10.1080/19490976.2025.2581445},
pmid = {41277418},
issn = {1949-0984},
mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice, Inbred C57BL ; Mice ; Bacteria/classification/genetics/isolation & purification/metabolism ; Disease Models, Animal ; Male ; Female ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; Fungi/classification/genetics/isolation & purification ; Middle Aged ; },
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the human colon. Dysbiotic gut microbiota play a central role in its pathogenesis, and alterations in microbial composition and function are closely linked to disease activity. Humanized gnotobiotic mice are increasingly used to study how dysbiotic, human-derived microbial communities shape intestinal inflammation. However, the fidelity of microbiota engraftment and its impact on host physiology and metabolism remain incompletely understood. In this study, we performed a multiomics analysis following fecal microbiota transfer (FMT) from eight patients with active UC into germ-free C57BL/6N mice (five mice per donor). The mice were monitored over three weeks. Longitudinal analysis of microbial communities was performed using 16S rRNA (bacteria) and ITS2 (fungi) amplicon sequencing. Microbial metabolic flux was inferred via genome-scale metabolic modeling, and plasma metabolites were assessed by targeted metabolomics. We observed donor-specific physiological changes in recipient mice, including variations in body weight and adipose tissue. Spontaneous colonic inflammation occurred in one group and was subsequently linked to unintended transfer of Clostridioides difficile, which was previously clinically unrecognised in the donor. While bacterial engraftment overall was generally donor-specific and stable across mice, fungal taxa were transferred inconsistently and at low abundance. Despite similar overall plasma metabolomic profiles, select metabolites, including 3-indoleacetic acid, were differentially associated with specific microbial taxa. Moreover, metabolic modeling revealed disrupted metabolic exchange networks in the mouse microbiota compared to the original human donor communities. In conclusion, while human FMT into germ-free mice reliably transmits bacterial features, it introduces metabolic alterations and fails to fully reproduce the fungal microbiome. These findings underscore the need for cautious interpretation of microbiota-driven effects in gnotobiotic models and highlight the limitations of current approaches in replicating the full complexity of human gut ecosystems.},
}

Animals
Humans
*Gastrointestinal Microbiome
*Colitis, Ulcerative/microbiology/therapy/metabolism
*Fecal Microbiota Transplantation
Germ-Free Life
Mice, Inbred C57BL
Mice
Bacteria/classification/genetics/isolation & purification/metabolism
Disease Models, Animal
Male
Female
Feces/microbiology
RNA, Ribosomal, 16S/genetics
Dysbiosis/microbiology
Fungi/classification/genetics/isolation & purification
Middle Aged

@article {pmid41277303,
year = {2025},
author = {Guldan, M and Al-Shiab, R and Rustamov, A and Ozbek, L and Ferro, CJ and Kanbay, M},
title = {The Exposome Era in Kidney Transplantation: A New Frontier in Graft Outcomes and Precision Medicine.},
journal = {Clinical transplantation},
volume = {39},
number = {11},
pages = {e70384},
doi = {10.1111/ctr.70384},
pmid = {41277303},
issn = {1399-0012},
mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Precision Medicine/methods ; *Exposome ; *Graft Survival ; *Graft Rejection/etiology/prevention & control ; Prognosis ; *Environmental Exposure/adverse effects ; Risk Factors ; },
abstract = {Despite substantial advances in surgical technique and immunosuppressive therapy, kidney transplantation continues to face limitations in long-term graft and patient survival. Increasingly, attention is shifting toward the exposome, the comprehensive profile of environmental, social, and biological exposures accumulated across the lifespan, as a critical yet under-investigated determinant of transplant outcomes. Evidence from diverse domains, including air pollution, heavy metal burden, dietary composition, infections, microbiome dynamics, psychosocial context, and digital health engagement, suggests that these factors exert profound effects on immune regulation, metabolic health, and graft integrity. By applying innovative approaches such as exposome-wide association studies, high-resolution biomonitoring, and multi-omics integration, researchers can begin to unravel complex exposure-disease relationships and identify previously unrecognized modifiable risks. Positioning the exposome within the kidney transplantation paradigm offers a pathway toward precision environmental medicine, enabling refined risk stratification, novel preventive strategies, and ultimately improved durability of both graft function and patient survival. However, exposome influences are highly individualized and interact in complex, non-additive ways; current evidence remains largely associative and hypothesis-generating rather than causal.},
}

Humans
*Kidney Transplantation/adverse effects
*Precision Medicine/methods
*Exposome
*Graft Survival
*Graft Rejection/etiology/prevention & control
Prognosis
*Environmental Exposure/adverse effects
Risk Factors

@article {pmid41277280,
year = {2025},
author = {Hewetson, M},
title = {Science-in-brief: The equine microbiome-What have we learned 5 years on?.},
journal = {Equine veterinary journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/evj.70127},
pmid = {41277280},
issn = {2042-3306},
}

@article {pmid41277251,
year = {2025},
author = {Bron, A and Beltramo, C and Durif, C and Arora, T and Deschamps, C and Couturier, I and Domingo-Almenara, X and Otero, YF and Denis, S and Van de Wiele, T and Blanquet-Diot, S},
title = {Small intestine is not colon: a new in vitro model of the human ileum microbiome integrating the mucosal microenvironment and feeding status.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2579353},
doi = {10.1080/19490976.2025.2579353},
pmid = {41277251},
issn = {1949-0984},
mesh = {Humans ; *Ileum/microbiology ; *Gastrointestinal Microbiome/physiology ; *Colon/microbiology ; Adult ; *Intestinal Mucosa/microbiology ; Fatty Acids, Volatile/metabolism ; *Bacteria/classification/metabolism/genetics/isolation & purification ; Fermentation ; Male ; Feces/microbiology ; Models, Biological ; Female ; Bile Acids and Salts/metabolism ; },
abstract = {The small intestinal microbiota plays a key role in human health but is understudied due to the invasiveness of sampling. There is no available model of the human ileal microbiome simulating the key nutritional and physicochemical parameters shaping this ecosystem, which has been fully validated based on in vivo data. Here, the Mucosal Artificial Ileum (M-ARILE) was set up to reproduce the pH, transit time, anoxic conditions, dynamics of feeding and microenvironments (luminal versus mucosal) found in a healthy human mid-ileum. To validate the newly developed in vitro system, nine-day fermentations were performed under either ileal or colonic conditions using the same fecal inoculum (n = 3 adult volunteers). The gut microbiota composition and metabolic activities were monitored daily. Distinct microbial signatures and metabolite profiles were obtained between in vitro ileum and colon conditions. In accordance with in vivo data, Peptostreptococcaceae, Clostridiaceae and Enterococcaceae were enriched in the ileum and associated with lower short-chain fatty acid production but higher O2 percentages. Interestingly, the abundances of key populations, such as Akkermansiaceae, and bile acid profiles were dependent on the feeding status of the M-ARILE. This new model provides a powerful platform for mechanistic studies on the role of ileal microbes in human nutrition and health considering inter-individual variabilities.},
}

Humans
*Ileum/microbiology
*Gastrointestinal Microbiome/physiology
*Colon/microbiology
Adult
*Intestinal Mucosa/microbiology
Fatty Acids, Volatile/metabolism
*Bacteria/classification/metabolism/genetics/isolation & purification
Fermentation
Male
Feces/microbiology
Models, Biological
Female
Bile Acids and Salts/metabolism

@article {pmid41276725,
year = {2025},
author = {Fan, X and Wang, Z and Sun, L and Qin, Y and Liu, Y and Wu, S and Du, L},
title = {Quercetin as a Novel Antidepressant: Mechanistic Insights into Its Neuroprotective and Anti-inflammatory Effects.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {155},
pmid = {41276725},
issn = {1559-1182},
support = {KYCX23_3622//the Postgraduate Research and Practice Innovation Program of Jiangsu Province/ ; 82001425//the National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Quercetin/pharmacology/therapeutic use ; Male ; *Antidepressive Agents/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; Hippocampus/drug effects/metabolism ; Mice ; Depression/drug therapy/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Nitric Oxide Synthase Type II/metabolism ; X-Box Binding Protein 1/metabolism ; Endoplasmic Reticulum Stress/drug effects ; Stress, Psychological/drug therapy/complications ; },
abstract = {Depression is a globally recognized leading cause of mental health disability and mortality worldwide, severely affecting individuals' daily lives and relationships. At present, the limitation of first-line antidepressants has brought great difficulties to the treatment of depression. Therefore, the development of new antidepressants is imminent. Quercetin is considered as a potential antidepressant drug due to its potent anti-inflammatory, antioxidant, and neuroprotective effects. We explored the antidepressant effect of quercetin by establishing a mouse model (Adult male C57BL/6 J mice) of depression induced by chronic unpredictable stress (CUS). Analysis of the antidepressant effect of quercetin was conducted using multi-omics. The sociability and the protein expression levels of Hsp90, XBP1 and iNOS in the hippocampus of mice were evaluated through behavioral and molecular biology experiments. We found that quercetin treatment alleviated social impairment in mice and could target Hsp90 to inhibit the upregulation of XBP1 and iNOS. In addition, based on microbiome as well as untargeted metabolomics results of hippocampal brain regions, quercetin was found to increase the abundance of Lactobacillus and modulate the levels of inosine, Creatinine, and Lithocholic acid metabolites in the hippocampus. To sum up, in the present study, we revealed the molecular mechanism of quercetin alleviating depression-like behavior in CUS mice by inhibiting CUS-induced endoplasmic reticulum stress, neuroinflammation, gut microbiota dysbiosis, and metabolic disorders through multi-omics joint analysis. This provides a complementary scientific explanation for the antidepressant effects of quercetin.},
}

Animals
*Quercetin/pharmacology/therapeutic use
Male
*Antidepressive Agents/pharmacology/therapeutic use
Mice, Inbred C57BL
*Neuroprotective Agents/pharmacology/therapeutic use
*Anti-Inflammatory Agents/pharmacology/therapeutic use
Hippocampus/drug effects/metabolism
Mice
Depression/drug therapy/metabolism
HSP90 Heat-Shock Proteins/metabolism
Nitric Oxide Synthase Type II/metabolism
X-Box Binding Protein 1/metabolism
Endoplasmic Reticulum Stress/drug effects
Stress, Psychological/drug therapy/complications

@article {pmid41276714,
year = {2025},
author = {Mustafa, MA and Vadia, N and Varma, P and Al-Shaker, H and Mohanty, B and Dhyani, A and Kaur, I and Chauhan, AS and Garg, G},
title = {The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {151},
pmid = {41276714},
issn = {1559-1182},
mesh = {*Alzheimer Disease/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism/pathology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; },
abstract = {Microbiota residing in the human gastrointestinal tract play a critical role in maintaining homeostasis through immune regulation, metabolic activity, and signaling to the central nervous system. Recent studies have highlighted the influence of gut microbiota on neurodegenerative diseases, particularly Alzheimer's disease (AD), through the microbiota-gut-brain axis. This bidirectional communication system involves neural, hormonal, and immunological pathways, linking gut health directly with brain function. Disruption of the gut microbial balance-known as dysbiosis-has been associated with increased amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, neuroinflammation, and impaired neurotransmission, all of which are key pathological features of AD. Microbial metabolites such as short-chain fatty acids, trimethylamine N-oxide, and gasotransmitters influence the permeability of the blood-brain barrier and modulate neuroimmune responses. Emerging evidence also indicates that gut microbiota may contribute to the early onset and progression of AD through systemic inflammation and metabolic dysfunction. Modulating the gut microbiome, therefore, presents a novel avenue for therapeutic intervention. This review aims to synthesize current findings on how gut microbiota alterations contribute to AD pathology. Furthermore, it explores therapeutic strategies-including diet, probiotics, prebiotics, polyphenols, and fecal microbiota transplantation-that hold potential in restoring microbial balance and mitigating cognitive decline in AD.},
}

*Alzheimer Disease/therapy/microbiology
Humans
*Gastrointestinal Microbiome/physiology
Animals
*Brain/metabolism/pathology
Dysbiosis
Probiotics/therapeutic use
*Brain-Gut Axis

@article {pmid41276282,
year = {2025},
author = {Gao, W and Lee, HY and Min, KJ},
title = {Aging and the microbiome: implications for health and disease.},
journal = {BMB reports},
volume = {},
number = {},
pages = {},
pmid = {41276282},
issn = {1976-670X},
abstract = {The gut microbiota plays a fundamental role in maintaining host homeostasis, and the aging process profoundly influences its composition and function. Accumulating evidence suggests that alterations in the gut microbiota are not just a consequence of aging, but also an active driver of age-related physiological decline. In particular, age-dependent gut microbiota dysbiosis has emerged as a critical factor contributing to host aging and aging-related diseases. This review systematically summarizes alterations in the gut microbiota (e.g., reduced alpha diversity, depletion of beneficial commensals, and enrichment of pathobionts) during the aging process, and discusses the spatiotemporal dynamics and causal relationships between microbial aging and host aging. The regulatory mechanisms by which the gut microbiota influences aging-related diseases, such as metabolic disorders (e.g., obesity, type 2 diabetes, and cardiovascular disease), immunosenescence, and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), are also elucidated. Finally, microbiota-targeted intervention strategies (e.g., probiotics, prebiotics, and postbiotics) are explored, together with advanced research strategies.},
}

@article {pmid41276192,
year = {2025},
author = {Boonstra, R and Castillo, J and Karels, TJ and Dobson, FS and Palme, R and Bosson, CO},
title = {Assessing stress in a mammals from plasma and feces: A nutritional mismatch between the diet needed and the food present.},
journal = {General and comparative endocrinology},
volume = {},
number = {},
pages = {114856},
doi = {10.1016/j.ygcen.2025.114856},
pmid = {41276192},
issn = {1095-6840},
abstract = {A lack of agreement between the diet an animal needs for reproduction and survival and the food present in its environment has major impact on its fitness. The complexity of their digestive system is critical and may affect stress axis function. The squirrel family (sciurids) have a very simple gut and do not have the microbiome to digest high fiber foods well. Thus, they forage preferentially on forbs, seeds, and fungi, and avoid hard-to-digest grasses. We compared two measures of their stress axis - plasma free cortisol, a glucocorticoid (GC), and fecal cortisol metabolites (FCMs) - in Columbian ground squirrels (Urocitellus columbianus) from two meadows as they were building up body reserves in July for their pending hibernation. One meadow was natural with an abundance of forbs and the other unnatural with an abundance of grasses that had been seeded as a horse pasture. Our two measures went in the opposite direction: GC levels were lower on the natural meadow but FCMs were higher, whereas GC levels were higher on the grass meadow but FCMs lower. The fecal fiber content was lower on the natural meadow. Thus, when interpreting FCM levels, it is critical to understand both the digestive system of the study mammal and its diet to interpret stress axis function.},
}

@article {pmid41275986,
year = {2025},
author = {Raj, DS and Gao, B and Sohn, MB and Brydges, C and Srivastava, A and Rabb, H and Cheung, AK and Fiehn, O and Kendrick, C and Gassman, JJ and Tariq, A and Isakova, T and Fried, LF and Wolf, M and Raphael, KL and Middleton, JP and Abdalla, Y and , },
title = {Prebiotic Administration to CKD Patients Modifies Their Microbiome and Metabolism.},
journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.jrn.2025.10.015},
pmid = {41275986},
issn = {1532-8503},
abstract = {BACKGROUND AND HYPOTHESIS: Prebiotics are believed to improve gut microbial dysbiosis and dysmetabolism in chronic kidney disease (CKD) patients. However, impact of prebiotics on gut microbial metagenome and dynamic changes in metabolome has not been clearly defined.

METHODS: We conducted a non-randomized, open-label, three-phase pilot trial, to investigate the effect of daily oral oligofructose-enriched inulin (p-inulin) on stool functional metagenome and changes in plasma, urine and stool metabolites in 13 CKD patients. The study comprised a pre-treatment phase (8 weeks), p-inulin treatment phase (12 weeks), and post-treatment phase (8 weeks).

RESULTS: During treatment phase, there was a significant increase in the abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Lachnospiraceae species. Microbial pathways related to carbohydrate degradation and amino acid biosynthesis were enriched during the treatment phase, but urea biosynthetic pathway was attenuated. In the plasma metabolic biosynthetic pathways for valine, leucine and isoleucine were activated during the treatment phase. Microbial genes related to lipid metabolism were enriched during post-treatment. Abundance of several polar and non-polar lipids were altered in plasma and stool samples during treatment and post-treatment phases. Pathway analysis for lipids indicated suppression of triglyceride biosynthesis in plasma and enhanced triglyceride degradation in stool during the treatment phase. Secondary bile acid levels in plasma, urine and stool were significantly reduced during p-inulin consumption. Urine levels of indoxyl sulfate and p-cresol sulfate were reduced during treatment phase.

CONCLUSION: P-inulin administration to CKD patients resulted a distinct shift in toxin-generating proteolysis to amino acid biosynthesis and favorable changes in lipid metabolism.},
}

@article {pmid41275828,
year = {2025},
author = {Lin, J and Qian, B and Li, Z and Chen, J and Gao, K and Li, Q and Shen, J and Shen, R and Guo, Y and Hua, Y},
title = {Conjugated deoxycholic acid-microbiota interaction mitigate liver cirrhosis via inducing anti-inflammation response of macrophages.},
journal = {International immunopharmacology},
volume = {168},
number = {Pt 2},
pages = {115909},
doi = {10.1016/j.intimp.2025.115909},
pmid = {41275828},
issn = {1878-1705},
abstract = {BACKGROUND: Cirrhosis is a liver fibrosis disease caused by chronic liver disease, often accompanied by disorders of the gut microbiome and bile acid metabolism. The study aimed to probe the roles and mechanisms of the gut microbiota-bile acids (BAs) interaction in effecting the progression of liver cirrhosis.

METHODS: We analyzed gut microbiome composition and serum bile acid levels in cirrhotic patients, cirrhosis mouse models, vancomycin-treated mice, and BAs-treated mice. Key cirrhosis-related bacteria and BAs were identified, and their effects were tested in vivo and in vitro. Biochemical analysis and immunohistochemistry were used to assess liver cirrhosis, inflammation, and macrophage phenotypic changes.

RESULTS: In cirrhosis patients and mice, Actinobacteria levels were significantly lower, and Coriobacteriia and Coriobacteriales (subgroups of Actinobacteria) were notably reduced. Serum bile acids were elevated, with a decrease in conjugated secondary bile acids, especially conjugated deoxycholic bile acid (C-DCA), including glyco-deoxycholic acid (GDCA, predominant in humans) and tauro-deoxycholic acid (TDCA, predominant in mice). TDCA treatment inhibited cirrhosis and hepatocyte apoptosis, while promoting Coriobacteriia growth. Vancomycin inhibited Actinobacteria, Coriobacteriia, and Coriobacteriales, and reduced serum TDCA levels. TDCA suppressed macrophage aggregation in cirrhotic liver tissues. GO and KEGG analysis revealed GDCA inhibited inflammation-related genes in macrophages. GDCA upregulated anti-inflammatory genes (IL-4, IL-10, IL-13) and downregulated pro-inflammatory markers (P-STAT3, TLR2). Additionally, TGR5, a bile acid receptor, was upregulated in GDCA-treated macrophages.

CONCLUSIONS: This study reveals that the crosstalk of C-DCA and Coriobacteriales, originating from Actinobacteria, may be negatively associated with the progress of cirrhosis, and C-DCA may induce the transition of macrophages to an anti-inflammatory phenotype, thereby mitigating the inflammatory response.},
}

@article {pmid41275731,
year = {2025},
author = {Shahin, A and Schyr, R and Sharon, E and Coppenhagen-Glazer, S and Koren, O and Elazary, R and Ben-Zvi, D and Raveh, D and Hazan, R and Houri-Haddad, Y},
title = {Bariatric Surgery Alters Oral Microbiome: Evidence From Obese Patients and a Mouse Model.},
journal = {International dental journal},
volume = {76},
number = {1},
pages = {104026},
doi = {10.1016/j.identj.2025.104026},
pmid = {41275731},
issn = {1875-595X},
abstract = {BACKGROUND: Bariatric surgery (BaS) is a safe and effective treatment for severe obesity, yet recent studies suggested that it may impact the gut and oral microbiomes. Oral dysbiosis is associated with an increased risk of oral diseases, including periodontitis and dental caries. However, the effects of BaS on oral health and microbiome changes are poorly understood.

OBJECTIVES: To examine the impact of obesity and BaS on oral health and microbiota in obese patients and an induced experimental periodontitis (EP) obese mouse model.

METHODS: The oral health of pre-BaS, post-BaS (6 months post-surgery), and control volunteers was assessed by scoring gingivitis, caries, and periodontitis. The oral microbiome was analyzed using 16S rRNA Next-Generation sequencing (NGS). Systemic parameters, maxillary bone volume, and oral and fecal microbiome were investigated in male obese C57BL/6 mice with and without EP before and after BaS treatment.

RESULTS: The study included 36 pre-BaS patients, 14 post-BaS patients, and 56 controls. Distinct oral microbial profiles were noted for each cohort. Pre-BaS patients exhibited higher oral microbial diversity and a greater prevalence of periodontitis-associated bacteria than controls, which further increased post-BaS. Caries- and halitosis-associated bacteria were significantly more abundant after BaS. Similarly, obese mice with EP and that underwent BaS showed elevated oral microbial diversity, paralleling human findings. EP alone significantly reduced gut microbiome diversity, regardless of BaS.

CONCLUSIONS: BaS exacerbates obesity-related microbial dysbiosis, increasing the risk of periodontal and dental diseases. Paradoxically, while BaS improves systemic and cardiometabolic health, it appears to worsen oral outcomes, underscoring the need for integrated medical-dental care and preventive protocols in this population.},
}

@article {pmid41275703,
year = {2025},
author = {Chen, Y and Deng, Y and Zhang, E and Hao, N and Ou, Z and Yan, R and Zhou, M and Zhang, H and Zhou, D and Wu, X},
title = {Serum metabolome and gut microbiome to analyze potential mechanisms of catamenial epilepsy.},
journal = {Epilepsy & behavior : E&B},
volume = {174},
number = {},
pages = {110808},
doi = {10.1016/j.yebeh.2025.110808},
pmid = {41275703},
issn = {1525-5069},
abstract = {BACKGROUND: Catamenial epilepsy (CE) is marked by an increase in seizure frequency during specific phases of the menstrual cycle. Advanced techniques such as serum metabolomics and 16S rRNA sequencing are being employed to investigate potential mechanisms and therapeutic approaches for managing CE.

METHODS: A total of 30 epilepsy patients (15 with CE and 15 temporal epilepsy) along with 15 healthy controls, were enrolled in this study. Human fecal samples and serum were collected for metabolomics analysis and 16S rDNA sequencing, respectively.

RESULTS: A total of 117 candidate metabolites and eight gut microbiota specific to CE were identified. Glycerophospholipid pathways were the most enriched among the candidate metabolites. Notably, serum lysophosphatidylinositol (LPI) 20:4 was associated with an increased seizure frequency. Additionally, differential gut metabolites were found to affect γ-aminobutyric acid degradation. A network linking sex hormones, metabolites, and gut microorganisms was constructed.

CONCLUSION: Findings clarify metabolite-microbiome-brain axis interactions, aiding CE pathogenesis understanding.},
}

@article {pmid41275685,
year = {2025},
author = {Zlender, T and Brezočnik, L and Podgorelec, V and Rupnik, M},
title = {MicrobiomePrime: A primer pair selection tool for microbial source tracking validated on a comprehensive collection of animal gut and fecal waste microbiomes.},
journal = {Water research},
volume = {289},
number = {Pt B},
pages = {124990},
doi = {10.1016/j.watres.2025.124990},
pmid = {41275685},
issn = {1879-2448},
abstract = {Microbial source tracking (MST) enables identification of fecal contamination sources in water, providing crucial support for water quality management and public health protection. PCR-based detection of host-associated markers remains a central approach in MST. However, the success of this method relies on designing assays that can accurately and efficiently amplify marker sequences. Here, we introduce MicrobiomePrime, the first fully automated bioinformatics pipeline that leverages k-mer based analysis to design highly sensitive and specific primer pairs for MST directly from any type of amplicon sequencing data. By automating this process, MicrobiomePrime streamlines assay development, enabling researchers and water quality laboratories to create novel MST assays without requiring extensive bioinformatics expertise. The pipeline was tested on 16S rRNA gene amplicon sequencing data from 715 animal fecal samples and 52 stored animal waste samples (manure and slurry), representing over 50 mammalian and avian species, along with 186 publicly available human fecal microbiome samples. Using this dataset, we designed a suite of novel MST assays targeting diverse fecal sources-including cattle, pig, dog, and nutria-as well as cattle and pig fecal waste, which are microbially distinct from fresh feces. In vitro validation of 51 assays resulted in high performance of multiple assays with 18 of them achieving exceptional, 100 % specificity, demonstrating the utility of MicrobiomePrime for developing robust MST assays. MicrobiomePrime is available on GitHub: https://github.com/tanjazlender/MicrobiomePrime.},
}

@article {pmid41275619,
year = {2025},
author = {Dubé-Zinatelli, E and Cappelletti, L and Ismail, N},
title = {The vaginal microbiome in bacterial vaginosis: Pathogenesis, reproductive impacts, and emerging therapies.},
journal = {Journal of reproductive immunology},
volume = {172},
number = {},
pages = {104804},
doi = {10.1016/j.jri.2025.104804},
pmid = {41275619},
issn = {1872-7603},
abstract = {Bacterial vaginosis (BV), the leading gynecological condition affecting women of reproductive age globally, is marked by a reduction in the dominant protective bacterial species Lactobacillus within the vaginal microbiome (VMB). This condition is triggered by an overgrowth of anaerobic bacteria and leads to many gynecological and reproductive repercussions, such as increased susceptibility to sexually transmitted infections and infertility. Moreover, BV's effects extend to pregnancy, contributing to adverse obstetric outcomes such as miscarriages, preterm delivery, and postpartum complications. While antibiotics remain the standard treatment for BV, their efficacy is compromised by high recurrence rates due to their inability to restore Lactobacillus and concerns about their negative impact on neonatal health during pregnancy. Recent research suggests probiotics as promising complementary or alternative therapies with their capacity to restore Lactobacillus in the VMB. In this review, we provide an in-depth examination of the impact of BV on gynecological health, pregnancy and fetal development and explore the latest advancements in BV treatments, including probiotics, vaginal microbiome transplantation (VMT), and biofilm disrupters, as preventative and therapeutic measures in addressing the multigenerational effects of this condition.},
}

@article {pmid41275375,
year = {2025},
author = {Su, Z and Zhang, X and Wang, Q and Tang, Q and Yang, D and Liu, Y},
title = {amplysis: an R package for microbial composition and diversity analysis using 16S rRNA amplicon data.},
journal = {Briefings in functional genomics},
volume = {24},
number = {},
pages = {},
pmid = {41275375},
issn = {2041-2657},
support = {//Guangxi Education Agency/ ; //Guangxi Province Talent Project/ ; 42377012//National Natural Science Foundation of China/ ; },
mesh = {*RNA, Ribosomal, 16S/genetics ; *Software ; *Microbiota/genetics ; *Computational Biology/methods ; Biodiversity ; Bacteria/genetics/classification ; },
abstract = {The downstream analysis of 16S rRNA sequencing data remains a significant challenge for researchers lacking extensive bioinformatics expertise, often requiring proficiency in diverse tools and methodologies. To address this, we present amplysis, an R package designed to streamline the analysis and visualization of 16S rRNA amplicon sequencing data through an intuitive, code-light workflow. amplysis integrates data importing, processing, statistical analysis, and visualization into a unified framework. Key features include data normalization, microbial composition profiling, alpha/beta diversity analysis, ordination methods (e.g. Principal Component Analysis), and publication-ready visualization tools. The package's utility was demonstrated through three case studies, one of which analyzed microbial community responses to hexachlorocyclohexane (HCH) degradation in groundwater environments. Using amplysis, we efficiently generated phylum/genus-level abundance plots, alpha-diversity indices, and Principal Coordinates Analysis ordination, revealing significant shifts in community structure and diversity under HCH stress. The other case studies utilized publicly available data from published studies by other researchers. These results underscore the package's ability to simplify complex analyses while ensuring reproducibility and high-quality output. By integrating modular, user-friendly functions, amplysis lowers the barrier to robust microbiome data exploration. The package is available on GitHub (https://github.com/min-perilla/amplysis), offering a valuable resource for researchers in microbial ecology and environmental genomics.},
}

*RNA, Ribosomal, 16S/genetics
*Software
*Microbiota/genetics
*Computational Biology/methods
Biodiversity
Bacteria/genetics/classification

@article {pmid41275232,
year = {2025},
author = {Sun, C and Li, J and Xu, H and Du, J and Muthusamy, P and Liu, K and Wei, S and Zhang, L},
title = {"Immunopause" no more: exercise to counter immunosenescence in aging.},
journal = {Immunity & ageing : I & A},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12979-025-00549-1},
pmid = {41275232},
issn = {1742-4933},
abstract = {The global demographic shift towards an aging population has amplified the public health challenge posed by immunosenescence, a progressive remodeling of the immune system that compromises host defenses. This age-related decline is characterized by a reduction in adaptive immunity, marked by a diminished pool of naïve T-cells and an increased susceptibility to infections and poor vaccine responses. Simultaneously, it is defined by a paradoxical state of chronic low-grade inflammation, or "inflammaging," which accelerates age-related pathologies. This review posits "immunopause" as a conceptual framework for a state of severe immune decline, a state often viewed as an inevitable consequence of aging. However, the evidence synthesized herein challenges this view by positioning physical exercise as a potent, non-pharmacological intervention capable of countering this process. The report systematically reviews the cellular, molecular, and systemic mechanisms through which exercise exerts its beneficial effects, including the rejuvenation of T-cell repertoires, the regulation of cytokine networks, and the modulation of multi-organ axes involving myokines and the gut microbiome. By improving the efficacy of existing immune cells and shifting the systemic inflammatory milieu, chronic physical activity promotes a more "youthful" and functional immune phenotype. This synthesis not only underscores exercise's potential to enhance vaccine efficacy and serve as an adjuvant therapy for age-related diseases but also argues for a paradigm shift: from viewing immune aging as an immutable process to recognizing it as a modifiable state. The report concludes that exercise provides a scientifically validated strategy to extend healthspan and prevent the pathological state of immunopause.},
}

@article {pmid41275194,
year = {2025},
author = {Yang, X and Liao, R and Cai, Y and Wang, J},
title = {Deep metaproteomic mapping of gingival crevicular fluid reveals distinct microbial community at prepubertal and circumpubertal stages.},
journal = {BMC oral health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12903-025-07348-6},
pmid = {41275194},
issn = {1472-6831},
abstract = {BACKGROUND: Orthodontic diagnosis and treatment planning are closely associated with the pubertal growth spurt. Previously, we developed a simplified MS-based protocol for deep quantitative analysis of human gingival crevicular fluid (GCF) proteome for skeletal maturity indicators. The purpose of this study is to perform an in-depth and comparative analysis of the GCF metaproteome at prepubertal and circumpubertal stages to aid oral health and skeletal maturity evaluation.

METHODS: Based on our previously obtained and published LC-MS data, the GCF metaproteome of 45 children (24 subjects from prepubertal group and 21 subjects from circumpubertal group) were analyzed by searching against the Human Oral Microbiome Database using FragPipe software. Differentially expressed bacterial proteins between two groups were analyzed using Wilcoxon rank sum test. Differentially abundant taxa between two groups were evaluated using linear discriminant effect size (LEfSe) analysis.

RESULTS: A total of 192 genera were identified in GCF. Neisseria (Neisseriales), Comamonadaceae, Burkholderiales, Proteobacteria and Betaproteobacteria were the most abundant bacterial taxa at prepubertal stage. Firmicutes, Saccharibacteria_TM7_[G-1] (Saccharibacteria TM7), Bacterium_HMT349, Bacilli and Alphaproteobacteria were the most abundant bacterial taxa of GCF microbiota at circumpubertal stage. Compared to that in the prepubertal group, enrichment of Firmicutes (Bacillus) was observed in the circumpubertal group.

CONCLUSIONS: Based on our developed and already published single-pot, solid-phase enhanced sample-preparation (SP3)-based liquid chromatography (LC) - high-field asymmetric waveform ion mobility spectrometry (FAIMS)-MS protocol for deep quantitative analysis of human GCF metaproteome, we were able to generate the largest dataset of the human GCF metaproteome (14376 bacterial proteins) to date and revealed distinct microbial community at prepubertal and circumpubertal stages. The proposed protocol and findings will be useful to aid oral health and skeletal maturity evaluation for orthodontic diagnosis and treatment planning.},
}

@article {pmid41275070,
year = {2025},
author = {Gao, H and Wang, Y and Zhao, Y and Jiao, X and Guo, Z and Zheng, L and Li, Y and Su, Y and Wang, Z and Bai, J and Yao, J and Bushman, FD and Luo, S and Song, X and Liang, G},
title = {Human gut prophage landscape identifies a prophage-mediated fucosylation mechanism alleviating colitis.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66733-5},
pmid = {41275070},
issn = {2041-1723},
support = {32200036//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82341116//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92474105//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32270945//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Functions of the human gut virome are little understood, particularly for the hyperabundant prophages integrated in prokaryotic genomes. Here we identified 254,273 prophage sequences in 47.7% of 289,232 human gut metagenomic genomes, significantly expanding the known taxonomic and functional diversity of prophages in the human gut microbiome. Analysis of 8503 gut metagenomic samples showed the ratios of lysogens (cells harboring prophages) to non-lysogens varied widely associated with age, health condition, and geography, with the latter linked to industrialization. Notably, the alterations of the prophage-encoded genes exhibited disease-specific patterns. For inflammatory bowel diseases, the prophage-encoded futC gene, encoding α-1,2-fucosyltransferase, was less prevalent in affected patients. This enzyme was experimentally validated to direct 2-fucosyllactose (2'-FL) biosynthesis in vitro. Here we show that 2'-FL could diminish colitis in mice induced by treatment with dextran sodium sulfate. Mechanistically, 2'-FL promoted maintenance of mucosal barrier integrity, leading to intestinal IgA secretion and intraepithelial CD4[+]CD8αα[+] T cell development mediated by the gut microbiome. Together, our findings thus link lysogeny to human age, geography, and disease, and demonstrate an immunomodulatory mechanism of prophage-encoded genes in alleviating colitis.},
}

@article {pmid41275034,
year = {2025},
author = {Qian, B and Fang, Z},
title = {The association between oral microbiome diversity and rheumatoid arthritis: a nationwide cross-sectional study.},
journal = {Clinical rheumatology},
volume = {},
number = {},
pages = {},
pmid = {41275034},
issn = {1434-9949},
abstract = {OBJECTIVE: The association between oral microbiome diversity and rheumatoid arthritis (RA) remains unclear. This study aims to investigate the association between oral microbiome diversity and RA.

METHODS: In this nationwide cross-sectional study, 5284 participants from the 2009-2012 National Health and Nutrition Examination Survey (NHANES) cycles were included. To explore the potential association between α-diversity and self-reported RA, weighted logistic regression and weighted restricted cubic spline (RCS) analyses were carried out. Subgroup analysis was performed to examine the robustness of the results. Finally, β-diversity in non-RA and RA groups was examined using principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA).

RESULTS: Our findings suggested that α-diversity was negatively correlated with RA, and the subsequent RCS analysis supported that the lower the variety of bacteria, the higher the likelihood of having RA. In the subgroup analysis, no apparent interaction effect was detected. PCoA and PERMANOVA demonstrated significant differences in the composition of the oral microbiome between non-RA and RA groups in terms of β-diversity.

CONCLUSION: Oral microbiome diversity was significantly associated with RA. This finding may offer new clinical insights into the treatment and prevention of RA, while also enhancing our understanding of its relationship with periodontitis. Key Points • By utilizing NHANES data, this study reveals the association between oral microbiome diversity and RA. • Lower α-diversity was closely related to higher RA prevalence. • PCoA and PERMANOVA showed that β-diversity differed in non-RA and RA groups.},
}

@article {pmid41274892,
year = {2025},
author = {Pröschle-Donoso, T and Díaz, R and Vásquez-Dean, J and Serebrinsky-Duek, K and Pezoa-Soto, I and Martin, AJM and Garrido, D},
title = {Emergent roles of infant gut microbes during the utilization of human milk oligosaccharides.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-025-00865-w},
pmid = {41274892},
issn = {2055-5008},
support = {Fondequip EQM190070//Agencia Nacional de Investigación e Innovación/ ; Fondecyt 1230764//Agencia Nacional de Investigación y Desarrollo/ ; },
abstract = {Bifidobacterium spp. are representative species of the infant gut microbiome. Human milk oligosaccharides (HMOs) are complex carbohydrates in breast milk, guiding gut microbiome assembly by establishing complex microbial interactions. Here, a synthetic community of seven infant gut microbes was subjected to single species dropouts in bioreactors using three HMOs. Substrate use, acid production, biomass, and metatranscriptomics revealed that B. bifidum was critical for degradation product formation and supporting cross-feeding. Removing B. longum subsp. infantis, known for intracellular HMO use, accelerated global growth and HMO consumption, suggesting competitive interactions. Some dropouts led to the accumulation of sialic acid, fucose, or lactose. Metatranscriptomics showed niche expansion, upregulated central metabolism and cross-feeding dependencies when certain species were removed. Modeling highlighted that HMO degradation rates strongly influence community dynamics. Overall, this study identifies key ecological roles in infant gut microbes and deepens our understanding of how HMOs shape microbiota assembly and function.},
}

@article {pmid41274878,
year = {2025},
author = {Ferretti, P and Allert, M and Johnson, KE and Rossi, M and Heisel, T and Gonia, S and Knights, D and Fields, DA and Albert, FW and Demerath, EW and Gale, CA and Blekhman, R},
title = {Assembly of the infant gut microbiome and resistome are linked to bacterial strains in mother's milk.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66497-y},
pmid = {41274878},
issn = {2041-1723},
support = {R01HD109830//U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; R21HD099473//U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; F32HD105364//U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; R01HD080444//U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; },
abstract = {The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as sole nutrition for the infant, little is known about how variation in the milk microbiome shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiomes using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. Microbial taxonomic overlap between milk and the infant gut was driven by Bifidobacterium longum, and infant microbiomes dominated by B. longum showed greater temporal stability than those dominated by other species. We identified numerous instances of strain sharing between milk and the infant gut, involving both commensal (e.g. B. longum) and pathobiont species (e.g. K. pneumoniae). Shared strains also included typically oral species such as S. salivarius and V. parvula, suggesting possible transmission from the infant's oral cavity to the mother's milk. At one month, the infant gut microbiome was enriched in biosynthetic pathways, suggesting that early colonisers might be more metabolically independent than those present at six months. Lastly, we observed significant overlap in antimicrobial resistance gene carriage within mother-infant pairs. Together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome.},
}

@article {pmid41274873,
year = {2025},
author = {Peng, H and Andreu-Sanchez, S and Ruiz-Moreno, AJ and Fernández-Pato, A and Wu, J and Gacesa, R and Zhernakova, A and Wang, D and Fu, J},
title = {Longitudinal gut microbiota tracking reveals the dynamics of horizontal gene transfer.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66612-z},
pmid = {41274873},
issn = {2041-1723},
abstract = {Horizontal gene transfer (HGT) is a major driver of bacterial evolution, but its role in shaping the human gut microbiome over time remains poorly understood. Here, we present a longitudinal metagenomic analysis of 676 fecal samples from 338 individuals in the Lifelines-DEEP study collected ~4 years apart, using a newly developed workflow to detect recent HGT events from metagenome-assembled genomes. We identified 5,644 high-confidence HGT events occurring within the past ~10,000 years across 116 gut bacterial species. We find that species pairs with an HGT relationship were significantly more likely to maintain stable co-abundance relationships over the 4-year period, suggesting that gene exchange contributes to community stability. Notably, HGT and strain replacement act together to disseminate mobile genes in the population. Furthermore, our observation that an individual's mobile gene pool remains highly personalized and stable over time indicates that host lifestyles drive specific gene transfer. For example, proton pump inhibitor usage is linked to increased transfer of multidrug transporter genes. Our findings demonstrate, at the individual gut microbiome level, that HGT is both an integral and stabilizing force in the human gut ecosystem and an important mechanism for disseminating adaptive functions, underscoring HGT potential for tracking host lifestyle.},
}

@article {pmid41274681,
year = {2025},
author = {Imai, M and Kawachi, M and Wakui, A and Miyazawa, M and Sekiguchi, M and Kato, Y and Sato, H and Naruse, Y and Asano, N and Morohashi, M and Sano, H and Abiko, Y and Washio, J and Tanaka, K and Takahashi, N and Sato, T},
title = {Microbial profiling of bold green tea bottled beverages: A screening experiment.},
journal = {Journal of oral biosciences},
volume = {67},
number = {4},
pages = {100697},
doi = {10.1016/j.job.2025.100697},
pmid = {41274681},
issn = {1880-3865},
mesh = {Humans ; *Tea/microbiology ; Adult ; *Saliva/microbiology ; Young Adult ; *Beverages/microbiology ; Male ; *Bacteria/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Female ; DNA, Bacterial ; },
abstract = {OBJECTIVES: To explore the storage potential and drinking safety of leftover bottled tea beverages from various manufacturers after directly drinking from the bottle, we conducted a screening experiment on the growth of salivary bacteria in plastic bottles of bold green tea.

METHODS: Resting whole saliva (n = 14) was collected from each participant (aged 19-25 years). The saliva samples (1.0 mL of each diluted saliva sample [5.0 × 10[5] CFU/mL]), were inoculated into plastic bottles containing 280 mL of green tea, which included six types of bold green tea beverages. The bottles were stored at 37 °C for 24 h; subsequently, 1.0 mL of each sample was inoculated onto a blood agar plate and incubated anaerobically at 37 °C. Genomic DNA was extracted from the resulting individual colonies and the bacterial species were identified by 16S rDNA sequencing.

RESULTS: More than 60 % of the samples of six types of bold green tea beverages, Bold Oi Ocha®, Suntory Bold Green Tea Iyemon®, Bold Oi Ocha Premium Strong®, Healthya®, Bold Ayataka®, and Catechin Green Tea® showed low bacterial levels (<10[3] CFU/mL) after 1 day of storage. However, in some cases, former members of the genus Lactobacillus, such as Limosilactobacillus and Lactiplantibacillus spp., were specifically detected as the predominant bacteria (37.6-100 %), although these bacteria usually account for the minority among the oral microbiome.

CONCLUSIONS: Although the antibacterial effects of catechins may have affected the total bacterial counts and compositions, no clear correlation was observed between total tea catechin concentrations and total bacterial growth inhibitory effects.},
}

Humans
*Tea/microbiology
Adult
*Saliva/microbiology
Young Adult
*Beverages/microbiology
Male
*Bacteria/isolation & purification
RNA, Ribosomal, 16S/genetics
Female
DNA, Bacterial

@article {pmid41274528,
year = {2025},
author = {Canzian, J and Jacobs, F and Floreani, A and Miggiano, C and Tiberio, P and Pozzi, C and Santoro, A and Zambelli, A and Rescigno, M and De Sanctis, R},
title = {Intratumoral Microbiome in Breast Cancer: A Hidden Player in Tumor Development, Progression and Treatment response.},
journal = {Critical reviews in oncology/hematology},
volume = {},
number = {},
pages = {105035},
doi = {10.1016/j.critrevonc.2025.105035},
pmid = {41274528},
issn = {1879-0461},
abstract = {The intratumoral microbiome has recently emerged as a critical component of the tumor microenvironment in breast cancer (BC). BC exhibits a uniquely rich and diverse microbial community, characterized by phyla such as Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. In addition, distinct microbial signatures were observed in different molecular subtypes, with hormone receptor-positive BC showing the highest microbial diversity and the most robust microbiome. These microbial constituents interact with neoplastic and immune cells, influencing estrogen metabolism, DNA damage, epithelial-to-mesenchymal transition (EMT), inflammation, and response to anticancer therapy. For instance, Fusobacterium nucleatum is among the main microbial components implicated in BC, contributing to carcinogenesis, tumor growth, and metastasis through mechanisms involving DNA damage (e.g., activating the E-cadherin/β-catenin signaling pathway), EMT (e.g., inducing the expression of EMT markers, including cadherins and vimentin), and immunoregulatory effects (e.g., regulating IL-1β expression and activating the TLR4/NF-κB signaling pathway). It has also been shown to induce chemoresistance by enhancing cancer cell stemness and viability, whereas its elimination improves sensitivity to anticancer therapies and immunotherapy. Besides investigating the specific activity of microbial components, recent studies have focused on the intratumoral microbiome prognostic role. Methodological variability remains a significant barrier to standardization and cross-study comparisons. Nevertheless, subtype-specific microbial signatures have demonstrated prognostic and predictive value, correlating with stage, treatment response, and immune cell infiltration. Understanding the interplay between the intratumoral microbiome, host genetics, and treatment response may ultimately inform the development of microbiome-based biomarkers and therapeutic strategies, positioning the tumor microbiota as a potential modifiable target in personalized BC care.},
}

@article {pmid41274315,
year = {2025},
author = {Najjar, I and Gandolpho, LS and Santos, JPD and Siqueira, CP and Ikechukwu, MB and Ribeiro, ÁCDS and Roch, M and Sierra, R and Andrey, D and Arrais-Rodrigues, C and Gales, AC},
title = {Phage therapy for KPC-producing Klebsiella pneumoniae decolonization in high-risk patients : The KIDNAP Study Protocol - A prospective feasibility and proof of concept study in the Brazilian context.},
journal = {International journal of antimicrobial agents},
volume = {},
number = {},
pages = {107673},
doi = {10.1016/j.ijantimicag.2025.107673},
pmid = {41274315},
issn = {1872-7913},
abstract = {BACKGROUND: There has been renewed interest in phages amidst growing antimicrobial resistance. Their potential for intestinal decolonization is interesting due to their specificity, minimal side effects and microbiota preservation. In addition, phage-resistant bacterial mutants that arise during treatment may become more susceptible to antibiotics and less virulent, possibly leading to better clinical outcomes.

OBJECTIVES: This study's primary objective is to measure the efficacy of phage-based intestinal decolonization of KPC-producing Klebsiella Pneumoniae (KPC-Kp) at 14 days post-treatment, as well as its feasibility, which is defined as >80% achieving at least 7 days of treatment. Secondary objectives will include phage safety at 14 days post-treatment, intestinal KPC-Kp load change over time, characterization of phage-resistant KPC-Kp mutants, microbiome changes, and infection-related outcomes and general clinical outcomes 3 months after the end of treatment.

METHODS: This feasibility and proof-of-concept study aims to include 15 high-risk patients recruited from a tertiary Hospital in São Paulo who will receive individualized phage combinations for a mean duration of 14 days. Safety data will be reviewed by an independent Safety Monitoring Board. Description of microbiological techniques is provided.

CONCLUSION: To the best of our knowledge this is the first published protocol that aims to establish a standardized, individualized phage-treatment framework for intestinal decolonization in a high-endemicity setting. It will also explore phage-bacterial interactions and their broader impact on bacterial virulence and susceptibility profiles. It represents a stepping stone towards implementing phage therapy in South America, and bringing knowledge and capacities to the countries most impacted by escalating AMR.},
}

@article {pmid41274275,
year = {2025},
author = {Zhang, T and Chen, SY and Zhang, C and Chen, R and Zhou, PF and Li, ZC and He, Q and Fu, XH and Wen, W and Zhang, CP and Yao, MY and Geng, JJ},
title = {HLA-B27 modulates the composition of the gut microbiota and drives a proinflammatory intestinal microecology.},
journal = {Human immunology},
volume = {87},
number = {1},
pages = {111616},
doi = {10.1016/j.humimm.2025.111616},
pmid = {41274275},
issn = {1879-1166},
abstract = {The pathogenesis of autoimmune diseases such as spondyloarthritis (SpA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) involves genetic factors and gut microbiota dysbiosis, which have been widely reported in patients and animal models. Although genetic factors are known to reshape the gut microbiota, the mechanistic role of the host gene-reshaped gut microbiota in mediating inflammatory diseases remains poorly characterized. This study focused on HLA-B27 to investigate its impact on the gut microbial composition and its association with HLA-B27 related autoimmune inflammatory diseases. The expression of HLA-B27/β2M significantly altered the diversity of the gut microbiota in mice, leading to changes in bacterial species and their functions. Concurrently, HLA-B27/β2M profoundly modified the gut metabolic profile, resulting in increased levels of multiple prostaglandins and decreased levels of anti-inflammatory metabolites. Multi-omics integrated analysis demonstrated that HLA-B27/β2M promoted the synthesis of Gram-negative bacteria while suppressing Gram-positive bacteria, findings validated in both omics datasets. Further validation confirmed that these HLA-B27/β2M-driven alterations in the gut microbial composition caused a shift toward a proinflammatory microbial community. These findings first revealed that genetic factors significantly reshaped the gut microbiota composition and further drove the microbial ecosystem toward a proinflammatory state. This study provides a foundation for identifying gut microbial signature targets in HLA-B27 associated diseases.},
}

@article {pmid41274019,
year = {2025},
author = {Chen, R and Qian, J and Wang, Q and Li, Y and Xu, Z and Zhang, M and Wang, M and Nie, H and Yang, W and Tong, X and Yan, F},
title = {Periodontitis exacerbates metabolic dysfunction-associated steatotic liver disease via the gut microbiota-derived tryptophan metabolism-AHR axis in obesity.},
journal = {EBioMedicine},
volume = {122},
number = {},
pages = {106037},
doi = {10.1016/j.ebiom.2025.106037},
pmid = {41274019},
issn = {2352-3964},
abstract = {BACKGROUND: Periodontitis is linked to metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms remain unclear.

METHODS: Periodontitis was investigated in male mice with high-fat diet (HFD)-induced MASLD. Gut microbiome and metabolomic profiling were conducted using16S rRNA gene sequencing, along with both untargeted and targeted metabolomic profiling via liquid chromatography-tandem mass spectrometry. Intestinal barrier integrity was evaluated by histopathological analysis. Faecal microbiota transplantation was conducted and the vital role of the aryl hydrocarbon receptor (AHR) was confirmed using Ahr gene knockout (Ahr[-/-]) mice. The protective roles of tryptophan derivative indole-3-propionic acid (IPA) and the tryptophan-metabolising probiotic Limosilactobacillus reuteri were assessed following their administration via oral gavage. The impact of endotoxin-mediated hyperinflammation on hepatic mitochondrial dynamics was examined in vitro.

FINDINGS: Periodontitis promoted MASLD, gut microbiota dysbiosis, and tryptophan metabolism depletion, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin overexpression in HFD-fed mice. Periodontitis-accelerated MASLD was attenuated in HFD-fed Ahr[-/-] mice. In an AHR-dependent manner, IPA or L. reuteri alleviated the detrimental effects of periodontitis on MASLD progression, intestinal barrier impairment, systemic inflammation, and endotoxin translocation to the liver. Conditioned medium from endotoxin-stimulated THP-1 cells promoted mitochondrial fission in HepG2 cells by upregulating Drp1 expression.

INTERPRETATION: Periodontitis exacerbates MASLD by disrupting the gut microbiota-tryptophan metabolism-AHR axis, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin translocation. Endotoxin plays a pivotal role in promoting hepatic mitochondrial fission during the exacerbation of MASLD by periodontitis. AHR agonists offer a novel intervention strategy for patients with comorbid MASLD and periodontitis.

FUNDING: This work was supported by the Jiangsu Province Key Research and Development Program [No. BE2022670]; National Natural Science Foundation of China [No. 82270979]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [No. JSDW202246]; and High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University [No. 0224C001].},
}