@article {pmid40957793,
year = {2025},
author = {Castrillón-Lozano, JA and Lozano-Arce, JA and Arroyave-Zuluaga, RL},
title = {Fecal microbiota transplantation in recurrent Clostridioides difficile: Is greater methodological rigor and the analysis of other populations relevant?.},
journal = {Revista de gastroenterologia de Mexico (English)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.rgmxen.2025.09.022},
pmid = {40957793},
issn = {2255-534X},
}

@article {pmid40957789,
year = {2025},
author = {Núñez, P and Quera, R and von Muhlenbrock, C},
title = {Response to "Fecal microbiota transplantation in recurrent Clostridioides difficile: Is greater methodological rigor and the analysis of other populations relevant?".},
journal = {Revista de gastroenterologia de Mexico (English)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.rgmxen.2025.09.023},
pmid = {40957789},
issn = {2255-534X},
}

@article {pmid40957477,
year = {2025},
author = {Sala, L and Carlini, V and Macas-Granizo, MB and Trabucchi, E and Pontiroli, AE and Berra, C and Naselli, A and D'Anzeo, M and Porta, A and Delgado, JM and Vianello, E and Dozio, E and Romanelli, MC and Drago, L},
title = {The eternal struggle between titans: Fecal microbiota transplant (FMT) versus metformin in type 2 diabetes (T2D) gut dysmotility.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.09.021},
pmid = {40957477},
issn = {2090-1224},
abstract = {BACKGROUND: The prevalence of dysbiosis in type 2 diabetes (T2D) is increasing globally as a consequence of an imbalance in the distribution of gut microbial populations. Dysmotility of the gastrointestinal tract has emerged as a contributor to pathophysiology of T2D, where impaired motility may exacerbate dysbiosis and metabolic dysfunction. Current management of T2D, such as Metformin (Metf), demonstrate efficacy in improving metabolic parameters but are linked to gastrointestinal side effects, the mechanisms of which remain poorly understood. Novel promising therapeutic agents, based on the modulation of the gut microbiota has emerged for the treatment of metabolic disorders, particularly for T2D, in which Fecal microbiota transplant (FMT) assumes the major weight as strategy to improves insulin sensitivity and glucose tolerance, and potentially ameliorating gut motility. Although FMT represents a potential therapeutic alternative, its comparative effectiveness and safety profile relative to Metf in this specific setting remain to be established.

AIM OF THE REVIEW: This review aims to evaluate and compare these two potent modulators of microbial landscape, Metf and FMT, in addressing insulin resistance (IR) and gastrointestinal dysmotility in T2D. The study seeks to systematically delineate the mechanisms underlying their effects and assess their therapeutic potential, safety, and clinical efficacy.

The physiological roles of the gut microbiota and their metabolites are explored, highlighting their contribution to the onset and progression of metabolic disorders, particularly T2D. We examined the mechanisms through which Metf and FMT influence gut microbiota, insulin sensitivity, and glucose tolerance. Novel therapeutic approaches, including the combined use of Metf and FMT, are discussed in terms of molecular mechanisms, clinical outcomes, and safety profiles. Finally, the potential integration of these strategies into T2D management and their impact on gastrointestinal dysfunction are considered as areas for further research.},
}

@article {pmid40752380,
year = {2025},
author = {Sendo, S and Vela, AJ and Ro, M and Thiruppathy, D and Wilkinson, EL and Zhao, Z and Hsieh, WC and Yang, S and Coras, R and Bergot, AS and Guma, M and Nguyen, A and McBride, DA and Devkota, S and Thomas, R and Shah, NJ and Svensson, MND and Zengler, K and Stanford, SM and Bottini, N},
title = {Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.},
journal = {Journal of autoimmunity},
volume = {156},
number = {},
pages = {103452},
doi = {10.1016/j.jaut.2025.103452},
pmid = {40752380},
issn = {1095-9157},
mesh = {Animals ; *Haploinsufficiency ; Mice ; *Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics ; *Gastrointestinal Microbiome/immunology ; Humans ; *Arthritis, Rheumatoid/immunology/genetics/microbiology ; *Dysbiosis/immunology ; Disease Models, Animal ; *Arthritis, Juvenile/immunology/genetics/microbiology ; *Arthritis, Experimental/immunology ; Female ; Male ; Fecal Microbiota Transplantation ; },
abstract = {Gut dysbiosis is observed in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), however, how it promotes disease in interaction with other environmental and genetic risk factors remains unclear. Here we assessed interactions between gut dysbiosis and RA/JIA-associated loss of function haplotypes of the RA/JIA-associated PTPN2 gene by inducing mannan-induced arthritis in germ-free PTPN2[+/+] and PTPN2 haploinsufficient (PTPN2[+/-]) SKG mice reconstituted with fecal microbiota from six patients with seropositive RA. Mannan-induced arthritis and lymph node T cell immunophenotypes were identical in germ free PTPN2[+/+] vs PTPN2[+/-] SKG mice. While no difference in arthritis severity was seen among PTPN2[+/+] mice recipient of RA gut microbiota, two microbiomes (RA#02 and RA#86) enhanced arthritis in PTPN2[+/-] mice. The microbiome of RA patient microbiota recipient mice exclusively clustered by patient of origin and the RA#86 microbiome was found to carry a significant expansion of Prevotella genera, which is associated with RA dysbiosis. RA#86 microbiota-recipient PTPN2[+/-] mice selectively displayed increased joint GM-CSF expression and an expansion of CD4[+]RORγt[+]FoxP3[-] T cells in the joints, without evidence of increased intestinal inflammation, gut barrier leakage or expansion of P. copri in post-mannan fecal samples. Monocolonization with P. copri caused enhanced arthritis and CD4[+]RORγt[+]FoxP3[-] T cells expansion in PTPN2[+/-] vs PTPN2[+/+] mice. Our data support current views about P. copri promotion of autoimmune arthritis and suggest that its pathogenicity can be amplified via interaction with a dysbiotic context and risk factors that enhance gut mucosa immune responses.},
}

Animals
*Haploinsufficiency
Mice
*Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics
*Gastrointestinal Microbiome/immunology
Humans
*Arthritis, Rheumatoid/immunology/genetics/microbiology
*Dysbiosis/immunology
Disease Models, Animal
*Arthritis, Juvenile/immunology/genetics/microbiology
*Arthritis, Experimental/immunology
Female
Male
Fecal Microbiota Transplantation

@article {pmid40952592,
year = {2025},
author = {Chen, C and Wang, GQ and Li, DD and Zhang, F},
title = {Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets.},
journal = {Molecular biomedicine},
volume = {6},
number = {1},
pages = {64},
pmid = {40952592},
issn = {2662-8651},
support = {No. 82160690//National Natural Science Foundation of China/ ; No. ZK [2021]-014//Science and Technology Foundation of Guizhou Province/ ; No. 2020-39//Collaborative Innovation Center of Chinese Ministry of Education/ ; },
abstract = {The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central nervous system (CNS) through immune, neural, endocrine, and metabolic pathways. Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases. This review outlines the key molecular mechanisms by which gut microbes modulate neuroinflammation, blood-brain barrier integrity, protein misfolding, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and overlapping pathways through which gut dysbiosis may contribute to pathogenesis. We further explore the translational potential of microbiota-targeted therapies, including probiotics, fecal microbiota transplantation, dietary interventions, and small-molecule modulators. While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers. Challenges remain in deciphering causal relationships, accounting for inter-individual variability, and ensuring reproducibility in therapeutic outcomes. Future research should integrate multi-omics strategies, longitudinal human cohorts, and mechanistic models to clarify the role of the MGBA in neurodegeneration. Collectively, understanding the MGBA provides a transformative perspective on neurodegenerative disease mechanisms and offers innovative therapeutic avenues that bridge neurology, microbiology, and precision medicine.},
}

@article {pmid40952509,
year = {2025},
author = {Bretthauer, M},
title = {[What is confirmed in colorectal cancer screening?].},
journal = {Innere Medizin (Heidelberg, Germany)},
volume = {},
number = {},
pages = {},
pmid = {40952509},
issn = {2731-7099},
abstract = {BACKGROUND: The incidence and mortality of colorectal cancer in Germany has declined in recent years. Nevertheless, colorectal cancer is still the second most common cancer in women (after breast cancer) and the third most common in men in Germany (after prostate cancer and lung cancer). Screening for colorectal cancer is well-established in many countries. The two most recommended screening strategies are colonoscopy and fecal immunochemical testing (FIT, stool test for occult blood).

OBJECTIVE: This article explains important conceptual and practical differences between the two strategies offered in Germany and summarizes the latest high-quality evidence for the benefits of the most frequently used screening tests. The aim is to provide physicians with decision aids for patients who show interest in colorectal cancer screening.

MATERIAL AND METHODS: Confirmed high-quality evidence from randomized trials on the benefits of screening for colorectal cancer with respect to incidence and mortality.

RESULTS: The lifetime risk to develop colorectal cancer in Germany is 5% for women and 6.5% for men. According to a large randomized trial, a screening colonoscopy reduces the risk of colorectal cancer from 1.2% to 0.8-0.9% after 10 years. New high-quality evidence from a recent Spanish randomized trial also showed that the benefits of FIT screening every other year are comparable to those of 1 colonoscopy over 10 years. The risks of perforation and bleeding during colonoscopy are 0.01% and 0.1%, respectively.

CONCLUSION: During the medical patient clarification on screening, it is recommended that the abovenamed facts on benefits and risks should be included and explained.},
}

@article {pmid40952001,
year = {2025},
author = {Raich, SS and Majzoub, ME and Haifer, C and Paramsothy, S and Shamim, MMI and Borody, TJ and Leong, RW and Kaakoush, NO},
title = {Bacterial taxonomic and functional changes following oral lyophilized donor fecal microbiota transplantation in patients with ulcerative colitis.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0099125},
doi = {10.1128/msystems.00991-25},
pmid = {40952001},
issn = {2379-5077},
abstract = {UNLABELLED: Oral lyophilized fecal microbiota transplantation (FMT) can induce remission in patients with active ulcerative colitis (UC); however, our understanding of how this form of FMT alters the patient microbiome remains limited. Here, we analyzed data from a recent randomized, double-blind, placebo-controlled clinical trial of FMT in UC to assess donor species colonization and factors responsible for efficacy using this form of therapy. The gut microbiome of donors and patients was profiled longitudinally using deep shotgun metagenomic sequencing, and microbiome diversity, species-genome bin presence, functional profiles, and the resistome were studied. The gut microbiome of patients treated with oral lyophilized FMT significantly increased in species-genome bin richness and shifted in composition toward the donor profiles; this was not observed in patients receiving placebo. While species-genome bin richness was not associated with clinical response in this trial, we identified donor- and patient-specific features associated with the induction of remission and maintenance of response. However, the presence of a Clostridium species-genome bin, as well as L-citrulline biosynthesis contributed by Alistipes spp., was seen in responders treated by either donor. Several of the above outcomes were found to be consistent when data were analyzed at the level of metagenome-assembled genomes. FMT was also found to deplete the resistome within patients treated with antibiotics to levels lower than the UC baseline. Single donor oral lyophilized FMT substantially modifies taxonomic diversity and composition as well as microbiome function and the resistome in patients with UC, with several features identified as strongly linked to response regardless of the donor used.

IMPORTANCE: There is a limited amount of work examining the effects of oral lyophilized fecal microbiota transplantation (FMT) on the microbiome of patients with ulcerative colitis (UC), and less so studies examining species-level dynamics and functional changes using this form of FMT. We performed deep shotgun metagenomic sequencing to provide an in-depth species-genome bin-level analysis of the microbiome of patients with UC receiving oral lyophilized FMT from a single donor. We identified key taxonomic and functional features that transferred into patients and were associated with clinical response. We also determined how FMT impacts the resistome of patients with UC. We believe these findings will be important in ongoing efforts to not only improve the efficacy of FMT in UC but also allow for the transition to defined microbial therapeutics, foregoing the need for FMT donors.},
}

@article {pmid40951341,
year = {2025},
author = {Liao, L and Zeng, M and Liu, D and He, Y and Du, W and Cao, Y},
title = {Focus on gut microbes: new direction in cancer treatment.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1505656},
pmid = {40951341},
issn = {2234-943X},
abstract = {Gut microbes are emerging as critical regulators in cancer therapy, influencing the efficacy and toxicity of radiotherapy, chemotherapy, immunotherapy, targeted therapy, Traditional Chinese Medicine, and rehabilitation interventions. Acting through metabolic reprogramming, immune modulation, DNA damage, and tumor microenvironment remodeling, specific microbial taxa and their metabolites can either enhance or hinder treatment outcomes. However, these interactions are highly context-dependent and shaped by individual factors such as diet, geography, and host immunity. While microbial interventions such as probiotics, fecal microbiota transplantation, and engineered bacteria show promise, their translation into precise and safe clinical applications remains limited by interindividual variability, regulatory hurdles, and incomplete mechanistic understanding. Future efforts should focus on defining high-evidence microbial signatures, clarifying causal mechanisms, and developing personalized microbiome-based therapeutic strategies, potentially integrated with nanotechnology. This review underscores the need for interdisciplinary approaches to harness gut microbiota as co-targets in cancer treatment.},
}

@article {pmid40951313,
year = {2025},
author = {Dai, X and Chen, H and Zhang, M and Yang, Q and Huang, Z and Tang, L},
title = {Exercise improves endothelial progenitor cell's function in mice with Type 2 diabetes via gut microbiota modulation.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1606652},
pmid = {40951313},
issn = {2235-2988},
abstract = {INTRODUCTION: Evidence has proved that exercise increases migration and tube formation of rat EPCs. But the mechanism behind the improved function of EPCs by exercise remains unclear.

METHODS: This study conducted 8-week exercise interventions (aerobic, resistance, or combined) in 6-week-old type 2 diabetic mice, assessing post-exercise glucose, weight, GLP-1, and gut microbiota. Mice with optimal outcomes were selected as fecal donors for microbiota transplantation via gavage. Recipient mice were evaluated for GLP-1, microbiota changes, and endothelial progenitor cell (EPC) proliferation/migration.

RESULTS: Exercise altered microbial composition (e.g., increased Prevotellaceae and Ligilactobacillus), while fecal microbiota transplantation(FMT) enriched Akkermansia. Notably, FMT elevated plasma Glucagon-like peptide-1 (GLP-1) levels by 0.92 pmmol/L (P < 0.001) compared to controls, surpassing the modest, non-significant effects of exercise alone. Critically, FMT enhanced EPC's proliferation (P < 0.007 vs. controls) and migration (P < 0.05), mirroring exercise-induced improvements. While exercise reduced body weight (e.g., 10.58 g in aerobic training (AT), P < 0.001) and blood glucose, FMT amplified these metabolic benefits, lowering glucose by 9.22 mmol/L (P < 0.001).

DISCUSSION: Our findings suggest that exercise improves EPC's function in diabetic mice via gut microbiota modulation, with FMT synergistically enhancing GLP-1 secretion. The identified microbiota (Prevotellaceae, Ligilactobacillus, Akkermansia) may serve as therapeutic targets for T2DM(T2DM) and its cardiovascular complications.},
}

@article {pmid40951310,
year = {2025},
author = {Cui, X and Li, J and Yang, T},
title = {Editorial: Gut microbiota-derived metabolites and cardiovascular diseases.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1661489},
pmid = {40951310},
issn = {2235-2988},
}

@article {pmid40950584,
year = {2025},
author = {Cui, Y and An, P and Li, F and Duan, F and Mei, Z and Ye, Q and Wang, G and Zhang, H and Luo, Y},
title = {Strategies to reduce uric acid through gut microbiota intervention.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1654152},
pmid = {40950584},
issn = {1664-302X},
abstract = {Hyperuricaemia (HUA) is a metabolic disorder resulting from the dysregulation of purine metabolism. It is closely associated with gout and various metabolic syndromes, representing an increasing global public health challenge. Current treatment approaches for HUA and gout generally involve the lifelong administration of urate-lowering agents to maintain optimal serum urate concentrations. However, poor patient adherence, often due to potential hepatorenal toxicity, frequently leads to disease relapse. Recent evidence indicates that the gut microbiota plays a significant role in maintaining urate homeostasis through multiple mechanisms, including the modulation of purine metabolism, urate catabolism and excretion, regulation of inflammatory responses, and preservation of intestinal barrier integrity. These findings highlight the gut microbiota as a promising novel therapeutic target. This review synthesizes recent progress in three key areas: (1) the relationship between the gut microbiota and HUA; (2) microbial mechanisms underlying urate-lowering effects, such as microbial purine and urate metabolism, regulation of urate transporters like ABCG2, and production of anti-inflammatory metabolites; and (3) microbiota-based therapeutic interventions, including probiotics, engineered bacterial strains, fecal microbiota transplantation, and pharmabiotic strategies. Additionally, we explore the translational potential of microbiota modulation in clinical settings and outline directions for future research. By integrating mechanistic understanding with therapeutic innovation, this review offers researchers and clinicians a comprehensive framework for advancing microbiota-targeted approaches in the management of hyperuricaemia.},
}

@article {pmid40948871,
year = {2025},
author = {Thomas-Valdés, S and Jorquera, G},
title = {Editorial: Food-derived phytochemicals as regulators of gut microbiota.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1681732},
pmid = {40948871},
issn = {2296-861X},
}

@article {pmid40948444,
year = {2025},
author = {Bryson, S and Sisson, Z and Nelson, B and Grove, J and Reister, E and Liachko, I and Auch, B and Graiziger, C and Khoruts, A},
title = {Use of proximity ligation shotgun metagenomics to investigate the dynamics of plasmids and bacteriophages in the gut microbiome following fecal microbiota transplantation.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2559019},
doi = {10.1080/19490976.2025.2559019},
pmid = {40948444},
issn = {1949-0984},
abstract = {Proximity ligation shotgun metagenomics facilitate the analysis of the relationships between mobile genetic elements, such as plasmids and bacteriophages, and their specific bacterial hosts. We applied this technique to investigate the changes in the fecal microbiome of patients receiving fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infections (rCDI). FMT was associated with successful engraftment of donor bacteria along with their associated bacteriophages. While fecal microbial diversity increased in all patients, the extent of specific bacterial taxa engraftment varied among individual patients. Interestingly, some donor bacteriophages remained closely linked to their original bacterial hosts, while others expanded their associations across different bacterial taxa. Notably, FMT partially reduced the content of vancomycin resistance and extended-spectrum beta-lactamase genes in the fecal microbiome of rCDI patients.},
}

@article {pmid40948097,
year = {2025},
author = {Gao, BY and Chen, SC},
title = {Gut Microbiota Typing and Donor Factors Shape Fecal Microbiota Transplantation Response in Psoriatic Arthritis.},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43392},
pmid = {40948097},
issn = {2326-5205},
}

@article {pmid40948087,
year = {2025},
author = {Kragsnaes, MS and Qin, P and Kjeldsen, J and Kristiansen, K and Ellingsen, T},
title = {Response to: "Gut Microbiota Typing and Donor Factors Shape Fecal Microbiota Transplantation Response in Psoriatic Arthritis".},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43394},
pmid = {40948087},
issn = {2326-5205},
}

@article {pmid40947138,
year = {2025},
author = {Wang, W and Yu, Y and Wang, R and Wang, Y and Ding, X and Lu, G and Lu, C and Liang, C and Zhang, S and Yi, B and Bai, J and Zhang, L and Li, P and Wen, Q and Cui, B and Zhang, F},
title = {Holdemanella biformis augments washed microbiota transplantation for the treatment of radiation enteritis.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-335230},
pmid = {40947138},
issn = {1468-3288},
abstract = {BACKGROUND: Current microbiome-based therapeutics face two prominent issues: the limited clinical efficacy of probiotics and the significant variability in the efficacy of microbiota transplantation across different diseases. Although washed microbiota transplantation (WMT) is a new faecal microbiota transplantation, a single therapeutic agent cannot be universally effective for multiple dysbiosis-related diseases.

OBJECTIVE: We introduced a new therapeutic concept, X-augmented WMT (X-auWMT), which combines a disease-specific beneficial microbe, 'X', with WMT to enhance its effectiveness. Our goal was to identify a candidate 'X' bacterium to augment WMT efficacy and examine the efficacy of X-auWMT in animal models of radiation enteritis (RE).

DESIGN: We conducted a prospective, non-randomised cohort study on a cohort of abdominal or pelvic cancer patients who developed RE after radiotherapy to identify a potential beneficial microbe. We used RE mouse models to evaluate the efficacy of X-auWMT compared with WMT. Multiomics analyses and experiments were undertaken to elucidate the underlying mechanisms.

RESULTS: WMT significantly alleviated multiple clinical symptoms in RE patients compared with routine treatments. We identified Holdemanella biformis as a candidate 'X' bacterium within the RE cohort and developed Hb-auWMT. Hb-auWMT significantly mitigated radiation-induced injury compared with WMT, exhibiting enhanced anti-apoptotic effects, improved maintenance of epithelial hypoxia, increased Treg cell levels and elevated butyrate and valerate levels in the RE mouse model. PPAR-γ is an essential pathway for the therapeutic efficacy of Hb-auWMT.

CONCLUSIONS: This study overcomes the aforementioned recognised limitations with probiotics and microbiota transplantation and provides a new research paradigm in the concept of microbiome-based therapeutics.},
}

@article {pmid40947025,
year = {2025},
author = {Yang, X and Liu, Z and You, T and Feng, H and Sun, F and Yao, J and Gao, Y and Yang, Y and Chen, C and Qiu, J},
title = {High-temperature exposure induces neurobehavioral abnormalities in mice through disruption of the gut microbiota.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {120318},
doi = {10.1016/j.jad.2025.120318},
pmid = {40947025},
issn = {1573-2517},
abstract = {Rising global temperatures pose significant health risks. However, the neurobehavioral consequences of high-temperature exposure remain understudied. In this study, C57BL/6J mice were exposed to three temperature levels (26 °C, 38 °C, and 40 °C) for 3, 7, and 14 days. Fecal microbiota transplantation (FMT) was performed to further investigate the role of the gut microbiota. Two-sample MR was employed to estimate the causal impact of gut microbiota composition on inflammation and neurobehavioral abnormalities. We found that mice exposed to 40 °C for 14 days exhibited impaired motor coordination and spatial memory, reduced exploratory behavior, and increased anxiety. Neuronal damage was observed in the cerebral cortex and hippocampus, along with structural damage and barrier dysfunction in the ileum and colon. Moreover, high-temperature exposure elicited a significant rise in circulating lipopolysaccharide (LPS), a concomitant dysregulation of inflammatory cytokine, and pronounced activation of the NF-κB signaling pathway. FMT from healthy mice ameliorated these adverse effects. Although high temperature reshaped both fungal and bacterial communities, only bacterial dysbiosis correlated with neurobehavioral abnormalities. MR further indicated that gut microbiota perturbations may causally drive inflammatory responses and neurobehavioral abnormalities. In summary, high-temperature exposure evokes inflammatory responses and neurobehavioral abnormalities via gut bacterial dysbiosis.},
}

@article {pmid40946868,
year = {2025},
author = {Deutschbein, F and Ianiro, G},
title = {Fecal microbiota transplantation for primary Clostridioides difficile infection. Ready for prime time?.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.09.017},
pmid = {40946868},
issn = {1528-0012},
}

@article {pmid40946450,
year = {2025},
author = {Zharova, NV and Mikhailidi, FD and Kabanova, DA and Tatarintseva, AY and Polyakova, OL and Zharikov, YO and Zharov, NA and Ryagin, SN and Pontes-Silva, A and Zharikova, TS},
title = {Influence of microbiota composition on the pathogenesis of type 2 diabetes: Physiological aspects.},
journal = {Molecular aspects of medicine},
volume = {106},
number = {},
pages = {101410},
doi = {10.1016/j.mam.2025.101410},
pmid = {40946450},
issn = {1872-9452},
abstract = {The development of type 2 diabetes may be influenced by enterotypes and bacterial metabolites. The most important of these are short-chain fatty acids (SCFAs), which play a role in forming the gut-brain axis and in the process of lipogenesis. An increase in lipogenesis can lead to obesity. High levels of adipose tissue in the body trigger chronic inflammation and insulin resistance. This review examines how microbiota composition influences the pathogenesis of type 2 diabetes and the possibility of regulating microbiota through proper nutrition, fecal microbiota transplantation, and prebiotics and probiotics. Additionally, the review notes that an imbalance in the gut microbiota can contribute to diabetes progression and increase cancer risk through inflammatory and immune mechanisms.},
}

@article {pmid40945503,
year = {2025},
author = {Bartu, L and Faith, JJ},
title = {Searching for the perfect match: MINDFUL trial pairs FMT and fiber for ulcerative colitis.},
journal = {Med (New York, N.Y.)},
volume = {6},
number = {9},
pages = {100842},
doi = {10.1016/j.medj.2025.100842},
pmid = {40945503},
issn = {2666-6340},
abstract = {Every trial of fecal microbiota transplantation for ulcerative colitis inspires the same question at seminars and journal clubs: can you combine FMT with a diet or fiber to improve strain engraftment and outcomes? The MINDFUL clinical trial explores this question by testing the impact of FMT with or without psyllium fiber supplementation in 27 ulcerative colitis patients.},
}

@article {pmid40945252,
year = {2025},
author = {Zhao, Y and Wang, Q and Wu, Z and Zhou, Y and Gao, X and Gong, W and Qin, X and Ren, Y and Tian, J},
title = {Modified Xiaoyaosan rescues depression-like behavior via remodeling gut microbiota and leucine metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {147},
number = {},
pages = {157241},
doi = {10.1016/j.phymed.2025.157241},
pmid = {40945252},
issn = {1618-095X},
abstract = {BACKGROUND: Social avoidance is a hallmark symptom of depression. Although Modified Xiaoyaosan (MXYS) has been reported to attenuate this behavior, the underlying mechanisms remain poorly understood.

PURPOSE: This study aimed to investigate the mechanisms by which MXYS alleviates social avoidance, with particular emphasis on gut microbiota composition and leucine metabolism.

METHODS: A chronic social defeat stress (CSDS) mouse model was established to evaluate the antidepressant effects of MXYS. Fecal samples were subjected to LC-MS-based untargeted metabolomics and 16S rRNA sequencing to characterize alterations in gut microbiota and metabolites. Fecal microbiota transplantation (FMT) was conducted to verify the contribution of gut microbes to MXYS's antidepressant effects. Furthermore, targeted GC-MS, LC-MS/MS, and Western blotting analyses were employed to elucidate the mechanisms underlying leucine reduction. Finally, exogenous leucine supplementation was administered to determine its potential antidepressant efficacy.

RESULTS: MXYS treatment significantly ameliorated CSDS-induced social avoidance and other depression-like behaviors. Integrated metabolomic and 16S rRNA analyses identified leucine metabolism as a potential therapeutic target. MXYS modulated gut microbial composition and functional pathways, particularly those involved in leucine metabolism. FMT experiments confirmed the essential role of gut microbiota in mediating the antidepressant effects of MXYS. Targeted metabolic profiling and protein expression analyses revealed that enhanced microbial degradation of leucine contributed to its systemic reduction. Moreover, leucine supplementation robustly reversed depressive-like behaviors and attenuated hippocampal oxidative stress.

CONCLUSION: MXYS alleviates social avoidance in CSDS mice by modulating gut microbiota-mediated leucine degradation, thereby restoring systemic leucine levels and improving hippocampal oxidative stress.},
}

@article {pmid40944286,
year = {2025},
author = {Tini, S and Baima, J and Pigni, S and Antoniotti, V and Caputo, M and De Palma, E and Cerbone, L and Grosso, F and La Vecchia, M and Bona, E and Prodam, F},
title = {The Microbiota-Diet-Immunity Axis in Cancer Care: From Prevention to Treatment Modulation and Survivorship.},
journal = {Nutrients},
volume = {17},
number = {17},
pages = {},
doi = {10.3390/nu17172898},
pmid = {40944286},
issn = {2072-6643},
support = {2020NCKXBR_004; P2022Z4EB5; 2022ALX9ZM//Ministero dell'Università e della Ricerca/ ; Micromeso project//LILT/ ; },
abstract = {Growing evidence highlights the pivotal role of the gut microbiota in cancer development, progression, response to therapy, and survivorship. Diet plays a central role in shaping gut microbiota composition, influencing the immune system and overall host health. Plant-based diets and the Mediterranean diet promote health-associated microbial communities that increase the production of several metabolic-end products, including short-chain fatty acids that support mucosal barrier integrity, anti-inflammatory effects, and modulation of the immunity of the host. Conversely, Western dietary patterns promote cancer progression and negatively impact the response to standard treatments. Furthermore, gut microbiota influences the effectiveness of cancer therapies, including chemotherapy, radiotherapy and, mainly, immunotherapy. Modulating microbial species, their metabolites, or their activities in the cancer microenvironment through dietary interventions, common or engineered probiotics, prebiotics, postbiotics, antibiotics or fecal microbial transplant are emerging as promising strategies for cancer prevention and tailored management in survivorship. In this review, we explore the intricate interplay between diet, gut microbiota, and cancer, focusing on how specific microbial communities' impact therapeutic outcomes, and the challenges in the modulation of the microbiota environment through several interventions, including diet. This emerging paradigm paves the way for integrating nutrition and microbiota-targeted strategies as innovative tools in the context of precision medicine.},
}

@article {pmid40943741,
year = {2025},
author = {Ichim, C and Boicean, A and Todor, SB and Anderco, P and Bîrluțiu, V},
title = {Fecal Microbiota Transplantation in Patients with Alcohol-Associated Cirrhosis: A Clinical Trial.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
doi = {10.3390/jcm14175981},
pmid = {40943741},
issn = {2077-0383},
abstract = {Background: Gut microbiota dysregulation is increasingly recognized as a key contributor to the progression of liver cirrhosis and its complications, particularly hepatic encephalopathy. Fecal microbiota transplantation (FMT) has emerged as a novel therapeutic strategy aimed at restoring intestinal microbial homeostasis and modulating systemic inflammation. Methods: This prospective, single-center clinical trial evaluated the short-term safety and efficacy of FMT in patients with alcohol-related liver cirrhosis. Clinical assessment, liver stiffness (via elastography), steatosis (controlled attenuation parameter), inflammatory biomarkers, and extended biochemical panels were analyzed at baseline, one week and one month post-FMT. A control group receiving standard medical therapy was used for comparison. Results: FMT was associated with a significant reduction in hepatic encephalopathy severity (p = 0.014), sustained improvements in liver stiffness (p = 0.027) and decreased steatosis (p = 0.025). At one month, C-reactive protein and neutrophil-to-lymphocyte ratio both declined significantly (p = 0.043), indicating a measurable anti-inflammatory effect. No serious adverse events were recorded. In comparison with controls, FMT recipients showed lower systemic inflammation and improved neuropsychiatric status. Conclusions: FMT demonstrated a favorable safety profile and yielded early clinical and biochemical benefits in patients with cirrhosis. These preliminary findings support the potential utility of microbiota-based interventions in chronic liver disease and warrant validation in larger, multicenter trials.},
}

@article {pmid40943575,
year = {2025},
author = {Rubas, NC and Torres, A and Maunakea, AK},
title = {The Gut Microbiome and Epigenomic Reprogramming: Mechanisms, Interactions, and Implications for Human Health and Disease.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
doi = {10.3390/ijms26178658},
pmid = {40943575},
issn = {1422-0067},
support = {R01MD016593//National Institute on Minority Health and 510 Health Disparities/ ; R56MD014630//National Institute on Minority Health and 510 Health Disparities/ ; },
abstract = {The human gut microbiome is a metabolically active and ecologically dynamic consortium that profoundly influences host physiology, in part by modulating epigenetic mechanisms such as DNA and RNA methylation. These modifications regulate gene expression and phenotypic plasticity and are shaped by a combination of environmental factors, such as diet, stress, xenobiotics, and bioactive microbial metabolites. Despite growing evidence linking microbial signals to host epigenetic reprogramming, the underlying molecular pathways remain incompletely understood. This review highlights recent mechanistic discoveries and conceptual advances in understanding microbiome-host epigenome interactions. We discuss evolutionarily conserved pathways through which gut microbiota regulate host methylation patterns, including one-carbon metabolism, polyamine biosynthesis, short-chain fatty acid signaling, and extracellular vesicle-mediated communication. We also examine how host factors such as aging, diet, immune activity, and sociocultural context reciprocally influence microbial composition and function. Beyond basic mechanisms, we outline translational frontiers-including biomarker discovery, live biotherapeutic interventions, fecal microbiota transplantation, and adaptive clinical trial designs-that may enable microbiome-informed approaches to disease prevention and treatment. Advances in high-throughput methylation mapping, artificial intelligence, and single-cell multi-omics are accelerating our ability to model these complex interactions at high resolution. Finally, we emphasize the importance of rigorous standardization and ethical data governance through frameworks such as the FAIR and CARE principles. Deepening our understanding of how the gut microbiome modulates host epigenetic programs offers novel opportunities for precision health strategies and equitable clinical translation.},
}

@article {pmid40943409,
year = {2025},
author = {Tonch-Cerbu, AK and Boicean, AG and Stoia, OM and Teodoru, M},
title = {Gut Microbiota-Derived Metabolites in Atherosclerosis: Pathways, Biomarkers, and Targets.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
doi = {10.3390/ijms26178488},
pmid = {40943409},
issn = {1422-0067},
abstract = {The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut-heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research.},
}

@article {pmid40941154,
year = {2025},
author = {Zhang, J and Wei, ZJ and Fan, G},
title = {Emerging Understanding of Gut Microbiome in Colorectal Cancer and Food-Related Intervention Strategies.},
journal = {Foods (Basel, Switzerland)},
volume = {14},
number = {17},
pages = {},
doi = {10.3390/foods14173040},
pmid = {40941154},
issn = {2304-8158},
support = {2022YFF1100306//National Key Research & Development Program of China/ ; 2023AAC03272//the Natural Science Foundation of Ningxia Hui Autonomous Region/ ; },
abstract = {Colorectal cancer (CRC) is one of the most common cancers, accounting for approximately 10% of all new cancer cases globally. An increasing number of studies have revealed that the gut microbiome is strongly associated with the pathogenesis and progression of CRC. Based on these advances, this review delineates the mechanistic links between specific microbes and CRC, as well as emerging food-related nutritional intervention strategies. In vivo and in vitro studies have pinpointed the implications of key microbes such as Fusobacterium nucleatum, certain strains of Escherichia coli, enterotoxigenic Bacteroides fragilis, and Enterococcus faecalis, among others, and metabolite involvement and immune responses. Particular attention is paid to the roles of intratumoral microbiota in the development and treatment of CRC, given their direct interaction with tumor cells. Various food-related nutritional intervention strategies have been developed to mitigate CRC risk, including probiotics, antibiotics, or the administration of bioactive compounds such as luteoloside. Finally, we outline critical research directions regarding the influence of animal lineage, carcinoma location, population demographics, the application of advanced in vitro models, and the mediatory roles of gut-associated epithelial cells. In summary, this review might consolidate our current knowledge on the contribution of gut microbiota to CRC and highlights the microbe-based strategies to enhance nutritional interventions for this disease.},
}

@article {pmid40940892,
year = {2025},
author = {Mohamed, AS and Bhuju, R and Martinez, E and Basta, M and Deyab, A and Mansour, C and Tejada, D and Deshpande, V and Elias, S and Nagesh, VK},
title = {The Gut Microbiome's Impact on the Pathogenesis and Treatment of Gastric Cancer-An Updated Literature Review.},
journal = {Cancers},
volume = {17},
number = {17},
pages = {},
doi = {10.3390/cancers17172795},
pmid = {40940892},
issn = {2072-6694},
abstract = {The gut microbiota plays a critical role in maintaining gastrointestinal homeostasis, immune regulation, and metabolic processes. Recent evidence has highlighted its significant influence on gastric carcinogenesis. Helicobacter pylori, a well-established class I carcinogen, remains the most prominent microbial risk factor for gastric cancer. However, emerging studies indicate that alterations in the broader gastric and intestinal microbial communities, referred to as dysbiosis, may also contribute to tumor initiation, progression, and immune evasion. These microbial shifts can lead to chronic inflammation, genotoxic metabolite production, and modulation of signaling pathways such as NF-κB and Wnt/β-catenin. This review explores the current understanding of the gut microbiome's contribution to gastric cancer pathogenesis, including microbial signatures associated with precancerous lesions and the tumor microenvironment. Furthermore, the potential of microbiota-based biomarkers and therapeutic interventions, including probiotics, prebiotics, and fecal microbiota transplantation, is discussed as part of emerging precision medicine strategies.},
}

@article {pmid40937436,
year = {2025},
author = {Huang, X and Yu, Y and Tian, N and Huang, J and Zhang, X and Yu, R},
title = {Human microbiota-associated animal models: a review.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1644187},
pmid = {40937436},
issn = {2235-2988},
abstract = {Human microbiota-associated (HMA) animal models have become indispensable tools for investigating microbe-host interactions and disease pathogenesis. However, standardization challenges persist across different research groups when such models are used in fecal microbiota transplantation (FMT) protocols. Establishing a successful HMA model involves multiple stages, including donor screening, fecal suspension preparation, recipient preparation, and FMT. The outcomes of these stages are influenced by donor characteristics, recipient type, microbial viability, and dietary factors. This review examined the critical components of HMA model production, including the inclusion and exclusion criteria for human donors, collection time and processing methodology for fecal samples, recipient animal preparation strategies, and FMT regimens with engraftment validation. The key findings revealed that short-term antibiotic, probiotic, or laxative use constitutes an essential donor exclusion criterion. The time and method of fecal collection should be standardized as much as possible. Fecal samples should be processed as soon as possible, in anaerobic environments, with the addition of suitable protectants if they must be preserved at low temperatures. Microbial community profiling via 16S rRNA gene sequencing represents the primary method for analyzing microbiome composition and verifying microbiota engraftment efficacy throughout FMT procedures. The most commonly used recipients for HMA modeling included germ-free and pseudo-germ-free animals generated through antibiotic-mediated microbiota depletion. Although FMT with a single gavage of fecal suspension proved sufficient for model establishment, multiple frequencies and longer FMT durations significantly improved the efficiency of donor microbiota colonization. Overall, these findings are expected to aid the establishment of a standardized and reproducible protocol for preparing HMA models.},
}

@article {pmid40937422,
year = {2025},
author = {Bu, S and Cheng, X and Chen, M and Yu, Y},
title = {Ulcerative Colitis: Advances in Pathogenesis, Biomarkers, and Therapeutic Strategies.},
journal = {Pharmacogenomics and personalized medicine},
volume = {18},
number = {},
pages = {219-238},
pmid = {40937422},
issn = {1178-7066},
abstract = {Ulcerative colitis represents an inflammatory bowel disease with multiple contributing factors, marked by persistent inflammation of the colonic mucosa, which can lead to a reduced life expectancy and an elevated likelihood of requiring colectomy as well as developing colorectal cancer. Despite impacting roughly 5 million individuals worldwide, the intricate mechanisms underlying ulcerative colitis are still inadequately defined, hindering the development of effective treatments. Extra-intestinal complications, including enteropathic arthritis, are also addressed in the context of disease burden and management. This review explores the multifaceted pathogenesis of ulcerative colitis, emphasizing critical factors such as abnormalities in the epithelial barrier, irregular immune responses, the release of inflammatory mediators, and alterations in gut microbiota composition. We also underscore recent advancements in diagnostic biomarkers that improve the accuracy of disease detection and monitoring. Conventional medicinal strategies are reviewed alongside the emergence of biological therapies, notably those that target tumor necrosis factor (TNF), interleukins, and integrins, which have significantly altered management approaches. Established therapies (eg, 5-aminosalicylic acid, corticosteroids) and emerging agents (eg, JAK inhibitors, S1P modulators) are clearly delineated. Combination strategies-such as dual biologic regimens or JAK inhibitors combined with anti-integrin agents-are also discussed in dedicated subsections. We discuss novel therapies that utilize small molecule targeting, particularly those that inhibit Janus kinase (JAK) and modulate sphingosine-1-phosphate (S1P) receptors, presenting promising avenues for treatment. Additionally, fecal microbiota transplantation (FMT) is evaluated as a therapeutic option, as it shows promise in restoring microbial balance. Collectively, these advances underscore the pivotal roles of immune dysregulation, biologic therapies, and microbiota modulation in reshaping precision management of ulcerative colitis. This synthesis of current knowledge underscores the necessity for continued research to refine therapeutic strategies and improve patient outcomes in ulcerative colitis.},
}

@article {pmid40937050,
year = {2025},
author = {Peña, JA and Mazhuvanchery, CB and Santos, MJMN and Naz, S and Cruz, CC and Wali, S and Varatharajalu, K and Okhuysen, PC and Vuong, NN and Wang, Y},
title = {Bezlotoxumab for the prevention of recurrent Clostridioides difficile infection for patients with cancer.},
journal = {Annals of gastroenterology},
volume = {38},
number = {5},
pages = {519-525},
pmid = {40937050},
issn = {1108-7471},
abstract = {BACKGROUND: Several clinical factors increase the susceptibility of cancer patients to Clostridioides difficile infection (CDI), often resulting in lower CDI treatment response rates and higher rates of recurrent CDI (rCDI). Bezlotoxumab, a monoclonal antibody targeting and neutralizing C. difficile toxin B, demonstrates a significant reduction in rCDI rates compared to standard of care alone in the general population. However, the effectiveness of bezlotoxumab in the cancer patient population requires further investigation. We assessed the incidence of rCDI within 90 days of bezlotoxumab treatment in patients with cancer.

METHODS: This was a single-center retrospective cohort study conducted at a tertiary care cancer center, including patients who received bezlotoxumab with standard-of-care antibiotics for CDI or rCDI between March 2016 and January 2023. Descriptive analyses were conducted.

RESULTS: A total of 177 patients with cancer who received bezlotoxumab were included. Most (76.8%) experienced <2 CDI episodes, whereas 23.2% experienced ≥2 episodes. Bezlotoxumab was administered a median of 10 days (interquartile range [IQR] 5-12.5) after symptom onset, and fidaxomicin was the most frequently used concurrent antibiotic (41.2%). Eleven patients (6.2%) underwent fecal microbiota transplantation before or after bezlotoxumab treatment. The overall 90-day rCDI recurrence rate was 6.2% (11 patients), with a median time to recurrence of 50 days (IQR 25-58).

CONCLUSIONS: Bezlotoxumab demonstrated high efficacy in reducing rCDI within a 90-day period after administration, compared to rates in the non-cancer population. The findings suggest that administration of bezlotoxumab for rCDI prevention should be considered, given the improvement in the outcome of this high-risk group.},
}

@article {pmid40936935,
year = {2025},
author = {Wang, Y and Zhuang, K and Yi, Q and Wu, Y and Luo, Y and Ouyang, Y and Li, L and Li, C and Luo, H},
title = {High humidity environment increases FBG by impairing the intestinal barrier.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1625609},
pmid = {40936935},
issn = {1664-3224},
abstract = {INTRODUCTION: Climate and environmental changes pose significant threats to human metabolic health; however, the specific effects of individual environmental factors on metabolic diseases remain poorly understood. This study aimed to investigate the impact of a high humidity environment (HH) on fasting blood glucose (FBG), intestinal barrier integrity, and gut microbiota composition.

METHODS: We analyzed clinical samples collected during HH exposure and performed a controlled male mouse experiment. FBG and hormone levels were assessed, and intestinal barrier integrity was evaluated using western blot and immunofluorescence staining. Gut microbiota composition was profiled via 16S rDNA sequencing. Mechanistic insights were obtained through fecal microbiota transplantation (FMT), Mendelian randomization (MR) analysis, and metabolomic profiling. An antibiotic cocktail (ABX) intervention was applied to determine the reversibility of HH-induced effects.

RESULTS: Clinical samples collected under HH conditions showed elevated FBG, increased glucagon (GC) levels, impaired intestinal barrier function, and decreased serum gamma-aminobutyric acid (GABA) concentrations. 16S rDNA sequencing revealed increased abundances of Alistipes, Parabacteroides, and Akkermansia. Metabolomic analysis demonstrated reduced serum GABA levels, which correlated with intestinal barrier disruption and activation of the MDP-NOD2 pathway in pancreatic β-cells. HH exposure also downregulated GAD67 expression, reducing GABA synthesis and leading to enhanced GC secretion from islet α-cells. FMT suggested that gut microbiota alterations mediated HH-induced FBG elevation. ABX treatment effectively reversed these metabolic and microbial changes.

DISCUSSION: Our findings demonstrate that a high humidity environment disrupts gut microbiota homeostasis, impairs the intestinal barrier, and reduces GABA synthesis in pancreatic β-cells, thereby promoting the development of type 2 diabetes mellitus (T2DM).},
}

@article {pmid40935212,
year = {2025},
author = {Wang, Z and Zhu, Y and Wang, G and Sun, M and Yao, W and Ba, Q},
title = {Eucommia alleviates high fat diet-induced MASLD via the F. prausnitzii/butyrate/GPR43/GLP-1 signaling.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120587},
doi = {10.1016/j.jep.2025.120587},
pmid = {40935212},
issn = {1872-7573},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disorder worldwide, and remains without truly effective therapies. Eucommia ulmoides Oliver (Eucommia), a traditional Chinese medicinal herb, is widely known for its hepatoprotective actions, but its therapeutic potential in MASLD and underlying mechanisms remain largely unexplored.

AIM OF THE STUDY: In vitro and in vivo studies, the protective effect of Eucommia bark extract (EBE) on MASLD was elucidated, and investigate its hepatoprotective mechanism.

MATERIALS AND METHODS: A high-fat diet (HFD)-induced MASLD mouse model was used to evaluate the therapeutic efficacy of EBE. Mice were orally administered EBE throughout HFD feeding, and metabolic parameters, liver histology, and key signaling pathways were systematically assessed. To investigate the underlying mechanisms, gut microbiota composition was analyzed by 16S rRNA sequencing, and fecal microbiota transplantation from EBE-treated donors was performed to determine the microbiota-mediated effects.

RESULTS: EBE dramatically attenuated HFD-induced weight gain, oxidative stress, inflammation, lipid accumulation, and fibrosis in MASLD mice. Mechanistically, EBE raised circulating glucagon-like peptide-1 (GLP-1) levels, enhanced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation downstream of GLP-1 receptor (GLP-1R), thereby suppressing lipogenesis and promoting lipophagy. Although EBE did not directly trigger GLP-1 release in STC-1 cells, microbiome profiling revealed a selective bloom of Faecalibacterium prausnitzii (F. prausnitzii) - a major butyric acid producer-leading to elevated colonic butyric acid. Butyrate activated G protein-coupled receptor 43 (GPR43) on enteroendocrine cells to drive GLP-1 synthesis, a response abolished by GPR43 knockdown. Crucially, fecal microbiota transplantation from EBE-treated donors recapitulated these metabolic improvements in recipient mice.

CONCLUSION: EBE ameliorates MASLD by reshaping the gut microbiota to enrich F. prausnitzii-derived butyrate, which in turn stimulates endogenous GLP-1 secretion and activates the hepatic GLP-1R/AMPK axis to preserves lipid metabolism disorders.},
}

@article {pmid40933575,
year = {2025},
author = {Ye, F and Li, H and Li, H and Mu, X},
title = {Identification of novel gut microbiota-related biomarkers in cerebral hemorrhagic stroke.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1636860},
doi = {10.3389/fmed.2025.1636860},
pmid = {40933575},
issn = {2296-858X},
abstract = {INTRODUCTION: Hemorrhagic stroke, especially intracerebral hemorrhage (ICH), is the most fatal type of stroke and a major cause of mortality and disability. Due to ambiguous symptoms and limited biomarkers, early diagnosis and prognosis remain challenging. Recent evidence suggests that gut microbiota dysregulation influences neuroinflammation and outcomes in ICH, but the underlying molecular mechanisms remain unclear.

METHODS: Transcriptome data from the GSE24265 dataset were analyzed to identify differentially expressed genes (DEGs) in ICH. Gut microbiota-related genes (GMRGs) were obtained from GeneCards and literature, and overlapping genes were defined as gut microbiota-related DEGs (GMRDEGs). Functional enrichment, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analyses were performed. Hub genes were screened using LASSO, RandomForest, and SVM-RFE algorithms. Validation was conducted in plasma samples from ICH patients (n=20) and controls (n < 20) by qRT-PCR, and in a collagenase-induced ICH mouse model. The therapeutic effect of fecal microbiota transplantation (FMT) was evaluated through neurological scoring, hematoma volume, brain edema, intestinal barrier protein expression, inflammatory cytokines, and hub gene expression.

RESULTS: We identified 806 DEGs in ICH, among which 65 overlapped with GMRGs. These GMRDEGs were enriched in immune processes and pathways such as TNF and IL-17 signaling. PPI network analysis highlighted IL1B, IL6, and CCL2 as central nodes. Machine learning identified four hub genes-LEF1, ITGAX, BLVRB, and ATF4. All were significantly upregulated in ICH tissues and plasma, correlating with immune cell infiltration. In vivo, FMT reduced hematoma volume and brain edema, improved neurological function, restored intestinal barrier proteins, decreased inflammatory cytokines, and downregulated hub gene expression.

DISCUSSION: LEF1, ITGAX, BLVRB, and ATF4 were identified as gut microbiota-related biomarkers of ICH. Their modulation by FMT highlights the role of the brain-gut axis in ICH and suggests potential diagnostic biomarkers and therapeutic targets.},
}

@article {pmid40933007,
year = {2025},
author = {Le, J and Hakimjavadi, H and Parsana, R and Chamala, S and Michail, S},
title = {Fecal Microbiota Transplantation Induces Sustained Gut Microbiome Changes in Pediatric Ulcerative Colitis: A Combined Randomized and Open-Label Study.},
journal = {Gastro hep advances},
volume = {4},
number = {10},
pages = {100741},
doi = {10.1016/j.gastha.2025.100741},
pmid = {40933007},
issn = {2772-5723},
abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a promising tool to modulate the gut microbiome in pediatric ulcerative colitis (UC). We investigated the long-term impact of FMT on the gut microbiome and identified microbial signatures associated with disease severity and clinical outcomes.

METHODS: This study combined a randomized, double-blind trial comparing FMT to autologous placebo with an open-label extension to assess FMT's effects on the gut microbiome in pediatric UC patients over 48 weeks. Stool samples were collected at baseline and postintervention, and clinical response was evaluated using the Pediatric Ulcerative Colitis Activity Index. Shotgun metagenomic sequencing characterized the fecal microbiome's composition and functional potential. Taxon set enrichment analysis identified microbial taxon sets associated with UC and FMT.

RESULTS: FMT induced significant, sustained increases in gut microbial diversity over 48 weeks. Key changes included decreases in Klebsiella oxytoca and increases in Coprobacter fastidiosus post-FMT. Microbial signatures were associated with disease severity, including increased indole producers and decreased mucin degraders in mild UC compared to remission. Patients with clinical improvement post-FMT showed decreased Fusobacterium nucleatum and Veillonella parvula. Klebsiella pneumoniae and Klebsiella variicola decreased after open-label FMT.

CONCLUSION: FMT induces sustained changes in the pediatric UC gut microbiome, with distinct microbial signatures associated with disease severity and clinical outcomes. However, the high autologous placebo response rate underscores the need for further research to elucidate the mechanisms underlying FMT and placebo responses. Our study provides insights into the gut microbiome's role in pediatric UC, laying the foundation for developing personalized microbiome-targeted therapies. ClinicalTrials.gov number, NCT02291523.},
}

@article {pmid40930564,
year = {2025},
author = {Rauber, C and Roberti, MP and Vehreschild, MJ and Tsakmaklis, A and Springfeld, C and Teufel, A and Ettrich, T and Jochheim, L and Kandulski, A and Missios, P and Mohr, R and Reichart, A and Waldschmidt, DT and Sauer, LD and Sander, A and Schirmacher, P and Jäger, D and Michl, P and Dill, MT},
title = {Protocol: Faecal microbiota transfer in liver cancer to overcome resistance to atezolizumab/bevacizumab - a multicentre, randomised, placebo-controlled, double-blind phase II trial (the FLORA trial).},
journal = {BMJ open},
volume = {15},
number = {9},
pages = {e097802},
doi = {10.1136/bmjopen-2024-097802},
pmid = {40930564},
issn = {2044-6055},
mesh = {Humans ; *Liver Neoplasms/therapy/drug therapy ; *Bevacizumab/therapeutic use ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Antibodies, Monoclonal, Humanized/therapeutic use ; *Carcinoma, Hepatocellular/therapy/drug therapy ; Drug Resistance, Neoplasm ; Clinical Trials, Phase II as Topic ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Immune Checkpoint Inhibitors/therapeutic use ; Gastrointestinal Microbiome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {INTRODUCTION: Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

METHODS AND ANALYSIS: This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

ETHICS AND DISSEMINATION: The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

TRIAL REGISTRATION NUMBER: NCT05690048.},
}

Humans
*Liver Neoplasms/therapy/drug therapy
*Bevacizumab/therapeutic use
Double-Blind Method
*Fecal Microbiota Transplantation/methods
*Antibodies, Monoclonal, Humanized/therapeutic use
*Carcinoma, Hepatocellular/therapy/drug therapy
Drug Resistance, Neoplasm
Clinical Trials, Phase II as Topic
Randomized Controlled Trials as Topic
Multicenter Studies as Topic
Immune Checkpoint Inhibitors/therapeutic use
Gastrointestinal Microbiome
Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid40930304,
year = {2025},
author = {Nguyen, L and Feuerstadt, P and Allegretti, JR and Axelrad, J},
title = {Fecal Microbiota-based therapies compared to Fecal Microbiota Transplantation for Preventing recurrent C. difficile Infection.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2025.08.029},
pmid = {40930304},
issn = {1542-7714},
}

@article {pmid40930289,
year = {2025},
author = {Ou, G and Liu, T and Wu, S and Wang, H and Wang, S and Wu, J and Chen, Y and Deng, L and Xu, L and Xu, H and Chen, X},
title = {Huopu Xialing Decoction Mitigates Influenza A-Induced Pulmonary Injury by inhibiting METTL3-Nlrp3(m6A) Mediated NLRP3 Inflammasome Activation.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120577},
doi = {10.1016/j.jep.2025.120577},
pmid = {40930289},
issn = {1872-7573},
abstract = {Huopu Xialing Decoction (HXD) is a traditional Chinese medicine (TCM) formula widely used in the clinical treatment of respiratory viral infections. Despite its established application, the pharmacological mechanisms underlying its therapeutic effects against influenza remain to be fully elucidated.

AIM OF THE STUDY: This study aimed to investigate the protective effects of HXD against influenza A virus-induced lung inflammation and to explore the role of gut microbiota and epigenetic regulation in mediating these effects.

MATERIALS AND METHODS: An intranasal FM1 influenza virus infection model was established in mice. Lung histopathology was assessed by HE staining, and interleukin-1β (IL-1β) levels were measured using ELISA. Global N6-methyladenosine (m[6]A) methylation in lung tissues was detected by dot blot. RNA sequencing and SELECT™-m[6]A-qPCR were employed to identify and validate METTL3-mediated m[6]A modifications. 16S rRNA sequencing was used to profile gut microbiota alterations, and fecal microbiota transplantation (FMT) experiments were conducted to evaluate the role of microbiota in HXD-mediated effects.

RESULTS: HXD treatment significantly alleviated influenza-induced lung injury, suppressed IL-1β expression, and reduced METTL3-dependent m[6]A methylation of Nlrp3 mRNA. This was associated with decreased expression of NLRP3 inflammasome components, including ASC, pro-Caspase-1, cleaved-Caspase-1, GSDMD-N, and IL-1β. Furthermore, HXD modulated gut microbiota composition, marked by increased abundance of Lactobacillus and reduced Staphylococcus, which contributed to the downregulation of the pulmonary METTL3-Nlrp3 (m[6]A) axis.

CONCLUSION: HXD attenuates influenza-induced pulmonary inflammation by modulating the gut-lung axis and inhibiting METTL3-mediated m6A modification of Nlrp3, leading to suppression of NLRP3 inflammasome activation. These findings provide pharmacological evidence supporting the traditional use of HXD in respiratory infections and highlight the interplay between gut microbiota and epitranscriptomic regulation in the action of TCM.},
}

@article {pmid40930236,
year = {2025},
author = {Zhang, F and Ding, K and Zhang, LM and Liu, DY and Dong, X and Wang, MN and Zhou, FL and Sun, YW and Zhang, WK and Yan, Y and He, J and Xu, JK},
title = {The role of the gut microbiota in neuropsychiatric disorders and therapy.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102894},
doi = {10.1016/j.arr.2025.102894},
pmid = {40930236},
issn = {1872-9649},
abstract = {The vast microbial community residing in the gut is known as the gut microbiota (GM). Alterations in the compositional equilibrium of the GM, a phenomenon termed GM dysbiosis, have been increasingly associated with the pathogenesis of various diseases, particularly neuropsychiatric disorders. The microbiota-gut-brain axis (MGBA) serves as a bidirectional communication system that connects the gut to the brain. Notably, several prevalent neuropsychiatric disorders, including depression, Alzheimer's disease (AD), and Parkinson's disease (PD), collectively affect over one billion individuals globally. Emerging scientific evidence has consistently demonstrated the presence of GM dysbiosis in various neuropsychiatric disorders, suggesting a potential etiological role of GM in these conditions through MGBA-mediated mechanisms. In this comprehensive review, we systematically discussed the GM and MGBA, and presented evidence from both animal and human studies that highlighted the significance of GM in the occurrence and development of neuropsychiatric disorders. Subsequently, we emphasized the potential impact of GM and its metabolites on neuropsychiatric disorders. Next, we summarized the drugs used to treat diseases by regulating the GM. Finally, we proposed strategies to ameliorate the malignant progression of neuropsychiatric disorders by manipulating the composition of the GM. These strategies encompass the application of probiotics, prebiotics and synbiotics, postbiotics, fecal microbiota transplantation (FMT), dietary interventions. Collectively, targeted GM therapy has the potential to be an effective treatment for neuropsychiatric disorders.},
}

@article {pmid40929883,
year = {2025},
author = {Song, TY and Yang, XF and Wang, JY and Yin, LH and Zhao, XR and Wang, N and Xu, YW and Qi, Y and Xiong, CQ and Xu, LN},
title = {Gut microbiota-based metabolism contributes to the protection of pseudolaric acid B against MAFLD.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {147},
number = {},
pages = {157235},
doi = {10.1016/j.phymed.2025.157235},
pmid = {40929883},
issn = {1618-095X},
abstract = {BACKGROUND: The pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD) involves gut microbiota dysbiosis. This study investigated pseudolaric acid B (PAB), a diterpenoid from Pseudolarix kaempferi, for its potential to ameliorate MAFLD via microbiota-metabolite-host signaling pathways.

METHOD: We evaluated the effects of PAB on MAFLD in high-fat diet (HFD)-fed mice. 16S rRNA sequencing and metabolomics analyzed the regulations of PAB on gut microbiota and metabolites. The fecal microbiota transplantation (FMT) experiment was conducted to validate the causal role of the gut microbiota in the efficacy of PAB. Mechanistic studies employed molecular docking, microscale thermal migration (MST), western blot, immunofluorescence, and PCR to elucidate how PAB alleviates hepatic lipid metabolism dysregulation in MAFLD via microbial metabolites. In vivo intervention with candidate metabolites assessed improvement of disease phenotypes.

RESULTS: PAB effectively alleviatd the symptoms of HFD-induced MAFLD in mice, and repaired dysbiosis of intestinal microbiota, especially g_Faecalibaculum, g_Allobaculum, g_Ileibacterium, and g_Dubosiella, which were markedly down-regulated by PAB and showed a positive correlation with liver injury. FMT confirmed the relevance of PAB efficacy to the microbial community structure. Moreover, PAB intervention led to a dramatically enrichment of the tryptophan metabolism pathway, with cinnabarinic acid (CA), a microbial tryptophan metabolite, exhibiting a significat negative correlation with the abundance of the down-regulated bacteria. CA supplementation alleviated HFD-induced MAFLD in mice, indicating the hepatoprotective effect of CA. Molecular docking and MST revealed CA binds stablly to aryl hydrocarbon receptor (AhR) with higher affinity/stability, indicating a direct interaction between them. Mechanistically, PAB increased CA level and then activited AhR, downregulated hepatic lipogenesis genes by AhR-mediated IL-22/JAK1/STAT3 pathway.

CONCLUSION: PAB exerts a protective effect against MAFLD via restructuring the gut microbiota ecosystem, and activating CA/AhR/IL-22 signaling axis to reduce lipogenesis. These findings reveal a novel microbiota-metabolite-host mechanism and highlight PAB as a promising prebiotic-based therapeutic candidate for MAFLD.},
}

@article {pmid40928298,
year = {2025},
author = {Ge, J and Ye, Y and Yang, J and Di, Y and Jia, J and Bai, J and Jia, X and Wu, Z and Liu, X and Duan, X},
title = {Phosvitin Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice via Gut Microbiota Modulation.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c09135},
pmid = {40928298},
issn = {1520-5118},
abstract = {Dietary proteins have been demonstrated to alleviate ulcerative colitis. Phosvitin (PSV), a highly phosphorylated protein, possesses biological functions such as anti-inflammatory and antioxidant activities. This study aimed to investigate the preventive effects of PSV on dextran sulfate sodium (DSS)-induced colitis in mice and its underlying mechanisms. Following 4 weeks of PSV intervention (50 mg/kg b.w.), a colitis model was established by administering 2.5% DSS for 1 week. Results showed that PSV intervention significantly attenuated intestinal inflammation, reduced proinflammatory cytokine levels (e.g., TNF-α), and preserved intestinal barrier integrity. Furthermore, PSV modulated the gut microbiota by enhancing microbial diversity, decreasing the abundance of Escherichia-Shigella and Akkermansia, while increasing the abundance of Lachnospiraceae and Clostridium. Fecal microbiota transplantation (FMT) experiments further demonstrated the pivotal role of gut microbiota in PSV-mediated colitis prevention, as FMT from PSV-treated donor mice markedly alleviated colitis symptoms, achieving efficacy comparable to that of direct PSV intervention. These findings suggest that PSV alleviates colitis primarily through gut microbiota modulation.},
}

@article {pmid40927726,
year = {2025},
author = {Eiman, L and Moazzam, K and Anjum, S and Kausar, H and Sharif, EAM and Ibrahim, WN},
title = {Gut dysbiosis in cancer immunotherapy: microbiota-mediated resistance and emerging treatments.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1575452},
pmid = {40927726},
issn = {1664-3224},
mesh = {Humans ; *Dysbiosis/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Animals ; *Drug Resistance, Neoplasm ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Tumor Microenvironment/immunology ; },
abstract = {Cancer is a multifaceted disease driven by a complex interplay of genetic predisposition, environmental factors and lifestyle habits. With the accelerating pace of cancer research, the gut microbiome has emerged as a critical modulator of human health and immunity. Disruption in the gut microbial populations and diversity, known as dysbiosis, has been linked with the development of chronic inflammation, oncogenesis, angiogenesis and metastasis. This review discusses the microbial species associated with various types of cancer and the pathways involved in their tumorigenic effect including mechanisms like inflammatory cytokine response, immune modulation, genotoxicity and modification of the tumor microenvironment. Diagnostic tools such as metagenomics, metabolomics, and the use of dysbiosis indexes help in the detection of gut bacterial imbalances, enabling early detection of cancer and potential intervention. Gut dysbiosis diminishes the efficacy of cancer treatments including immunotherapies, and creates immunotherapy resistance by altering drug metabolism and driving immunometabolic reprogramming, allowing tumor cells to evade immune attack. Immunometabolic reprogramming through gut microbiota modulation provides a new avenue to be explored that can restore anti-tumor immunity and reverse resistance to cancer treatments. This review also highlights the use of fecal microbiota transplantation and probiotics to mitigate chances of dysbiosis-related cancer progression. Through a comprehensive assessment of the role of gut microbiota in cancer, this review underscores the need for the use of gut microbial biomarkers for cancer detection and microbiome-targeting strategies to individualize cancer treatment.},
}

Humans
*Dysbiosis/immunology/therapy
*Gastrointestinal Microbiome/immunology
*Neoplasms/therapy/immunology/microbiology
*Immunotherapy/methods
Animals
*Drug Resistance, Neoplasm
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Tumor Microenvironment/immunology

@article {pmid40927374,
year = {2025},
author = {Tan, S and Peng, C and Lin, X and Peng, C and Yang, Y and Liu, S and Huang, L and Bian, Y and Li, Y and Xu, C},
title = {Correction: Clinical efficacy of non-pharmacological treatment of functional constipation: a systematic review and network meta-analysis.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1680092},
doi = {10.3389/fcimb.2025.1680092},
pmid = {40927374},
issn = {2235-2988},
abstract = {[This corrects the article DOI: 10.3389/fcimb.2025.1565801.].},
}

@article {pmid40926100,
year = {2025},
author = {Gibson, TE and Kim, Y and Acharya, S and Kaplan, DE and DiBenedetto, N and Lavin, R and Berger, B and Allegretti, JR and Bry, L and Gerber, GK},
title = {Learning ecosystem-scale dynamics from microbiome data with MDSINE2.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {40926100},
issn = {2058-5276},
support = {BRICS HR0011-15-C-0094//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; R01GM130777//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35GM149270//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35GM143056//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R21AI154075//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35GM141861//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30DK056338//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; MTM2 2025512//National Science Foundation (NSF)/ ; },
abstract = {Although dynamical systems models are a powerful tool for analysing microbial ecosystems, challenges in learning these models from complex microbiome datasets and interpreting their outputs limit use. We introduce the Microbial Dynamical Systems Inference Engine 2 (MDSINE2), a Bayesian method that learns compact and interpretable ecosystems-scale dynamical systems models from microbiome timeseries data. Microbial dynamics are modelled as stochastic processes driven by interaction modules, or groups of microbes with similar interaction structure and responses to perturbations, and additionally, noise characteristics of data are modelled. Our open-source software package provides multiple tools for interpreting learned models, including phylogeny/taxonomy of modules, and stability, interaction topology and keystoneness. To benchmark MDSINE2, we generated microbiome timeseries data from two murine cohorts that received faecal transplants from human donors and were then subjected to dietary and antibiotic perturbations. MDSINE2 outperforms state-of-the-art methods and identifies interaction modules that provide insights into ecosystems-scale interactions in the gut microbiome.},
}

@article {pmid40925203,
year = {2025},
author = {Kapoor, B and Gulati, M},
title = {Gut microbiome and rheumatoid arthritis: Revisiting the gut-joint axis.},
journal = {International immunopharmacology},
volume = {165},
number = {},
pages = {115503},
doi = {10.1016/j.intimp.2025.115503},
pmid = {40925203},
issn = {1878-1705},
abstract = {Over the past few decades, the scientific perspective on gut microbiota has undergone a profound transformation, particularly with the emergence and advancement of microbiome research. Next-generation sequencing technologies have emerged as a foundational tool in microbiome research, facilitating comprehensive characterization of microbial communities across diverse sample types and ecological niches. Significant alterations in gut microbiota composition have been observed in disease states compared to healthy individuals, suggesting a direct association between gut dysbiosis and host health status. Initially, alterations in gut microbiota were primarily thought to be associated with gastrointestinal disorders. With advancing research, however, it has become evident that gut dysbiosis is also implicated in a broad spectrum of extra-intestinal conditions, including neurological, dermatological, metabolic, and musculoskeletal diseases. The present review provides a comprehensive analysis of preclinical and clinical studies elucidating the role of gut dysbiosis in the pathogenesis and progression of rheumatoid arthritis. Advancements in the understanding of the gut-joint axis have facilitated the development of novel therapeutic modalities, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, that have been comprehensively discussed in present review.},
}

@article {pmid40925130,
year = {2025},
author = {Sahu, KK and Yadav, K and Pradhan, M and Sharma, M and Dubey, A and Sucheta, and Kirubakaran, JJ},
title = {Pharmacological insights into gut microbiota modulation in systemic lupus erythematosus: Mechanisms, treatment strategies, and clinical implications.},
journal = {The Journal of pharmacology and experimental therapeutics},
volume = {392},
number = {9},
pages = {103659},
doi = {10.1016/j.jpet.2025.103659},
pmid = {40925130},
issn = {1521-0103},
abstract = {Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by widespread inflammation and immune system dysregulation. Recent research suggests that the gut microbiota may play a role in the development of SLE by modulating immune system responses, affecting cytokine production, and altering the activity of T and B cells lymphocytes. As a result, there is a growing interest in microbiota-targeted therapies, including probiotics, dietary changes, and fecal microbiota transplantation. These methods may help restore the balance of microbes and reduce disease activity, but there are still a number of problems to solve. For example, microbiota composition varies greatly from person to person, and it is not clear how dysbiosis causes disease onset. There are also safety concerns about fecal microbiota transplantation. Experimental and clinical studies have started to shed light on the complicated ways in which microbial communities and immune function affect each other in SLE. These studies provide useful information, but their results are often inconsistent. As research continues, integrative methods like metagenomics and metabolomics may help find microbial signatures linked to disease, helping create more accurate and personalized treatments. The gut microbiome is a promising yet still developing area of research that could help us learn more about autoimmune diseases and their treatment, such as SLE. SIGNIFICANCE STATEMENT: Grasping the complex interplay between gut microbiota and systemic lupus erythematosus (SLE) has provided an avenue for therapeutic intervention. This study emphasizes the importance of gut dysbiosis in immune dysregulation, with connections between microbial translocation, molecular mimicry, and inflammatory pathways as contributing factors to the progression of SLE. This work sets the stage for novel and targeted approaches to treating SLE and improving patient outcomes by investigating microbiota-centric treatment options, such as probiotics, dietary interventions, and fecal microbiota transplantation.},
}

@article {pmid40923448,
year = {2025},
author = {He, MC and Ferrini, A and Parvizi, J},
title = {Periprosthetic joint infection: Time to think outside the box.},
journal = {Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA},
volume = {},
number = {},
pages = {},
doi = {10.1002/ksa.70056},
pmid = {40923448},
issn = {1433-7347},
abstract = {Despite undisputed success of orthopaedic procedures, surgical site infections (SSI) such as periprosthetic joint infection (PJI) continues to compromise the outcome and result in major clinical and economic burden. The overall rate of infection is expected to rise in the future resulting in significant associated mortality and morbidity. Traditional concepts have largely attributed the source of PJI to exogenous pathogens. However, recent studies indicate that pathogens from the patient's own microbiome, colonizing the skin, nasal passages, gut microbiota, and even the surgical site play a major role in causing SSIs. Immune cell-mediated 'Trojan Horse' pathways have been posited as the mechanism of how bacteria reach and persist at the surgical site. In light of these developing insights, novel therapeutic strategies are under investigation. Some exciting developments include the use of membrane-permeable antibiotics, bacteriophage therapy targeting intracellular pathogens as well as probiotics, prebiotics, or faecal microbiota transplantation. Overall, targeting the endogenous microbiome represents a promising frontier for improving the prevention and management of PJI in the era of rapidly increasing total joint arthroplasty procedures.},
}

@article {pmid40920777,
year = {2025},
author = {Nendl, A and Raju, SC and Braadland, PR and Nordborg, A and Bratseth, V and Broch, K and Jørgensen, SF and Aukrust, P and Kristiansen, K and Hov, JR and Trøseid, M and Awoyemi, A},
title = {Circulating metabolites in patients with chronic heart failure are not related to gut leakage or gut dysbiosis.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0331692},
doi = {10.1371/journal.pone.0331692},
pmid = {40920777},
issn = {1932-6203},
mesh = {Humans ; *Dysbiosis/blood/microbiology/metabolism ; *Heart Failure/blood/microbiology/metabolism/physiopathology ; Male ; Female ; *Gastrointestinal Microbiome ; Middle Aged ; Aged ; Feces/microbiology ; Chronic Disease ; Case-Control Studies ; Metabolomics ; Metabolome ; },
abstract = {BACKGROUND: The gut microbiota produces numerous metabolites that can enter the circulation and exert effects outside the gut. Several studies have reported altered gut microbiota composition and circulating metabolites in patients with chronic heart failure (HF) compared to healthy controls. Limited data is available on the interplay between dysbiotic features of the gut microbiota and altered circulating metabolites in HF patients. We aimed to examine differences in circulating metabolites between people with and without chronic HF, and their association with gut microbiota dysbiosis and cardiac function.

METHODS: We collected plasma, serum, and stool samples from 123 adult patients with stable chronic HF and left ventricular ejection fraction (LVEF) ≤40%, and healthy controls (plasma: n = 51, stool samples: n = 69). Metabolomic and lipidomic profiling of plasma was performed using liquid chromatography with tandem mass spectrometry. Principal component analysis was used to explore differences in circulating profiles. Over-representation analysis was performed to identify pathways in which relevant metabolites were involved. Stool samples were sequenced using shotgun metagenomics. We calculated a dysbiosis index based on differential abundances of microbial taxa in patients vs. controls.

RESULTS: After adjusting for age, sex, and sampling location, we identified 67 enriched metabolites and 24 enriched lipids, and 115 depleted metabolites and 6 depleted lipids in HF patients compared to healthy controls. LVEF, N-terminal pro B-type natriuretic peptide, gut leakage markers, dysbiosis index, and fiber intake were not significantly related to any of the differentially abundant metabolites or lipids. Pathways related to energy metabolism differed most between HF patients and controls, however medication adjustment abolished all differences in circulating profiles.

CONCLUSIONS: Patients with chronic HF had distinct metabolomic and lipidomic profiles and energy metabolism differed significantly compared to healthy controls before adjusting for medication use. However, the alterations were not related to gut dysbiosis, gut leakage markers, cardiac function, or fiber intake.},
}

Humans
*Dysbiosis/blood/microbiology/metabolism
*Heart Failure/blood/microbiology/metabolism/physiopathology
Male
Female
*Gastrointestinal Microbiome
Middle Aged
Aged
Feces/microbiology
Chronic Disease
Case-Control Studies
Metabolomics
Metabolome

@article {pmid40919202,
year = {2025},
author = {Liu, W and Cheng, Y and Han, X and Xia, J and Wei, Q and Chang, B and Li, Q},
title = {Rivaroxaban alleviates hepatic sinusoidal obstruction syndrome in mice by modulating the gut microbiota and inhibiting the PI3K/Akt signaling pathway.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1607131},
pmid = {40919202},
issn = {1664-302X},
abstract = {INTRODUCTION: Hepatic sinusoidal obstruction syndrome (HSOS) is a vascular liver disease with a high mortality rate, and treatment methods are limited. Rivaroxaban is an oral anticoagulant. This study aimed to investigate the pharmacological effect and potential mechanism of rivaroxaban on HSOS.

METHODS: In this study, we induced an HSOS mouse model in male C57BL/6J mice by administering monocrotaline orally. The mice were randomly divided into four groups: the control group, the rivaroxaban (RIV) group, the monocrotaline (MCT) group, and the monocrotaline + rivaroxaban (MCT + RIV) group. Liver function and histopathology were evaluated. 16S rDNA sequencing of the small intestinal contents, transcriptomic sequencing of small intestine tissues, real-time qPCR, Western blot analysis of liver tissues, and correlation analysis were conducted. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) experiments were also performed to explore the role of the gut microbiota.

RESULTS: Compared with the MCT group, rivaroxaban alleviated serum biochemical liver function analysis and liver histopathology in the MCT + RIV group. Additionally, 16S rDNA sequencing of the small intestinal contents revealed that, compared with the MCT group, the MCT + RIV group presented increased relative abundances of Allobaculum and Pediococcus but decreased relative abundances of Streptococcus, Staphylococcus, and Candidatus Arthromitus. Mechanistically, integrated analyses, including transcriptomic sequencing of small intestin e tissues, real-time qPCR, Western blot analysis of liver tissues, and correlation analysis, demonstrated that rivaroxaban protected against MCT-HSOS by inhibiting the PI3K/Akt signaling pathway. In addition, antimicrobial cocktail (ABX) treatment eliminated the beneficial effects of rivaroxaban on liver function and histopathological injury, whereas fecal microbiota transplantation (FMT) from rivaroxaban-treated donors significantly ameliorated liver dysfunction and histological damage in MCT-HSOS mice.

DISCUSSION: These findings suggest that rivaroxaban alleviates hepatic sinusoidal obstruction syndrome in mice by modulating the gut microbiota and inhibiting the PI3K/Akt signaling pathway. Rivaroxaban may be a promising therapeutic option for treating HSOS.},
}

@article {pmid40917756,
year = {2025},
author = {Vescovo, T and Bontempi, G and Bayat, M and Piredda, L and Fidaleo, M and Strippoli, R and Antonioli, M},
title = {Gut microbiota interplay with autophagy-EMT dynamics in colorectal cancer.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1608248},
pmid = {40917756},
issn = {2296-634X},
abstract = {The human microbiota is composed of a complex community of microorganisms essential for maintaining host homeostasis, especially in the gastrointestinal tract. Emerging evidence suggests that dysbiosis is linked to various cancers, including colorectal cancer (CRC). The microbiota contributes to CRC development and progression by influencing inflammation, genotoxic stress, and key cell growth, proliferation, and differentiation pathways. Certain bacterial species, including Fusobacterium nucleatum and Escherichia coli, play a role in tumorigenesis by facilitating epithelial-mesenchymal transition (EMT), perturbing autophagy, and supporting immune evasion. In contrast, beneficial microorganisms such as Bifidobacterium and Lactobacillus provide protective effects by boosting immune surveillance and supporting the integrity of the intestinal barrier. This review examines the complex connection between gut microbiota and CRC, emphasizing how changes in microbial composition facilitate tumor development and influence treatment outcomes. We cover recent progress in microbiota-based biomarkers for CRC diagnosis and prognosis, showcasing their promise for early detection and improved patient stratification. Furthermore, we explore microbiota-focused therapeutic methods such as probiotics, prebiotics, faecal microbiota transplantation (FMT), and precision antibiotics, which show potential to complement standard CRC treatments. By highlighting the latest advancements in this area, we emphasise how microbiome research is transforming our comprehension of CRC and leading to new diagnostic and treatment approaches.},
}

@article {pmid40916806,
year = {2025},
author = {Javan, N and Ghotaslou, R and Samadi Kafil, H and Memar, MY and Sadeghi, J and Ghotaslou, P},
title = {Overcoming Multi-Drug-Resistant Klebsiella pneumoniae Infections.},
journal = {Microbial drug resistance (Larchmont, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1177/10766294251375937},
pmid = {40916806},
issn = {1931-8448},
abstract = {Antimicrobial resistance (AMR) is one of the most important concerns in the world, occurring for both Gram-positive and Gram-negative bacteria. Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium belonging to the family of Enterobacteriaceae and also plays an important role in development of nosocomial infections. Three forms have emerged as a result of AMR including multi-drug resistant (MDR), extensively drug-resistant, and pan-drug-resistant. Nowadays, physicians cannot save most of the patients that suffer from MDR K. pneumoniae infections by typical antibiotics, so they should try other useful alternative treatments. Our aim in this review study was to search about the latest useful alternative methods against MDR K. pneumoniae infections. We collected some articles from PubMed, MEDLINE, and Google Scholar by the keywords of multi-drug-resistant K. pneumoniae, AMR, and alternative treatments, where finally 183 articles were selected. Also, inclusion criteria and exclusion criteria were identified separately. It was understood that there are novel therapeutic options against MDR K. pneumoniae infections, which include odilorhabdins, drug delivery systems, antibody drug conjugation treatments, nano-antibiotics, bacteriocins, probiotics, fecal transplant therapy, predatory bacteria, combined antibiotics, double-carbapenem therapy, synthetic lipopeptides, and phage therapy.},
}

@article {pmid40916606,
year = {2025},
author = {Piwchan, S and Aumpan, N and Chonprasertsuk, S and Pornthisarn, B and Siramolpiwat, S and Bhanthumkomol, P and Nunanan, P and Issariyakulkarn, N and Wongcha-Um, A and Miftahussurur, M and Mahachai, V and Yamaoka, Y and Vilaichone, RK},
title = {Fecal Microbiota Transplantation by Rectal Enema Improves Short-Term Insulin Resistance in Metabolic Syndrome: A Pilot Randomized Controlled Trial.},
journal = {Journal of obesity & metabolic syndrome},
volume = {},
number = {},
pages = {},
doi = {10.7570/jomes25014},
pmid = {40916606},
issn = {2508-7576},
abstract = {BACKGROUND: The gut microbiota plays a vital role in various physiological processes, including metabolism. Fecal microbiota transplantation (FMT) involves transferring fecal matter from a healthy donor to rebalance a patient's intestinal dysbiosis. The impact of FMT on metabolic syndrome (MetS) is subject to debate. This study assesses the effects of FMT on MetS when administered by rectal enema.

METHODS: In a double-blind, randomized controlled trial, subjects with MetS were assigned to receive either FMT (n=8) or a sham intervention (n=10) via rectal enema. Participants were followed at 6 and 12 weeks. The primary outcome was changes in the homeostatic model assessment of insulin resistance (HOMA-IR). Secondary outcomes included fasting blood glucose (FBG), body mass index (BMI), inflammatory markers, and hepatic steatosis. The mean adjusted difference (MAD) and 95% confidence interval (CI) between groups were reported as treatment effects using a linear marginal model for repeated measures.

RESULTS: The study included patients with a mean age of 50.4±10.7 years. Baseline BMI and HOMA-IR were similar between groups. Over 6 weeks, FMT significantly improved HOMA-IR (MAD, -1.63; 95% CI, -2.63 to -0.64; P=0.001). The FMT group also showed improvements in serum FBG and high-sensitivity C-reactive protein compared with levels in the sham group (P=0.044 and P=0.025, respectively). However, no significant changes in MetS-associated variables or liver steatosis were evident at 12 weeks. Stool microbiota analysis revealed a reduced relative abundance of Desulfovibrio, Bacteroides, and Parabacteroides after FMT.

CONCLUSION: FMT by rectal enema produced favorable changes in IR in patients with MetS. FMT may be an effective treatment for patients with metabolism-related diseases. Further research into the long-term benefits of the procedure is warranted.},
}

@article {pmid40914633,
year = {2025},
author = {Coman, T and Andreozzi, F and Bay, JO and Cornillon, J and Guillaume, T and Hamzy, F and Souchet, L and Turlure, P and Marçais, A and Dachy, F and Beguin, Y and Bulabois, CE and Daghri, S and Huynh, A and Magro, L and Chalandon, Y},
title = {[Acute graft-versus-host disease therapy: Which third line treatment after steroids and ruxolitinib? (SFGM-TC)].},
journal = {Bulletin du cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bulcan.2025.05.014},
pmid = {40914633},
issn = {1769-6917},
abstract = {Acute graft-versus-host disease (GVHDa) is one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT) patients. While the first-line consensus treatment has been based on systemic corticosteroid therapy for many years, ruxolitinib has recently been approved and has become the standard second-line treatment. Nevertheless, the effectiveness of ruxolitinib remains limited to 40 % of cortico-resistant patients, raising the crucial question of selecting a third-line treatment. Among the therapeutic modalities described, this workshop selected fecal microbiota transplantation (FMT), mesenchymal stromal cells (MSC) injection, and extracorporeal photopheresis (ECP) as the most promising or with a benefit/risk balance that favors their prescription at this stage. The workshop also highlighted the importance of research aimed at identifying markers or score calculations that guide toward a risk-adapted approach as early as possible. To date, aside from calprotectin, no marker or score is routinely used, but all are the subject of intense research. Finally, measures associated with specific treatment remain crucial, and new developments in dietary contributions, infection prophylaxis, and tissue regeneration are also addressed.},
}

@article {pmid40913864,
year = {2025},
author = {Xiang, X and Zhu, Y and Wang, T and Zhu, J and Ding, P and Cheng, K and Ming, Y},
title = {Gut microbiota and metabolites related intra-patient variability of tacrolimus pharmacokinetics predicted adverse one-year outcomes following kidney transplantation.},
journal = {International immunopharmacology},
volume = {165},
number = {},
pages = {115506},
doi = {10.1016/j.intimp.2025.115506},
pmid = {40913864},
issn = {1878-1705},
abstract = {Kidney transplantation (KT) is an effective treatment for end-stage renal disease, with over 90 % of recipients requiring lifelong tacrolimus (Tac). However, The Tac pharmacokinetics exhibit high intra-patient variability (IPV), posing significant challenges. This study included 102 KT recipients at our center from October 2022 to December 2023. Patients were stratified into high- and low-IPV groups based on the median coefficient of variation of the the Tac trough concentration-to-dose ratio during the first post-transplant month. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomics analysis, while clinical outcomes within the first year were assessed for associations with the Tac IPV. Microbiome analysis revealed significant beta diversity differences (p = 0.0451) and 19 differential taxa, including g__Clostridia_vadinBB60_group enriched in high-IPV patients and g__Clostridia_UCG_014 in the low-IPV group. Metabolomics identified 1298 differential metabolites, with 729 enriched in high-IPV patients. Network analysis highlighted cholesterol and unsaturated fatty acid biosynthesis as central pathways, while both microbial functional predictions and metabolic enrichment analyses emphasized bile secretion. A random forest model validated the classification potential of these biomarkers, and associations between differential taxa and metabolites were observed. Clinical correlation analysis indicated the high Tac IPV as an independent protective factor against post-transplant hyperuricemia but a positive predictor of new-onset diabetes. This study is the first to link the Tac IPV, gut microbiota, metabolism, and one-year outcomes, offering novel insights into personalized care and the mechanisms underlying the Tac IPV.},
}

@article {pmid40913709,
year = {2025},
author = {Jamal, A and Kamal, MA and Alqurashi, YE and Al-Malki, ES and Naiyer, MM and Hussain, SA and Hattiwale, HM},
title = {The microbiome-cancer axis as a hidden contributor to early-onset tumorigenesis.},
journal = {Medical oncology (Northwood, London, England)},
volume = {42},
number = {10},
pages = {464},
pmid = {40913709},
issn = {1559-131X},
mesh = {Humans ; *Neoplasms/microbiology ; *Carcinogenesis/pathology ; *Gastrointestinal Microbiome ; *Microbiota ; Dysbiosis/microbiology ; Age of Onset ; },
abstract = {The global incidence of early-onset cancer has surged by nearly 80% over the past three decades, yet the underlying causes remain poorly understood. While genetics and lifestyle are among the traditional risk factors, emerging evidence implicates the human microbiome as a potent and overlooked contributor to early tumorigenesis. Increases in the studies that are exploring the tissue-specific microbiome signatures such as the enrichment of Actinomyces and Bacteroidia in early-onset colorectal cancer, or Enterobacter and Neisseria in pancreatic tumors offer compelling evidence for age-stratified microbial contributions. Additionally, the recent works on the establishment of gut-testis, oral-gut, and gut-liver microbial axes are being explored to understand the modulation of systemic immune and endocrine landscapes in younger individuals that might unravel their unique predisposition to malignancy. Further, the microbiome-cancer axis has been regarded as a hidden driver in the initiation and progression of early-onset malignancies across diverse tissue types. Understanding this link will provide the missing mechanistic insights showcasing how microbial dysbiosis, biofilm formation, and microbially derived metabolites promote oncogenic inflammation, DNA damage, and immune evasion contributing to early-onset cancers. Considering the potential of these studies, microbial biomarkers with diagnostic promises that include probiotics, fecal microbiota transplantation, and diet have also been explored as emerging tools for prevention and therapy. Through this study, we aim to understand early-onset cancer through a patient microbiota and underscore an urgent need to integrate microbial dynamics into cancer surveillance and intervention strategies, especially for young and largely asymptomatic populations.},
}

Humans
*Neoplasms/microbiology
*Carcinogenesis/pathology
*Gastrointestinal Microbiome
*Microbiota
Dysbiosis/microbiology
Age of Onset

@article {pmid40913635,
year = {2025},
author = {Ali, AQ and Mersal, EA and Samer, R and Alhjmohammad, SA and Alabdrabalridha, ZH and Alseeni, FY and Dawood, AF and Abdel All, MO and Abdelmoneim, AM and Shawky, TM},
title = {Berberine contributes to protecting against the cadmium-induced pancreatic damage: role of intestinal microbiome modulation and barrier function.},
journal = {Journal of molecular histology},
volume = {56},
number = {5},
pages = {296},
pmid = {40913635},
issn = {1567-2387},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Berberine/pharmacology ; *Cadmium/toxicity ; Rats ; Rats, Wistar ; Male ; *Pancreas/drug effects/pathology ; Intestinal Mucosa/drug effects/metabolism/microbiology ; *Protective Agents/pharmacology ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; },
abstract = {Cadmium (Cad) is a worldwide heavy metal pollutant associated with global health challenges. Alteration of the intestinal microbiome, due to chemicals' exposure, plays a vital role in the pathogenesis of gastrointestinal diseases such as pancreatic disorders. Hence, modulation of the gut microbiota might be a targeted approach to manage pancreatic diseases. Using murine modeling, this study consisted of two dependent experiments to investigate the curative potential of berberine (BBR) in a Wistar rat model of Cad-provoked pancreatic toxicity and the possible contribution of gut microbiota to BBR protection. In experiment 1, Cad-induced pancreatic injury was established in rats via 8-week oral gavage of Cad at 4 mg/kg. The treatment group was exposed to BBR at 200 mg/kg body weight, oral gavage for 8 weeks. In experiment 2, transplantation of the fecal microbiome was done, in which the fecal microbiota in each group of experiment 1 was orally gavaged to the healthy rats of each corresponding group in experiment 2, once weekly for 8 weeks. The serum amylase and lipase levels, pancreatic inflammatory and oxidative markers, histological, and immunohistochemical analyses were evaluated. The markers of gut mucosal barrier, and mRNA expression of cell junction proteins were investigated for possible intestinal injury. 16S rRNA sequencing was applied to identify the gut bacterial changes and possible pancreatic bacterial translocation. Cad induced intestinal barrier disruption and elicited a state of pancreatic inflammation and apoptosis as indicated by TGF-β and BAX immunohistochemistry, which were relieved by BBR. A decreased firmicutes/bacteroidetes ratio and microbial migration due to interrupted intestinal mucosal barrier were reported. Furthermore, BBR restored the bacterial richness and proportions in the gut, thereby maintaining the intestinal microbial community, fixing the intestinal mucosal barrier structure, and inhibiting the pathway of bacterial migration. BBR protected against Cad-induced pancreatic damage, mostly through safeguarding the intestinal barrier function. Modulation of the intestinal bacterial community, repairing the gut barrier structure, and interference with the pancreatic bacterial migration and colonization were suggested BBR effects, potentially alleviating Cad-related pancreatic injury.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Berberine/pharmacology
*Cadmium/toxicity
Rats
Rats, Wistar
Male
*Pancreas/drug effects/pathology
Intestinal Mucosa/drug effects/metabolism/microbiology
*Protective Agents/pharmacology
Disease Models, Animal
RNA, Ribosomal, 16S/genetics

@article {pmid40912813,
year = {2025},
author = {Yang, X and Li, S and Feng, Y and Guo, Y and Guo, Z and Hu, Y},
title = {A novel extracellular mannan from Bacillus velezensis ameliorates metabolic-associated fatty liver disease by modulating gut microbiota in mice model.},
journal = {Carbohydrate polymers},
volume = {368},
number = {Pt 1},
pages = {124150},
doi = {10.1016/j.carbpol.2025.124150},
pmid = {40912813},
issn = {1879-1344},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Bacillus/chemistry ; *Mannans/pharmacology/chemistry/isolation & purification/therapeutic use ; Mice ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; *Fatty Liver/drug therapy/metabolism ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism/pathology ; },
abstract = {Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752. Structural analysis revealed that BVP1 is a neutral α-mannan consisting of a backbone of 1,2,6-linked α-D-Manp, with branches composed of T-linked α-D-Manp, 1,2-linked α-D-Manp, and 1,3-linked α-D-Manp. Animal experiments showed that BVP1 significantly alleviated hepatic steatosis, liver injury and inflammation, and enhanced antioxidant activity in MAFLD mice. Single-nucleus RNA sequencing analysis revealed that BVP1 could restore HFD-induced imbalances in liver sinusoidal endothelial cells, hepatic stellate cells, macrophages and Kupffer cells by upregulating the expression of the lipid degradation gene Cps1 and downregulating the expression of the lipid synthesis gene Acsl1 in these cell subpopulations. Interestingly, BVP1 reshaped the gut microbiota and fecal metabolite profile by enriching beneficial bacteria and associated metabolites including salicylic acid, spermidine, and 4-hydroxyphenyl acetate. Fecal microbiota transplantation experiments verified that the anti-MAFLD effects are mediated by the BVP1-modified gut microbiota. Our findings highlight the potential of BVP1 as a promising therapeutic agent for MAFLD treatment.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Bacillus/chemistry
*Mannans/pharmacology/chemistry/isolation & purification/therapeutic use
Mice
Male
Mice, Inbred C57BL
Disease Models, Animal
*Fatty Liver/drug therapy/metabolism
Lipid Metabolism/drug effects
Liver/drug effects/metabolism/pathology

@article {pmid40912415,
year = {2025},
author = {Liu, X and He, J and Cui, L and Ye, Y and Luo, M and Xu, H and Zhai, Y and Zhao, Z and Huang, T and Li, Y and Wu, JL and Wen, J and Wang, Y and Zhou, T},
title = {Limosilactobacillus reuteri-Butyrate Axis in Depression Therapy: A Key Pathway Discovered Through a Novel Preclinical Human Flora-Associated Animal Model.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {107941},
doi = {10.1016/j.phrs.2025.107941},
pmid = {40912415},
issn = {1096-1186},
abstract = {The transition from preclinical to clinical drug development is critically impeded by interspecies disparities, which limit the predictive validity of preclinical efficacy for human outcomes. To address this limitation, we established a human flora-associated depression rat (HFADR) model through fecal microbiota transplantation (FMT). The HFADR model bridges the preclinical-clinical translation by recapitulating conserved microbial-host interactions identified through multi-omics analysis in a chronic unpredictable mild stress (CUMS) rat model and in patients with major depressive disorder. The HFADR model simulated the pathophysiological characteristics of clinical depression validated by gut-brain axis indices, including microbial composition, inflammatory biomarkers, brain-derived neurotrophic factor (BDNF), and monoamine neurotransmitters. Employing geniposide, a bioactive iridoid compound derived from medicinal plants, as a therapeutic prototype, the HFADR model revealed the novel Limosilactobacillus reuteri-butyrate axis as a conserved regulatory hub for the treatment of depression. Geniposide administration restored L. reuteri abundance in the HFADR model, which significantly correlated with improved gut-brain axis homeostasis. Metabolomics confirmed that L. reuteri exerts antidepressant effects via butyrate restoration in CUMS mice, with parallel butyrate level alterations observed in geniposide-treated HFADR model. Both L. reuteri supplementation and exogenous butyrate administration reversed depression-like behavior, mechanistically confirming the axis by reduced hippocampal astrocyte activation and elevated Nrf2 expression. This study established the HFADR model as a translational tool for evaluating microbiota-targeted therapies and identified the L. reuteri-butyrate axis as a novel therapeutic target. Our findings provide a theoretical and practical framework for refining preclinical models and advancing antidepressant development using microbiome-based strategies.},
}

@article {pmid40912148,
year = {2025},
author = {Gibril, BAA and Tu, X and Chai, X and Xu, J},
title = {Gut microbiota composition and dietary interventions modulate abdominal fat deposition in poultry: Mechanisms and applications.},
journal = {Poultry science},
volume = {104},
number = {11},
pages = {105754},
doi = {10.1016/j.psj.2025.105754},
pmid = {40912148},
issn = {1525-3171},
abstract = {Excessive abdominal fat deposition (AFD) in poultry reduces meat yield and efficiency. The gut microbiota regulates AFD through shifts in microbial composition and the production of metabolites. Reduced microbial diversity and fat-promoting taxa (e.g., Methanobrevibacter, Escherichia-Shigella) elevate AFD, while lean-linked bacteria (e.g., Bacteroides, Oscillospira) promote leanness. Dietary interventions, including botanical ingredients (e.g., honeycomb flavonoids elevating short-chain fatty acid producers), fermented feeds (e.g., cottonseed meal enriching butyrogenic taxa), probiotics (e.g., Lactobacillus johnsonii downregulating PPARγ/FAS), and additives (bile acids activating FXR/PPARα), modulate gut microbiota to reduce AFD by enhancing barrier function, suppressing pathogens, and regulating lipid metabolism. Fecal microbiota transplantation confirms microbiota-driven AFD reduction but faces donor-matching challenges. Breed-specific microbial signatures and context-dependent outcomes inform precision strategies to improve feed efficiency and lean yield.},
}

@article {pmid40911227,
year = {2025},
author = {Omar, TM and Alfarttoosi, KH and Sanghvi, G and Roopashree, R and Kashyap, A and Krithiga, T and Taher, WM and Alwan, M and Jawad, MJ and Al-Nuaimi, AMA},
title = {Engineering the Microbiome: a Novel Approach to Managing Autoimmune Diseases.},
journal = {Neuromolecular medicine},
volume = {27},
number = {1},
pages = {63},
pmid = {40911227},
issn = {1559-1174},
mesh = {Humans ; *Autoimmune Diseases/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology/genetics ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Inflammatory Bowel Diseases/therapy/microbiology ; Immune Tolerance ; Multiple Sclerosis/therapy/microbiology ; },
abstract = {Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, affecting millions of people and often requiring long-term treatment. Current therapies, such as immunosuppressants and biologics, help manage symptoms but can cause serious side effects. A promising new approach involves engineered microbiota-a method that modifies gut bacteria to influence immune function and potentially ease autoimmune conditions. The gut microbiome is crucial in regulating immunity, and imbalances in its composition have been linked to diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD). Engineered microbiota works by altering microbial communities, either by adding new strains, genetically modifying existing bacteria, or using carefully selected groups of microbes to control inflammation and immune responses. Recent studies in both animal models and human trials suggest this approach could help restore immune tolerance, reduce inflammation, and repair the gut barrier. However, challenges remain, including ensuring safety, long-term effectiveness, and meeting regulatory standards. Despite being in its early stages, engineered microbiota holds great promise as a future treatment for autoimmune diseases, paving the way for more precise and personalized therapies that leverage the power of the microbiome to improve health.},
}

Humans
*Autoimmune Diseases/therapy/microbiology/immunology
*Gastrointestinal Microbiome/immunology/genetics
Animals
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Inflammatory Bowel Diseases/therapy/microbiology
Immune Tolerance
Multiple Sclerosis/therapy/microbiology

@article {pmid40911047,
year = {2025},
author = {Che, Z and Xue, W and Zhao, X and Hu, C and Tian, Y},
title = {Regulatory Role and Biomarker Potential of Gut Microbiota Metabolites in the Progression of Metabolic dysfunction-associated steatotic liver disease (MASLD) to Hepatocellular Carcinoma (HCC).},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000914},
pmid = {40911047},
issn = {2155-384X},
abstract = {Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. It is now updated as metabolic dysfunction-associated steatotic liver disease (MASLD). The progression of MASLD to hepatocellular carcinoma (HCC) involves complex mechanisms, with the gut microbiota and its metabolites playing a pivotal role in this transformation through the "gut-liver axis." This review systematically summarizes the characteristics of gut microbiota dysbiosis in NAFLD patients and the regulatory mechanisms of its metabolites (e.g., short-chain fatty acids [SCFAs], secondary bile acids, trimethylamine N-oxide [TMAO], and lipopolysaccharides [LPS]) in the progression from MASLD to HCC. SCFAs exert protective effects in the early stages by enhancing the intestinal barrier and modulating immune and metabolic responses. However, metabolic disturbances, such as the "paradoxical effect" of butyrate and the lipogenic effect of acetate, may promote the formation of a tumor microenvironment in the later stages. Secondary bile acids (e.g., deoxycholic acid) exacerbate liver fibrosis and carcinogenesis by activating inflammatory pathways (NF-κB, MAPK), inducing oxidative stress, and inhibiting foresaid X receptor (FXR) signaling. TMAO directly drives HCC progression by activating the MAPK/NF-κB pathway, promoting epithelial-mesenchymal transition (EMT), and creating an immunosuppressive microenvironment. LPS accelerates fibrosis and metabolic reprogramming through TLR4-mediated chronic inflammation and hepatic stellate cell activation. This review highlights that the dynamic changes in gut microbiota metabolites are closely associated with MASLD -HCC progression. Specific monitoring of these metabolites may serve as potential biomarkers for early detection. Furthermore, gut-targeted therapies (e.g., fecal microbiota transplantation) have shown translational potential. Future studies are needed to further validate their clinical value and develop precise prevention and treatment strategies.},
}

@article {pmid40910235,
year = {2025},
author = {Kaabi, YA},
title = {The Role of Gut Microbiota in Modulating Inflammation and Insulin Resistance in Type 2 Diabetes Mellitus: Implications for Complication Management.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240393897250826074023},
pmid = {40910235},
issn = {1875-5666},
abstract = {Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and severe complications, including cardiovascular diseases, neuropathy, retinopathy, and nephropathy. This article examines the role of gut microbiota in modulating inflammation and insulin resistance in type 2 diabetes mellitus (T2DM), as well as its implications for managing complications associated with the disease. We analyzed published literature to elucidate mechanisms linking microbial dysbiosis, impaired gut barrier function, and chronic inflammation to glycemic control and T2DM complications. Key findings suggest that gut microbiota dysbiosis contributes to systemic inflammation and insulin resistance, thereby exacerbating the complications of type 2 diabetes mellitus (T2DM). Therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, promise to improve glycemic control and mitigate complications by restoring microbial balance. This review provides a comprehensive framework for understanding the role of the gut microbiota in type 2 diabetes mellitus (T2DM) and highlights potential therapeutic interventions to enhance the management of complications.},
}

@article {pmid40909921,
year = {2025},
author = {Shi, M and Wang, LF and Hu, WT and Liang, ZG},
title = {The gut microbiome in lung cancer: from pathogenesis to precision therapy.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1606684},
pmid = {40909921},
issn = {1664-302X},
abstract = {The gut microbiome has emerged as a key modulator of immune responses and treatment efficacy in oncology. Growing evidence links gut dysbiosis to resistance against immune checkpoint inhibitors (ICIs) in advanced cancers, prompting exploration of the gut-lung axis-a bidirectional network connecting intestinal microbiota with pulmonary health. Given lung cancer's status as the leading cause of cancer mortality worldwide, understanding this axis holds significant therapeutic potential. This review synthesizes current knowledge on gut microbiota's role in lung cancer development, diagnosis, and treatment. We highlight microbial signatures predictive of disease and therapy response, discuss microbiota-targeted interventions (e.g., probiotics, Fecal Microbiota Transplantation), and elucidate mechanistic insights into microbial-immune crosstalk. Finally, we outline future directions for leveraging the gut microbiome in personalized lung cancer management.},
}

@article {pmid40909294,
year = {2025},
author = {Zhou, L and Wu, Q and Jiang, L and Rao, J and Gao, J and Zhao, F and Wang, X},
title = {Role of the microbiota in inflammation-related related psychiatric disorders.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1613027},
pmid = {40909294},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Mental Disorders/microbiology/etiology/immunology/metabolism/therapy ; Animals ; *Inflammation/microbiology/immunology/metabolism ; Neuroimmunomodulation ; },
abstract = {The immune interactions within the gut-brain axis represent a critical etiological factor in psychiatric disorders. The gut microbiota and their metabolites serve as biological mediators that regulate neuroimmune activation and suppression in the central nervous system (CNS). During intestinal immune activation, pro-inflammatory cytokines (e.g., IL-6, TNF-α) propagate to the CNS via compromised blood-brain barrier (BBB) integrity or vagal afferent fibers, disrupting neurotransmitter metabolism and inducing microglial hyperactivation, thereby exacerbating neuroinflammation. Microglia, the principal immune sentinels of the CNS, adopt a pro-inflammatory phenotype upon peripheral inflammatory signaling characterized by morphological transformations, excessive chemokine/cytokine production (e.g., IL-1β, IL-6), and dysregulated neurotransmitter dynamics. These mechanisms are strongly implicated in neuropsychiatric conditions such as major depressive disorder, anxiety disorders, autism spectrum disorder, and schizophrenia. Emerging microbiota-targeted therapies, including probiotic interventions and fecal microbiota transplantation, demonstrate therapeutic potential by restoring tryptophan homeostasis and modulating systemic inflammation. This review synthesizes current evidence on the regulatory role of the gut microbiota in inflammation-related psychiatric disorders, specifically emphasizing the microbial modulation of neuroimmune crosstalk and neurotransmitter synthesis (e.g., serotonin, dopamine). Mechanistic insights into microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, are critically evaluated for their dual roles in psychiatric disorders. These findings advance a unified framework for managing psychiatric comorbidities through precision modulation of the gut-brain axis.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Mental Disorders/microbiology/etiology/immunology/metabolism/therapy
Animals
*Inflammation/microbiology/immunology/metabolism
Neuroimmunomodulation

@article {pmid40909137,
year = {2025},
author = {Chen, K and Sun, L and Liu, Y and Chen, R},
title = {Safety and efficacy of fecal microbiota transplantation in the treatment of Parkinson's disease: a systematic review of clinical trials.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1639911},
pmid = {40909137},
issn = {1662-4548},
abstract = {INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease with limited treatment options and increasing incidence. The Microbiota-Gut-Brain Axis (MGBA) offers new insights for PD treatment, as gut microbiota imbalances are linked to PD. Fecal microbiota transplantation (FMT) shows potential to improve gut dysbiosis and has gained attention for PD treatment.

METHODS: We conducted a review following PRISMA 2009 guidelines, searching PubMed, EMBASE, Web of Science, and Scopus up to December 1, 2024. We included clinical trials of FMT for PD patients, regardless of stage or type, with outcomes related to efficacy or safety. Non-clinical trials were excluded. Two investigators independently assessed studies, extracted data, and evaluated risk of bias and quality.

RESULTS: A total of 1,147 articles were retrieved, and six studies involving 104 patients were included. Four were randomized controlled trials, one was a cohort study, and one was a case series. Patients had a mean age of 63.2 years and disease duration of 5.6 years. After FMT, some patients showed improvements in UPDRS scores, H-Y grades, NMSS scores, and constipation symptoms, but results varied across studies. No serious FMT-related adverse events occurred. Most were mild gastrointestinal issues. Gut microbiota diversity and beneficial bacterial abundance changed after FMT, correlating with clinical outcomes. FMT materials were mostly from unrelated donors with diverse preparation and delivery methods.

DISCUSSION: FMT shows efficacy and safety in PD treatment but is insufficient as a standard due to study heterogeneity and small sample sizes. Future research needs larger samples, unified tools, and standardized FMT procedures. Combining FMT with other therapies may improve efficacy.},
}

@article {pmid40909091,
year = {2025},
author = {Vineesh, A and Shah, S and Shah, K and Zaigham Hassan, M and Sapkota, A and Khadka, SR and Rizwanullah, F and Dare Ibrahim, A and Kanduri Hanumantharayudu, S and Kumar Makam Surendraiah, P and Ahmed, B and Gyullu, N},
title = {Exploring the Relationship Between Gut Health and Autoimmune Diseases: A Systematic Review and Meta-Analysis.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89300},
pmid = {40909091},
issn = {2168-8184},
abstract = {Autoimmune diseases (AIDs) are multifaceted, chronic illnesses characterized by immune dysregulation and systemic inflammation. Newer evidence has pointed a finger at the human gut microbiota, a trillion-fold population of microorganisms that inhabits the human GI tract, as a major influential modulator of immune reactivity and a significant contributor to autoimmune pathogenesis. This systematic review will seek to address how the literature correlates with systematic changes in the gut microbiota in AIDs as well as explore mechanistic associations with biological processes like intestinal permeability and modulation of the immune system, coupled with determining the effectiveness of microbiota-directed interventions. An extensive literature search was conducted in PubMed, Embase, Cochrane Central, and Web of Science, involving the availability of studies until May 2025. The eligible studies included observational studies, randomized controlled trials, and relevant mechanistic research regarding autoimmune diseases and alterations of the gut microbiome or administered interventions. Data extraction and risk of bias (ROB) assessments were performed by two independent reviewers, and a narrative synthesis with an illustrative meta-analysis was applied. Inclusion criteria were met by 10 studies, encompassing various autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), autoimmune thyroid diseases (AITDs), and psoriasis. Familiar patterns of microbiome dysbiosis were identified, such as a reduction in microbial diversity, increased intestinal permeability, and the expansion of pro-inflammatory species like Ruminococcus gnavus. Dietary interventions, fecal microbiota transplantation, and probiotics demonstrated positive effects on clinical outcomes and immune measures across multiple studies. The meta-analysis revealed that microbiota-directed interventions significantly improved disease activity and immune response markers in AIDs, indicating a robust link between gut microbiota composition and autoimmune pathology. In autoimmune disorders, gut microbiota is a key factor in immunopathology. Gut biology as an adjunct interventional strategy provides potential in managing these diseases. Additional studies are required to help standardize methods and identify microbial targets specific to diseases that can then be addressed through therapeutic interventions.},
}

@article {pmid40908772,
year = {2025},
author = {Faysal, M and Zehravi, M and Sutradhar, B and Al Amin, M and Shanmugarajan, TS and Arjun, UVNV and Ethiraj, S and Durairaj, A and Dayalan, G and Ahamad, SK and Rab, SO and Raman, K and Emran, TB},
title = {The Microbiota-Gut-Brain Connection: A New Horizon in Neurological and Neuropsychiatric Disorders.},
journal = {CNS neuroscience & therapeutics},
volume = {31},
number = {9},
pages = {e70593},
doi = {10.1111/cns.70593},
pmid = {40908772},
issn = {1755-5949},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mental Disorders/microbiology/metabolism/therapy ; *Nervous System Diseases/microbiology/metabolism/therapy ; *Brain/metabolism ; Animals ; Dysbiosis ; *Brain-Gut Axis/physiology ; Probiotics ; },
abstract = {INTRODUCTION: The microbiota-gut-brain axis (MGBA), a complex two-way connection between the gut microbiota and the brain, has become a key regulator of neurological and neuropsychiatric disorders. Neurological disorders and gut microbiota dysbiosis are linked to these diseases. Changes in gut microbiota can lead to neurotransmitter imbalances, oxidative stress, and neuroinflammation. Gut dysbiosis may contribute to the development of diseases such as depression, autism, schizophrenia, bipolar disorder, Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, epilepsy, anxiety, and autism spectrum disorders through immunological regulation, neuroinflammation, and neurotransmitter metabolism changes.

METHOD: This review systematically sourced articles related to microbiota gut brain axis, neurological disorders, neuropsychiatric disorders and clinical studies from major medical databases, including Scopus, PubMed, and Web of Science.

RESULTS: This review explores the molecular processes underlying MGBA interactions, including vagus nerve signaling, systemic immunological responses, and metabolites produced by microorganisms. The discussion explores the potential of microbiome-targeted treatments like fecal microbiota transplantation, probiotics, and prebiotics as effective treatment methods. The comprehension of the MGBA can revolutionize neurology and psychiatry, introducing innovative diagnostic and therapeutic approaches. Multiple elements, including diet, metabolism, age, stress, and medications, shape the human gut microbiota, and intestinal imbalances can lead to CNS diseases. The MGBA interacts with gut bacteria, and gut dysbiosis is associated with neurological disorders.

CONCLUSIONS: The review demonstrates the correlation between gut microbiota and neurologically associated diseases, highlighting its importance in neurogenesis, mental development, emotions, and behaviors. MGBA, mediated by microbial metabolites, affects brain function and neuroinflammation. Interventions like fetal microbiota transplantation, probiotics, and prebiotics can improve microbial balance, but more clinical research is needed.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Mental Disorders/microbiology/metabolism/therapy
*Nervous System Diseases/microbiology/metabolism/therapy
*Brain/metabolism
Animals
Dysbiosis
*Brain-Gut Axis/physiology
Probiotics

@article {pmid40907403,
year = {2025},
author = {Zhang, D and Wu, J and Feng, H and Tang, P and Zhou, Y and Zhao, C and Liu, J and Feng, W and Peng, C},
title = {Gastrodin ameliorates ulcerative colitis via modulating gut microbial tryptophan metabolism and AhR/NLRP3 pathway.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {147},
number = {},
pages = {157217},
doi = {10.1016/j.phymed.2025.157217},
pmid = {40907403},
issn = {1618-095X},
abstract = {BACKGROUND: Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disorder, presents persistent therapeutic challenges in clinical management. Gastrodin (GAS) is an active compound isolated from traditional Chinese medicine Gastrodia elata (Tianma), exhibits robust anti-inflammatory bioactivity. However, the role of GAS in UC has not been thoroughly studied.

PURPOSE: The study aimed to investigate the protective effect of GAS against UC induced by DSS and its underlying mechanisms, with a particular emphasis on gut microbiota-metabolite interactions.

METHODS: The ameliorative effect of GAS on UC was examined, followed by 16S rRNA sequencing, targeted metabolomics, MALDI-MSI analysis, and western blotting analysis, fecal microbiota transplantation (FMT) to investigate the underlying mechanism of GAS on UC.

RESULTS: Evaluation of symptoms showed that GAS exhibited dose-dependent beneficial effects on UC. Targeted metabolites showed that GAS increased the production of tryptophan-derived metabolites, including kynurenic acid (Kyna), indole-3-acetic acid (IAA), indole-3-carboxaldehyde (IAld), and indole-3-lactic acid (ILA), etc. MALDI-MSI confirmed that GAS increased the levels of aryl hydrocarbon receptor (AhR) ligands IAld and IAA in the colon tissue. Western blotting showed that GAS mitigated colon inflammation through the activation of the AhR/NOD-like receptor protein 3 (NLRP3) pathway. Finally, FMT confirmed that GAS ameliorates UC in a microbiota-dependent manner and the involvement of gut microbiota derived AhR ligands and AhR/NLRP3 pathway.

CONCLUSION: GAS alleviates UC via modulating gut microbiota-derived tryptophan metabolites (Kyna, IAA, IAld, ILA) in a microbiota-dependent manner and suppressing AhR/NLRP3 pathway. Our study has important practical implications for the application of traditional Chinese medicine-derived active ingredients in the treatment of UC.},
}

@article {pmid40906320,
year = {2025},
author = {Ilozumba, MN and Gomez, MF and Lin, T and Himbert, C and Round, JL and Zac Stephens, W and Warby, CA and Hardikar, S and Li, CI and Figueiredo, JC and Damerell, V and Fillmore, GC and Pickron, B and Toriola, AT and Shibata, D and Holowatyj, AN and Kahlert, C and Sankar, K and Siegel, EM and Jedrzkiewicz, J and Gigic, B and Byrd, DA and Ose, J and Ulrich, CM},
title = {Pre-surgery gut microbial diversity and abundance are associated with post-surgery onset of cachexia in colorectal cancer patients: the ColoCare Study.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {40906320},
issn = {1573-7225},
support = {U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; 01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; 01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; },
abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and it is indicative of poor prognosis and progressive functional impairment. The role of the gut microbiome in the development of cachexia in colorectal cancer (CRC) patients has not been established.

METHODS: Pre-surgical stool samples from n = 103 stage I-III CRC patients in the ColoCare Study were analyzed using 16S rRNA gene sequencing (Illumina) to characterize fecal bacteria. We calculated estimates of alpha- and beta-diversity and a priori- and exploratory-selected bacterial relative abundance. Using Fearon criteria, cachexia onset at 6 months post-surgery was defined as > 5% weight loss over the past 6 months and/or body mass index (BMI) of < 20 kg/m[2] and weight loss of > 2%. Associations of microbial metrics with cachexia onset were estimated using multivariable logistic regression models.

RESULTS: Higher alpha-diversity was positively associated with cachexia onset, with stronger associations in females, patients < 65 years, those receiving adjuvant treatment, consuming high fiber, or with energy intake outside USDA recommendations (p < 0.05). Porphyromonas (OR = 0.51, 95% CI 0.26-0.89, p = 0.03) and Actinomyces (OR = 0.72, 95% CI 0.48-1.03, p = 0.08) were inversely associated with cachexia, although the association for Actinomyces did not reach statistical significance. Stratified analyses revealed a stronger inverse association between Porphyromonas and cachexia onset in males, patients with rectal or stage III tumors, those receiving neoadjuvant treatment, physically inactive individuals, and those consuming low fiber. However, these associations did not reach statistical significance (0.05 ≤ p < 0.10).

CONCLUSION: Higher gut microbial alpha-diversity and lower relative abundances of the genera Porphyromonas and Actinomyces in pre-surgery stool samples were associated with onset of cachexia in CRC patients six months post-surgery. This is the first study to explore a link between the gut microbiome and cachexia in CRC patients, providing novel insights into the biology of cachexia and potential clinical interventions.},
}

@article {pmid40906312,
year = {2025},
author = {Arjmand, B and Badamchizadeh, S and Mehran, P and Sarvari, M and Alavi-Moghadam, S and Arjmand, R and Rezaei-Tavirani, M and Janbabaei, G and Vaezi, M and Larijani, B},
title = {Gut Microbiome and its Impact on Outcomes following Hematopoietic Stem Cell Transplantation: a Comprehensive Review.},
journal = {Stem cell reviews and reports},
volume = {},
number = {},
pages = {},
pmid = {40906312},
issn = {2629-3277},
abstract = {Hematopoietic stem cell transplantation is an important treatment for hematological malignancy and disorders, but is fraught with high risks, including graft-versus-host disease, infection, and relapse. Recent evidence now identifies that the microbiome plays a significant role in influencing transplant outcomes, in which microbial dysbiosis-defined by reduced diversity and pathogen overgrowth-is linked to greater complications and death. Microbiome manipulation with approaches including beneficial microbial species, fiber, fecal transplants, and diet has the potential to mitigate these risks. Experiments show that the restoration of beneficial microbes can restore immunity, reduce graft-versus-host disease severity, and reduce infection. Some challenges remain, including standardization of protocols, long-term efficacy, and safety in immunocompromised recipients. Future research will be focused on mechanisms, trials, and new technology for microbiome-based therapy, with the ultimate goal of improving survival and quality of life for transplant recipients. Hereupon, this review addresses how microbiome engineering can revolutionize cancer treatment by optimizing gut microbial communities for better outcomes in hematopoietic stem cell transplantation (HSCT).},
}

@article {pmid40905977,
year = {2025},
author = {Liu, Y and Gao, J and Chen, L and Chen, Y and Jiang, J and Chen, H and Ma, L},
title = {Lithocholic acid ameliorates ulcerative colitis via the PXR/TLR4/NF-κB/NLRP3 signaling pathway and gut microbiota modulation.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {82},
number = {1},
pages = {336},
pmid = {40905977},
issn = {1420-9071},
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/drug therapy/pathology/metabolism/microbiology/chemically induced ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Toll-Like Receptor 4/metabolism ; *Pregnane X Receptor/metabolism ; *Signal Transduction/drug effects ; *Lithocholic Acid/pharmacology/therapeutic use ; *NF-kappa B/metabolism ; Male ; Mice, Inbred C57BL ; Mice ; Dextran Sulfate ; Disease Models, Animal ; Humans ; },
abstract = {Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, closely linked to dysbiosis of gut microbiota and imbalances in bile acids. Lithocholic acid (LCA), a secondary bile acid, plays a crucial role in maintaining gut health; however, its specific therapeutic potential in UC remains to be fully elucidated. This study investigates the efficacy of LCA in alleviating UC and explores the underlying mechanisms, particularly focusing on the PXR/TLR4/NF-κB/NLRP3 signaling pathway and gut microbiota modulation. Using a dextran sulfate sodium (DSS)-induced colitis model, our findings demonstrate that LCA administration significantly alleviates colitis symptoms, evidenced by reduced disease activity index (DAI), increased colon length, improved intestinal barrier function, and decreased colonic inflammation. Mechanistically, LCA activates the pregnane X receptor (PXR), which inhibits TLR4-mediated NF-κB/NLRP3 inflammasome activation, leading to reduced colonic inflammation and lower levels of pro-inflammatory cytokines. Furthermore, LCA remodels gut microbiota by promoting beneficial bacterial growth, such as Akkermansiaceae, Lactobacillaceae and Muribaculaceae, while suppressing pathogenic and opportunistic pathogens, including Enterobacteriaceae and Bacteroidaceae. The gut microbiota-dependent effects of LCA were corroborated through antibiotic treatment and fecal microbiota transplantation (FMT) experiments. Notably, the absence of intestinal flora affected PXR expression and activity, modifying the aforementioned effects. Overall, our findings reveal that LCA ameliorates experimental colitis by regulating the PXR/TLR4/NF-κB/NLRP3 signaling cascade and modulating gut microbiota composition. This study underscores LCA's potential as a targeted therapeutic strategy and a promising microbiota-focused approach for managing UC, offering new insights into the role of bile acids in intestinal health and disease management.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Colitis, Ulcerative/drug therapy/pathology/metabolism/microbiology/chemically induced
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Toll-Like Receptor 4/metabolism
*Pregnane X Receptor/metabolism
*Signal Transduction/drug effects
*Lithocholic Acid/pharmacology/therapeutic use
*NF-kappa B/metabolism
Male
Mice, Inbred C57BL
Mice
Dextran Sulfate
Disease Models, Animal
Humans

@article {pmid40904889,
year = {2025},
author = {Lv, J and Zhao, HP and Yu, Y and Wang, JH and Zhang, XJ and Guo, ZQ and Jiang, WY and Wang, K and Guo, L},
title = {From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.},
journal = {World journal of gastroenterology},
volume = {31},
number = {30},
pages = {108680},
pmid = {40904889},
issn = {2219-2840},
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Dyslipidemias/microbiology/therapy/metabolism/etiology ; Homeostasis ; *Lipid Metabolism ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Dysbiosis/microbiology/therapy ; },
abstract = {Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.},
}

*Gastrointestinal Microbiome/physiology
Humans
*Dyslipidemias/microbiology/therapy/metabolism/etiology
Homeostasis
*Lipid Metabolism
Animals
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Prebiotics/administration & dosage
Dysbiosis/microbiology/therapy

@article {pmid40904642,
year = {2025},
author = {Sun, Q and Jiang, Z and Yang, L and Liu, H and Song, P and Yuan, L},
title = {Towards an Asian paradigm of inflammatory bowel disease management: A comparative review of China and Japan.},
journal = {Intractable & rare diseases research},
volume = {14},
number = {3},
pages = {192-202},
pmid = {40904642},
issn = {2186-3644},
abstract = {This systematic review compares inflammatory bowel disease (IBD) management between China and Japan across epidemiology, clinical strategies, health insurance, and social security policies. Epidemiologically, the incidence of IBD is rapidly increasing in China, contributing to a growing disease burden. In contrast, Japan has a stabilized incidence but a rising prevalence, driven by an aging patient population. Clinically, step-up therapy remains the mainstream approach in China, limited by regional and financial disparities in biologic access. In contrast, Japan, benefiting from the "Designated Intractable Diseases" program, favors early intensive therapy with a focus on mucosal healing. In the area of precision medicine, China is advancing rapidly in therapeutic drug monitoring (TDM) for anti-TNF agents. In contrast, Japan leads in AI-assisted endoscopic assessment, despite slower adoption of TDM. Japan's comprehensive insurance covers most costs of IBD; China has significantly reduced drug prices via national negotiations, and yet reimbursement rates vary regionally. China has made progress in telemedicine and standardized fecal microbiota transplantation (FMT); Japan excels in AI endoscopy and use of an elemental diet. To optimize IBD care in the Asia-Pacific, China should enhance access to advanced therapies, implement hierarchical diagnosis/ treatment, and develop multi-tiered insurance. Japan must address aging-related challenges and insurance sustainability while expanding use of TDM. Sino-Japanese collaboration in genetics, microbiome research, and AI-driven diagnostics, supported by sustained policy dialogue, is key to advancing precision IBD care and shaping a scalable "Asian model" for chronic disease management.},
}

@article {pmid40904056,
year = {2025},
author = {Dassanayake, P and Diksha, D and Varela-Mattatall, G and Sun, Q and Donnelly, SC and Suchy, M and Bartolome, D and Furlong, S and Deans, L and Biernaski, H and Huston, Y and Thompson, RT and Burton, JP and Moran, G and Gelman, N and Prato, FS and Kovacs, MS and Thiessen, JD and Goldhawk, DE and Schellenberg, J and Fox, MS},
title = {Biodistribution and dosimetry of [89]Zirconium-labeled microbiota transplants in the pig gut.},
journal = {Medical physics},
volume = {52},
number = {9},
pages = {e18087},
doi = {10.1002/mp.18087},
pmid = {40904056},
issn = {2473-4209},
mesh = {Animals ; *Zirconium/chemistry ; *Radioisotopes/chemistry ; Swine ; Tissue Distribution ; Radiometry ; Female ; Escherichia coli ; *Gastrointestinal Microbiome ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Isotope Labeling ; },
abstract = {BACKGROUND: The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as Escherichia coli Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance. However, effective treatment will require optimizing delivery and understanding microbial dissemination and engraftment.

PURPOSE: We developed a method to monitor microbial migration and GI permeability post-ingestion using hybrid PET/MRI. To simulate probiotic therapy, bacteria were radiolabeled with [89]Zr, encapsulated, and administered to pigs. Organ level and whole-body dosimetry was determined from the time activity curves recorded over 7 days post ingestion.

METHODS: We administered [89]Zr-labeled Lactobacillus crispatus ATCC33820 (Gram-positive) to six female Duroc pigs (weight = 33.3 ± 4.6 kg) and E. coli Nissle 1917 (Gram-negative). Scans were performed between 6 h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7 ± 12.9 MBq. Whole-body PET scans were acquired simultaneously with MRI using a T2-weighted HASTE sequence. Images were processed using 3D-Slicer co-registering PET with MRI and semi-automated organ segmentation was performed. Gender-averaged human equivalent organ-level effective doses (ED) and whole body ED were calculated using OLINDA.

RESULTS: PET imaging showed [89]Zr-labeled L. crispatus and E. coli post-ingestion localized primarily within the GI tract before excretion within feces. The highest mean ED for [89]Zr-labeled L. crispatus and E. coli were in the distal colon (26.8 ± 4.9 µSv/MBq and 28.4 ± 7.9 µSv/MBq, respectively) and proximal colon (17.9 ± 3.7 µSv/MBq and 18.4 ± 5.1 µSv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5 ± 9.5 µSv/MBq (L. crispatus) and 66.7 ± 14.9 µSv/MBq (E. coli).

CONCLUSIONS: The whole-body ED for L. crispatus and E. coli is lower than reported values for ingested tracers, such as that from [89]Zr labelled antibodies and [111]In labelled "meals" used to determine gut transit times. Hence ingestion of [89]Zr labelled bacteria shows promise for becoming a human nuclear-medicine procedure to determine the effectiveness of probiotic therapies.},
}

Animals
*Zirconium/chemistry
*Radioisotopes/chemistry
Swine
Tissue Distribution
Radiometry
Female
Escherichia coli
*Gastrointestinal Microbiome
Positron-Emission Tomography
Magnetic Resonance Imaging
Isotope Labeling

@article {pmid40903950,
year = {2025},
author = {Liu, Y and Tang, T and Cai, H and Liu, Z},
title = {Bidirectional communication between the gut microbiota and the central nervous system.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00434},
pmid = {40903950},
issn = {1673-5374},
abstract = {In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism's health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, and Huntington's disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiotabased treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application.},
}

@article {pmid40903035,
year = {2025},
author = {Hou, Y and Wu, H and Zhang, Z and Wang, J and Chen, Q and Lian, C and He, D and Li, Z and Wei, W and Lin, X and Sun, D and Cao, B and Xu, T and Cai, M and Wang, G and Zhang, X and Duan, L and Hao, H and Zheng, X},
title = {Bacteroides intestinalis mediates the sensitivity to irinotecan toxicity via tryptophan catabolites.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2024-334699},
pmid = {40903035},
issn = {1468-3288},
abstract = {BACKGROUND: Late-onset diarrhoea remains a poorly managed concern for clinical irinotecan therapy. Although bacterial β-glucuronidases (β-GUS) mediated SN-38 production is prevailingly thought to mediate intestinal toxicity, β-GUS inhibitors confer limited benefits in the clinic.

OBJECTIVE: This study aimed to explore the role and mechanism of endogenous bacterial metabolites in susceptibility to irinotecan toxicity.

DESIGN: Gut microbiota profiles and metabolites in patients with colorectal cancer (CRC) with or without diarrhoea were investigated via 16S rRNA sequencing, shotgun metagenomics and metabolomics. The role of microbial metabolites was investigated in mice by metabolic bioengineering and intestinal organoid culture. The mechanism of microbial metabolites on intestinal stem cells was investigated by transcriptional profiling and chemical intervention.

RESULTS: Gut microbial configuration was differentially remodelled in diarrhoea and non-diarrhoea patients with irinotecan therapy, and the susceptibility was transmissible to recipient mice via transplantation of baseline faecal microbiome. Bacteroides intestinalis (B. intestinalis) was notably expanded in the diarrhoea-prone cohorts as well as in irinotecan-treated mice. B. intestinalis colonisation sensitised intestinal epithelia to irinotecan-induced chemical injury, partially via tryptophan metabolite indole-3-acetate (IAA). Both B. intestinalis and bioengineered bacteria that produce IAA exacerbated irinotecan-induced intestinal epithelial injury in mice. Mechanistically, IAA suppressed PI3K-Akt signalling, thereby impairing the renewal of intestinal epithelia under the insult of irinotecan. In clinical patients receiving irinotecan therapy, faecal IAA level was closely associated with the diarrhoea severity.

CONCLUSION: Our study uncovers the mechanism of endogenous bacterial metabolite in shaping the individual susceptibility to irinotecan toxicity and suggests IAA as a potential predictive biomarker.},
}

@article {pmid40902967,
year = {2025},
author = {Lu, Y and Liu, Y and Bai, X and Jiang, T and Chen, X and Wang, Y and Du, P and Sun, Y and Liu, C and Duan, J},
title = {Mechanisms of Podophyllotoxin-induced Enterotoxicity: A Multi-omics Integration of Gut Microbiota, Short-chain Fatty Acids, and Inflammatory Mediators.},
journal = {Toxicology},
volume = {},
number = {},
pages = {154274},
doi = {10.1016/j.tox.2025.154274},
pmid = {40902967},
issn = {1879-3185},
abstract = {Podophyllotoxin (PPT), a lignan extracted from the roots and stems of Podophyllum species, exhibits significant enterotoxicity that limits its clinical application. However, its underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms underlying PPT-induced enterotoxicity. Changes in body weight, fecal morphology, toxic phenotypes, and histopathological features were evaluated. 3D reconstruction, 16S rRNA sequencing, targeted short-chain fatty acids (SCFAs) analysis, and inflammatory cytokine assays were performed. The findings demonstrated that PPT induced pathological changes in rats, including weight loss, diarrhea, and colonic damage. PPT administration significantly reduced beneficial bacteria such as Lactobacillus, while increasing harmful bacteria such as Escherichia-Shigella. The predicted pathways of bacterial invasion of epithelial cells and lipopolysaccharide biosynthesis were significantly upregulated. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also increased. Additionally, the expression of undecaprenyl-diphosphate synthase (UPPS) and SCFAs production was reduced. These findings indicate that PPT may alter gut microbial composition, increase Escherichia-Shigella invasion in the intestinal epithelial cells, promote lipopolysaccharide production, enhance the release of pro-inflammatory cytokines, including TNF-α and IL-6, and inhibit UPPS expression and SCFAs generation, collectively contributing to enterotoxicity. This study provides novel insights into the mechanisms behind PPT-induced enterotoxicity, which is essential for preventing and treating PPT toxicity.},
}

@article {pmid40902672,
year = {2025},
author = {Sharma, S and Bashir, B and Kolekar, KA and Acharya, A and Gupta, M and Jena, R and Vishwas, S and Kaur, J and Gupta, G and Kumbhar, PS and Patle, D and Chaitanya, M and Gulati, M and Singh, SK},
title = {Tailoring the biomarkers of Alzheimer's disease using a gut microbiome-centric approach: Preclinical, clinical, and regulatory perspectives.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102888},
doi = {10.1016/j.arr.2025.102888},
pmid = {40902672},
issn = {1872-9649},
abstract = {Alzheimer's disease (AD), a progressive neurodegenerative disorder, poses significant therapeutic challenges due to its complex etiology and limited treatment options. Traditional pharmacotherapies targeting amyloid-β (Aβ) and cholinergic pathways offer modest benefits and are often associated with adverse effects. Emerging evidence implicates gut dysbiosis and the gut-brain axis in the pathogenesis and progression of AD. This review explores the multifactorial pathophysiology of AD and evaluates the therapeutic potential of gut-based interventions such as probiotics, prebiotics, synbiotics, metabiotics, postbiotics, and fecal microbiota transplantation (FMT) in mitigating disease pathology. Emphasis has also been given on role of miRNA released from FMT in management of AD. Preclinical and clinical studies demonstrate that these strategies can restore microbial homeostasis, reduce neuroinflammation, enhance gut barrier integrity, and improve cognitive outcomes. The regulatory aspects with use of probiotics based products and FMT is also highlighted. The modulation of neuroimmune, neuroendocrine, and neural pathways through microbiota-derived metabolites offers a promising avenue for AD management. Despite encouraging findings, further research is needed to address interindividual microbiome variability, delivery challenges, and the requirement for large-scale, randomized trials. Personalized gut-targeted approaches may open new horizons for the prevention and treatment of AD.},
}

@article {pmid40901606,
year = {2025},
author = {Al-Busafi, SA and Alwassief, A and Madian, A and Atalla, H and Alboraie, M and Elbahrawy, A and Eslam, M},
title = {Exploring the interplay between metabolic dysfunction-associated fatty liver disease and gut dysbiosis: Pathophysiology, clinical implications, and emerging therapies.},
journal = {World journal of hepatology},
volume = {17},
number = {8},
pages = {108730},
doi = {10.4254/wjh.v17.i8.108730},
pmid = {40901606},
issn = {1948-5182},
abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD) now affects roughly one-quarter of the world's population, reflecting the global spread of obesity and insulin resistance. Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis, where intestinal dysbiosis acts as a key driver of hepatic injury. Altered microbial communities disrupt epithelial integrity, promote bacterial translocation, and trigger endotoxin-mediated inflammation that accelerates steatosis, lipotoxicity, and fibrogenesis. Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis, amplifying cardiometabolic risk. Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts, linked to diet quality, sedentary behavior, adiposity, and host genetics. Newly developed microbiome-derived biomarkers, advanced elastography, and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification, although external validation remains limited. In early trials, interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics, rational diet patterns, next-generation fecal microbiota transplantation, and bile-acid-modulating drugs show encouraging histological and metabolic gains. Optimal care will likely couple these tools with weight-centered lifestyle programmes in a precision-medicine framework. Key challenges include inter-ethnic variability in microbiome signatures, the absence of consensus treatment algorithms, and regulatory barriers to live biotherapeutics. Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.},
}

@article {pmid40901203,
year = {2025},
author = {Elendu, C and Omeludike, EK and Aregbesola, ET and Mordi, P and Blewusi, GS and Ogidan, AO and Okeke, NG and Obidigbo, BT and Asini, AO and Ubi, ES and Etakewen, PO and Amahalu, CA and Foncham, RF and Gana, LT and Onwe, CJ and Ojeabuo, OF and Ojo, AO and Ikeaba, CS and Opara, NC},
title = {Fecal microbiota transplantation as a therapeutic modality for recurrent Clostridioides difficile infection: reviewing efficacy, safety, mechanisms of action, and outcomes.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {9},
pages = {5829-5850},
doi = {10.1097/MS9.0000000000003649},
pmid = {40901203},
issn = {2049-0801},
abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a significant global health challenge, characterized by high morbidity, substantial healthcare costs, and an increased risk of severe complications. C. difficile, a gram-positive, spore-forming bacterium, is the primary cause of healthcare-associated diarrhea. The pathogenesis of rCDI is closely tied to gut microbiota disruptions, often triggered by antibiotic use, immunosuppression, and prolonged hospital stays. While effective for initial episodes, standard antibiotic therapies paradoxically exacerbate microbiota dysbiosis, increasing the risk of recurrence. Approximately 20%-30% of patients experience a recurrence after the initial episode, with rates rising to 45%-65% in those with multiple episodes. Fecal microbiota transplantation (FMT) has arrived as a transformative therapy for rCDI, leveraging donor microbiota to restore gut homeostasis and suppress C. difficile colonization. Clinical trials consistently report success rates exceeding 80%, markedly surpassing outcomes with antibiotics. Innovations in delivery methods, including oral capsules, have enhanced FMT's accessibility and patient acceptability. However, concerns surrounding safety and standardization persist. Adverse events, such as gastrointestinal discomfort and rare cases of multidrug-resistant organism transmission, underscore the need for stringent donor screening protocols. Emerging evidence reveals complex mechanisms underpinning FMT's efficacy, including restoring microbial diversity, bile acid metabolism, and short-chain fatty acid production. Long-term benefits, such as sustained microbiota stability, and potential applications in other conditions, including inflammatory bowel disease and metabolic disorders, are promising but require further validation. Addressing challenges in donor selection, regulatory oversight, and personalized approaches will be critical to optimizing FMT as a safe and effective therapeutic strategy for rCDI.},
}

@article {pmid40901024,
year = {2025},
author = {Chen, N and Li, L and Han, Y and Chen, Z},
title = {The Role of Gut Microbiota in the Modulation of Pulmonary Immune Response to Viral Infection Through the Gut-Lung Axis.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {11755-11781},
doi = {10.2147/JIR.S525880},
pmid = {40901024},
issn = {1178-7031},
abstract = {Viral respiratory infections, including influenza, respiratory syncytial virus (RSV), and SARS-CoV-2, remain major global health challenges due to their high morbidity and mortality. Emerging evidence highlights the pivotal role of the gut-lung axis in regulating pulmonary immunity. The gut microbiota communicates with the lungs via endocrine, immune, and neuroimmune pathways-particularly through metabolites such as short-chain fatty acids (SCFAs) and vagus nerve-mediated signaling-which modulate immune cells including alveolar macrophages and dendritic cells. Disruption of gut microbial balance has been linked to impaired pulmonary immune responses and increased susceptibility to infection. This review synthesizes findings from animal models and clinical studies, demonstrating that interventions such as probiotics (eg, Lactobacillus gasseri), prebiotics (eg, galacto-oligosaccharides), fecal microbiota transplantation (FMT), and Traditional Chinese Medicine (eg, Astragalus, curcumin) can enhance antiviral cytokine production, restore gut-lung homeostasis, and reduce lung inflammation. For example, FMT from H7N9-survivor mice improved influenza resistance in recipients, and oral probiotics reduced respiratory failure risk in COVID-19 patients. These findings suggest that gut-lung axis modulation is a promising adjunctive approach for treating viral respiratory infections. Future research should prioritize personalized microbiome-based therapies and large-scale clinical trials to validate efficacy and safety.},
}

@article {pmid40900873,
year = {2025},
author = {Hafez, MM and Bahcecioglu, IH and Yalniz, M and Kouta, KA and Tawheed, A},
title = {Future of inflammatory bowel disease treatment: A review of novel treatments beyond guidelines.},
journal = {World journal of methodology},
volume = {15},
number = {4},
pages = {107643},
doi = {10.5662/wjm.v15.i4.107643},
pmid = {40900873},
issn = {2222-0682},
abstract = {Inflammatory bowel disease (IBD) is a chronic condition consisting of two main types: Crohn's disease and ulcerative colitis. Conventional treatments for these diseases include aminosalicylates, corticosteroids, immunomodulators, and biologics. However, these treatments have several drawbacks, including high costs for patients and numerous side effects. Recently, advanced treatments have been developed, such as small-molecule therapies, targeted biologics, innovative drug delivery systems, and microbiome-based interventions. Emerging therapies like anti-interleukin-23 monoclonal antibody inhibitors, sphingosine-1-phosphate receptor modulators, and Janus kinase inhibitors are more specialized in reducing immune activity. They enhance bioavailability, reduce side effects, and specifically target the gastrointestinal tract without affecting other systems. Innovative drug delivery systems for IBD, such as nanoparticles, hydrogels, and microgrippers, improve bioavailability and prolong drug release. The combination of conventional and advanced therapies may benefit from the synergistic effects of both. Furthermore, fecal microbiota transplantation and probiotics can help restore the balance of gastrointestinal microbiota, reducing disease flare-ups. Advances in artificial intelligence, endoscopic techniques, and stem cell therapies have shown great potential in treating IBD, although several significant challenges remain. Treating this disease requires multidisciplinary integration and the application of technology and telemedicine.},
}

@article {pmid40900872,
year = {2025},
author = {Singh, JP and Aleissa, M and Chitragari, G and Drelichman, ER and Mittal, VK and Bhullar, JS},
title = {Uncovering the role of microbiota and fecal microbiota transplantation in Crohn's disease: Current advances and future hurdles.},
journal = {World journal of methodology},
volume = {15},
number = {4},
pages = {106148},
doi = {10.5662/wjm.v15.i4.106148},
pmid = {40900872},
issn = {2222-0682},
abstract = {Crohn's disease (CD) is an idiopathic, chronic, and recurrent inflammatory condition of the gastrointestinal tract. Recent studies suggest a potential role of gut microbiota in CD, particularly dysbiosis-an imbalance in gut bacteria. While dysbiosis is consistently observed in CD, it remains uncertain whether it is a cause or a consequence of the disease. Given its association with CD, the therapeutic potential of fecal microbiota transplantation (FMT) has been explored. This review examines the role of gut microbiota in CD, evaluates the therapeutic potential of probiotics and FMT, and highlights current research findings and limitations. Key studies on the relationship between gut dysbiosis, probiotics, and FMT in CD were analyzed, with a focus on randomized trials, meta-analyses, and clinical observations. Dysbiosis is a consistent feature of CD, but its causative role remains unclear. Probiotics, prebiotics, and synbiotics have shown no efficacy in inducing or maintaining remission in CD. FMT shows potential as a therapeutic option for CD, but its efficacy remains inconsistent and inconclusive. The variability in outcomes, including diminished effects over time despite repeated FMT, underscores the need for larger, well-controlled trials. Only one randomized controlled trial (RCT) has compared FMT with sham transplantation, but the sample size was very small. Other studies are limited by factors such as small sample sizes, lack of control groups, short follow-up periods, and inconsistent methodologies, making it challenging to draw definitive conclusions. While gut dysbiosis likely plays a role in CD pathogenesis, its causative role remains uncertain. Current evidence does not support FMT as a reliable treatment for inducing or maintaining remission in CD, though it appears generally safe. Larger, standardized, RCTs are necessary to clarify the therapeutic role of FMT in CD management.},
}

@article {pmid40900041,
year = {2025},
author = {Xue, M and Zhang, X and Zhou, Y and Yan, J and Gao, H and Bai, Y and Shi, J and Liu, Y and Xu, Y and Zhang, N and Li, L and Shi, S and Liang, H},
title = {Sulfated Fucooligosaccharides Ameliorated Neuroinflammation in D-Galactose-Induced Aging Model Mice via the Gut-Brain Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c08350},
pmid = {40900041},
issn = {1520-5118},
abstract = {This study was aimed to reveal the neuroprotective effect of sulfated fucooligosaccharides (FOS) in an aging mouse model induced by d-galactose. The results showed that FOS treatment ameliorated inflammation, improved behavioral decline in memory and cognition, and exerted neuroprotective effects. FOS reduced microglia activation by decreasing the expression of P38 mitogen-activated protein kinase (P38 MAPK), cyclic-AMP response binding protein (CREB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, FOS improved intestinal mucosal barrier damage and reduced the release of lipopolysaccharide. FOS increased the diversity of the gut flora and promoted a significant enrichment of the Akkermansia genus. FOS also increased the butyric acid level and reduced the expression of histone deacetylase 3 (HDAC3), Toll-like receptor 4 (TLR4), and nuclear factor kappa-B (NF-κB). Fecal microbiota transplantation from the FOS-treated mice showed a similar effect to FOS treatment in inhibiting neuroinflammation and reduced d-galactose-induced cognitive dysfunction. The results suggested that FOS supplementation ameliorated d-galactose-induced neuron damage and exerted neuroprotective effects through the gut-brain axis.},
}

@article {pmid40899744,
year = {2025},
author = {Jin, JY and Yang, XY and Feng, R and Ye, ML and Xu, H and Wang, JY and Hu, JC and Zuo, HT and Lu, JY and Song, JY and Zhao, Y and Wang, Y and Tong, Q},
title = {Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {17},
pages = {e71004},
pmid = {40899744},
issn = {1530-6860},
support = {2022YFA0806400//the National Key R&D Program of China/ ; 2022YFC3601305//the National Key R&D Program of China/ ; 2021-I2M-1-028//the CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-1-027//the CAMS Innovation Fund for Medical Sciences/ ; 2023-I2M-2-006//the CAMS Innovation Fund for Medical Sciences/ ; 82173888//the National Natural Science Foundation of China/ ; 81973290//the National Natural Science Foundation of China/ ; Z141102004414062//the Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Diabetic Cardiomyopathies/metabolism/microbiology/therapy ; Energy Metabolism ; Oxidative Stress ; Metabolic Reprogramming ; },
abstract = {Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus, characterized by myocardial structural and functional abnormalities in the absence of overt coronary artery disease or hypertension. A growing body of evidence implicates the gut microbiota and its metabolites as key modulators of systemic metabolic homeostasis, influencing energy metabolism, inflammation, and oxidative stress. The gut microbiota emerges as a novel regulator of cardiac remodeling and metabolic reprogramming in DCM through the gut-heart axis. This review aims to synthesize current mechanistic insights into how gut microbiota and its bioactive metabolites contribute to metabolic reprogramming in DCM. It further evaluates the potential of microbiota-targeted interventions as emerging therapeutic strategies to mitigate disease progression and restore cardiac homeostasis. A narrative, mechanistically focused literature review was conducted using PubMed and Web of Science databases. It covered experimental, preclinical, and translational studies up to April 2025. Articles were selected based on relevance to gut microbial metabolism, host cardiac metabolic pathways, and therapeutic interventions linked to DCM. Gut microbiota-derived metabolites-including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids, lipopolysaccharides (LPS), tryptophan catabolites, and hydrogen sulfide-modulate cardiometabolic pathways via epigenetic regulation, altered energy substrate utilization, inflammatory signaling, and mitochondrial oxidative stress. These metabolites influence insulin resistance, lipid accumulation, mitochondrial dynamics, and cardiac fibrosis. Therapeutic strategies such as dietary modulation, probiotics, prebiotics, fecal microbiota transplantation, and drugs like SGLT2 inhibitors and GLP-1 receptor agonists have shown promising effects in modulating gut microbiota composition and alleviating DCM phenotypes in animal models. However, clinical evidence remains limited. The gut microbiota plays a pivotal role in the pathogenesis and potential treatment of DCM through its ability to reprogram host metabolism and inflammation. While preclinical data are compelling, further translational research-including humanized models and multi-omics integration-is required to validate microbiota-targeted therapies for cardiovascular applications. Targeting the microbiota-metabolite axis offers an innovative therapeutic avenue for personalized intervention in diabetic heart disease.},
}

Humans
*Gastrointestinal Microbiome/physiology
Animals
*Diabetic Cardiomyopathies/metabolism/microbiology/therapy
Energy Metabolism
Oxidative Stress
Metabolic Reprogramming

@article {pmid40899722,
year = {2025},
author = {Shi, X and Wan, L and Ni, S and Wu, X and Mu, J and Pei, W and Chen, Z and Xia, Y and Li, L and Zhang, Z},
title = {Chronic Exposure to Sunset Yellow Promotes Susceptibility to Experimental Colitis in Mice through Gut Microbiota.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c06410},
pmid = {40899722},
issn = {1520-5118},
abstract = {Sunset yellow (SY) is a widely used food additive. However, its impacts on ulcerative colitis (UC) development remain unclear. Here, SY exposure exacerbated dextran sulfate sodium (DSS)-induced UC symptoms in mice, including body weight loss, elevated disease activity index, histological damage, inflammation, gut barrier impairment, disruption of gut microbiota composition, and sulfur metabolism. Moreover, fecal microbiota transplantation from SY-exposed mice also exacerbated colitis in the recipient mice. Notably, SY exposure both in vivo and in vitro inhibited the growth of Akkermansia muciniphila (AKK). Nontargeted metabolomics revealed that SY exposure impaired glutathione (GSH) metabolism, as evidenced by reduced GSH and glutathione disulfide levels in both normal and colitis mice. In AKK, SY exposure significantly decreased GSH content, suppressed glutathione S-transferase activity, and disrupted sulfur metabolism. Importantly, GSH supplementation markedly reversed the SY-induced AKK growth inhibition. Collectively, these findings suggest that long-term SY exposure promotes experimental colitis in mice through gut microbiota-dependent GSH metabolic dysregulation.},
}

@article {pmid40899693,
year = {2025},
author = {Bo, T and Xu, X and Liu, H and Tang, L and Xu, H and Zhao, S and Lv, J and Wang, D},
title = {Convergent gut microbial functional strategies drive energy metabolism adaptation across Ursidae species and challenge the uniqueness of giant panda.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wraf201},
pmid = {40899693},
issn = {1751-7370},
abstract = {The gut microbiota is a key regulator of host energy metabolism, but its role in seasonal adaptation and evolution of bears is still unclear. Although giant pandas are considered an extraordinary member of the Ursidae family due to their specialized herbivory and low metabolic rate, there is still controversy over whether the metabolic regulation mechanism of their gut microbiota is unique. This study analyzed the seasonal dynamics of gut microbiota in giant pandas (Ailuropoda melanoleuca), Asian black bears (Ursus thibetanus), brown bears (Ursus arctos), and polar bears (Ursus maritimus), and combined with fecal microbiota transplantation (FMT) experiments, revealed the following findings. The microbial composition of the four bear species is similar, with both Firmicutes and Proteobacteria dominating. The enrichment of Firmicutes in winter enhances lipid metabolism, and adapts to dietary differences, indicating the existence of convergent microbial functional strategies in the Ursidae family. Our results demonstrate that bear gut microbiota promoted seasonal adaptation. In FMT experiments, bear gut microbiota in winter may had stronger functional capabilities on regulating host energy metabolism in mice, and regulate host appetite to increase energy intake. Finally, despite feeding on bamboo, giant pandas microbiota driven energy metabolism pathways (such as SCFAs) are highly conserved compared to other bears, suggesting a deep commonality in the adaptability of bear microbiota in evolution. Therefore, this study challenges the traditional view of microbial uniqueness of giant pandas, and emphasizes the co-evolutionary mechanism of energy metabolism adaptation in bear animals through microbial plasticity. In the future, it is necessary to integrate wild samples to eliminate the interference of captive diet and further analyze the genetic basis of host gut microbiota interactions.},
}

@article {pmid40541100,
year = {2025},
author = {Tang, X and Mao, M and Zhang, X and Gao, H and Wang, Z and Fang, R and Cheng, HW and Jiang, S},
title = {Cecal microbiota transplantation enhances calcium retention through modulation of gut microbiota and intestinal calcium transporter gene expression in chicks.},
journal = {Poultry science},
volume = {104},
number = {9},
pages = {105437},
pmid = {40541100},
issn = {1525-3171},
mesh = {Animals ; *Chickens/microbiology/genetics/metabolism/growth & development/physiology ; *Gastrointestinal Microbiome/physiology ; Cecum/microbiology ; Female ; *Fecal Microbiota Transplantation/veterinary ; *Avian Proteins/metabolism/genetics ; Random Allocation ; *Gene Expression ; *Calcium/metabolism ; },
abstract = {Bone development during early life is crucial for maintaining skeletal health and productivity in laying hens. The aim of this study was to investigate the effects of transferring cecal bacterial material of healthy adult hens on growth performance, gut integrity, microbial development, and bone metabolism of recipient chicks. Cecal contents were collected from 12 healthy Lohmann Pink-shell laying hens aged 47 weeks (donors). A total of 120 1-day-old Lohmann Pink chicks (recipients) were randomly assigned to 2 treatments for a 34-day trial: CONT (0.1 mL saline, Control) and CMT (0.1 mL cecal microbial solution). Each group had 10 replicates and 6 chicks per replicate. The pooled cecal sample as well as saline was administered via oral gavage once daily from day 1 to day 10, and then boosted on days 16, 23, and 30. One bird from each replicate was randomly taken for sample collection at day 34 (n=10). The results showed that CMT chicks had significantly higher Ca and P retention rates than CONT chicks. The mRNA expressions of intestinal Ca transporters, CaBP-D28K and VDR in the ileum and NCX1 in the jejunum, were also upregulated in CMT chicks. Additionally, the mRNA expression of a tight junction protein, ZO-1, was upregulated in the duodenum of CMT chicks. CMT chicks also had higher mRNA expressions of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α, in the intestinal tract. Furthermore, CMT chicks had a more diverse and mature gut microbial community compared to CONT chicks. The relative abundances of SCFA-produced bacteria (e.g., Bacteroides, Rikenellaceae_RC9_gut_group, and Prevotellaceae_UCG-001) were increased, while the relative abundances of Alistipes, Lactobacillus, and Barnesiella were reduced in CMT chicks. However, there were no CMT effects on body weight, organ indexes, bone morphology, and gene expression-associated with bone metabolism. This study demonstrates that transferring cecal bacteria from adult laying hens enhances calcium absorption and retention in newly hatched chicks by upregulating key calcium transporters and enhancing intestinal barrier integrity via modulating the gut microbiome.},
}

Animals
*Chickens/microbiology/genetics/metabolism/growth & development/physiology
*Gastrointestinal Microbiome/physiology
Cecum/microbiology
Female
*Fecal Microbiota Transplantation/veterinary
*Avian Proteins/metabolism/genetics
Random Allocation
*Gene Expression
*Calcium/metabolism

@article {pmid40898211,
year = {2025},
author = {Ma, X and Shi, W and Wang, Z and Li, S and Ma, R and Zhu, W and Wu, L and Feng, X and Cong, B and Li, Y},
title = {Butyric acid and valeric acid attenuate stress-induced ferroptosis and depressive-like behaviors by suppressing hippocampal neuroinflammation.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {974},
pmid = {40898211},
issn = {1479-5876},
support = {82130055//Key Projects of the National Natural Science Foundation of China/ ; 82293651//Major Projects of the National Natural Science Foundation of China/ ; 82072109//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Depression is closely associated with stress-induced hippocampal damage and dysfunction. Emerging evidence demonstrates that the gut microbiota and its metabolites, acting as probiotics or prebiotics, can modulate brain structure and function via the gut-brain axis, thereby offering therapeutic potential for ameliorating related neurological and psychiatric disorders. This study delves into the contribution of the gut microbiota and its metabolites to stress-induced ferroptosis of hippocampal neurons and the associated molecular pathways.

METHODS: This study used time-course stress paradigms combined with ferroptosis inhibitors to identify hippocampal neuronal ferroptosis. Fecal microbiota transplantation were conducted to analyze the role of gut microbiota in this process. Subsequently, 16 S rDNA sequencing and metabolomics techniques were applied to identify key gut microbiota and metabolites. Metabolites intervention were performed to examine their causal relationship with neuronal ferroptosis. Finally, we used histochemical and molecular assays to assess both intestinal and blood-brain barrier integrity as well as inflammation in peripheral blood and hippocampal tissue, along with GPR41/RhoA/Rock1 pathway changes, to preliminarily investigate the molecular mechanisms underlying stress-induced hippocampal neuronal ferroptosis.

RESULTS: We demonstrated that stress triggered hippocampal neuronal ferroptosis and subsequent depressive-like behaviors in mice. Fecal microbiota transplantation successfully replicated the ferroptosis phenotype. Butyric acid and valeric acid were identified as key metabolites significantly reduced in the serum of acutely and chronically stressed mice, respectively. Intervention with these metabolites markedly alleviated ferroptosis. Furthermore, valerate intervention increased hippocampal GPR41 expression and significantly suppressed the pro-inflammatory RhoA/Rock1 pathway in chronically stressed mice, thereby reducing neuroinflammation and ameliorating neuronal ferroptosis. However, butyrate intervention showed no significant effect on the GPR41/RhoA/Rock1 pathway.

CONCLUSION: Stress induces ferroptosis in hippocampal neurons, where reduced abundance of short-chain fatty acid-producing bacteria plays a key role. Key metabolites butyric acid and valeric acid alleviate neuroinflammation to improve ferroptosis via the gut-brain axis in acute and chronic stress, respectively. Specifically, valeric acid exerts neuroprotective effect through the GPR41/RhoA/Rock1 pathway, whereas butyric acid-mediated protection likely operates through alternative mechanisms.},
}

@article {pmid40895486,
year = {2025},
author = {Ge, S and Zhang, S and She, L and Gu, T and Wang, S and Huang, X and Wang, L and Miao, M},
title = {Synergistic therapy of Chinese herbal medicine and gut microbiota modulation for post-stroke cognitive recovery: focus on microbial metabolite and immunoinflammation.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1623843},
doi = {10.3389/fmicb.2025.1623843},
pmid = {40895486},
issn = {1664-302X},
abstract = {Post-stroke cognitive impairment (PSCI), a common complication following stroke, significantly impacts patients' quality of life and rehabilitation. Recent studies have highlighted the role of gut microbiota and their metabolites in modulating immunoinflammation and cognitive function via the gut-brain axis. Traditional Chinese medicine (TCM) and microbiota interventions including probiotics and fecal microbiota transplantation, have shown potential in reshaping gut microbial communities and metabolite profiles. Some studies suggest that combining these approaches via identical or related therapeutic mechanisms may yield enhanced efficacy in treating Post-Stroke Cognitive Impairment (PSCI). These findings establish a theoretical foundation for future research and clinical practice. This review systematically examines the mechanistic role of gut microbial metabolites in neuroimmune modulation and comprehensively evaluates the therapeutic potential of combined TCM and microbiota-targeted therapies for PSCI, adopting a multifactorial approach that addresses neuroinflammation, microbial dysbiosis, and metabolic dysregulation.},
}

@article {pmid40895468,
year = {2025},
author = {Yang, J and Chen, J and Li, D and Wu, Q and Zhang, Y and Li, Y and Deng, Y},
title = {Hyperuricemia and the gut microbiota: current research hotspots and future trends.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1620561},
doi = {10.3389/fmicb.2025.1620561},
pmid = {40895468},
issn = {1664-302X},
abstract = {BACKGROUND: Hyperuricemia (HUA), found widely in humans and birds, is a key physiological factor responsible for the development of gout. In recent years, the relationship between the gut microbiota and HUA has garnered significant attention from researchers. This study aims to explore the current research hotspots, knowledge gaps, and future research trends regarding the gut microbiota and HUA.

METHODS: We performed a thorough search of the literature on gut flora and HUA published between 2005 and 2024 using the Web of Science and PubMed databases. The resulting data were analyzed using VOSviewer, CiteSpace, and Bibliometrix.

RESULTS: Including 735 papers in total, the study found that the number of publications in the subject increased significantly between 2020 and 2024, with 2024 being the year with the highest number of publications. The primary research countries are highlighted as China and the United States, with institutions such as the University of California, San Diego, and Qingdao University making significant contributions. Sanjay K. Nigam and Chenyang Lu have made the most important contributions as authors. Keywords analysis highlighted high-frequency terms including "gastrointestinal microbiome," "uric acid," "hyperuricemia," "inflammation," "gout," and "probiotics." In the visualization map of the keyword timeline, emerging research hotspots include "diets," "dietary fiber," "fecal microbiota transplantation," and "gut-kidney axis."

CONCLUSION: This study is the first to conduct a quantitative literature analysis in the field of gut microbiota in HUA, revealing that the core research hotspots include disease-related microbiota characteristics, probiotic therapy, microecological intervention, and the gut-distal target organ axis. The emerging hotspots focus on dietary supplementation, fecal microbiota transplantation (FMT) treatment strategies, and in-depth research on the above organ axes. Provide valuable guidance for future research directions.},
}

@article {pmid40895097,
year = {2025},
author = {Jin, Y and Wang, H and Song, J},
title = {Gut-brain axis modulation in remote rehabilitation of Parkinson's disease: reconstructing the fecal metabolome and nigral network connectivity.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1644490},
doi = {10.3389/fneur.2025.1644490},
pmid = {40895097},
issn = {1664-2295},
abstract = {The pathogenesis of Parkinson's disease (PD) is gradually evolving from a central neurodegeneration-centered concept to a multi-pathway pathological model at the gut-brain system level. Studies have shown that PD patients commonly exhibit dysbiosis, reduced short-chain fatty acids (SCFAs; microbial fermentation products of dietary fiber that play key roles in host metabolism and immune regulation), abnormal tryptophan metabolism, and impaired gut barrier function. These alterations may contribute to dopaminergic neuronal damage through mechanisms including neuroinflammation, oxidative stress, and α-synuclein (α-syn) aggregation. The vagus nerve plays a critical role in bidirectional gut-brain signaling, and its dysfunction may represent a key route for pathological protein transmission from the periphery to the brain. In response, remote rehabilitation and gut-targeted interventions-including probiotics, prebiotics, dietary modulation, fecal microbiota transplantation (FMT), and transcutaneous vagus nerve stimulation (tVNS)-have shown potential in improving neurological function and inflammation in both animal and clinical studies. Multimodal data analyses have revealed significant associations between SCFA levels in fecal metabolomics and brain imaging features. Despite ongoing challenges in mechanistic extrapolation, biomarker sensitivity, and translational implementation, the integration of metagenomics, metabolomics, neuroimaging, and digital therapeutics-collectively referred to as multi-omics and digital profiling techniques-represents an emerging research direction with the potential to inform future clinical paradigms for precision remote management of PD.},
}

@article {pmid40894980,
year = {2025},
author = {Wang, YM},
title = {How to Approach Immune Checkpoint Inhibitor Enterocolitis.},
journal = {Gastroenterology & hepatology},
volume = {21},
number = {8},
pages = {501-503},
pmid = {40894980},
issn = {1554-7914},
}

@article {pmid40894608,
year = {2025},
author = {Lopez, ML and Kang, T and Espeleta, A and Rubtsova, VI and Baek, J and Songcuan, J and Moyer, EM and Kim, J and Song, WS and Jung, S and D'Sa, N and Anica, A and Tran, E and Chun, Y and Choi, W and Jang, KH and Kelly, ME and Tamburini, IJ and Alam, YH and Le, J and Ramirez, CB and Kataru, RP and Hong, SP and Nicholas, DA and Xue, KS and Lee, G and Bae, H and Jang, C},
title = {Intestinal catabolism of dietary fructose promotes obesity and insulin resistance via ileal lacteal remodeling.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.18.670963},
pmid = {40894608},
issn = {2692-8205},
abstract = {UNLABELLED: High-fructose corn syrup (HFCS) consumption is a risk factor for obesity and metabolic syndrome, yet the underlying mechanisms are incompletely understood. Catabolism of dietary fructose primarily occurs in the small intestine and liver, with fructose breakdown in the liver being pathological, while small intestinal fructose clearance protects the liver. Here, we unexpectedly found that inhibition of fructose catabolism specifically in the small intestine mitigates fructose-induced obesity and insulin resistance. Mechanistically, blocking intestinal fructose catabolism reduces dietary fat absorption, which is associated with a decrease in the surface area of the ileal lacteals and alterations in gut microbiome. Fecal transplantation experiments revealed that such a microbiome stimulates the intestine-resident macrophages, promoting lacteal growth and boosting dietary fat absorption. Given the preclinical and clinical studies reporting the effect of fructose catabolism suppression on mitigating diet-induced obesity, our data suggest that such effects are partly mediated by intestinal lacteal remodeling.

SIGNIFICANCE STATEMENT: Here, we uncover a previously unappreciated link between intestinal fructose catabolism and ileal lacteal remodeling, suggesting the mechanisms by which fructose intake promotes obesity. Using mice lacking the fructose-processing enzyme specifically in the intestine, we show that blocking intestinal fructose metabolism protects against diet-induced obesity by reducing fat absorption. Changes in gut microbiome and immune cell interactions drive this effect.},
}

@article {pmid40894444,
year = {2025},
author = {Xu, P},
title = {Gut Microbiota Metabolites Targeting the Immune Response in Sepsis: Mechanisms and Therapies.},
journal = {International journal of general medicine},
volume = {18},
number = {},
pages = {4709-4734},
doi = {10.2147/IJGM.S539237},
pmid = {40894444},
issn = {1178-7074},
abstract = {Sepsis is a global health challenge, affecting millions annually and remaining a leading cause of mortality in intensive care units. Gut microbiota plays a complex role in the onset and progression of sepsis, with its alterations reflecting disease severity. Recently, modulating gut microbiota and its metabolites has emerged as a promising therapeutic strategy for sepsis. This review highlights the role of gut microbiota in sepsis and systematically identifies key immune response targets directly influenced by gut microbiota metabolites, such as short-chain fatty acids (SCFAs), bile acids, and indoleacetic acid, among other important metabolites. Additionally, it offers a full overview of current research on gut microbiota-regulated therapeutic approaches, including fecal microbiota transplantation (FMT) and artificial intelligence (AI) applications. These insights offer a novel perspective for advancing the understanding of sepsis pathogenesis and its treatment.},
}

@article {pmid40893829,
year = {2025},
author = {Allegretti, JR},
title = {Current Status of Fecal Microbiota Transplantation for Inflammatory Bowel Disease Management.},
journal = {Gastroenterology & hepatology},
volume = {21},
number = {7},
pages = {451-453},
pmid = {40893829},
issn = {1554-7914},
}

@article {pmid40891897,
year = {2025},
author = {Bertin, L and Bonazzi, E and Facchin, S and Lorenzon, G and Maniero, D and DE Barba, C and Tomasulo, A and Fortuna, A and Zingone, F and Barberio, B and Savarino, EV},
title = {The microbiota-brain connection in neurological diseases: the ubiquitous short-chain fatty acids.},
journal = {Minerva gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.23736/S2724-5985.25.03866-5},
pmid = {40891897},
issn = {2724-5365},
abstract = {The connection between the gut and brain forms a sophisticated two-way communication system where compounds produced by intestinal bacteria, especially short-chain fatty acids, play essential roles in brain-related disease processes. Evidence across multiple neurological disorders reveals convergent pathophysiological pathways involving SCFAs, which modulate neurological function via histone deacetylase inhibition, G-protein coupled receptor activation, and blood-brain barrier regulation. Clinical investigations demonstrate disorder-specific signatures: reduced butyrate-producing bacteria correlate with Parkinson's disease progression; Alzheimer's disease exhibits significant reductions in key SCFAs; and diminished butyrate production disrupts immunoregulatory homeostasis in multiple sclerosis. Additionally, neurodevelopmental disorders like autism show distinctive microbiome alterations affecting both gut and brain function. Beyond SCFAs, microbiota influence neural communication through immune modulation, neurotransmitter production, and vagus nerve signaling. Interventional studies targeting the microbiome through precision probiotics, prebiotics, and fecal microbiota transplantation demonstrate preliminary efficacy, particularly in Parkinson's disease and autism. Methodological heterogeneity and challenges establishing causality remain significant limitations. Future priorities include longitudinal characterization of microbiome dynamics preceding symptom onset, development of personalized therapeutics, and implementation of predictive computational models. Progress in these domains could transform microbiome-based approaches from experimental interventions to precision medicine applications in neurological disease management.},
}

@article {pmid40890737,
year = {2025},
author = {Lu, G and Zhang, S and Wang, R and Wu, X and Chen, Y and Wen, Q and Cui, B and Zhang, F and Li, P},
title = {Fecal microbiota transplantation improves bile acid malabsorption in patients with inflammatory bowel disease: results of microbiota and metabolites from two cohort studies.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {511},
pmid = {40890737},
issn = {1741-7015},
support = {81873548//National Natural Science Foundation of China/ ; 82100583//National Natural Science Foundation of China/ ; 2020-3//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; },
abstract = {BACKGROUND: Bile acid malabsorption (BAM) or bile acid diarrhea (BAD) complicates more than 30% of Crohn's disease (CD), yet no non-invasive biomarker reliably identifies patients who will benefit from fecal microbiota transplantation (FMT). We investigated whether serum 7α-hydroxy-4-cholesten-3-one (C4), a hepatic bile-acid synthesis precursor, can predict BAM and FMT response in inflammatory bowel disease (IBD).

METHODS: We included 106 pairs of IBD patients treated with FMT from two longitudinal cohorts of prospective trials and 24 matched healthy individuals to identify a multi-omics analysis of microbiota-metabolism and evaluate real-world effectiveness of FMT. Fecal and serum samples before and after FMT along with medical information were collected and detected through 16S rRNA amplicon sequencing and untargeted liquid chromatography mass spectrometry. Mice models were used to preliminarily verify the exacerbation of colitis through administration of primary BAs and treated by FMT.

RESULTS: Patients in BAM group tended to achieve sustained higher and stable clinical response (66.67% vs. 49.41%) and remission (52.38% vs. 40.00%) than non-BAM group at 3 months after FMT, along with a significantly decrease of C4 (P < 0.001), improvement of obvious abdominal pain and diarrhea, which was especially obvious in CD patients with ileal resection and ileal /ileocolonic type. Random forest classifiers predicted BAM in IBD patients with 18 or top 4 differential OTUs, showing an area under the curve of 0.92 and 0.83, respectively. Furthermore, results from primary bile acid-induced colitis mice models reinforced these findings.

CONCLUSIONS: Serum C4 and a minimal gut microbiota may identify IBD patients with BAM who are most likely to achieve durable remission after FMT. These translatable biomarkers can guide precision use of microbiota-directed therapy.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01790061 and NCT01793831.},
}

@article {pmid40889045,
year = {2025},
author = {Wang, H and Wang, Y and Wu, H and Shen, C and Li, Y and Bai, B and Sun, X and Liu, Y and Zhang, Q and Shi, L},
title = {High-fat diet-induced obesity-related hypertension via altered gut microbiota-mediated histone butyrylation.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {40889045},
issn = {1869-1889},
abstract = {Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life. Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation, but the specific alterations and pathogenic mechanisms of gut microbiota in obesity-related hypertension (OrHTN) remain unclear. In this study, we observed a significant proliferation of Desulfobacterota and Proteobacteria, while a decrease in the abundance of several butyrate-producing bacterial genera, accompanied by decreased fecal and plasma butyrate levels in high-fat diet (HFD)-induced OrHTN rats. Histone 3 lysine 9 butyrylation (H3K9bu) modification in the kidney of OrHTN rats was reduced and downregulated the expression of the hypertension-related gene MAS1. Subsequent transplantation of cecal contents from OrHTN rats on HFD into recipient rats on a normal chow diet resulted in hypertension but without obesity. Furthermore, in vitro experiments suggested that sodium butyrate increased H3K9bu modification and the expression of MAS1 in a concentration-dependent manner. In conclusion, our findings suggest that gut microbiota may contribute to the development of OrHTN by altering the expression of hypertension-related genes through butyrate-mediated histone butyrylation. This work may provide new insights into the prevention and treatment of hypertension by targeting the regulation of gut microbiota and metabolites.},
}

@article {pmid40886868,
year = {2025},
author = {Wang, Z and Ren, X and Peng, Z and Zeng, M and Wang, Z and Chen, Q and Chen, J and Dai, X and Christian, M and Qie, X and He, Z},
title = {Flavonoid-rich extracts of Nelumbo nucifera leaves alleviate obesity in HFD-fed mice via microbiota-dependent modulation of brown fat thermogenesis.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120513},
doi = {10.1016/j.jep.2025.120513},
pmid = {40886868},
issn = {1872-7573},
abstract = {Nelumbo nucifera Gaertn (lotus) leaf is a commonly used traditional Chinese herbal medicine with a wide range of pharmacological properties, especially lipid-lowering and weight-loss effects. Accumulating evidence highlights activation of the thermogenic program of brown adipose tissue (BAT) as a promising anti-obesity strategy. However, it remains unclear whether such beneficial metabolic effects induced by the lotus leaf are related to its regulatory role in BAT function.

AIM OF THE STUDY: This work aims to investigate whether the lotus leaf reduces obesity by activating BAT and to elucidate whether the mechanism behind it is related to the regulation of gut microbiota.

MATERIAL AND METHODS: A mouse model of obesity was established using a high-fat diet (HFD), and the anti-obesity effect of flavonoid-rich lotus leaf extract (LLE) was determined in vivo. An animal energy metabolism monitoring system confirmed that LLE promoted energy expenditure. Then, RT-qPCR, immunohistochemistry, and Western blotting were conducted to detect the expression of genes and proteins involved in BAT thermogenesis. Subsequently, the underlying mechanisms were demonstrated by 16S rRNA gene sequencing and non-targeted metabolism analysis. Finally, fecal microbiota transplantation (FMT) was performed to investigate the LLE-dependent alleviation of obesity via the gut microbiota-BAT axis.

RESULTS: Our study demonstrated that LLE effectively reduced weight gain, ameliorated glucolipid disorders, and enhanced energy expenditure in HFD-fed mice. Notably, LLE augmented BAT activity by increasing thermogenic markers (e.g., SIRT1, PGC-1α, UCP1) and repressing inflammatory responses, potentially through activation of β3-AR/AMPK/p38 signaling pathways. Importantly, LLE could mitigate HFD-induced microbial dysbiosis (decrease in Proteobacteria, Verrucomicbiota, Acidobacteriota, Bacteroides, Dubosiella, and increase in Bilophila, Tyzzerella, Oscillibacter, Akkermansia, and Alistipes) and significantly altered 5 metabolite pathways, especially primary bile acid biosynthesis and linoleic acid metabolism. The FMT experiment confirmed that the microbial changes induced by LLE were associated with reduced body weight, enhanced energy expenditure, increased BAT activity, and thermogenesis.

CONCLUSIONS: Collectively, our findings reveal that lotus leaf promotes brown fat thermogenesis by modulating gut microbiota, identifying it as a promising new treatment target for obesity.},
}

@article {pmid40886596,
year = {2025},
author = {Li, W and Wang, N and Lyu, D and Yu, X and He, X and Yu, K and Qiu, Y and Jiao, X},
title = {Gut dysbiosis mediates neurotoxic effects of environmentally relevant tylosin exposure in adult zebrafish.},
journal = {Ecotoxicology and environmental safety},
volume = {303},
number = {},
pages = {118960},
doi = {10.1016/j.ecoenv.2025.118960},
pmid = {40886596},
issn = {1090-2414},
abstract = {Tylosin, a widely used veterinary macrolide antibiotic, raises environmental concerns due to its persistence and potential health risks. However, the neurotoxic effects of chronic low-dose tylosin exposure remain unclear. This study assessed the neurotoxicity of chronic exposure to environmentally relevant tylosin concentrations (5000 ng/L) in adult zebrafish. Behavioral tests indicated anxiety- and depression-like behaviors, including reduced exploration and increased freezing. Histopathology revealed neuronal degeneration, evidenced by decreased Nissl staining in key brain areas. Transcriptomic analysis identified significant changes in genes related to neuroinflammation, synaptic dysfunction, immune response, and steroid metabolism. Multi-omics approaches further showed substantial alterations in gut microbiota composition and metabolic profiles, particularly involving tryptophan metabolism and steroid hormone synthesis. These gut changes correlated with impaired intestinal barrier function, including fewer goblet cells and reduced tight junction and mucin-2 protein expression. Fecal microbiota transplantation confirmed the role of altered gut microbiota in inducing anxiety- and depression-like behaviors, highlighting microbiota-gut-brain axis involvement. Molecular docking identified microbial metabolites (MG 20:4, 2E-dodecenedioic acid, Ononin) interacting with critical neurodevelopmental and stress-response proteins (LRAT, BHLHE40, HSPA5), potentially linking microbiota shifts to brain dysfunction. Our results demonstrate that chronic environmental tylosin exposure induces neurotoxicity through gut dysbiosis and compromised intestinal barriers, disrupting essential neuroactive pathways. These findings emphasize the importance of considering microbiota-gut-brain axis disruption in environmental antibiotic risk assessments.},
}